Diagnostic and Prognostic Utility of the Synaptic Marker Neurogranin in Alzheimer Disease.

PubMed

Tarawneh, Rawan; D'Angelo, Gina; Crimmins, Dan; Herries, Elizabeth; Griest, Terry; Fagan, Anne M; Zipfel, Gregory J; Ladenson, Jack H; Morris, John C; Holtzman, David M

2016-05-01

Synaptic loss is an early pathologic substrate of Alzheimer disease (AD). Neurogranin is a postsynaptic neuronal protein that has demonstrated utility as a cerebrospinal fluid (CSF) marker of synaptic loss in AD. To investigate the diagnostic and prognostic utility of CSF neurogranin levels in a large, well-characterized cohort of individuals with symptomatic AD and cognitively normal controls. A cross-sectional and longitudinal observational study of cognitive decline in patients with symptomatic AD and cognitively normal controls was performed. Participants were individuals with a clinical diagnosis of early symptomatic AD and cognitively normal controls who were enrolled in longitudinal studies of aging and dementia at the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, from January 21, 2000, through March 21, 2011. Data analysis was performed from November 1, 2013, to March 31, 2015. Correlations between baseline CSF biomarker levels and future cognitive decline in patients with symptomatic AD and cognitively normal controls over time. A total of 302 individuals (mean [SE] age, 73.1 [0.4] years) were included in this study (95 patients [52 women and 43 men] with AD and 207 controls [125 women and 82 men]). The CSF neurogranin levels differentiated patients with early symptomatic AD from controls with comparable diagnostic utility (mean [SE] area under the receiver operating characteristic curve, 0.71 [0.03]; 95% CI, 0.64-0.77) to the other CSF biomarkers. The CSF neurogranin levels correlated with brain atrophy (normalized whole-brain volumes: adjusted r = -0.38, P = .02; hippocampal volumes: adjusted r = -0.36, P = .03; entorhinal volumes: adjusted r = -0.46, P = .006; and parahippocampal volumes: adjusted r = -0.47, P = .005, n = 38) in AD and with amyloid load (r = 0.39, P = .02, n = 36) in preclinical AD. The CSF neurogranin levels predicted future cognitive impairment (adjusted hazard ratio, 1.89; 95% CI, 1.29-2.78; P = .001 as a continuous measure, and adjusted hazard ratio, 2.78; 95% CI, 1.13-5.99; P = .02 as a categorical measure using the 85th percentile cutoff value) in controls and rates of cognitive decline (Clinical Dementia Rating sum of boxes score: β estimate, 0.29; P = .001; global composite scores: β estimate, -0.11; P = .001; episodic memory scores: β estimate, -0.18; P < .001; and semantic memory scores: β estimate, -0.06; P = .04, n = 57) in patients with symptomatic AD over time, similarly to the CSF proteins VILIP-1, tau, and p-tau181. The CSF levels of the synaptic marker neurogranin offer diagnostic and prognostic utility for early symptomatic AD that is comparable to other CSF markers of AD. Importantly, CSF neurogranin complements the collective ability of these markers to predict future cognitive decline in cognitively normal individuals and, therefore, will be a useful addition to the current panel of AD biomarkers.

Relationship between financial competence and cognitive function in patients with schizophrenia.

PubMed

Niekawa, Nobuyuki; Sakuraba, Yukie; Uto, Hanae; Kumazawa, Yoshiko; Matsuda, Osamu

2007-10-01

The present study examined financial competence in patients with schizophrenia and the relationship between their financial competence and cognitive function. The subjects consisted of 25 patients with schizophrenia (10 inpatients and 15 outpatients) and 22 normal controls who were community-dwelling people with no psychiatric disorders or cognitive deficit. To assess the subjects' cognitive function and financial competence, they completed the Japanese version of the Neurobehavioral Cognitive Status Examination (COGNISTAT), which has 10 subtests, and the Financial Competency Assessment Tool (FCAT), which has six subordinate domains of financial competence. Patients with schizophrenia performed significantly worse than the controls in all scores on the FCAT. The financial scores that were significantly different between the patients and the normal controls were significantly positively correlated with the scores on several COGNISTAT subtests (e.g. comprehension). These results suggest that patients with schizophrenia have problems with financial competence and that these problems may be accounted for by deficits in several cognitive functions.

Predictors of cognitive impairment in an early stage Parkinson's disease cohort.

PubMed

Hu, Michele T M; Szewczyk-Królikowski, Konrad; Tomlinson, Paul; Nithi, Kannan; Rolinski, Michal; Murray, Clara; Talbot, Kevin; Ebmeier, Klaus P; Mackay, Clare E; Ben-Shlomo, Yoav

2014-03-01

The impact of Parkinson's disease (PD) dementia is substantial and has major functional and socioeconomic consequences. Early prediction of future cognitive impairment would help target future interventions. The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), and fluency tests were administered to 486 patients with PD within 3.5 years of diagnosis, and the results were compared with those from 141 controls correcting for age, sex, and educational years. Eighteen-month longitudinal assessments were performed in 155 patients with PD. The proportion of patients classified with normal cognition, mild cognitive impairment (MCI), and dementia varied considerably, depending on the MoCA and MMSE thresholds used. With the MoCA total score at screening threshold, 47.7%, 40.5%, and 11.7% of patients with PD were classified with normal cognition, MCI, and dementia, respectively; by comparison, 78.7% and 21.3% of controls had normal cognition and MCI, respectively. Cognitive impairment was predicted by lower education, increased age, male sex, and quantitative motor and non-motor (smell, depression, and anxiety) measures. Longitudinal data from 155 patients with PD over 18 months showed significant reductions in MoCA scores, but not in MMSE scores, with 21.3% of patients moving from normal cognition to MCI and 4.5% moving from MCI to dementia, although 13.5% moved from MCI to normal; however, none of the patients with dementia changed their classification. The MoCA may be more sensitive than the MMSE in detecting early baseline and longitudinal cognitive impairment in PD, because it identified 25.8% of those who experienced significant cognitive decline over 18 months. Cognitive decline was associated with worse motor and non-motor features, suggesting that this reflects a faster progressive phenotype. © 2014 The Authors. International Parkinson and Movement Disorder Society published by Wiley Periodicals, Inc.

Diagnostic transitions in mild cognitive impairment subtypes.

PubMed

Forlenza, Orestes Vicente; Diniz, Breno Satler; Nunes, Paula Villela; Memória, Claudia Maia; Yassuda, Monica Sanches; Gattaz, Wagner Farid

2009-12-01

At least for a subset of patients, the clinical diagnosis of mild cognitive impairment (MCI) may represent an intermediate stage between normal aging and dementia. Nevertheless, the patterns of transition of cognitive states between normal cognitive aging and MCI to dementia are not well established. In this study we address the pattern of transitions between cognitive states in patients with MCI and healthy controls, prior to the conversion to dementia. 139 subjects (78% women, mean age, 68.5 +/- 6.1 years; mean educational level, 11.7 +/- 5.4 years) were consecutively assessed in a memory clinic with a standardized clinical and neuropsychological protocol, and classified as cognitively healthy (normal controls) or with MCI (including subtypes) at baseline. These subjects underwent annual reassessments (mean duration of follow-up: 2.7 +/- 1.1 years), in which cognitive state was ascertained independently of prior diagnoses. The pattern of transitions of the cognitive state was determined by Markov chain analysis. The transitions from one cognitive state to another varied substantially between MCI subtypes. Single-domain MCI (amnestic and non-amnestic) more frequently returned to normal cognitive state upon follow-up (22.5% and 21%, respectively). Among subjects who progressed to Alzheimer's disease (AD), the most common diagnosis immediately prior conversion was multiple-domain MCI (85%). The clinical diagnosis of MCI and its subtypes yields groups of patients with heterogeneous patterns of transitions between one given cognitive state to another. The presence of more severe and widespread cognitive deficits, as indicated by the group of multiple-domain amnestic MCI may be a better predictor of AD than single-domain amnestic or non-amnestic deficits. These higher-risk individuals could probably be the best candidates for the development of preventive strategies and early treatment for the disease.

Targeting Neural Synchrony Deficits is Sufficient to Improve Cognition in a Schizophrenia-Related Neurodevelopmental Model

PubMed Central

Lee, Heekyung; Dvorak, Dino; Fenton, André A.

2014-01-01

Cognitive symptoms are core features of mental disorders but procognitive treatments are limited. We have proposed a “discoordination” hypothesis that cognitive impairment results from aberrant coordination of neural activity. We reported that neonatal ventral hippocampus lesion (NVHL) rats, an established neurodevelopmental model of schizophrenia, have abnormal neural synchrony and cognitive deficits in the active place avoidance task. During stillness, we observed that cortical local field potentials sometimes resembled epileptiform spike-wave discharges with higher prevalence in NVHL rats, indicating abnormal neural synchrony due perhaps to imbalanced excitation–inhibition coupling. Here, within the context of the hypothesis, we investigated whether attenuating abnormal neural synchrony will improve cognition in NVHL rats. We report that: (1) inter-hippocampal synchrony in the theta and beta bands is correlated with active place avoidance performance; (2) the anticonvulsant ethosuximide attenuated the abnormal spike-wave activity, improved cognitive control, and reduced hyperlocomotion; (3) ethosuximide not only normalized the task-associated theta and beta synchrony between the two hippocampi but also increased synchrony between the medial prefrontal cortex and hippocampus above control levels; (4) the antipsychotic olanzapine was less effective at improving cognitive control and normalizing place avoidance-related inter-hippocampal neural synchrony, although it reduced hyperactivity; and (5) olanzapine caused an abnormal pattern of frequency-independent increases in neural synchrony, in both NVHL and control rats. These data suggest that normalizing aberrant neural synchrony can be beneficial and that drugs targeting the pathophysiology of abnormally coordinated neural activities may be a promising theoretical framework and strategy for developing treatments that improve cognition in neurodevelopmental disorders such as schizophrenia. PMID:24592242

The characteristics of patients with uncertain/mild cognitive impairment on the Alzheimer disease assessment scale-cognitive subscale.

PubMed

Pyo, Geunyeong; Elble, Rodger J; Ala, Thomas; Markwell, Stephen J

2006-01-01

The performances of the uncertain/mild cognitive impairment (MCI) patients on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) subscale were compared with those of normal controls, Alzheimer disease patients with CDR 0.5, and Alzheimer disease patients with CDR 1.0. The Uncertain/MCI group was significantly different from normal controls and Alzheimer disease CDR 0.5 or 1.0 groups on the ADAS-Cog except on a few non-memory subtests. Age was significantly correlated with total error score in the normal group, but there was no significant correlation between age and ADAS-Cog scores in the patient groups. Education was not significantly correlated with the ADAS-Cog scores in any group. Regardless of age and educational level, there were clear differences between the normal group and the Uncertain/MCI group, especially on the total error scores. We found that the total error score of the ADAS-Cog was the most reliable variable in detecting patients with mild cognitive impairment. The present study demonstrated that the ADAS-Cog is a promising tool for detecting and studying patients with mild cognitive impairment. The results also indicated that demographic variables such as age and education do not play a significant role in the diagnosis of mild cognitive impaired patients based on the ADAS-Cog scores.

[Characteristics of cerebral glucose metabolism in patients with cognitive impairment in Parkinson's disease].

PubMed

Homenko, Ju G; Susin, D S; Kataeva, G V; Irishina, Ju A; Zavolokov, I G

To study the relationship between early cognitive impairment symptoms and cerebral glucose metabolism in different brain regions (according to the positron emission tomography (PET) data) in Parkinson's disease (PD) in order to increase the diagnostic and treatment efficacy. Two groups of patients with PD (stage I-III), including 11 patients without cognitive disorders and 13 with mild cognitive impairment (MCI), were examined. The control group included 10 age-matched people with normal cognition. To evaluate cognitive state, the Mini mental state examination (MMSE), the Frontal assessment battery (FAB) and the 'clock drawing test' were used. The regional cerebral glucose metabolism rate (CMRglu) was assessed using PET with 18F-fluorodeoxyglucose (FDG). In PD patients, CMRglu were decreased in the frontal (Brodmann areas (BA) 9, 10, 11, 46, 47), occipital (BA 19) and parietal (BA 39), temporal (BA 20, 37), and cingulate cortex (BA 32) compared to the control group. Cerebral glucose metabolism was decreased in the frontal (BA 8, 9, 10, 45, 46, 47), parietal (BA 7, 39, 40) and cingulate cortex (BA 23, 24, 31, 32) in the group of PD patients with MCI compared to PD patients with normal cognition. Hypometabolism in BA 7, 8, 23, 24, 31, 40 was revealed only in comparison of PD and PD-MCI groups, and did not appear in case of comparison of cognitively normal PD patients with the control group. It is possible to suggest that the mentioned above brain areas were associated with cognitive impairment. The revealed glucose hypometabolism pattern possibly has the diagnostic value for the early and preclinical diagnosis of MCI in PD and control of treatment efficacy.

Getting better, but not well: A 1.5 year follow-up of cognitive performance and cortisol levels in clinical and non-Clinical burnout.

PubMed

Oosterholt, Bart G; Maes, Joseph H R; Van der Linden, Dimitri; Verbraak, Marc J P M; Kompier, Michiel A J

2016-05-01

The purpose was to reexamine cognitive performance and cortisol levels of initial clinical burnout patients, non-clinical burnout individuals, and healthy controls. After 1.5-years of the initial measurement, clinical burnout patients showed a reduction of burnout symptoms and general physical and psychological complaints, but these were still elevated compared with controls. Nonetheless, they continued to report cognitive problems and still showed a minor impaired cognitive test performance. However, they no longer reported larger subjective costs associated with cognitive test performance and their cortisol awakening response (CAR) returned to a normal level. Compared with controls, non-clinical burnout individuals still reported the same, elevated, level of burnout symptoms, general physical and psychological complaints, and cognitive problems. Their cognitive test performance and associated subjective costs remained normal. However, they seemed to continue to display a lowered CAR. To conclude, after 1.5-years, clinical burnout patients got better, but not 'well', and non-clinical burnout individuals remained not 'well'. Copyright © 2016 Elsevier B.V. All rights reserved.

Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

PubMed

Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

2016-02-01

Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized.

Normal Genetic Variation, Cognition, and Aging

PubMed Central

Greenwood, P. M.; Parasuraman, Raja

2005-01-01

This article reviews the modulation of cognitive function by normal genetic variation. Although the heritability of “g” is well established, the genes that modulate specific cognitive functions are largely unidentified. Application of the allelic association approach to individual differences in cognition has begun to reveal the effects of single nucleotide polymorphisms on specific and general cognitive functions. This article proposes a framework for relating genotype to cognitive phenotype by considering the effect of genetic variation on the protein product of specific genes within the context of the neural basis of particular cognitive domains. Specificity of effects is considered, from genes controlling part of one receptor type to genes controlling agents of neuronal repair, and evidence is reviewed of cognitive modulation by polymorphisms in dopaminergic and cholinergic receptor genes, dopaminergic enzyme genes, and neurotrophic genes. Although allelic variation in certain genes can be reliably linked to cognition—specifically to components of attention, working memory, and executive function in healthy adults—the specificity, generality, and replicability of the effects are not fully known. PMID:15006290

Effects of Noise Level and Cognitive Function on Speech Perception in Normal Elderly and Elderly with Amnestic Mild Cognitive Impairment.

PubMed

Lee, Soo Jung; Park, Kyung Won; Kim, Lee-Suk; Kim, HyangHee

2016-06-01

Along with auditory function, cognitive function contributes to speech perception in the presence of background noise. Older adults with cognitive impairment might, therefore, have more difficulty perceiving speech-in-noise than their peers who have normal cognitive function. We compared the effects of noise level and cognitive function on speech perception in patients with amnestic mild cognitive impairment (aMCI), cognitively normal older adults, and cognitively normal younger adults. We studied 14 patients with aMCI and 14 age-, education-, and hearing threshold-matched cognitively intact older adults as experimental groups, and 14 younger adults as a control group. We assessed speech perception with monosyllabic word and sentence recognition tests at four noise levels: quiet condition and signal-to-noise ratio +5 dB, 0 dB, and -5 dB. We also evaluated the aMCI group with a neuropsychological assessment. Controlling for hearing thresholds, we found that the aMCI group scored significantly lower than both the older adults and the younger adults only when the noise level was high (signal-to-noise ratio -5 dB). At signal-to-noise ratio -5 dB, both older groups had significantly lower scores than the younger adults on the sentence recognition test. The aMCI group's sentence recognition performance was related to their executive function scores. Our findings suggest that patients with aMCI have more problems communicating in noisy situations in daily life than do their cognitively healthy peers and that older listeners with more difficulties understanding speech in noise should be considered for testing of neuropsychological function as well as hearing.

C145 as a short-latency electrophysiological index of cognitive compensation in Alzheimer's disease

PubMed Central

Chapman, Robert M.; Porsteinsson, Anton P.; Gardner, Margaret N.; Mapstone, Mark; McCrary, John W.; Sandoval, Tiffany C.; Guillily, Maria D.; DeGrush, Elizabeth; Reilly, Lindsey A.

2012-01-01

Brain plasticity and cognitive compensation in the elderly are of increasing interest, and Alzheimer's disease (AD) offers an opportunity to elucidate how the brain may overcome damage. We provide neurophysiological evidence of a short-latency ERP component (C145) linked to stimulus relevancy that may reflect cognitive compensation in early-stage Alzheimer's disease (AD). Thirty-six subjects with early-stage, mild AD and 36 like-aged normal elderly (Controls) had their EEG recorded while performing our Number-Letter task, a cognitive/perceptual paradigm that manipulates stimulus relevancies. ERP components, including C145, were extracted from ERPs using Principal Components Analysis. C145 amplitudes and spatial distributions were compared among Controls, AD subjects with high performance on the Number-Letter task, and AD subjects with low performance. Compared to AD subjects, Control subjects showed enhanced C145 processing of visual stimuli in the occipital region where differential processing of relevant stimuli occurred. AD high performers recruited central brain areas in processing task relevancy. Controls and AD low performers did not show a significant task relevancy effect in these areas. We conclude that short-latency ERP components can detect electrophysiological differences in early-stage AD that reflect altered cognition. Differences in C145 amplitudes between AD and normal elderly groups regarding brain locations and types of task effects suggest compensatory mechanisms can occur in the AD brain to overcome loss of normal functionality, and this early compensation may have a profound effect on the cognitive efficiency of AD individuals. PMID:22886016

Screening for cognitive impairment in older individuals. Validation study of a computer-based test.

PubMed

Green, R C; Green, J; Harrison, J M; Kutner, M H

1994-08-01

This study examined the validity of a computer-based cognitive test that was recently designed to screen the elderly for cognitive impairment. Criterion-related validity was examined by comparing test scores of impaired patients and normal control subjects. Construct-related validity was computed through correlations between computer-based subtests and related conventional neuropsychological subtests. University center for memory disorders. Fifty-two patients with mild cognitive impairment by strict clinical criteria and 50 unimpaired, age- and education-matched control subjects. Control subjects were rigorously screened by neurological, neuropsychological, imaging, and electrophysiological criteria to identify and exclude individuals with occult abnormalities. Using a cut-off total score of 126, this computer-based instrument had a sensitivity of 0.83 and a specificity of 0.96. Using a prevalence estimate of 10%, predictive values, positive and negative, were 0.70 and 0.96, respectively. Computer-based subtests correlated significantly with conventional neuropsychological tests measuring similar cognitive domains. Thirteen (17.8%) of 73 volunteers with normal medical histories were excluded from the control group, with unsuspected abnormalities on standard neuropsychological tests, electroencephalograms, or magnetic resonance imaging scans. Computer-based testing is a valid screening methodology for the detection of mild cognitive impairment in the elderly, although this particular test has important limitations. Broader applications of computer-based testing will require extensive population-based validation. Future studies should recognize that normal control subjects without a history of disease who are typically used in validation studies may have a high incidence of unsuspected abnormalities on neurodiagnostic studies.

Diagnostic and Prognostic Utility of the Synaptic Marker Neurogranin in Alzheimer Disease

PubMed Central

Tarawneh, Rawan; D’Angelo, Gina; Crimmins, Dan; Herries, Elizabeth; Griest, Terry; Fagan, Anne M.; Zipfel, Gregory J.; Ladenson, Jack H.; Morris, John C.; Holtzman, David M.

2016-01-01

IMPORTANCE Synaptic loss is an early pathologic substrate of Alzheimer disease (AD). Neurogranin is a postsynaptic neuronal protein that has demonstrated utility as a cerebrospinal fluid (CSF) marker of synaptic loss in AD. OBJECTIVE To investigate the diagnostic and prognostic utility of CSF neurogranin levels in a large, well-characterized cohort of individuals with symptomatic AD and cognitively normal controls. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional and longitudinal observational study of cognitive decline in patients with symptomatic AD and cognitively normal controls was performed. Participants were individuals with a clinical diagnosis of early symptomatic AD and cognitively normal controls who were enrolled in longitudinal studies of aging and dementia at the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University School of Medicine, from January 21, 2000, through March 21, 2011. Data analysis was performed from November 1, 2013, to March 31, 2015. MAIN OUTCOMES AND MEASURES Correlations between baseline CSF biomarker levels and future cognitive decline in patients with symptomatic AD and cognitively normal controls overtime. RESULTS A total of 302 individuals (mean [SE] age, 73.1 [0.4] years) were included in this study (95 patients [52 women and 43 men] with AD and 207 controls [125 women and 82 men]). The CSF neurogranin levels differentiated patients with early symptomatic AD from controls with comparable diagnostic utility (mean [SE] area under the receiver operating characteristic curve, 0.71 [0.03]; 95% CI, 0.64–0.77) to the other CSF biomarkers. The CSF neurogranin levels correlated with brain atrophy (normalized whole-brain volumes: adjusted r = −0.38, P = .02; hippocampal volumes: adjusted r = −0.36, P = .03; entorhinal volumes: adjusted r = −0.46, P = .006; and parahippocampal volumes: adjusted r = −0.47, P = .005, n = 38) in AD and with amyloid load (r = 0.39, P = .02, n = 36) in preclinical AD. The CSF neurogranin levels predicted future cognitive impairment (adjusted hazard ratio, 1.89; 95% CI, 1.29–2.78; P = .001 as a continuous measure, and adjusted hazard ratio, 2.78; 95% CI, 1.13–5.99; P = .02 as a categorical measure using the 85th percentile cutoff value) in controls and rates of cognitive decline (Clinical Dementia Rating sum of boxes score: β estimate, 0.29; P = .001; global composite scores: β estimate, −0.11; P = .001; episodic memory scores: β estimate, −0.18; P < .001; and semantic memory scores: β estimate, −0.06; P = .04, n = 57) in patients with symptomatic AD over time, similarly to the CSF proteins VILIP-1, tau, and p-tau181. CONCLUSIONS AND RELEVANCE The CSF levels of the synaptic marker neurogranin offer diagnostic and prognostic utility for early symptomatic AD that is comparable to other CSF markers of AD. Importantly, CSF neurogranin complements the collective ability of these markers to predict future cognitive decline in cognitively normal individuals and, therefore, will be a useful addition to the current panel of AD biomarkers. PMID:27018940

Interactions of the Salience Network and Its Subsystems with the Default-Mode and the Central-Executive Networks in Normal Aging and Mild Cognitive Impairment.

PubMed

Chand, Ganesh B; Wu, Junjie; Hajjar, Ihab; Qiu, Deqiang

2017-09-01

Previous functional magnetic resonance imaging (fMRI) investigations suggest that the intrinsically organized large-scale networks and the interaction between them might be crucial for cognitive activities. A triple network model, which consists of the default-mode network, salience network, and central-executive network, has been recently used to understand the connectivity patterns of the cognitively normal brains versus the brains with disorders. This model suggests that the salience network dynamically controls the default-mode and central-executive networks in healthy young individuals. However, the patterns of interactions have remained largely unknown in healthy aging or those with cognitive decline. In this study, we assess the patterns of interactions between the three networks using dynamical causal modeling in resting state fMRI data and compare them between subjects with normal cognition and mild cognitive impairment (MCI). In healthy elderly subjects, our analysis showed that the salience network, especially its dorsal subnetwork, modulates the interaction between the default-mode network and the central-executive network (Mann-Whitney U test; p < 0.05), which was consistent with the pattern of interaction reported in young adults. In contrast, this pattern of modulation by salience network was disrupted in MCI (p < 0.05). Furthermore, the degree of disruption in salience network control correlated significantly with lower overall cognitive performance measured by Montreal Cognitive Assessment (r = 0.295; p < 0.05). This study suggests that a disruption of the salience network control, especially the dorsal salience network, over other networks provides a neuronal basis for cognitive decline and may be a candidate neuroimaging biomarker of cognitive impairment.

Co-Segregation of Social Cognition, Executive Function and Local Processing Style in Children with ASD, Their Siblings and Normal Controls

ERIC Educational Resources Information Center

Oerlemans, Anoek M.; Droste, Katharina; van Steijn, Daphne J.; de Sonneville, Leo M. J.; Buitelaar, Jan K.; Rommelse, Nanda N.

2013-01-01

Cognitive research proposes that social cognition (SC), executive functions (EF) and local processing style (weak CC) may be fruitful areas for research into the familial-genetic underpinnings of Autism Spectrum Disorders (ASD). The performance of 140 children with ASD, 172 siblings and 127 controls on tasks measuring SC (face recognition,…

Effects of a Sedentary Intervention on Cognitive Function.

PubMed

Edwards, Meghan K; Loprinzi, Paul D

2018-03-01

To examine the effects of a free-living, sedentary-inducing intervention on cognitive function. Randomized controlled, parallel group intervention. University campus. Thirty-three young adults (n = 23 intervention; n = 10 control). The intervention group was asked to eliminate all exercise and minimize steps to ≤5000 steps/day for 1 week, whereas the control group was asked to continue normal physical activity (PA) levels for 1 week. Both groups completed a series of 8 cognitive function assessments (assessing multiple parameters of cognition) preintervention and immediately postintervention. The intervention group was asked to resume normal PA levels for 1 week postintervention and completed the cognitive assessments for a third time at 2 weeks postintervention. Split-plot repeated-measures analysis of variance. The results of our statistical analyses showed that the group × time interaction effect was not significant ( P > .05) for any of the evaluated cognitive parameters. These findings demonstrate the need for future experimental investigations of sedentary behavior to better understand its effects on cognitive function. However, although previous work has demonstrated favorable effects of acute and chronic PA on cognitive function, our findings suggest that a 1-week period of reduced PA does not detrimentally affect cognitive function, which may have encouraging implications for individuals going through a temporary relapse in PA.

Adolescent Anorexia Nervosa: cognitive performance after weight recovery.

PubMed

Lozano-Serra, Estefanía; Andrés-Perpiña, Susana; Lázaro-García, Luisa; Castro-Fornieles, Josefina

2014-01-01

Although there is no definitive consensus on the impairment of neuropsychological functions, most studies of adults with Anorexia Nervosa (AN) find impaired functioning in cognitive domains such as visual-spatial abilities. The objective of this study is to assess the cognitive functions in adolescents with AN before and after weight recovery and to explore the relationship between cognitive performance and menstruation. Twenty-five female adolescents with AN were assessed by a neuropsychological battery while underweight and then following six months of treatment and weight recovery. Twenty-six healthy female subjects of a similar age were also evaluated at both time points. Underweight patients with AN showed worse cognitive performance than control subjects in immediate recall, organization and time taken to copy the Rey's Complex Figure Test (RCFT). After weight recovery, AN patients presented significant improvements in all tests, and differences between patients and controls disappeared. Patients with AN and persistence of amenorrhea at follow-up (n=8) performed worse on Block Design, delayed recall of Visual Reproduction and Stroop Test than patients with resumed menstruation (n=14) and the control group, though the two AN groups were similar in body mass index, age and psychopathological scale scores. Weight recovery improves cognitive functioning in adolescents with AN. The normalization of neuropsychological performance is better in patients who have recovered at least one menstrual cycle. The normalization of hormonal function seems to be essential for the normalization of cognitive performance, even in adolescents with a very short recovery time. © 2013.

Neuropsychological mechanisms of Digit Symbol Substitution Test impairment in Asperger Disorder.

PubMed

Yoran-Hegesh, Roni; Kertzman, Semion; Vishne, Tali; Weizman, Abraham; Kotler, Moshe

2009-03-31

Our aim was to investigate the neurocognitive mechanisms recruited by adolescents with Asperger Disorder (AD), in comparison to controls, and to detect the underlying mechanisms during the complex information processing required for the performance of the Digit Symbol Substitution Test (DSST). Male adolescents (n=23; mean age 15.1+/-3.6 years) with a DSM-IV diagnosis of AD were compared with a normal male control group with similar demographic characteristics (n=43; mean age: 15.1+/-3.6 years). A computerized neurocognitive battery was administered and included: Inspection Time (IT), Finger Tapping Test (FTT), Simple Reaction Time (SRT), Choice Reaction Time (CRT), Digit Running task (DRT), Stroop test and Digit Symbol Substitution Test (DSST). Adolescents with AD performed significantly worse than controls on the DSST. This impaired DSST performance was related to cognitive mechanisms different from those employed by normal controls. Motor slowness and inability to deal with increased amounts of information affected the performance of the AD group, while shifting of attention was the limiting factor in the controls. Both groups were similarly dependent on response selection. This study demonstrated differences in performance in complex cognitive tasks between adolescents with AD and normal controls that may be related to differences in neurocognitive mechanisms underlying information processing. Future neuroimaging studies are needed to clarify the neural network involved in the differences in cognitive performance between AD subjects and normal controls.

Rarity of the Alzheimer Disease–Protective APP A673T Variant in the United States

PubMed Central

Wang, Li-San; Naj, Adam C.; Graham, Robert R.; Crane, Paul K.; Kunkle, Brian W.; Cruchaga, Carlos; Gonzalez Murcia, Josue D.; Cannon-Albright, Lisa; Baldwin, Clinton T.; Zetterberg, Henrik; Blennow, Kaj; Kukull, Walter A.; Faber, Kelley M.; Schupf, Nicole; Norton, Maria C.; Tschanz, JoAnn T.; Munger, Ronald G.; Corcoran, Christopher D.; Rogaeva, Ekaterina; Lin, Chiao-Feng; Dombroski, Beth A.; Cantwell, Laura B.; Partch, Amanda; Valladares, Otto; Hakonarson, Hakon; St George-Hyslop, Peter; Green, Robert C.; Goate, Alison M.; Foroud, Tatiana M.; Carney, Regina M.; Larson, Eric B.; Behrens, Timothy W.; Kauwe, John S. K.; Haines, Jonathan L.; Farrer, Lindsay A.; Pericak-Vance, Margaret A.; Mayeux, Richard; Schellenberg, Gerard D.

2015-01-01

IMPORTANCE Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States. OBJECTIVE To determine the frequency of the APP A673T variant in a large group of elderly cognitively normal controls and AD cases from the United States and in 2 case-control cohorts from Sweden. DESIGN, SETTING, AND PARTICIPANTS Case-control association analysis of variant APP A673T in US and Swedish white individuals comparing AD cases with cognitively intact elderly controls. Participants were ascertained at multiple university-associated medical centers and clinics across the United States and Sweden by study-specific sampling methods. They were from case-control studies, community-based prospective cohort studies, and studies that ascertained multiplex families from multiple sources. MAIN OUTCOMES AND MEASURES Genotypes for the APP A673T variant were determined using the Infinium HumanExome V1 Beadchip (Illumina, Inc) and by TaqMan genotyping (Life Technologies). RESULTS The A673T variant genotypes were evaluated in 8943 US AD cases, 10 480 US cognitively normal controls, 862 Swedish AD cases, and 707 Swedish cognitively normal controls. We identified 3 US individuals heterozygous for A673T, including 1 AD case (age at onset, 89 years) and 2 controls (age at last examination, 82 and 77 years). The remaining US samples were homozygous for the alanine (A673) allele. In the Swedish samples, 3 controls were heterozygous for A673T and all AD cases were homozygous for the A673 allele. We also genotyped a US family previously reported to harbor the A673T variant and found a mother-daughter pair, both cognitively normal at ages 72 and 84 years, respectively, who were both heterozygous for A673T; however, all individuals with AD in the family were homozygous for A673. CONCLUSIONS AND RELEVANCE The A673T variant is extremely rare in US cohorts and does not play a substantial role in risk for AD in this population. This variant may be primarily restricted to Icelandic and Scandinavian populations. PMID:25531812

Acquisition of Linguistic and Cognitive Skills by Children with Cleft Palate.

ERIC Educational Resources Information Center

Broen, Patricia A.; Devers, Monica C.; Doyle, Shirley S.; Prouty, Jo McCauley; Moller, Karlind T.

1998-01-01

This study compared cognitive and linguistic development of young children with (N=28) and without (N=29) cleft palate. Children with cleft palate, although well within the normal range, performed significantly below the control group on cognitive and linguistic tests. Cognitive differences were linguistic in nature and were related to hearing…

Development and validation of a new cognitive screening test: The Hong Kong Brief Cognitive Test (HKBC).

PubMed

Chiu, Helen F K; Zhong, Bao-Liang; Leung, Tony; Li, S W; Chow, Paulina; Tsoh, Joshua; Yan, Connie; Xiang, Yu-Tao; Wong, Mike

2018-07-01

To develop and examine the validity of a new brief cognitive test with less educational bias for screening cognitive impairment. A new cognitive test, Hong Kong Brief Cognitive Test (HKBC), was developed based on review of the literature, as well as the views of an expert panel. Three groups of subjects aged 65 or above were recruited after written consent: normal older people recruited in elderly centres, people with mild NCD (neurocognitive disorder), and people with major NCD. The brief cognitive test, Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment Scale (MoCA), were administered to the subjects. The performance of HKBC in differentiating subjects with major NCD, mild NCD, and normal older people were compared with the clinical diagnosis, as well as the MMSE and MoCA scores. In total, 359 subjects were recruited, with 99 normal controls, 132 subjects with major NCD, and 128 with mild NCD. The mean MMSE, MoCA, and HKBC scores showed significant differences among the 3 groups of subjects. In the receiving operating characteristic curve analysis of the HKBC in differentiating normal subjects from those with cognitive impairment (mild NCD + major NCD), the area under the curve was 0.955 with an optimal cut-off score of 21/22. The performances of MMSE and MoCA in differentiating normal from cognitively impaired subjects are slightly inferior to the HKBC. The HKBC is a brief instrument useful for screening cognitive impairment in older adults and is also useful in populations with low educational level. Copyright © 2018 John Wiley & Sons, Ltd.

Dysfunctional whole brain networks in mild cognitive impairment patients: an fMRI study

NASA Astrophysics Data System (ADS)

Liu, Zhenyu; Bai, Lijun; Dai, Ruwei; Zhong, Chongguang; Xue, Ting; You, Youbo; Tian, Jie

2012-03-01

Mild cognitive impairment (MCI) was recognized as the prodromal stage of Alzheimer's disease (AD). Recent researches have shown that cognitive and memory decline in AD patients is coupled with losses of small-world attributes. However, few studies pay attention to the characteristics of the whole brain networks in MCI patients. In the present study, we investigated the topological properties of the whole brain networks utilizing graph theoretical approaches in 16 MCI patients, compared with 18 age-matched healthy subjects as a control. Both MCI patients and normal controls showed small-world architectures, with large clustering coefficients and short characteristic path lengths. We detected significantly longer characteristic path length in MCI patients compared with normal controls at the low sparsity. The longer characteristic path lengths in MCI indicated disrupted information processing among distant brain regions. Compared with normal controls, MCI patients showed decreased nodal centrality in the brain areas of the angular gyrus, heschl gyrus, hippocampus and superior parietal gyrus, while increased nodal centrality in the calcarine, inferior occipital gyrus and superior frontal gyrus. These changes in nodal centrality suggested a widespread rewiring in MCI patients, which may be an integrated reflection of reorganization of the brain networks accompanied with the cognitive decline. Our findings may be helpful for further understanding the pathological mechanisms of MCI.

Abnormal activation of the occipital lobes during emotion picture processing in major depressive disorder patients

PubMed Central

Li, Jianying; Xu, Cheng; Cao, Xiaohua; Gao, Qiang; Wang, Yan; Wang, Yanfang; Peng, Juyi; Zhang, Kerang

2013-01-01

A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cognitive changes. However, there is still controversy regarding abnormalities in brain functions or correlation between cognitive impairment and brain function changes. Thus, it is important to design an emotion-related task for research into brain function changes. We selected positive, neutral, and negative pictures from the International Affective Picture System. Patients with major depressive disorder were asked to judge emotion pictures. In addition, functional MRI was performed to synchronously record behavior data and imaging data. Results showed that the total correct rate for recognizing pictures was lower in patients compared with normal controls. Moreover, the consistency for recognizing pictures for depressed patients was worse than normal controls, and they frequently recognized positive pictures as negative pictures. The consistency for recognizing pictures was negatively correlated with the Hamilton Depression Rating Scale. Functional MRI suggested that the activation of some areas in the frontal lobe, temporal lobe, parietal lobe, limbic lobe, and cerebellum was enhanced, but that the activation of some areas in the frontal lobe, parietal lobe and occipital lobe was weakened while the patients were watching positive and neutral pictures compared with normal controls. The activation of some areas in the frontal lobe, temporal lobe, parietal lobe, and limbic lobe was enhanced, but the activation of some areas in the occipital lobe were weakened while the patients were watching the negative pictures compared with normal controls. These findings indicate that patients with major depressive disorder have negative cognitive disorder and extensive brain dysfunction. Thus, reduced activation of the occipital lobe may be an initiating factor for cognitive disorder in depressed patients. PMID:25206466

Cognitive Strategies for Mentally Handicapped Clients.

ERIC Educational Resources Information Center

Hiebert, Bryan; Malcolm, Doreen

There is a need when working with mentally handicapped people to develop interventions that can be used within a self-control framework. One intervention that has demonstrated success in a self-control context with normally intelligent people is Cognitive Stress Inoculation Training (CSIT). In CSIT clients are taught to recognize current self-talk…

Computerized Cognitive Screen (CoCoSc): A Self-Administered Computerized Test for Screening for Cognitive Impairment in Community Social Centers.

PubMed

Wong, Adrian; Fong, Ching-Hang; Mok, Vincent Chung-Tong; Leung, Kam-Tat; Tong, Raymond Kai-Yu

2017-01-01

Computerized cognitive tests may serve as a preliminary, low-cost method to identify individuals with suspected cognitive impairment in the community. To develop a self-administered computerized test, namely the "Computerized Cognitive Screen (CoCoSc), Hong Kong version", for screening of individuals with cognitive impairment (CI) in community settings. The CoCoSc is a 15-min computerized cognitive screen covering memory, executive functions, orientation, attention and working memory, and prospective memory administered on a touchscreen computer. Individuals with CI and cognitively normal controls were administered the CoCoSc and the Montreal Cognitive Assessment (MoCA). Validity of the CoCoSc was assessed based on the relationship with the MoCA using Pearson correlation. Receiver operating characteristic curve (ROC) was used to examine the ability of the CoCoSc to differentiate CI from controls. Fifty-nine individuals with CI and 101 controls were recruited. Seventy-five (46.9%) participants had ≤6 years of education. Performance on the CoCoSc differed between normal and CI groups in both low and high education subgroups. Total scores of the CoCoSc and MoCA were significantly correlated (r = 0.71, p < 0.001). The area under ROC was 0.78, p < 0.001 for the CoCoSc total score in differentiating the CI group from the cognitively normal group. A cut-off of ≤30 on the CoCoSc was associated with a sensitivity of 0.78 and specificity of 0.69. The CoCoSc was well accepted by attendees of community social centers. The CoCoSc is a promising computerized cognitive screen for self-administration in community social centers. It is feasible for testing individuals with high or low education levels.

Cognitive impairment in systemic lupus erythematosus women with elevated autoantibodies and normal single photon emission computerized tomography.

PubMed

Peretti, Charles-Siegfried; Peretti, Charles Roger; Kozora, Elizabeth; Papathanassiou, Dimitri; Chouinard, Virginie-Anne; Chouinard, Guy

2012-01-01

Systemic lupus erythematosus (SLE) is known to induce psychiatric disorders, from psychoses to maladaptive coping. Brain autoantibodies were proposed to explain SLE neuropsychiatric disorders and found to be elevated before the onset of clinical symptoms. We assessed cognition in Caucasian SLE women with elevated autoantibodies without overt neuropsychiatric syndromes, in conjunction with single photon emission computerized tomography (SPECT). 31 women meeting SLE criteria of the American College of Rheumatology (ACR) were included. Patients who met the ACR neuropsychiatric definition were excluded. Matched controls were 23 healthy women from the Champagne-Ardenne region, France. Participants completed neuropsychological and autoantibodies measurements, and 19 completed SPECT. 61% (19/31) of women with SLE and 53% (9/17) of those with normal SPECT had significant global cognitive impairment defined as 4 T-scores <40 in cognitive tests, compared to 0% (0/23) of controls. SLE women also had significantly greater cognitive dysfunction (mean T-score) on the Wechsler Adult Intelligence Scale (WAIS) visual backspan, Trail Making Test A and B, WAIS Digit Symbol Substitution Test and Stroop Interference, compared to controls. Elevated antinuclear antibody correlated with impairment in the WAIS visual span, WAIS visual backspan, and cancellation task; elevated anti-double-stranded DNA antibody and anticardiolipin correlated respectively with impairment in the Trail Making Test A and WAIS auditive backspan. Two SLE women had abnormal SPECT. A high prevalence of cognitive deficits was found in Caucasian SLE women compared to normal women, which included impairment in cognitive domains important for daily activities. Elevated autoantibodies tended to correlate with cognitive dysfunction. Copyright © 2012 S. Karger AG, Basel.

Self-rated driving habits among older adults with clinically-defined mild cognitive impairment, clinically-defined dementia, and normal cognition.

PubMed

O'Connor, Melissa L; Edwards, Jerri D; Bannon, Yvonne

2013-12-01

Older adults with clinically-defined dementia may report reducing their driving more than cognitively normal controls. However, it is unclear how these groups compare to individuals with clinically-defined mild cognitive impairment (MCI) in terms of driving behaviors. The current study investigated self-reported driving habits among adults age 60 and older with clinical MCI (n=41), clinical mild dementia (n=40), and normal cognition (n=43). Participants reported their driving status, driving frequency (days per week), and how often they avoided accessing the community, making left turns, driving at night, driving in unfamiliar areas, driving on high-traffic roads, and driving in bad weather. After adjusting for education, a MANCOVA revealed that participants with MCI and dementia avoided unfamiliar areas and high-traffic roads significantly more than normal participants. Participants with dementia also avoided left turns and accessing the community more than those with normal cognition and MCI (p<0.05 for all). The other driving variables did not significantly differ between groups. Thus, older adults with clinically-defined MCI, as well as those with dementia, avoided some complex driving situations more than cognitively intact adults. However, all diagnostic groups had similar rates of driving cessation and frequency. Future research should examine the safety implications of such findings. Copyright © 2013 Elsevier Ltd. All rights reserved.

Aphasia from the inside: The cognitive world of the aphasic patient.

PubMed

Ardila, Alfredo; Rubio-Bruno, Silvia

2017-05-23

The purpose of this study was to analyze the question: how do people with aphasia experience the world? Three questions are approached: (1) how is behavior controlled in aphasia, considering that a normal linguistic control is no longer available; (2) what is the pattern of intellectual abilities in aphasia; and (3) what do aphasia patients' self-report regarding the experience of living without language. In aphasia, behavior can no longer be controlled through the "second signal system" and only the first signal system remains. Available information suggests that sometimes no verbal abilities may be affected in aphasia. However, an important variability is observed: whereas, in some patients, evident nonverbal defects are found; in other patients, performance verbal abilities are within normal limits. Several self-reports of recovered aphasic patients explain the experience of living without language. Considering that language represents the major instrument of cognition, in aphasia, surrounding information is evidently interpreted in a partially different way and cognitive strategies are reorganized, resulting in an idiosyncratic cognitive world.

Development and Standardization of a New Cognitive Assessment Test Battery for Chinese Aphasic Patients: A Preliminary Study.

PubMed

Wu, Ji-Bao; Lyu, Zhi-Hong; Liu, Xiao-Jia; Li, Hai-Peng; Wang, Qi

2017-10-05

Nonlinguistic cognitive impairment has become an important issue for aphasic patients, but currently there are few neuropsychological cognitive assessment tests for it. To get more information on cognitive impairment of aphasic patients, this study aimed to develop a new cognitive assessment test battery for aphasic patients, the Non-language-based Cognitive Assessment (NLCA), and evaluate its utility in Chinese-speaking patients with aphasia. The NLCA consists of five nonverbal tests, which could assess five nonlinguistic cognitive domains such as visuospatial functions, attention test, memory, reasoning, and executive functions of aphasic patients. All tests are modified from the nonverbal items of the current existed tests with some changes to the characteristics of Chinese culture. The NLCA was tested in 157 participants (including 57 aphasic patients, 50 mild cognitive impairment (MCI) patients, and 50 normal controls), and was compared with other well-established relative neuropsychological tests on the reliability, validity, and utility. The NLCA was fully applicable in the MCI patients and the normal controls, almost working in the aphasic patients (57/62 patients, 91.9%). The NLCA scores were 66.70 ± 6.30, 48.67 ± 15.04, and 77.58 ± 2.56 for the MCI group, the aphasic group, and the control group, respectively , and a significant difference was found among three groups (F = 118.446, P < 0.001). The Cronbach's alpha of the NLCA as an index of internal consistency was 0.805, and the test-retest and interrater reliability was adequate (r=0.977 and r= 0.970, respectively). The correlations of the cognitive subtests and their validation instruments were between 0.540 and 0.670 (all P < 0.05). Spearman's correlation analysis indicated that the coefficient of internal consistency of each subtest itself was higher than other subtests. When choosing the Montreal Cognitive Assessment score of <26 as the diagnostic criteria of cognitive impairment, the area under the curve for all participants in the control and MCI groups was 0.942 (95% confidence interval: 0.895-0.989), and an optimal cutoff point of 75.00 seemed to provide the best balance between sensitivity and specificity. Age (r = -0.406, P < 0.001) was the main influence factor for the NLCA. The NLCA could efficiently differentiate the cognitive impairment patients from the normal controls and is a reliable and valid cognitive assessment test battery to specially find nonlinguistic cognitive function for aphasic patients.

Cognitive Vulnerability in Patients with Generalized Anxiety Disorder, Dysthymic Disorder and Normal Individuals.

PubMed

Al-Ghorabaie, Fateme Moin; Noferesti, Azam; Fadaee, Mahdi; Ganji, Nima

2016-08-01

The purpose of this study was to assess cognitive vulnerability and response style in clinical and normal individuals. A sample of 90 individuals was selected for each of the 3 groups of Generalized Anxiety disorder, Dysthymic disorder and normal individuals. They completed MCQ and RSQ. Results analyzed by MANOVA and post hoc showed significant differences among groups. Dysthymic group and GAD reported higher scores on cognitive confidence compared to the normal group. Individuals with GAD showed highly negative beliefs about need to control thought, compared to the other groups, but in cognitive self-consciousness they have no differences with the normal group. In regard to uncontrollability, danger and positive beliefs, GAD group had higher levels than the other groups. Although normal and GAD group didn't show any significant differences in response style, there was a significant difference between Dysthymic group and other groups in all response styles.  Beliefs and meta-cognitive strategies can be distinguished between clinical and non clinical individuals. Also, findings support the Self-Regulatory Executive Function model. ary committee was effective in recognizing, designing and implementing tailored interventions for reduction of medication errors. A systematic approach is urgently needed to decrease organizational susceptibility to errors, through providing required resources to monitor, analyze and implement effective interventions.

β-Amyloid Deposition Is Associated with Decreased Right Prefrontal Activation during Task Switching among Cognitively Normal Elderly

PubMed Central

Steffener, Jason; Razlighi, Qolamreza R.; Habeck, Christian; Stern, Yaakov

2016-01-01

The accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease (AD), has been associated with functional alterations, often in an episodic memory system with a particular emphasis on medial temporal lobe function. The topography of Aβ deposition, however, largely overlaps with frontoparietal control (FPC) regions implicated in cognitive control that has been shown to be impaired in early mild AD. To understand the neural mechanism underlying early changes in cognitive control with AD, we examined the impact of Aβ deposition on task-evoked FPC activation using functional magnetic resonance imaging (fMRI) in humans. Forty-three young and 62 cognitively normal older adults underwent an fMRI session during an executive contextual task in which task difficulty varied: single (either letter case or vowel/consonant judgment task) vs dual (switching between letter case and vowel/consonant decisions) task. Older subjects additionally completed 18F-florbetaben positron emission tomography scans and were classified as either amyloid positive (Aβ+) or negative (Aβ−). Consistent with previous reports, age-related increases in brain activity were found in FPC regions commonly identified across groups. For both task conditions, Aβ-related increases in brain activity were found compared with baseline activity. For higher cognitive control load, however, Aβ+ elderly showed reduced task-switching activation in the right inferior frontal cortex. Our findings suggest that with Aβ deposition, brain activation in the cognitive control region reaches a maximum with lower control demand and decreases with higher control demand, which may underlie early impairment in cognitive control with AD progression. SIGNIFICANCE STATEMENT The accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease, spatially overlaps with frontoparietal control (FPC) regions implicated in cognitive control, but the impact of Aβ deposition on FPC regions is largely unknown. Using functional magnetic resonance imaging with a task-switching task, we found Aβ-related increases in FPC regions compared with baseline activity. For higher cognitive control load, however, Aβ-related hypoactivity was found in the right inferior frontal cortex, a region highly implicated in cognitive control. The findings suggest that with Aβ deposition, task-related brain activity may reach a plateau early and undergo downstream pathways of neural dysfunction, which may relate to the early impairment of cognitive control seen in the progression of Aβ pathology. PMID:26865619

[Cognitive markers to discriminate between mild cognitive impairment and normal ageing].

PubMed

Rodríguez Rodríguez, Nely; Juncos-Rabadán, Onésimo; Facal Mayo, David

2008-01-01

mild cognitive impairment (MCI) has been characterized as a transitional stage between normal ageing and dementia. The aim of the present study was to examine differences between normal ageing and MCI in the performance of several cognitive tests. These differences might serve as differential markers. we performed a longitudinal study (24 months) with two evaluations at 12-monthly intervals using the CAMCOG-R and a verbal learning test [test de aprendizaje verbal España-Complutense (TAVEC)]. The sample was composed of 25 persons aged more than 50 years old (five men and 20 women), distributed into two groups: the control group and the MCI group. To assign persons to either of the two groups, Petersen's MCI criteria were applied to Mini-Mental State Examination (MMSE) scores. repeated measures ANOVA (2 groups x 2 assessment) showed significant differences between the MCI and control group in the CAMCOG-R scores in orientation, language, memory, abstract thinking, executive function and global score and in the TAVEC scores for immediate recall and short- and long-term free and clued recall. No significant differences were found between the first and second assessment or in the interaction group assessment. the results of the present study confirm that the CAMCOG-R and the TAVEC effectively discriminate between normal ageing and MCI and can be used complementarily.

Cognitive Impairment among Patients with Chronic Obstructive Pulmonary Disease Compared to Normal Individuals.

PubMed

Samareh Fekri, Mitra; Hashemi-Bajgani, Seyed-Mehdi; Naghibzadeh-Tahami, Ahmad; Arabnejad, Fateme

2017-01-01

Chronic obstructive pulmonary disease (COPD) is one of the most important causes of morbidity and mortality worldwide. The complications of COPD are numerous, and cognitive impairment is one of the most common complications that relates to mortality and morbidity directly. The present study was conducted with the aim of evaluating the prevalence of cognitive impairment in patients with COPD in comparison to normal individuals. In this case-control study, 87 patients with COPD, whose diagnoses were confirmed by a pulmonologist based on the spirometry test findings, were included. The mini-mental state examination (MMSE) questionnaire was administered for assessing the cognitive impairment. Arterial oxygen saturation was measured. The MMSE questionnaires were administered to 60 healthy, age-and-sex-matched individuals without a history of myocardial infarction or cerebrovascular infarction, and their arterial oxygen saturations were measured. The data were analyzed using the SPSS (version 20) software. In the case group, 42 patients (48.27%) had no cognitive impairment, 39 (44.82%) had mild, and 6 (6.89%) had moderate cognitive impairment. In the control group, 38 (63.33%) had no cognitive impairment, 20 (33.33%) mild and 2 (3.33 %) moderate cognitive impairment. There were significant relationships between the cognitive impairment and arterial oxygen saturation, severity of COPD, and higher age. The prevalence of cognitive impairment was 51.71% in the case group and 36.66% in the control group. According the results of the present study, COPD increased the risk of cognitive impairment significantly and is related to the severity of COPD, arterial oxygen saturation, and higher age.

The Dream as a Model for Psychosis: An Experimental Approach Using Bizarreness as a Cognitive Marker

PubMed Central

Scarone, Silvio; Manzone, Maria Laura; Gambini, Orsola; Kantzas, Ilde; Limosani, Ivan; D'Agostino, Armando; Hobson, J. Allan

2008-01-01

Many previous observers have reported some qualitative similarities between the normal mental state of dreaming and the abnormal mental state of psychosis. Recent psychological, tomographic, electrophysiological, and neurochemical data appear to confirm the functional similarities between these 2 states. In this study, the hypothesis of the dreaming brain as a neurobiological model for psychosis was tested by focusing on cognitive bizarreness, a distinctive property of the dreaming mental state defined by discontinuities and incongruities in the dream plot, thoughts, and feelings. Cognitive bizarreness was measured in written reports of dreams and in verbal reports of waking fantasies in 30 schizophrenics and 30 normal controls. Seven pictures of the Thematic Apperception Test (TAT) were administered as a stimulus to elicit waking fantasies, and all participating subjects were asked to record their dreams upon awakening. A total of 420 waking fantasies plus 244 dream reports were collected to quantify the bizarreness features in the dream and waking state of both subject groups. Two-way analysis of covariance for repeated measures showed that cognitive bizarreness was significantly lower in the TAT stories of normal subjects than in those of schizophrenics and in the dream reports of both groups. The differences between the 2 groups indicated that, under experimental conditions, the waking cognition of schizophrenic subjects shares a common degree of formal cognitive bizarreness with the dream reports of both normal controls and schizophrenics. Though very preliminary, these results support the hypothesis that the dreaming brain could be a useful experimental model for psychosis. PMID:17942480

The role of sleep on cognition and functional connectivity in patients with multiple sclerosis.

PubMed

van Geest, Quinten; Westerik, B; van der Werf, Y D; Geurts, J J G; Hulst, H E

2017-01-01

Sleep disturbances are common in multiple sclerosis (MS), but its impact on cognition and functional connectivity (FC) of the hippocampus and thalamus is unknown. Therefore, we investigated the relationship between sleep disturbances, cognitive functioning and resting-state (RS) FC of the hippocampus and thalamus in MS. 71 MS patients and 40 healthy controls underwent neuropsychological testing and filled out self-report questionnaires (anxiety, depression, fatigue, and subjective cognitive problems). Sleep disturbances were assed with the five-item version of the Athens Insomnia Scale. Hippocampal and thalamic volume and RS FC of these regions were determined. Twenty-three patients were categorized as sleep disturbed and 48 as normal sleeping. No differences were found between disturbed and normal sleeping patients concerning cognition and structural MRI. Sleep disturbed patients reported more subjective cognitive problems, and displayed decreased FC between the thalamus and middle and superior frontal gyrus, inferior frontal operculum, anterior cingulate cortex, inferior parietal gyrus, precuneus, and angular gyrus compared to normal sleeping patients. We conclude that sleep disturbances in MS are not (directly) related to objective cognitive functioning, but rather to subjective cognitive problems. In addition, sleep disturbances in MS seem to coincide with a specific pattern of decreased thalamic FC.

Cognitive bias in symptomatic and recovered agoraphobics.

PubMed

Stoler, L S; McNally, R J

1991-01-01

Symptomatic agoraphobics, recovered agoraphobics, and normal control subjects completed a series of sentence stems that had either ambiguous or unambiguous meanings, and had either a potentially threatening or a nonthreatening connotation. The written completions made by subjects to these stems were classified as indicating either a biased (i.e. threat-related) or unbiased interpretation of the meaning of the stem, and if a biased interpretation was made, whether the subject indicated efforts at adaptive coping with the perceived threat. Results indicated that symptomatic agoraphobics exhibited strong biases for interpreting information as threatening, relative to normal control subjects. Moreover, recovered agoraphobics resembled symptomatic agoraphobics more than normal control subjects, thus indicating that cognitive biases may persist following cessation of panic attacks and reductions in avoidance behavior. However, recovered agoraphobics also exhibited tendencies to cope adaptively with perceived threats whereas symptomatic agoraphobics did not.

Longitudinal Association of Dementia and Depression.

PubMed

Snowden, Mark B; Atkins, David C; Steinman, Lesley E; Bell, Janice F; Bryant, Lucinda L; Copeland, Catherine; Fitzpatrick, Annette L

2015-09-01

Depression is an important precursor to dementia, but less is known about the role dementia plays in altering the course of depression. We examined whether depression prevalence, incidence, and severity are higher in those with dementia versus those with mild cognitive impairment (MCI), or normal cognition. Prospective cohort study using the longitudinal Uniform Data Set of the National Alzheimer's Coordinating Center (2005-2013). 34 Alzheimer Disease research centers. 27,776 subjects with dementia, MCI, or normal cognition. Depression status was determined by a clinical diagnosis of depression within the prior 2 years and by a Geriatric Depression Scale-Short Form score >5. Rates of depression were significantly higher in subjects with MCI and dementia compared with those with normal cognition at index visit. Controlling for demographics and common chronic conditions, logistic regression analysis revealed elevated depression in those with MCI (OR: 2.40 [95% CI: 2.25, 2.56]) or dementia (OR: 2.64 [95% CI: 2.43, 2.86]) relative to those with normal cognition. In the subjects without depression at the index visit (N = 18,842), those with MCI and dementia had higher probabilities of depression diagnosis 2 years post index visit than those with normal cognition: MCI = 21.7%, dementia = 24.7%, normal cognition = 10.5%. MCI and dementia were associated with significantly higher rates of depression in concurrent as well as prospective analyses. These findings suggest that efforts to effectively engage and treat older adults with dementia will need also to address co-occurring depression. Copyright © 2015 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

The effect of dual tasking on foot kinematics in people with functional ankle instability.

PubMed

Tavakoli, Sanam; Forghany, Saeed; Nester, Christopher

2016-09-01

Some cases of repeated inversion ankle sprains are thought to have a neurological basis and are termed functional ankle instability (FAI). In addition to factors local to the ankle, such as loss of proprioception, cognitive demands have the ability to influence motor control and may increase the risk of repetitive lateral sprains. The purpose of this study was to investigate the effect of cognitive demand on foot kinematics in physically active people with functional ankle instability. 21 physically active participants with FAI and 19 matched healthy controls completed trials of normal walking (single task) and normal walking while performing a cognitive task (dual task). Foot motion relative to the shank was recorded. Cognitive performance, ankle kinematics and movement variability in single and dual task conditions was characterized. During normal walking, the ankle joint was significantly more inverted in FAI compared to the control group pre and post initial contact. Under dual task conditions, there was a statistically significant increase in frontal plane foot movement variability during the period 200ms pre and post initial contact in people with FAI compared to the control group (p<0.05). Dual task also significantly increased plantar flexion and inversion during the period 200ms pre and post initial contact in the FAI group (p<0.05). participants with FAI demonstrated different ankle movement patterns and increased movement variability during a dual task condition. Cognitive load may increase risk of ankle instability in these people. Copyright © 2016 Elsevier B.V. All rights reserved.

Performance in normal subjects on a novel battery of driving-related sensory-motor and cognitive tests.

PubMed

Innes, Carrie R H; Jones, Richard D; Anderson, Tim J; Hollobon, Susan G; Dalrymple-Alford, John C

2009-05-01

Currently, there is no international standard for the assessment of fitness to drive for cognitively or physically impaired persons. A computerized battery of driving-related sensory-motor and cognitive tests (SMCTests) has been developed, comprising tests of visuoperception, visuomotor ability, complex attention, visual search, decision making, impulse control, planning, and divided attention. Construct validity analysis was conducted in 60 normal, healthy subjects and showed that, overall, the novel cognitive tests assessed cognitive functions similar to a set of standard neuropsychological tests. The novel tests were found to have greater perceived face validity for predicting on-road driving ability than was found in the equivalent standard tests. Test-retest stability and reliability of SMCTests measures, as well as correlations between SMCTests and on-road driving, were determined in a subset of 12 subjects. The majority of test measures were stable and reliable across two sessions, and significant correlations were found between on-road driving scores and measures from ballistic movement, footbrake reaction, hand-control reaction, and complex attention. The substantial face validity, construct validity, stability, and reliability of SMCTests, together with the battery's level of correlation with on-road driving in normal subjects, strengthen our confidence in the ability of SMCTests to detect and identify sensory-motor and cognitive deficits related to unsafe driving and increased risk of accidents.

Neuroimaging of cognitive dysfunction and depression in aging retired National Football League players: a cross-sectional study.

PubMed

Hart, John; Kraut, Michael A; Womack, Kyle B; Strain, Jeremy; Didehbani, Nyaz; Bartz, Elizabeth; Conover, Heather; Mansinghani, Sethesh; Lu, Hanzhang; Cullum, C Munro

2013-03-01

OBJECTIVES To assess cognitive impairment and depression in aging former professional football (National Football League [NFL]) players and to identify neuroimaging correlates of these dysfunctions. DESIGN We compared former NFL players with cognitive impairment and depression, cognitively normal retired players who were not depressed, and matched healthy control subjects. SETTING Research center in the North Texas region of the United States. PATIENTS Cross-sectional sample of former NFL players with and without a history of concussion recruited from the North Texas region and age-, education-, and IQ-matched controls. Thirty-four retired NFL players (mean age, 61.8 years) underwent neurological and neuropsychological assessment. A subset of 26 players also underwent detailed neuroimaging; imaging data in this subset were compared with imaging data acquired in 26 healthy matched controls. MAIN OUTCOME MEASURES Neuropsychological measures, clinical diagnoses of depression, neuroimaging mea-sures of white matter pathology, and a measure of cerebral blood flow. RESULTS Of the 34 former NFL players, 20 were cognitively normal. Four were diagnosed as having a fixed cognitive deficit; 8, mild cognitive impairment; 2, dementia; and 8, depression. Of the subgroup in whom neuroimaging data were acquired, cognitively impaired participants showed the greatest deficits on tests of naming, word finding, and visual/verbal episodic memory. We found significant differences in white matter abnormalities in cognitively impaired and depressed retired players compared with their respective controls. Regional blood flow differences in the cognitively impaired group (left temporal pole, inferior parietal lobule, and superior temporal gyrus) corresponded to regions associated with impaired neurocognitive performance (problems with memory, naming, and word finding). CONCLUSIONS Cognitive deficits and depression appear to be more common in aging former NFL players compared with healthy controls. These deficits are correlated with white matter abnormalities and changes in regional cerebral blood flow.

Anterior Cingulate Cortex and Cognitive Control: Neuropsychological and Electrophysiological Findings in Two Patients with Lesions to Dorsomedial Prefrontal Cortex

ERIC Educational Resources Information Center

Lovstad, M.; Funderud, I.; Meling, T.; Kramer, U. M.; Voytek, B.; Due-Tonnessen, P.; Endestad, T.; Lindgren, M.; Knight, R. T.; Solbakk, A. K.

2012-01-01

Whereas neuroimaging studies of healthy subjects have demonstrated an association between the anterior cingulate cortex (ACC) and cognitive control functions, including response monitoring and error detection, lesion studies are sparse and have produced mixed results. Due to largely normal behavioral test results in two patients with medial…

The Associations between Visual Attention and Facial Expression Identification in Patients with Schizophrenia.

PubMed

Lin, I-Mei; Fan, Sheng-Yu; Huang, Tiao-Lai; Wu, Wan-Ting; Li, Shi-Ming

2013-12-01

Visual search is an important attention process that precedes the information processing. Visual search also mediates the relationship between cognition function (attention) and social cognition (such as facial expression identification). However, the association between visual attention and social cognition in patients with schizophrenia remains unknown. The purposes of this study were to examine the differences in visual search performance and facial expression identification between patients with schizophrenia and normal controls, and to explore the relationship between visual search performance and facial expression identification in patients with schizophrenia. Fourteen patients with schizophrenia (mean age=46.36±6.74) and 15 normal controls (mean age=40.87±9.33) participated this study. The visual search task, including feature search and conjunction search, and Japanese and Caucasian Facial Expression of Emotion were administered. Patients with schizophrenia had worse visual search performance both in feature search and conjunction search than normal controls, as well as had worse facial expression identification, especially in surprised and sadness. In addition, there were negative associations between visual search performance and facial expression identification in patients with schizophrenia, especially in surprised and sadness. However, this phenomenon was not showed in normal controls. Patients with schizophrenia who had visual search deficits had the impairment on facial expression identification. Increasing ability of visual search and facial expression identification may improve their social function and interpersonal relationship.

High body mass index is associated with impaired cognitive control.

PubMed

Sellaro, Roberta; Colzato, Lorenza S

2017-06-01

The prevalence of weight problems is increasing worldwide. There is growing evidence that high body mass index (BMI) is associated with frontal lobe dysfunction and cognitive deficits concerning mental flexibility and inhibitory control efficiency. The present study aims at replicating and extending these observations. We compared cognitive control performance of normal weight (BMI < 25) and overweight (BMI ≥ 25) university students on a task tapping either inhibitory control (Experiment 1) or interference control (Experiment 2). Experiment 1 replicated previous findings that found less efficient inhibitory control in overweight individuals. Experiment 2 complemented these findings by showing that cognitive control impairments associated with high BMI also extend to the ability to resolve stimulus-induced response conflict and to engage in conflict-driven control adaptation. The present results are consistent with and extend previous literature showing that high BMI in young, otherwise healthy individuals is associated with less efficient cognitive control functioning. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cluster analysis of cognitive performance in elderly and demented subjects.

PubMed

Giaquinto, S; Nolfe, G; Calvani, M

1985-06-01

48 elderly normals, 14 demented subjects and 76 young controls were tested for basic cognitive functions. All the tests were quantified and could therefore be subjected to statistical analysis. The results show a difference in the speed of information processing and in memory load between the young controls and elderly normals but the age groups differed in quantitative terms only. Cluster analysis showed that the elderly and the demented formed two distinctly separate groups at the qualitative level, the basic cognitive processes being damaged in the demented group. Age thus appears to be only a risk factor for dementia and not its cause. It is concluded that batteries based on precise and measurable tasks are the most appropriate not only for the study of dementia but for rehabilitation purposes too.

Abstract Word Definition in Patients with Amnestic Mild Cognitive Impairment

PubMed Central

Kim, Soo Ryon; Baek, Min Jae; Kim, HyangHee

2015-01-01

The aims of this study were to investigate concrete and abstract word definition ability (1) between patients with amnestic mild cognitive impairment (aMCI) and normal adults and (2) between the aMCI subtypes (i.e., amnestic single-domain MCI and amnestic multidomain MCI; asMCI and amMCI) and normal controls. The 68 patients with aMCI (29 asMCI and 39 amMCI) and 93 age- and education-matched normal adults performed word definition tasks composed of five concrete (e.g., train) and five abstract nouns (e.g., jealousy). Task performances were analyzed on total score, number of core meanings, and number of supplementary meanings. The results were as follows. First, the aMCI patients scored significantly poorer than the normal controls in only abstract word definition. Second, both subtypes of aMCI performed worse than the controls in only abstract word definition. In conclusion, a definition task of abstract rather than concrete concepts may provide richer information to show semantic impairment of aMCI. PMID:26347214

PET Imaging of Tau Deposition in the Aging Human Brain

PubMed Central

Schonhaut, Daniel R.; O’Neil, James P.; Janabi, Mustafa; Ossenkoppele, Rik; Baker, Suzanne L.; Vogel, Jacob W.; Faria, Jamie; Schwimmer, Henry D.; Rabinovici, Gil D.; Jagust, William J.

2016-01-01

SUMMARY Tau pathology is a hallmark of Alzheimer’s disease (AD) but also occurs in normal cognitive aging. Using the tau PET agent 18F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid, and was associated with decline in global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. The present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition. PMID:26938442

PET Imaging of Tau Deposition in the Aging Human Brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schöll, Michael; Lockhart, Samuel N.; Schonhaut, Daniel R.

Tau pathology is a hallmark of Alzheimer’s disease (AD) but also occurs in normal cognitive aging. In this study, using the tau PET agent 18F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline inmore » global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. In conclusion, the present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.« less

PET Imaging of Tau Deposition in the Aging Human Brain

DOE PAGES

Schöll, Michael; Lockhart, Samuel N.; Schonhaut, Daniel R.; ...

2016-03-02

Tau pathology is a hallmark of Alzheimer’s disease (AD) but also occurs in normal cognitive aging. In this study, using the tau PET agent 18F-AV-1451, we examined retention patterns in cognitively normal older people in relation to young controls and AD patients. Age and β-amyloid (measured using PiB PET) were differentially associated with tau tracer retention in healthy aging. Older age was related to increased tracer retention in regions of the medial temporal lobe, which predicted worse episodic memory performance. PET detection of tau in other isocortical regions required the presence of cortical β-amyloid and was associated with decline inmore » global cognition. Furthermore, patterns of tracer retention corresponded well with Braak staging of neurofibrillary tau pathology. In conclusion, the present study defined patterns of tau tracer retention in normal aging in relation to age, cognition, and β-amyloid deposition.« less

Neurocognitive findings in Prader-Willi syndrome and early-onset morbid obesity.

PubMed

Miller, Jennifer; Kranzler, John; Liu, Yijun; Schmalfuss, Ilona; Theriaque, Douglas W; Shuster, Jonathan J; Hatfield, Ann; Mueller, O Thomas; Goldstone, Anthony P; Sahoo, Trilochan; Beaudet, Arthur L; Driscoll, Daniel J

2006-08-01

To examine whether early-onset morbid obesity is associated with cognitive impairment, neuropathologic changes, and behavioral problems. This case-control study compared head MRI scans and cognitive, achievement, and behavioral evaluations of subjects with Prader-Willi syndrome (PWS), early-onset morbid obesity (EMO), and normal-weight sibling control subjects from both groups. Head MRI was done on 17 PWS, 18 EMO, and 21 siblings, and cognitive, achievement, and behavioral evaluations were done on 19 PWS, 17 EMO, and 24 siblings. The mean General Intellectual Ability score of the EMO group was 77.4 +/- 17.8; PWS, 63.3 +/- 14.2; and control subjects, 106.4 +/- 13.0. Achievement scores for the three groups were EMO, 78.7 +/- 18.8; PWS, 71.2 +/- 17.0; and control subjects, 104.8 +/- 17.0. Significant negative behaviors and poor adaptive skills were found in the EMO group. White matter lesions were noted on brain MRI in 6 subjects with PWS and 5 with EMO. None of the normal-weight control subjects had these findings. Individuals with EMO have significantly lower cognitive function and more behavioral problems than control subjects with no history of childhood obesity. Both EMO and PWS subjects have white matter lesions on brain MRI that have not previously been described.

Brain-Derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study

PubMed Central

Diniz, Breno Satler; Reynolds, Charles F.; Begley, Amy; Dew, Mary Amanda; Anderson, Stewart J.; Lotrich, Francis; Erickson, Kirk I.; Lopez, Oscar; Aizenstein, Howard; Sibille, Etienne L.; Butters, Meryl A.

2014-01-01

Changes in brain-derived neurotrophic factor (BDNF) level are implicated in the pathophysiology of cognitive decline in depression and neurodegenerative disorders in older adults. We aimed to evaluate the longitudinal association over two years between BDNF and persistent cognitive decline in individuals with remitted late-life depression and Mild Cognitive Impairment (LLD+MCI) compared to either individuals with remitted LLD and no cognitive decline (LLD+NCD) or never-depressed, cognitively normal, elderly control participants. We additionally evaluated the effect of double-blind, placebo-controlled donepezil treatment on BDNF levels in all of the remitted LLD participants (across the levels of cognitive function). We included 160 elderly participants in this study (72 LLD+NCD, 55 LLD+MCI and 33 never-depressed cognitively normal elderly participants). At the same visits, cognitive assessments were conducted and blood sampling to determine serum BDNF levels were collected at baseline assessment and after one and two years of follow-up. We utilized repeated measure, mixed effect models to assess: (1) the effects of diagnosis (LLD+MCI, LLD+NCD, and controls), time, and their interaction on BDNF levels; and (2) the effects of donepezil treatment (donepezil vs. placebo), time, baseline diagnosis (LLD+MCI vs. LLD+NCD), and interactions between these contrasts on BDNF levels. We found a significant effect of time on BDNF level (p=0.02) and a significant decline in BDNF levels over 2 years of follow-up in participants with LLD+MCI (p=0.004) and controls (p=0.04). We found no effect of donepezil treatment on BDNF level. The present results suggest that aging is an important factor related to decline in BDNF level. PMID:24290367

Frontoparietal cognitive control of verbal memory recall in Alzheimer's disease.

PubMed

Dhanjal, Novraj S; Wise, Richard J S

2014-08-01

Episodic memory retrieval is reliant upon cognitive control systems, of which 2 have been identified with functional neuroimaging: a cingulo-opercular salience network (SN) and a frontoparietal executive network (EN). In Alzheimer's disease (AD), pathology is distributed throughout higher-order cortices. The hypotheses were that this frontoparietal pathology would impair activity associated with verbal memory recall; and that central cholinesterase inhibition (ChI) would modulate this, improving memory recall. Functional magnetic resonance imaging was used to study normal participants and 2 patient groups: mild cognitive impairment (MCI) and AD. Activity within the EN and SN was observed during free recall of previously heard sentences, and related to measures of recall accuracy. In normal subjects, trials with reduced recall were associated with greater activity in both the SN and EN. Better recall was associated with greater activity in medial regions of the default mode network. By comparison, AD patients showed attenuated responses in both the SN and EN compared with either controls or MCI patients, even after recall performance was matched between groups. Following ChI, AD patients showed no modulation of activity within the SN, but increased activity within the EN. There was also enhanced activity within regions associated with episodic and semantic memory during less successful recall, requiring greater cognitive control. The results indicate that in AD, impaired responses of cognitive control networks during verbal memory recall are partly responsible for reduced recall performance. One action of symptom-modifying treatment is partially to reverse the abnormal function of frontoparietal cognitive control and temporal lobe memory networks. © 2014 American Neurological Association.

Use of the EMPOWER brochure to deprescribe sedative-hypnotic drugs in older adults with mild cognitive impairment.

PubMed

Martin, Philippe; Tannenbaum, Cara

2017-01-31

Evidence-based mailed educational brochures about the harms of sedative-hypnotic use lead to discontinuation of chronic benzodiazepine use in older adults. It remains unknown whether patients with mild cognitive impairment (MCI) are able to understand the information in the EMPOWER brochures, and whether they achieve similar rates of benzodiazepine discontinuation. Post-hoc analysis of the EMPOWER randomized, double-blind, wait-list controlled trial that assessed the effect of a direct-to-consumer educational intervention on benzodiazepine discontinuation. 303 community-dwelling chronic users of benzodiazepine medication aged 65-95 years were recruited from general community pharmacies in the original trial, 261 (86%) of which completed the trial extension phase. All participants of the control arm received the EMPOWER brochure during the trial extension. Normal cognition (n = 139) or MCI (n = 122) was determined during baseline cognitive testing using the Montreal Cognitive Assessment questionnaire. Changes in knowledge pre- and post-intervention were assessed with a knowledge questionnaire and changes in beliefs were calculated using the Beliefs about Medicines Questionnaire. Logistic regression was used to compare knowledge gained, change in beliefs and benzodiazepine cessation rates between participants with and without MCI. Complete discontinuation of benzodiazepines was achieved in 39 (32.0% [24.4,40.7]) participants with MCI and in 53 (38.1% [30.5,46.4]) with normal cognition (adjusted OR 0.79, 95% CI [0.45-1.38]). Compared to individuals with normal cognition, MCI had no effect on the acquisition of new knowledge, change in beliefs about benzodiazepines or elicitation of cognitive dissonance. The EMPOWER brochure is effective for reducing benzodiazepines in community-dwelling older adults with mild cognitive impairment. Our ClinicalTrials.gov identifier is NCT01148186 , June 21 st 2010.

Glutamate-glutamine and GABA in brain of normal aged and patients with cognitive impairment.

PubMed

Huang, Dandan; Liu, Dan; Yin, Jianzhong; Qian, Tianyi; Shrestha, Susan; Ni, Hongyan

2017-07-01

To explore the changes of glutamate-glutamine (Glx) and gamma-aminobutyric acid (GABA) in the brain in normal old age and cognitive impairment using magnetic resonance spectroscopy (MRS). Seventeen normal young controls (NYC), 15 normal elderly controls (NEC), 21 patients with mild cognitive impairment (MCI) and 17 with Alzheimer disease (AD) patients were included in this study. Glx and GABA+ levels in the anterior cingulate cortex (ACC) and right hippocampus (rHP) were measured by using a MEGA-PRESS sequence. Glx/Cr and GABA+/Cr ratios were compared between NYC and NEC and between the three elderly groups using analysis of covariance (ANCOVA); the tissue fractions of voxels were used as covariates. The relationships between metabolite ratios and cognitive performance were analysed using Spearman correlation coefficients. For NEC and NYC groups, Glx/Cr and GABA+/Cr ratios were lower in NEC in ACC and rHP. For the three elderly groups, Glx/Cr ratio was lower in AD in ACC compared to NEC and MCI; Glx/Cr ratio was lower in AD in rHP compared to NEC. There was no significant decrease for GABA+/Cr ratio. Glx and GABA levels may decrease simultaneously in normal aged, and Glx level decreased predominantly in AD, and it is helpful in the early diagnosis of AD. • Glx and GABA levels may decrease simultaneously in normal aged. • Glx level may decrease predominantly in Alzheimer disease. • The balance in excitatory-inhibitory systems may be broken in AD. • Decreased Glx level may be helpful in early diagnosis of AD.

Performance of Bipolar Disorder Patients in Attention Testing: Comparison with Normal Controls and Among Manic, Depressive, and Euthymic Phases.

PubMed

Camelo, Evelyn V M; Mograbi, Daniel; de Assis da Silva, Rafael; Bifano, Jaqueline; Wainstok, Mayra; Silveira, Luciana Angélica Silva; Netto, Tânia; Santana, Cristina M T; Cheniaux, Elie

2017-03-01

Several studies on cognition in bipolar disorder (BD) have been developed on the last decade. Neuropsychological evaluation of attention in BD patients is fundamental since alterations in attention affect other cognitive functions. Evaluate if performance of BD patients in attention tests varies according to each phase of the disease and verify if there are differences in attention when comparing BD patients with normal controls. The study included 101 BD patients, with ages between 18 and 65 years, being 52 euthymic, 22 manic and 27 depressive, besides 30 normal controls. All subjects were evaluated though Hamilton Depression Scale, Young Mania Rating Scale and Global Assessment of Functioning, bipolar version (CGI-BP). Attention was evaluated through a neuropsychological battery. Normal controls had a better performance in selective attention tests than BD patients. No differences were found among manic, depressive and euthymic phases. Attention is markedly impaired in BD. Nevertheless, the results of this study do not imply that the severity of the attention deficit in BD patients varies according to decease phase.

Executive functions deficit in mild cognitive impairment.

PubMed

Traykov, Latchezar; Raoux, Nadine; Latour, Florence; Gallo, Livia; Hanon, Olivier; Baudic, Sophie; Bayle, Catherine; Wenisch, Emilie; Remy, Philippe; Rigaud, Anne-Sophie

2007-12-01

To investigate whether patients diagnosed with amnestic mild cognitive impairment (MCI) have also impairment in attention/executive functions, and therefore to clarify whether all subcomponents of executive control are equally affected in MCI. MCI refers to the transitional state between normal aging and dementia. Amnestic MCI is characterized by impaired episodic memory, although subtle impairment of executive functions has been noted on neuropsychologic tests. We investigated 20 MCI patients and 20 normal controls using episodic memory, attention/executive functions, language, and praxis tests. MCI patients had significantly lower scores on all measures of the Free and Cued Selective Reminding Test (P<0.05 to 0.01) than controls. Furthermore, MCI had a greater number of perseverations (P<0.01) on Modified Card Sorting Test and the lowest performance on the Stroop Test (P<0.02). Our findings showed impairment in episodic memory performance in MCI as compared with that of controls. In addition, MCI patients had problems with response inhibition, switching, and cognitive flexibility, which encompass various aspects of executive functions. This suggests that MCI may be identified by using a more detailed procedure for the assessment of cognitive decline than the evaluation of memory alone.

Differential hippocampal protein expression between normal aged rats and aged rats with postoperative cognitive dysfunction: A proteomic analysis.

PubMed

Li, Yang; Wang, Saiying; Ran, Ke; Hu, Zhonghua; Liu, Zhaoqian; Duan, Kaiming

2015-08-01

The aim of the present study was to investigate the differences in the expression of hippocampal proteins between normal control aged rats and aged rats with postoperative cognitive dysfunction (POCD). A total of 24 aged rats were randomly divided into a surgery group (n=12) and a control group (n=12). The rats in the surgery group were treated with 2 h isoflurane anesthesia and splenectomy, while the rats in the control group received 40% oxygen for 2 h without surgery. The cognitive functions of the two groups were examined using a Y-maze test. The protein expression profiles of the hippocampus of six aged rats (three rats with POCD and three from the normal control group) were assessed using two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization time of flight mass spectrometry. A total of three differential proteins were further confirmed between the POCD rats and normal rats using reverse transcription quantitative polymerase chain reaction (RT-qPCR). The expression levels of 21 proteins in the rats with POCD were significantly different compared with the normal control rats. These proteins were functionally clustered to synaptic plasticity (three proteins), oxidative stress (four proteins), energy production (six proteins), neuroinflammation (three proteins) and glutamate metabolism (two proteins). In addition, three proteins (fatty acid binding protein 7, brain, glutamate dehydrogenase 1 and glutamine synthetase), associated with astrocytic function, were significantly different in the rats with POCD compared with those in the normal control (P<0.05). Similar changes in the mRNA expression levels of the three proteins in the hippocampi of POCD rats were also detected using RT-qPCR. Neuroinflammation, glutamate toxicity and oxidative stress were possibly involved in the pathological mechanism underlying POCD in aged rats. In addition, astrocytes may also be important in POCD in aged rats.

Subjective cognitive complaints contribute to misdiagnosis of mild cognitive impairment.

PubMed

Edmonds, Emily C; Delano-Wood, Lisa; Galasko, Douglas R; Salmon, David P; Bondi, Mark W

2014-09-01

Subjective cognitive complaints are a criterion for the diagnosis of mild cognitive impairment (MCI), despite their uncertain relationship to objective memory performance in MCI. We aimed to examine self-reported cognitive complaints in subgroups of the Alzheimer's Disease Neuroimaging Initiative (ADNI) MCI cohort to determine whether they are a valuable inclusion in the diagnosis of MCI or, alternatively, if they contribute to misdiagnosis. Subgroups of MCI were derived using cluster analysis of baseline neuropsychological test data from 448 ADNI MCI participants. Cognitive complaints were assessed via the Everyday Cognition (ECog) questionnaire, and discrepancy scores were calculated between self- and informant-report. Cluster analysis revealed Amnestic and Mixed cognitive phenotypes as well as a third Cluster-Derived Normal subgroup (41.3%), whose neuropsychological and cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker profiles did not differ from a "robust" normal control group. This cognitively intact phenotype of MCI participants overestimated their cognitive problems relative to their informant, whereas Amnestic MCI participants with objective memory impairment underestimated their cognitive problems. Underestimation of cognitive problems was associated with positive CSF AD biomarkers and progression to dementia. Overall, there was no relationship between self-reported cognitive complaints and objective cognitive functioning, but significant correlations were observed with depressive symptoms. The inclusion of self-reported complaints in MCI diagnostic criteria may cloud rather than clarify diagnosis and result in high rates of misclassification of MCI. Discrepancies between self- and informant-report demonstrate that overestimation of cognitive problems is characteristic of normal aging while underestimation may reflect greater risk for cognitive decline.

Response-Conflict Moderates the Cognitive Control of Episodic and Contextual Load in Older Adults

PubMed Central

Eich, Teal S.; Rakitin, Brian C.

2016-01-01

Objectives: Decline in cognitive control is one of the primary cognitive changes in normal aging. Reaching a consensus regarding the nature of these age-related changes, however, is complicated by the complexity of cognitive control as a construct. Methods: Healthy older and younger adults participated in a multifactorial test of cognitive control. Within participants, the procedure varied as a function of the amount contextual load, episodic load, and response-conflict load present. Results: We found that older adults showed impaired performance relative to younger adults. We also found, however, that the response selection process underlying the response-conflict manipulation was a major moderator of age-related differences in both the contextual and episodic load conditions—suggesting a hierarchical organization. Discussion: These findings are consistent with previous findings, suggesting that deficits in cognitive control in older adults are directly related to the resolution of response-conflict and that other apparent deficits may be derivative upon the more basic response-conflict related deficit. PMID:26224757

Investigating the relationship between FMR1 allele length and cognitive ability in children: a subtle effect of the normal allele range on the normal ability range?

PubMed

Loat, C S; Craig, G; Plomin, R; Craig, I W

2006-09-01

The FMR1 gene contains a trinucleotide repeat tract which can expand from a normal size of around 30 repeats to over 200 repeats, causing mental retardation (Fragile X Syndrome). Evidence suggests that premutation males (55-200 repeats) are susceptible to a late-onset tremor/ataxia syndrome and females to premature ovarian failure, and that intermediate alleles ( approximately 41-55 repeats) and premutations may be in excess in samples with special educational needs. We explored the relationship between FMR1 allele length and cognitive ability in 621 low ability and control children assessed at 4 and 7 years, as well as 122 students with high IQ. The low and high ability and control samples showed no between-group differences in incidence of longer alleles. In males there was a significant negative correlation between allele length and non-verbal ability at 4 years (p = 0.048), academic achievement in maths (p = 0.003) and English (p = 0.011) at 7 years, and IQ in the high ability group (p = 0.018). There was a significant negative correlation between allele length and a standardised score for IQ and general cognitive ability at age 7 in the entire male sample (p = 0.002). This suggests that, within the normal spectrum of allele length, increased repeat numbers may have a limiting influence on cognitive performance.

Molecular imaging of serotonin degeneration in mild cognitive impairment.

PubMed

Smith, Gwenn S; Barrett, Frederick S; Joo, Jin Hui; Nassery, Najlla; Savonenko, Alena; Sodums, Devin J; Marano, Christopher M; Munro, Cynthia A; Brandt, Jason; Kraut, Michael A; Zhou, Yun; Wong, Dean F; Workman, Clifford I

2017-09-01

Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions and is found in high concentrations in the serotonergic cell bodies of origin of these projections (raphe nuclei). Twenty-eight participants with mild cognitive impairment (age 66.6±6.9, 16 males) and 28 healthy, cognitively normal, demographically matched controls (age 66.2±7.1, 15 males) underwent magnetic resonance imaging for measurement of grey matter volumes and high-resolution positron emission tomography with well-established radiotracers for the serotonin transporter and regional cerebral blood flow. Beta-amyloid imaging was performed to evaluate, in combination with the neuropsychological testing, the likelihood of subsequent cognitive decline in the participants with mild cognitive impairment. The following hypotheses were tested: 1) the serotonin transporter would be lower in mild cognitive impairment compared to controls in cortical and limbic regions, 2) in mild cognitive impairment relative to controls, the serotonin transporter would be lower to a greater extent and observed in a more widespread pattern than lower grey matter volumes or lower regional cerebral blood flow and 3) lower cortical and limbic serotonin transporters would be correlated with greater deficits in auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. Reduced serotonin transporter availability was observed in mild cognitive impairment compared to controls in cortical and limbic areas typically affected by Alzheimer's disease pathology, as well as in sensory and motor areas, striatum and thalamus that are relatively spared in Alzheimer's disease. The reduction of the serotonin transporter in mild cognitive impairment was greater than grey matter atrophy or reductions in regional cerebral blood flow compared to controls. Lower cortical serotonin transporters were associated with worse performance on tests of auditory-verbal and visual-spatial memory in mild cognitive impairment, not in controls. The serotonin system may represent an important target for prevention and treatment of MCI, particularly the post-synaptic receptors (5-HT4 and 5-HT6), which may not be as severely affected as presynaptic aspects of the serotonin system, as indicated by the observation of lower serotonin transporters in MCI relative to healthy controls. Copyright © 2017 Elsevier Inc. All rights reserved.

Vascular disease and risk factors are associated with cognitive decline in the alzheimer disease spectrum.

PubMed

Lorius, Natacha; Locascio, Joseph J; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Viswanathan, Anand; Marshall, Gad A

2015-01-01

We investigated the relationship between vascular disease and risk factors versus cognitive decline cross-sectionally and longitudinally in normal older control, mild cognitive impairment, and mild Alzheimer disease (AD) dementia subjects. A total of 812 participants (229 normal older control, 395 mild cognitive impairment, 188 AD) underwent cognitive testing, brain magnetic resonance imaging, and clinical evaluations at baseline and over a period of 3 years. General linear, longitudinal mixed-effects, and Cox proportional hazards models were used. Greater homocysteine level and white matter hyperintensity volume were associated with processing speed impairment (homocysteine: P=0.02; white matter hyperintensity: P<0.0001); greater Vascular Index score was associated with memory impairment (P=0.007); and greater number of apolipoprotein E ε4 (APOE4) alleles was associated with global cognitive impairment (P=0.007) at baseline. Apolipoprotein E ε4 was associated with greater rate of increase in global cognitive impairment (P=0.002) and processing speed impairment (P=0.001) over time, whereas higher total cholesterol was associated with greater rate of increase in global cognitive impairment (P=0.02) and memory impairment (P=0.06) over time. These results suggest a significant association of increased vascular disease and risk factors with cognitive impairment at baseline and over time in the AD spectrum in a sample that was selected to have low vascular burden at baseline.

The effects of malnutrition on the motor, perceptual, and cognitive functions of Filipino children.

PubMed

Reyes, M R; Valdecanas, C M; Reyes, O L; Reyes, T M

1990-01-01

The motor, perceptual, and cognitive abilities of 99 Filipino children, aged 4-6 years with a documented history of malnutrition from a nutritionally depressed area of Manila were determined using the Revised Manila Motor-Perceptual Screening Test. They were classified into four groups of: (1) normal; (2) acutely malnourished; (3) stunted but not malnourished; and (4) chronically malnourished using the Waterlow classification. Thirty-one normal children of comparable ages and background from a nationwide pool were similarly tested and served as the control group. Motor (p = 0.001) and perceptual skill (p less than 0.03 to less than 0.001) scores were significantly lower than in their normal counterparts, especially in the chronically malnourished children. Cognitive abilities were not evidently affected by malnutrition.

Does tip-of-the-tongue for proper names discriminate amnestic mild cognitive impairment?

PubMed

Juncos-Rabadán, Onésimo; Facal, David; Lojo-Seoane, Cristina; Pereiro, Arturo X

2013-04-01

Difficulty in retrieving people's names is very common in the early stages of Alzheimer's disease and mild cognitive impairment. Such difficulty is often observed as the tip-of-the-tongue (TOT) phenomenon. The main aim of this study was to explore whether a famous people's naming task that elicited the TOT state can be used to discriminate between amnestic mild cognitive impairment (aMCI) patients and normal controls. Eighty-four patients with aMCI and 106 normal controls aged over 50 years performed a task involving naming 50 famous people shown in pictures. Univariate and multivariate regression analyses were used to study the relationships between aMCI and semantic and phonological measures in the TOT paradigm. Univariate regression analyses revealed that all TOT measures significantly predicted aMCI. Multivariate analysis of all these measures correctly classified 70% of controls (specificity) and 71.6% of aMCI patients (sensitivity), with an AUC (area under curve ROC) value of 0.74, but only the phonological measure remained significant. This classification value was similar to that obtained with the Semantic verbal fluency test. TOTs for proper names may effectively discriminate aMCI patients from normal controls through measures that represent one of the naming processes affected, that is, phonological access.

Are prescription stimulants "smart pills"? The epidemiology and cognitive neuroscience of prescription stimulant use by normal healthy individuals.

PubMed

Smith, M Elizabeth; Farah, Martha J

2011-09-01

Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience literatures in search of answers to these questions. Epidemiological issues addressed include the prevalence of nonmedical stimulant use, user demographics, methods by which users obtain prescription stimulants, and motivations for use. Cognitive neuroscience issues addressed include the effects of prescription stimulants on learning and executive function, as well as the task and individual variables associated with these effects. Little is known about the prevalence of prescription stimulant use for cognitive enhancement outside of student populations. Among college students, estimates of use vary widely but, taken together, suggest that the practice is commonplace. The cognitive effects of stimulants on normal healthy people cannot yet be characterized definitively, despite the volume of research that has been carried out on these issues. Published evidence suggests that declarative memory can be improved by stimulants, with some evidence consistent with enhanced consolidation of memories. Effects on the executive functions of working memory and cognitive control are less reliable but have been found for at least some individuals on some tasks. In closing, we enumerate the many outstanding questions that remain to be addressed by future research and also identify obstacles facing this research. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

Detection of Mild Cognitive Impairment and early stage dementia with an audio-recorded cognitive scale

PubMed Central

Sewell, Margaret C.; Luo, Xiaodong; Neugroschl, Judith; Sano, Mary

2014-01-01

BACKGROUND Physicians often miss a diagnosis of Mild Cognitive Impairment (MCI) or early dementia and screening measures can be insensitive to very mild impairments. Other cognitive assessments may take too much time or be frustrating to seniors. This study examined the ability of an audio-recorded scale, developed in Australia, to detect MCI or mild Alzheimer’s disease and compared cognitive domain specific performance on the audio-recorded scale to in-person battery and common cognitive screens. METHOD Seventy-six subjects from the Mount Sinai Alzheimer’s Disease Research Center were recruited. Subjects were 75 years or older, with clinical diagnosis of AD or MCI (n=51) or normal control (n=25). Participants underwent in-person neuropsychological testing followed by testing with the Audio-recorded Cognitive Screen (ARCS). RESULTS ARCS provided better discrimination between normal and impaired elders than either the Mini-Mental Status Exam (MMSE) or the clock drawing test. The in-person battery and ARCS analogous variables were significantly correlated, most in the .4 to .7 range, including verbal memory, executive function/attention, naming, and verbal fluency. The area under the curve generated from ROC curves indicated high and equivalent discrimination for ARCS and the in-person battery (0.972 vs. 0.988; p=0.23). CONCLUSION The ARCS demonstrated better discrimination between normal controls and those with mild deficits than typical screening measures. Performance on cognitive domains within the ARCS was well correlated with the in-person battery. Completion of the ARCS was accomplished despite mild difficulty hearing the instructions even in very elderly subjects, indicating that it may be a useful measure in primary care settings. PMID:23635663

Corpus callosal atrophy and associations with cognitive impairment in Parkinson disease

PubMed Central

Bledsoe, Ian O.; Merkitch, Doug; Dinh, Vy; Bernard, Bryan; Stebbins, Glenn T.

2017-01-01

Objective: To investigate atrophy of the corpus callosum on MRI in Parkinson disease (PD) and its relationship to cognitive impairment. Methods: One hundred patients with PD and 24 healthy control participants underwent clinical and neuropsychological evaluations and structural MRI brain scans. Participants with PD were classified as cognitively normal (PD-NC; n = 28), having mild cognitive impairment (PD-MCI; n = 47), or having dementia (PDD; n = 25) by Movement Disorder Society criteria. Cognitive domain (attention/working memory, executive function, memory, language, visuospatial function) z scores were calculated. With the use of FreeSurfer image processing, volumes for total corpus callosum and its subsections (anterior, midanterior, central, midposterior, posterior) were computed and normalized by total intracranial volume. Callosal volumes were compared between participants with PD and controls and among PD cognitive groups, covarying for age, sex, and PD duration and with multiple comparison corrections. Regression analyses were performed to evaluate relationships between callosal volumes and performance in cognitive domains. Results: Participants with PD had reduced corpus callosum volumes in midanterior and central regions compared to healthy controls. Participants with PDD demonstrated decreased callosal volumes involving multiple subsections spanning anterior to posterior compared to participants with PD-MCI and PD-NC. Regional callosal atrophy predicted cognitive domain performance such that central volumes were associated with the attention/working memory domain; midposterior volumes with executive function, language, and memory domains; and posterior volumes with memory and visuospatial domains. Conclusions: Notable volume loss occurs in the corpus callosum in PD, with specific neuroanatomic distributions in PDD and relationships of regional atrophy to different cognitive domains. Callosal volume loss may contribute to clinical manifestations of PD cognitive impairment. PMID:28235816

Higher fasting glucose is associated with poorer cognition among healthy young adults.

PubMed

Hawkins, Misty A W; Gunstad, John; Calvo, Dayana; Spitznagel, Mary Beth

2016-02-01

Obesity is associated with cognitive deficits; however, the mechanisms are unclear, especially among otherwise healthy adults. Our objectives were to examine (a) whether obesity is linked to elevations in fasting glucose and (b) whether these elevations are associated with cognitive impairment among otherwise healthy young adults. Participants were 35 normal weight adults and 35 young adults with obesity who completed a task from the Automated Neuropsychological Assessment Metrics-4 (ANAM-4). Measured body mass index (BMI) and fasting blood glucose levels (mg/dL) were examined. Persons with obesity had higher fasting glucose levels than normal weight persons (p = .03). After applying Bonferroni correction for multiple tests, higher fasting glucose predicted less accurate performance on tests of inhibitory control: Go/No-Go Commission Errors (β = .33, p = .004). No effects were observed for sustained attention or working memory (ps ≥. 049). Persons with glucose levels in the prediabetes range had nearly twice as many errors as those with normal glucose, a large effect that was independent of BMI. Young adults who were obese but otherwise healthy had higher fasting glucose levels compared with normal weight peers. Higher glucose levels were associated with poorer cognitive performance on tests of inhibitory control, especially among individuals with prediabetes levels. Thus, subclinical elevations in blood glucose may contribute to cognitive impairment and, ultimately, greater impulsivity-well in advance of the development of chronic disease states (e.g., insulin resistance or Type 2 diabetes) and independently of excess adiposity--though prospective studies are needed to determine directionality of this relationship. (c) 2016 APA, all rights reserved).

Default, Cognitive and Affective Brain Networks in Human Tinnitus

DTIC Science & Technology

Tinnitus is a major health problem among those currently and formerly in military service. This project hypothesizes that many of the clinically...significant, non-auditory aspects of the tinnitus condition involve two major brain networks: the cognitive control network (CCN) and the default mode...function can be assessed. Subjects in three groups are being compared: (1) control subjects with clinically-normal hearing thresholds and no tinnitus

The older people, omega-3, and cognitive health (EPOCH) trial design and methodology: A randomised, double-blind, controlled trial investigating the effect of long-chain omega-3 fatty acids on cognitive ageing and wellbeing in cognitively healthy older adults

PubMed Central

2011-01-01

Background Some studies have suggested an association between omega-3 long-chain polyunsaturated fatty acids (n-3 LC PUFAs) and better cognitive outcomes in older adults. To date, only two randomised, controlled trials have assessed the effect of n-3 LC PUFA supplementation on cognitive function in older cognitively healthy populations. Of these trials only one found a benefit, in the subgroup carrying the ApoE-ε4 allele. The benefits of n-3 LC PUFA supplementation on cognitive function in older normal populations thus still remain unclear. The main objective of the current study was to provide a comprehensive assessment of the potential of n-3 LC PUFAs to slow cognitive decline in normal elderly people, and included ApoE-ε4 allele carriage as a potential moderating factor. The detailed methodology of the trial is reported herein. Methods The study was a parallel, 18-month, randomised, double-blind, placebo-controlled intervention with assessment at baseline and repeated 6-monthly. Participants (N = 391, 53.7% female) aged 65-90 years, English-speaking and with normal cognitive function, were recruited from metropolitan Adelaide, South Australia. Participants in the intervention arm received capsules containing fish-oil at a daily dosage of 1720 mg of docosahexaenoic acid and 600 mg of eicosapentaenoic acid while the placebo arm received the equivalent amount of olive oil in their capsules. The primary outcome is rate of change in cognitive performance, as measured by latent variables for the cognitive constructs (encompassing Reasoning, Working Memory, Short-term Memory, Retrieval Fluency, Inhibition, Simple and Choice-Reaction Time, Perceptual Speed, Odd-man-out Reaction Time, Speed of Memory Scanning, and Psychomotor Speed) and assessed by latent growth curve modeling. Secondary outcomes are change in the Mini-mental State Examination, functional capacity and well-being (including health status, depression, mood, and self-report cognitive functioning), blood pressure, and biomarkers of n-3 LC PUFA status, glucose, lipid metabolism, inflammation, oxidative stress, and DNA damage. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12607000278437 PMID:22011460

Characteristics of Mild Cognitive Impairment Using the Thai Version of the Consortium to Establish a Registry for Alzheimer's Disease Tests: A Multivariate and Machine Learning Study.

PubMed

Tunvirachaisakul, Chavit; Supasitthumrong, Thitiporn; Tangwongchai, Sookjareon; Hemrunroj, Solaphat; Chuchuen, Phenphichcha; Tawankanjanachot, Itthipol; Likitchareon, Yuthachai; Phanthumchinda, Kamman; Sriswasdi, Sira; Maes, Michael

2018-04-04

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) developed a neuropsychological battery (CERAD-NP) to screen patients with Alzheimer's dementia. Mild cognitive impairment (MCI) has received attention as a pre-dementia stage. To delineate the CERAD-NP features of MCI and their clinical utility to externally validate MCI diagnosis. The study included 60 patients with MCI, diagnosed using the Clinical Dementia Rating, and 63 normal controls. Data were analysed employing receiver operating characteristic analysis, Linear Support Vector Machine, Random Forest, Adaptive Boosting, Neural Network models, and t-distributed stochastic neighbour embedding (t-SNE). MCI patients were best discriminated from normal controls using a combination of Wordlist Recall, Wordlist Memory, and Verbal Fluency Test. Machine learning showed that the CERAD features learned from MCI patients and controls were not strongly predictive of the diagnosis (maximal cross-validation 77.2%), whilst t-SNE showed that there is a considerable overlap between MCI and controls. The most important features of the CERAD-NP differentiating MCI from normal controls indicate impairments in episodic and semantic memory and recall. While these features significantly discriminate MCI patients from normal controls, the tests are not predictive of MCI. © 2018 S. Karger AG, Basel.

Pharmacologic Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review.

PubMed

Fink, Howard A; Jutkowitz, Eric; McCarten, J Riley; Hemmy, Laura S; Butler, Mary; Davila, Heather; Ratner, Edward; Calvert, Collin; Barclay, Terry R; Brasure, Michelle; Nelson, Victoria A; Kane, Robert L

2018-01-02

Optimal treatment to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia is uncertain. To summarize current evidence on the efficacy and harms of pharmacologic interventions to prevent or delay cognitive decline, MCI, or dementia in adults with normal cognition or MCI. Several electronic databases from January 2009 to July 2017, bibliographies, and expert recommendations. English-language trials of at least 6 months' duration enrolling adults without dementia and comparing pharmacologic interventions with placebo, usual care, or active control on cognitive outcomes. Two reviewers independently rated risk of bias and strength of evidence; 1 extracted data, and a second checked accuracy. Fifty-one unique trials were rated as having low to moderate risk of bias (including 3 that studied dementia medications, 16 antihypertensives, 4 diabetes medications, 2 nonsteroidal anti-inflammatory drugs [NSAIDs] or aspirin, 17 hormones, and 7 lipid-lowering agents). In persons with normal cognition, estrogen and estrogen-progestin increased risk for dementia or a combined outcome of MCI or dementia (1 trial, low strength of evidence); high-dose raloxifene decreased risk for MCI but not for dementia (1 trial, low strength of evidence); and antihypertensives (4 trials), NSAIDs (1 trial), and statins (1 trial) did not alter dementia risk (low to insufficient strength of evidence). In persons with MCI, cholinesterase inhibitors did not reduce dementia risk (1 trial, low strength of evidence). In persons with normal cognition and those with MCI, these pharmacologic treatments neither improved nor slowed decline in cognitive test performance (low to insufficient strength of evidence). Adverse events were inconsistently reported but were increased for estrogen (stroke), estrogen-progestin (stroke, coronary heart disease, invasive breast cancer, and pulmonary embolism), and raloxifene (venous thromboembolism). High attrition, short follow-up, inconsistent cognitive outcomes, and possible selective reporting and publication. Evidence does not support use of the studied pharmacologic treatments for cognitive protection in persons with normal cognition or MCI. Agency for Healthcare Research and Quality.

Reduced telomere length in subjects with dementia and diabetes mellitus type 2 is independent of apolipoprotein E4 genotype.

PubMed

Kota, Lakshmi Narayanan; Bharath, Srikala; Purushottam, Meera; Paul, Pradip; Sivakumar, Palanimuthu Thangaraju; Varghese, Mathew; Jain, Sanjeev

2014-12-01

Apolipoprotein E4 gene is associated with increased risk of dementia with comorbid diabetes mellitus. Both dementia and diabetes mellitus type 2 are independently associated with telomere shortening. We assessed relative telomere length and apolipoprotein E genotype in subjects with dementia (n=70) and cognitively normal control groups (n=55) with and without comorbid diabetes mellitus type 2. Relative telomere length was highest in the control group (Q2=0.91) followed by dementia (Q2=0.48) and dementia with comorbid diabetes mellitus type 2 (Q2=0.39). Apolipoprotein E4 allele frequency was highest in dementia with comorbid diabetes mellitus type 2 (0.26). Apolipoprotein E4 allele was not significantly associated with telomere attrition in both dementia and cognitively normal group irrespective of comorbid diabetes mellitus type 2 (P>0.05). The findings suggest that relative telomere length is unrelated to apolipoprotein E4 genotype in dementia and cognitive normal subjects with or without comorbid diabetes mellitus type 2. Copyright © 2014 Elsevier B.V. All rights reserved.

Expression of DISC1-interactome members correlates with cognitive phenotypes related to schizophrenia.

PubMed

Rampino, Antonio; Walker, Rosie May; Torrance, Helen Scott; Anderson, Susan Maguire; Fazio, Leonardo; Di Giorgio, Annabella; Taurisano, Paolo; Gelao, Barbara; Romano, Raffaella; Masellis, Rita; Ursini, Gianluca; Caforio, Grazia; Blasi, Giuseppe; Millar, J Kirsty; Porteous, David John; Thomson, Pippa Ann; Bertolino, Alessandro; Evans, Kathryn Louise

2014-01-01

Cognitive dysfunction is central to the schizophrenia phenotype. Genetic and functional studies have implicated Disrupted-in-Schizophrenia 1 (DISC1), a leading candidate gene for schizophrenia and related psychiatric conditions, in cognitive function. Altered expression of DISC1 and DISC1-interactors has been identified in schizophrenia. Dysregulated expression of DISC1-interactome genes might, therefore, contribute to schizophrenia susceptibility via disruption of molecular systems required for normal cognitive function. Here, the blood RNA expression levels of DISC1 and DISC1-interacting proteins were measured in 63 control subjects. Cognitive function was assessed using neuropsychiatric tests and functional magnetic resonance imaging was used to assess the activity of prefrontal cortical regions during the N-back working memory task, which is abnormal in schizophrenia. Pairwise correlations between gene expression levels and the relationship between gene expression levels and cognitive function and N-back-elicited brain activity were assessed. Finally, the expression levels of DISC1, AKAP9, FEZ1, NDEL1 and PCM1 were compared between 63 controls and 69 schizophrenic subjects. We found that DISC1-interactome genes showed correlated expression in the blood of healthy individuals. The expression levels of several interactome members were correlated with cognitive performance and N-back-elicited activity in the prefrontal cortex. In addition, DISC1 and NDEL1 showed decreased expression in schizophrenic subjects compared to healthy controls. Our findings highlight the importance of the coordinated expression of DISC1-interactome genes for normal cognitive function and suggest that dysregulated DISC1 and NDEL1 expression might, in part, contribute to susceptibility for schizophrenia via disruption of prefrontal cortex-dependent cognitive functions.

Expression of DISC1-Interactome Members Correlates with Cognitive Phenotypes Related to Schizophrenia

PubMed Central

Rampino, Antonio; Walker, Rosie May; Torrance, Helen Scott; Anderson, Susan Maguire; Fazio, Leonardo; Di Giorgio, Annabella; Taurisano, Paolo; Gelao, Barbara; Romano, Raffaella; Masellis, Rita; Ursini, Gianluca; Caforio, Grazia; Blasi, Giuseppe; Millar, J. Kirsty; Porteous, David John; Thomson, Pippa Ann; Bertolino, Alessandro; Evans, Kathryn Louise

2014-01-01

Cognitive dysfunction is central to the schizophrenia phenotype. Genetic and functional studies have implicated Disrupted-in-Schizophrenia 1 (DISC1), a leading candidate gene for schizophrenia and related psychiatric conditions, in cognitive function. Altered expression of DISC1 and DISC1-interactors has been identified in schizophrenia. Dysregulated expression of DISC1-interactome genes might, therefore, contribute to schizophrenia susceptibility via disruption of molecular systems required for normal cognitive function. Here, the blood RNA expression levels of DISC1 and DISC1-interacting proteins were measured in 63 control subjects. Cognitive function was assessed using neuropsychiatric tests and functional magnetic resonance imaging was used to assess the activity of prefrontal cortical regions during the N-back working memory task, which is abnormal in schizophrenia. Pairwise correlations between gene expression levels and the relationship between gene expression levels and cognitive function and N-back-elicited brain activity were assessed. Finally, the expression levels of DISC1, AKAP9, FEZ1, NDEL1 and PCM1 were compared between 63 controls and 69 schizophrenic subjects. We found that DISC1-interactome genes showed correlated expression in the blood of healthy individuals. The expression levels of several interactome members were correlated with cognitive performance and N-back-elicited activity in the prefrontal cortex. In addition, DISC1 and NDEL1 showed decreased expression in schizophrenic subjects compared to healthy controls. Our findings highlight the importance of the coordinated expression of DISC1-interactome genes for normal cognitive function and suggest that dysregulated DISC1 and NDEL1 expression might, in part, contribute to susceptibility for schizophrenia via disruption of prefrontal cortex-dependent cognitive functions. PMID:24940743

Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure

PubMed Central

Treit, Sarah; Zhou, Dongming; Chudley, Albert E.; Andrew, Gail; Rasmussen, Carmen; Nikkel, Sarah M.; Samdup, Dawa; Hanlon-Dearman, Ana; Loock, Christine; Beaulieu, Christian

2016-01-01

Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5–19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol exposure, but raise concerns about the predictive value of this metric at an individual-subject level. PMID:26928125

Relationships between Head Circumference, Brain Volume and Cognition in Children with Prenatal Alcohol Exposure.

PubMed

Treit, Sarah; Zhou, Dongming; Chudley, Albert E; Andrew, Gail; Rasmussen, Carmen; Nikkel, Sarah M; Samdup, Dawa; Hanlon-Dearman, Ana; Loock, Christine; Beaulieu, Christian

2016-01-01

Head circumference is used together with other measures as a proxy for central nervous system damage in the diagnosis of fetal alcohol spectrum disorders, yet the relationship between head circumference and brain volume has not been investigated in this population. The objective of this study is to characterize the relationship between head circumference, brain volume and cognitive performance in a large sample of children with prenatal alcohol exposure (n = 144) and healthy controls (n = 145), aged 5-19 years. All participants underwent magnetic resonance imaging to yield brain volumes and head circumference, normalized to control for age and sex. Mean head circumference, brain volume, and cognitive scores were significantly reduced in the prenatal alcohol exposure group relative to controls, albeit with considerable overlap between groups. Males with prenatal alcohol exposure had reductions in all three measures, whereas females with prenatal alcohol exposure had reduced brain volumes and cognitive scores, but no difference in head circumference relative to controls. Microcephaly (defined here as head circumference ≤ 3rd percentile) occurred more often in prenatal alcohol exposed participants than controls, but 90% of the exposed sample had head circumferences above this clinical cutoff indicating that head circumference is not a sensitive marker of prenatal alcohol exposure. Normalized head circumference and brain volume were positively correlated in both groups, and subjects with very low head circumference typically had below-average brain volumes. Conversely, over half of the subjects with very low brain volumes had normal head circumferences, which may stem from differential effects of alcohol on the skeletal and nervous systems. There were no significant correlations between head circumference and any cognitive score. These findings confirm group-level reductions in head circumference and increased rates of microcephaly in children with prenatal alcohol exposure, but raise concerns about the predictive value of this metric at an individual-subject level.

Weaker cognitive control abilities of Pi (Spleen) qi-deficient individuals supported Chinese medicine diagnosis.

PubMed

Lin, Hui-Yan; Zhao, Yan-Ping; Xu, Gui-Ping; Li, Yun-Si; Xie, Wei-Yun; Bai, Li-Hua; Jin, Hua

2017-07-28

To investigate whether Pi (Spleen) qi-deficiency affected psychological and neural responses in relevance to cognitive control. Pi qi-deficient and balanced participants were asked to perform the Stroop task, a classical cognitive control paradigm. In this paradigm, participants had to judge the color of the prompted word. The word's meaning indicated the color (the consistent condition) or not (the inconsistent condition), or were unrelated to the color (the neutral condition). Electroencephalograph (EEG) was recorded during the task. Event-related potential (ERP) results showed that Pi qi-deficient individuals failed to exhibit a normal Stroop effect as Balanced individuals did, such as the accuracy differences between the consistent and the inconsistent conditions as well as the N450 effect (P>0.05). Meanwhile, Pi qi-deficient individuals displayed larger P2 and P3 amplitudes than balanced individuals did during performing the cognitive control task (P<0.05). Pi qi-deficiency had psychological and neural basis at least in cognitive control aspect.

Neuropsychological performance in advanced age: influences of demographic factors and Apolipoprotein E: findings from the Cache County Memory Study.

PubMed

Welsh-Bohmer, Katheen A; Ostbye, Truls; Sanders, Linda; Pieper, Carl F; Hayden, Kathleen M; Tschanz, JoAnn T; Norton, Maria C

2009-01-01

The Cache County Study of Memory in Aging (CCMS) is an epidemiological study of Alzheimer's disease (AD), mild cognitive disorders, and aging in a population of exceptionally long-lived individuals (7th to 11th decade). Observation of population members without dementia provides an opportunity for establishing the range of normal neurocognitive performance in a representative sample of the very old. We examined neurocognitive performance of the normal participants undergoing full clinical evaluations (n = 507) and we tested the potential modifying effects of apolipoprotein E (APOE) genotype, a known genetic risk factor for the later development of AD. The results indicate that advanced age and low education are related to lower test scores across nearly all of the neurocognitive measures. Gender and APOE epsilon4 both had negligible and inconsistent influences, affecting only isolated measures of memory and expressive speech (in case of gender). The gender and APOE effects disappeared once age and education were controlled. The study of this exceptionally long-lived population provides useful normative information regarding the broad range of "normal" cognition seen in advanced age. Among elderly without dementia or other cognitive impairment, APOE does not appear to exert any major effects on cognition once other demographic influences are controlled.

Association between educational attainment and amyloid deposition across the spectrum from normal cognition to dementia: neuroimaging evidence for protection and compensation.

PubMed

Arenaza-Urquijo, Eider M; Bejanin, Alexandre; Gonneaud, Julie; Wirth, Miranka; La Joie, Renaud; Mutlu, Justine; Gaubert, Malo; Landeau, Brigitte; de la Sayette, Vincent; Eustache, Francis; Chételat, Gaël

2017-11-01

The brain mechanisms underlying the effect of intellectual enrichment may evolve along the normal aging Alzheimer's disease (AD) cognitive spectrum and may include both protective and compensatory mechanisms. We assessed the association between early intellectual enrichment (education, years) and average cortical florbetapir standardized uptake value ratio as well as performed voxel-wise analyses in a total of 140 participants, including cognitively normal older adults, mild cognitive impairment (MCI), and AD patients. Higher education was associated with lower cortical florbetapir positron emission tomography (florbetapir-PET) uptake, notably in the frontal lobe in normal older adults, but with higher uptake in frontal, temporal, and parietal regions in MCI after controlling for global cognitive status. No association was found in AD. In MCI, we observed an increased fluorodeoxyglucose positron emission tomography (FDG-PET) uptake with education within the regions of higher florbetapir-PET uptake, suggesting a compensatory increase. Early intellectual enrichment may be associated with protection and compensation for amyloid beta (Aβ) deposition later in life, before the onset of dementia. Previous investigations have been controversial as regard to the effects of intellectual enrichment variables on Aβ deposition; the present findings call for approaches aiming to evaluate mechanisms of resilience across disease stages. Copyright © 2017 Elsevier Inc. All rights reserved.

Normal weight children have higher cognitive performance - Independent of physical activity, sleep, and diet.

PubMed

Hjorth, Mads F; Sørensen, Louise B; Andersen, Rikke; Dyssegaard, Camilla B; Ritz, Christian; Tetens, Inge; Michaelsen, Kim F; Astrup, Arne; Egelund, Niels; Sjödin, Anders

2016-10-15

Aside from the health consequences, observational studies indicate that being overweight may also negatively affect cognitive function. However, existing evidence has to a large extent not controlled for the possible confounding effect of having different lifestyles. Therefore, the objective was to examine the independent associations between weight status and lifestyle indicators with cognitive performance in 8-11year old Danish children. The analyses included 828 children (measured in 2011-2012) each having one to three measurement occasions separated by approximately 100days. Dietary intake, physical activity, sedentary time, and sleep duration were measured using dietary records and accelerometers. The Children's Sleep Habits Questionnaire was used to access sleep problems and the Andersen test was carried out to estimate cardio-respiratory fitness (CRF). Weight status (underweight, normal weight, and overweight/obese) was defined according to body mass index and cognitive performance was assessed using the d2-test of attention, a reading test, and a math test. A linear mixed model including a number of fixed and random effects was used to test associations between lifestyle indicators as well as BMI category and cognitive performance. After adjustment for demographics, socioeconomics, and multiple lifestyle indicators, normal weight children had higher cognitive test scores than overweight/obese and underweight children of up to 89% and 48% of expected learning within one school year (P<0.05). Daily breakfast consumption, fewer sleep problems, higher CRF, less total physical activity, more sedentary time, and less light physical activity were associated with higher cognitive performance independently of each other in at least one of the three cognitive tests (P<0.05). Normal weight children had higher cognitive performance compared to overweight/obese as well as underweight children, independent of multiple lifestyle indicators. Copyright © 2016 Elsevier Inc. All rights reserved.

Prayer at Midlife is Associated with Reduced Risk of Cognitive Decline in Arabic Women

PubMed Central

Inzelberg, Rivka; Afgin, Anne E; Massarwa, Magda; Schechtman, Edna; Israeli-Korn, Simon D.; Strugatsky, Rosa; Abuful, Amin; Kravitz, Efrat; Farrer, Lindsay A.; Friedland, Robert P.

2013-01-01

Midlife habits may be important for the later development of Alzheimer's disease (AD). We estimated the contribution of midlife prayer to the development of cognitive decline. In a door-to-door survey, residents aged ≥65 years were systematically evaluated in Arabic including medical history, neurological, cognitive examination, and a midlife leisure-activities questionnaire. Praying was assessed by the number of monthly praying hours at midlife. Stepwise logistic regression models were used to evaluate the effect of prayer on the odds of mild cognitive impairment (MCI) and AD versus cognitively normal individuals. Of 935 individuals that were approached, 778 [normal controls (n=448), AD (n=92) and MCI (n=238)] were evaluated. A higher proportion of cognitively normal individuals engaged in prayer at midlife [(87%) versus MCI (71%) or AD (69%) (p<0.0001)]. Since 94% of males engaged in prayer, the effect on cognitive decline could not be assessed in men. Among women, stepwise logistic regression adjusted for age and education, showed that prayer was significantly associated with reduced risk of MCI (p=0.027, OR=0.55, 95% CI 0.33-0.94), but not AD. Among individuals endorsing prayer activity, the amount of prayer was not associated with MCI or AD in either gender. Praying at midlife is associated with lower risk of mild cognitive impairment in women. PMID:23116476

Are Prescription Stimulants “Smart Pills”?

PubMed Central

Smith, M. Elizabeth; Farah, Martha J.

2013-01-01

Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience literatures in search of answers to these questions. Epidemiological issues addressed include the prevalence of nonmedical stimulant use, user demographics, methods by which users obtain prescription stimulants, and motivations for use. Cognitive neuroscience issues addressed include the effects of prescription stimulants on learning and executive function, as well as the task and individual variables associated with these effects. Little is known about the prevalence of prescription stimulant use for cognitive enhancement outside of student populations. Among college students, estimates of use vary widely but, taken together, suggest that the practice is commonplace. The cognitive effects of stimulants on normal healthy people cannot yet be characterized definitively, despite the volume of research that has been carried out on these issues. Published evidence suggests that declarative memory can be improved by stimulants, with some evidence consistent with enhanced consolidation of memories. Effects on the executive functions of working memory and cognitive control are less reliable but have been found for at least some individuals on some tasks. In closing, we enumerate the many outstanding questions that remain to be addressed by future research and also identify obstacles facing this research. PMID:21859174

Prayer at midlife is associated with reduced risk of cognitive decline in Arabic women.

PubMed

Inzelberg, Rivka; Afgin, Anne E; Massarwa, Magda; Schechtman, Edna; Israeli-Korn, Simon D; Strugatsky, Rosa; Abuful, Amin; Kravitz, Efrat; Farrer, Lindsay A; Friedland, Robert P

2013-03-01

Midlife habits may be important for the later development of Alzheimer's disease (AD). We estimated the contribution of midlife prayer to the development of cognitive decline. In a door-to-door survey, residents aged ≥65 years were systematically evaluated in Arabic including medical history, neurological, cognitive examination, and a midlife leisure-activities questionnaire. Praying was assessed by the number of monthly praying hours at midlife. Stepwise logistic regression models were used to evaluate the effect of prayer on the odds of mild cognitive impairment (MCI) and AD versus cognitively normal individuals. Of 935 individuals that were approached, 778 [normal controls (n=448), AD (n=92) and MCI (n=238)] were evaluated. A higher proportion of cognitively normal individuals engaged in prayer at midlife [(87%) versus MCI (71%) or AD (69%) (p<0.0001)]. Since 94% of males engaged in prayer, the effect on cognitive decline could not be assessed in men. Among women, stepwise logistic regression adjusted for age and education, showed that prayer was significantly associated with reduced risk of MCI (p=0.027, OR=0.55, 95% CI 0.33-0.94), but not AD. Among individuals endorsing prayer activity, the amount of prayer was not associated with MCI or AD in either gender. Praying at midlife is associated with lower risk of mild cognitive impairment in women.

Which Neuropsychological Tests Predict Progression to Alzheimer’s Disease in Hispanics?

PubMed Central

Weissberger, Gali H.; Salmon, David P.; Bondi, Mark W.; Gollan, Tamar H.

2013-01-01

Objective To investigate which neuropsychological tests predict eventual progression to Alzheimer’s disease (AD) in both Hispanic and non-Hispanic individuals. Although our approach was exploratory, we predicted that tests that underestimate cognitive ability in healthy aging Hispanics might not be sensitive to future cognitive decline in this cultural group. Method We compared first-year data of 22 older adults (11 Hispanic) who were diagnosed as cognitively normal but eventually developed AD (decliners), to 60 age- and education-matched controls (27 Hispanic) who remained cognitively normal. To identify tests that may be culturally biased in our sample, we compared Hispanic with non-Hispanic controls on all tests and asked which tests were sensitive to future decline in each cultural group. Results Compared to age-, education-, and gender-matched non-Hispanic controls, Hispanic controls obtained lower scores on tests of language, executive function, and some measures of global cognition. Consistent with our predictions, some tests identified non-Hispanic, but not Hispanic, decliners (vocabulary, semantic fluency). Contrary to our predictions, a number of tests on which Hispanics obtained lower scores than non-Hispanics nevertheless predicted eventual progression to AD in both cultural groups (e.g., Boston Naming Test [BNT], Trails A and B). Conclusions Cross-cultural variation in test sensitivity to decline may reflect greater resistance of medium difficulty items to decline and bilingual advantages that initially protect Hispanics against some aspects of cognitive decline commonly observed in non-Hispanics with preclinical AD. These findings highlight a need for further consideration of cross-cultural differences in neuropsychological test performance and development of culturally unbiased measures. PMID:23688216

Is cerebral microbleed prevalence relevant as a biomarker in amnestic mild cognitive impairment and mild Alzheimer's disease?

PubMed

Rabelo, Ana Gb; Teixeira, Camila Vl; Magalhães, Thamires Nc; Carletti-Cassani, Ana Flávia Mk; Amato Filho, Augusto Cs; Joaquim, Helena Pg; Talib, Leda L; Forlenza, Orestes; Ribeiro, Patrícia Ao; Secolin, Rodrigo; Lopes-Cendes, Iscia; Cendes, Fernando; Balthazar, Marcio Lf

2017-10-01

Introduction The search for a reliable neuroimaging biomarker in Alzheimer's disease is a matter of intense research. The presence of cerebral microbleeds seems to be a potential biomarker. However, it is not clear if the presence of microbleeds has clinical usefulness to differentiate mild Alzheimer's disease and amnestic mild cognitive impairment from normal aging. We aimed to verify if microbleed prevalence differs among three groups: mild Alzheimer's disease, amnestic mild cognitive impairment due to Alzheimer's disease, and normal controls. Moreover, we studied whether microbleeds were associated with apolipoprotein E allele ɛ4 status, cerebrospinal fluid amyloid-beta, total and phosphorylated tau protein levels, vascular factors, and cognition. Methods Twenty-eight mild Alzheimer's disease patients, 34 with amnestic mild cognitive impairment and 36 cognitively normal elderly subjects underwent: magnetic resonance imaging with a susceptibility-weighted imaging sequence on a 3T scanner, apolipoprotein E genotyping and a full neuropsychological evaluation. Only amnestic mild cognitive impairment and mild Alzheimer's disease underwent cerebrospinal fluid analysis. We compared the groups and verified if microbleeds were predicted by all other variables. Results Mild Alzheimer's disease presented a higher prevalence of apolipoprotein E allele ɛ4 in relation to amnestic mild cognitive impairment and control group. No significant differences were found between groups when considering microbleed presence. Logistic regression tests failed to find any relationship between microbleeds and the variables. We performed three different regression models using different independent variables: Model 1 - amyloid-beta, phosphorylated tau protein, total tau, apolipoprotein E allele ɛ4 status, age, and sex; Model 2 - vascular risk factors, age, and sex; Model 3 - cognitive scores sex, age, and education. Conclusion Although microbleeds might be related to the Alzheimer's disease process, their presence is not a good candidate for a neuroimaging biomarker of the disease, especially in its early phases.

Neurobiological findings associated with high cognitive performance in older adults: a systematic review.

PubMed

Borelli, Wyllians Vendramini; Schilling, Lucas Porcello; Radaelli, Graciane; Ferreira, Luciana Borges; Pisani, Leonardo; Portuguez, Mirna Wetters; da Costa, Jaderson Costa

2018-04-18

ABSTRACTObjectives:to perform a comprehensive literature review of studies on older adults with exceptional cognitive performance. We performed a systematic review using two major databases (MEDLINE and Web of Science) from January 2002 to November 2017. Quantitative analysis included nine of 4,457 studies and revealed that high-performing older adults have global preservation of the cortex, especially the anterior cingulate region, and hippocampal volumes larger than normal agers. Histological analysis of this group also exhibited decreased amyloid burden and neurofibrillary tangles compared to cognitively normal older controls. High performers that maintained memory ability after three years showed reduced amyloid positron emission tomography at baseline compared with high performers that declined. A single study on blood plasma found a set of 12 metabolites predicting memory maintenance of this group. Structural and molecular brain preservation of older adults with high cognitive performance may be associated with brain maintenance. The operationalized definition of high-performing older adults must be carefully addressed using appropriate age cut-off and cognitive evaluation, including memory and non-memory tests. Further studies with a longitudinal approach that include a younger control group are essential.

Social Markers of Mild Cognitive Impairment: Proportion of Word Counts in Free Conversational Speech.

PubMed

Dodge, Hiroko H; Mattek, Nora; Gregor, Mattie; Bowman, Molly; Seelye, Adriana; Ybarra, Oscar; Asgari, Meysam; Kaye, Jeffrey A

2015-01-01

Detecting early signs of Alzheimer's disease (AD) and mild cognitive impairment (MCI) during the pre-symptomatic phase is becoming increasingly important for costeffective clinical trials and also for deriving maximum benefit from currently available treatment strategies. However, distinguishing early signs of MCI from normal cognitive aging is difficult. Biomarkers have been extensively examined as early indicators of the pathological process for AD, but assessing these biomarkers is expensive and challenging to apply widely among pre-symptomatic community dwelling older adults. Here we propose assessment of social markers, which could provide an alternative or complementary and ecologically valid strategy for identifying the pre-symptomatic phase leading to MCI and AD. The data came from a larger randomized controlled clinical trial (RCT), where we examined whether daily conversational interactions using remote video telecommunications software could improve cognitive functions of older adult participants. We assessed the proportion of words generated by participants out of total words produced by both participants and staff interviewers using transcribed conversations during the intervention trial as an indicator of how two people (participants and interviewers) interact with each other in one-on-one conversations. We examined whether the proportion differed between those with intact cognition and MCI, using first, generalized estimating equations with the proportion as outcome, and second, logistic regression models with cognitive status as outcome in order to estimate the area under ROC curve (ROC AUC). Compared to those with normal cognitive function, MCI participants generated a greater proportion of words out of the total number of words during the timed conversation sessions (p=0.01). This difference remained after controlling for participant age, gender, interviewer and time of assessment (p=0.03). The logistic regression models showed the ROC AUC of identifying MCI (vs. normals) was 0.71 (95% Confidence Interval: 0.54 - 0.89) when average proportion of word counts spoken by subjects was included univariately into the model. An ecologically valid social marker such as the proportion of spoken words produced during spontaneous conversations may be sensitive to transitions from normal cognition to MCI.

Effects of exercise and diet change on cognition function and synaptic plasticity in high fat diet induced obese rats

PubMed Central

2013-01-01

Background Nutritional imbalance-induced obesity causes a variety of diseases and in particular is an important cause of cognitive function decline. This study was performed on Sprague Dawley (SD) rats with 13-weeks of high fat diet-induced obesity in connection to the effects of regular exercise and dietary control for 8 weeks on the synaptic plasticity and cognitive abilities of brain. Methods Four weeks-old SD rats were adopted classified into normal-normal diet-sedentary (NNS, n = 8), obesity-high fat diet-sedentary (OHS, n = 8), obesity-high fat diet-training (OHT, n = 8), obesity-normal diet-sedentary (ONS, n = 8) and obesity- normal diet-training (ONT, n = 8). The exercise program consisted of a treadmill exercise administered at a speed of 8 m/min for 1–4 weeks, and 14 m/min for 5–8 weeks. The Western blot method was used to measure the expression of NGF, BDNF, p38MAPK and p-p38MAPK proteins in hippocampus of the brain, and expressions of NGF, BDNF, TrkA, TrkB, CREB and synapsin1 mRNA were analyzed through qRT-PCR. Results The results suggest cognitive function-related protein levels and mRNA expression to be significantly decreased in the hippocampus of obese rats, and synaptic plasticity as well as cognitive function signaling sub-pathway factors were also significantly decreased. In addition, 8-weeks exercises and treatment by dietary change had induced significant increase of cognitive function-related protein levels and mRNA expression as well as synaptic plasticity and cognitive function signaling sub-pathway factors in obese rats. In particular, the combined treatment had presented even more positive effect. Conclusions Therefore, it was determined that the high fat diet-induced obesity decreases plasticity and cognitive function of the brain, but was identified as being improved by exercises and dietary changes. In particular, it is considered that regular exercise has positive effects on memory span and learning capacity unlike dietary control. PMID:24098984

Cognitive functions, electroencephalographic and diffusion tensor imaging changes in children with active idiopathic epilepsy.

PubMed

A Yassine, Imane; M Eldeeb, Waleed; A Gad, Khaled; A Ashour, Yossri; A Yassine, Inas; O Hosny, Ahmed

2018-07-01

Neurocognitive impairment represents one of the most common comorbidities occurring in children with idiopathic epilepsy. Diagnosis of the idiopathic form of epilepsy requires the absence of any macrostructural abnormality in the conventional MRI. Though changes can be seen at the microstructural level imaged using advanced techniques such as the Diffusion Tensor Imaging (DTI). The aim of this work is to study the correlation between the microstructural white matter DTI findings, the electroencephalographic changes and the cognitive dysfunction in children with active idiopathic epilepsy. A comparative cross-sectional study, included 60 children with epilepsy based on the Stanford-Binet 5th Edition Scores was conducted. Patients were equally assigned to normal cognitive function or cognitive dysfunction groups. The history of the epileptic condition was gathered via personal interviews. All patients underwent brain Electroencephalography (EEG) and DTI, which was analyzed using FSL. The Fractional Anisotropy (FA) was significantly higher whereas the Mean Diffusivity (MD) was significantly lower in the normal cognitive function group than in the cognitive dysfunction group. This altered microstructure was related to the degree of the cognitive performance of the studied children with epilepsy. The microstructural alterations of the neural fibers in children with epilepsy and cognitive dysfunction were significantly related to the younger age of onset of epilepsy, the poor control of the clinical seizures, and the use of multiple antiepileptic medications. Children with epilepsy and normal cognitive functions differ in white matter integrity, measured using DTI, compared with children with cognitive dysfunction. These changes have important cognitive consequences. Copyright © 2018 Elsevier Inc. All rights reserved.

Pilot study of cognition in children with unilateral hearing loss.

PubMed

Ead, Banan; Hale, Sandra; DeAlwis, Duneesha; Lieu, Judith E C

2013-11-01

The objective of this study was to obtain preliminary data on the cognitive function of children with unilateral hearing loss in order to identify, quantify, and interpret differences in cognitive and language functions between children with unilateral hearing loss and with normal hearing. Fourteen children ages 9-14 years old (7 with severe-to-profound sensorineural unilateral hearing loss and 7 sibling controls with normal hearing) were administered five tests that assessed cognitive functions of working memory, processing speed, attention, and phonological processing. Mean composite scores for phonological processing were significantly lower for the group with unilateral hearing loss than for controls on one composite and four subtests. The unilateral hearing loss group trended toward worse performance on one additional composite and on two additional phonological processing subtests. The unilateral hearing loss group also performed worse than the control group on the complex letter span task. Analysis examining performance on the two levels of task difficulty revealed a significant main effect of task difficulty and an interaction between task difficulty and group. Cognitive function and phonological processing test results suggest two related deficits associated with unilateral hearing loss: (1) reduced accuracy and efficiency associated with phonological processing, and (2) impaired executive control function when engaged in maintaining verbal information in the face of processing incoming, irrelevant verbal information. These results provide a possible explanation for the educational difficulties experienced by children with unilateral hearing loss. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Selective visual attention for ugly and beautiful body parts in eating disorders.

PubMed

Jansen, Anita; Nederkoorn, Chantal; Mulkens, Sandra

2005-02-01

Body image disturbance is characteristic of eating disorders, and current treatments use body exposure to reduce bad body feelings. There is however little known about the cognitive effects of body exposure. In the present study, eye movement registration (electroculography) as a direct index of selective visual attention was used while eating symptomatic and normal control participants were exposed to digitalized pictures of their own body and control bodies. The data showed a decreased focus on their own 'beautiful' body parts in the high symptomatic participants, whereas inspection of their own 'ugly' body parts was given priority. In the normal control group a self-serving cognitive bias was found: they focused more on their own 'beautiful' body parts and less on their own 'ugly' body parts. When viewing other bodies the pattern was reversed: high symptom participants allocated their attention to the beautiful parts of other bodies, whereas normal controls concentrated on the ugly parts of the other bodies. From the present findings the hypothesis follows that a change in the processing of information might be needed for body exposure to be successful.

The COFU3 Study. Improvement in cognitive function, attention, mental performance with Pycnogenol® in healthy subjects (55-70) with high oxidative stress.

PubMed

Belcaro, G; Dugall, M; Ippolito, E; Hu, S; Saggino, A; Feragalli, B

2015-12-01

This 12-month product registry study evaluated the effects of supplementation with French pine bark extract (Pycnogenol(®)) on cognitive function, attention, and mental performance in healthy subjects with high oxidative stress. Healthy subjects (age range 55-70) were screened - within a cardiovascular screening program - for oxidative stress. Out of 150 subjects, high oxidative stress was present in 44; the use of the supplement Pycnogenol(®) was suggested (100 mg/day). These subjects decided to use Pycnogenol(®) and accepted to be evaluated by assessing cognitive functions. A group of subjects with comparable oxidative stress was followed as a reference. IQ Code (Informant Questionnaire on Cognitive Decline in the Elderly), daily tasks, cognitive function, oxidative stress and the short Blessed tests (SBT) were used (in defined scales) to evaluate cognitive functions (COFU). As for the IQ Code, at 12 months there was a significantlty total lower score in Pycnogenol(®) patients and also a lower value (P<0.05) for 14 out of 16 items in the questionnaire. Daily tasks: all items were improved (P<0.05) with supplementation in comparison with controls. The improvement was seen for all 12 items (P<0.05) with the supplement. Cognitive function values (visual scale line) indicated a significant improvement (P<0.05) in all elements present in the questionnaire with the 12-month supplementation (no significant variations in controls). Oxidative stress was comparable in both groups at inclusion. It was significantly decreased with Pycnogenol(®) (-28.07%; P<0.05) at 12 months; there was no decrease in controls. The short blessed test (SBT) value was significantly increased in controls (P<0.05); but significantly decreased in the Pycnogenol(®) group (P<0.05). Values for supplemented patients at 12 months were almost within the normal range (21 out or 38 were below the normal value of 4). Tolerability and compliance for Pycnogenol(®) were optimal with >97% of the doses of the supplement correctly used. No side effects were observed, recorded or described. Pycnogenol(®) supplementation for 12 months appears to improve cognitive function and oxidative stress in normal subjects between 55 and 70 years of age.

Cognitive Impairment and Whole Brain Diffusion in Patients with Neuromyelitis Optica after Acute Relapse

ERIC Educational Resources Information Center

He, Diane; Wu, Qizhu; Chen, Xiuying; Zhao, Daidi; Gong, Qiyong; Zhou, Hongyu

2011-01-01

The objective of this study investigated cognitive impairments and their correlations with fractional anisotropy (FA) and mean diffusivity (MD) in patients with neuromyelitis optica (NMO) without visible lesions on conventional brain MRI during acute relapse. Twenty one patients with NMO and 21 normal control subjects received several cognitive…

Serum trace metal levels in Alzheimer's disease and normal control groups.

PubMed

Park, Jun-Hyun; Lee, Dong-Woo; Park, Kyung Su; Joung, Hyojee

2014-02-01

To determine whether serum trace metals are related to abnormal cognition in Alzheimer's disease (AD). We studied serum lead (Pb), cadmium (Cd), mercury (Hg), and arsenic(As) in 89 patients with AD and in 118 cognitively normal individuals. We analyzed the results of the blood tests and the food intake. Serum Pb levels correlated with word list recall (P = .039) and word list recognition (P = .037). Without age adjustment, serum Cd levels (P = .044) were significantly higher in the AD group. After stratified age adjustment, the levels of selected trace metals did not differ significantly between AD and normal individuals. Food intakes regarding selected trace metals were not significantly different between the 2 groups. In this study, serum Pb, Cd, Hg, and As levels were not directly related to abnormal cognition in AD. Serum Pb levels were significantly negatively correlated with verbal memory scores.

The potential role of melatonin on sleep deprivation-induced cognitive impairments: implication of FMRP on cognitive function.

PubMed

Kwon, K J; Lee, E J; Kim, M K; Jeon, S J; Choi, Y Y; Shin, C Y; Han, S-H

2015-08-20

While prolonged sleep deprivation (SD) could lead to profound negative health consequences, such as impairments in vital biological functions of immunity and cognition, melatonin possesses powerful ameliorating effects against those harmful insults. Melatonin has strong antioxidant and anti-inflammatory effects that help to restore body's immune and cognitive functions. In this study, we investigated the possible role of melatonin in reversing cognitive dysfunction induced by SD in rats. Our experimental results revealed that sleep-deprived animals exhibited spatial memory impairment in the Morris water maze tasks compared with the control groups. Furthermore, there was an increased glial activation most prominent in the hippocampal region of the SD group compared to the normal control (NC) group. Additionally, markers of oxidative stress such as 4-hydroxynonenal (4-HNE) and 7,8-dihydro-8-oxo-deoxyguanine (8-oxo-dG) were significantly increased, while fragile X-mental retardation protein (FMRP) expression was decreased in the SD group. Interestingly, melatonin treatment normalized these events to control levels following SD. Our data demonstrate that SD induces oxidative stress through glial activation and decreases FMRP expression in the neurons. Furthermore, our results suggest the efficacy of melatonin for the treatment of sleep-related neuronal dysfunction, which occurs in neurological disorders such as Alzheimer's disease and autism. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

[Reason and emotion: integration of cognitive-behavioural and experiential interventions in the treatment of long evolution food disorders].

PubMed

Vilariño Besteiro, M P; Pérez Franco, C; Gallego Morales, L; Calvo Sagardoy, R; García de Lorenzo, A

2009-01-01

This paper intends to show the combination of therapeutical strategies in the treatment of long evolution food disorders. This fashion of work entitled "Modelo Santa Cristina" is based on several theoretical paradigms: Enabling Model, Action Control Model, Change Process Transtheoretical Model and Cognitive-Behavioural Model (Cognitive Restructuring and Learning Theories). Furthermore, Gestalt, Systemic and Psychodrama Orientation Techniques. The purpose of the treatment is both the normalization of food patterns and the increase in self-knowledge, self-acceptance and self-efficacy of patients. The exploration of ambivalence to change, the discovery of the functions of symptoms and the search for alternative behaviours, the normalization of food patterns, bodily image, cognitive restructuring, decision taking, communication skills and elaboration of traumatic experiences are among the main areas of intervention.

Volumetric correlates of memory and executive function in normal elderly, mild cognitive impairment and Alzheimer’s disease

PubMed Central

Duarte, Audrey; Hayasaka, Satoru; Du, Antao; Schuff, Norbert; Jahng, Geon-Ho; Kramer, Joel; Miller, Bruce; Weiner, Michael

2007-01-01

In Alzheimer’s disease (AD), atrophy negatively impacts cognition while in healthy adults, inverse relationships between brain volume and cognition may occur. We investigated correlations between gray matter volume and cognition in elderly controls, AD and mild cognitive impairment (MCI) patients with memory and executive deficits. AD demonstrated substantial loss in temporal, parietal and frontal regions while MCI exhibited moderate volume loss in temporal and frontal regions. In controls, memory and executive function were negatively correlated with frontal regions, while in AD, memory was positively correlated with temporal and frontal gyri, and executive function with frontal regions. The combination of the two patterns may explain the lack of correlations in MCI. Developmental versus pathological contributions to these relationships are discussed. PMID:16904823

Physical Fitness and Serum Vitamin D and Cognition in Elderly Koreans.

PubMed

Ahn, Jeong-Deok; Kang, Hyunsik

2015-12-01

Poor physical fitness and low serum vitamin D are known to be modifiable risk factors for cognitive declines with normal aging. We investigated the association of physical fitness and serum vitamin D levels with global cognitive function in older adults. In this cross-sectional study, a total of 412 older Korean adults (108 men aged 74.4 ± 6.0 years and 304 women aged 73.1 ± 5.4 years) completed the Korean version of Mini-Mental State Examination (MMSE) to assess global cognitive performance and the senior fitness test to assess strength, flexibility, agility, and endurance domains of physical fitness. Body mass index, percent body fat, serum vitamin D, geriatric depression scale (GDS), level of education, smoking, and history of cardiovascular or cerebrovascular disease were also assessed as covariates. Age, sex, GDS, and body fatness were negatively associated with MMSE-based cognitive performance. Serum vitamin D and physical fitness were positively associated with MMSE-based cognitive performance. Multivariate linear regression showed that agility (partial R(2) = -0.184, p = 0.029) and endurance (partial R(2) = 0.191, p = 0.022) domains of physical fitness along with serum vitamin D (partial R(2) = 0.210, p = 0.012) were significant predictors for global cognitive performance after controlling for covariates (i.e., age, sex, education, GDS, body fatness, and comorbidity index). The current findings of the study suggest that promotion of physical fitness and vitamin D supplementation should be key components of interventions to prevent cognitive decline with normal aging. Key pointsCognitive declines are associated with normal aging as well as modifiable lifestyle risk factors, and there is an increasing need to identify the modifiable risk factors for the onset of cognitive declines and to provide evidence-based strategies for healthy and successful aging.In Korea, little is known about the relationships of physical fitness and serum vitamin D with cognitive function in older adults, and we determined the associations between a) serum vitamin D levels and cognitive function and b) physical fitness and cognitive function among community-dwelling elderly Koreans.The current findings of the study suggest that agility and endurance domains of physical fitness along with serum vitamin D were significant predictors for global cognitive performance after controlling for covariates.

Physical Fitness and Serum Vitamin D and Cognition in Elderly Koreans

PubMed Central

Ahn, Jeong-Deok; Kang, Hyunsik

2015-01-01

Poor physical fitness and low serum vitamin D are known to be modifiable risk factors for cognitive declines with normal aging. We investigated the association of physical fitness and serum vitamin D levels with global cognitive function in older adults. In this cross-sectional study, a total of 412 older Korean adults (108 men aged 74.4 ± 6.0 years and 304 women aged 73.1 ± 5.4 years) completed the Korean version of Mini-Mental State Examination (MMSE) to assess global cognitive performance and the senior fitness test to assess strength, flexibility, agility, and endurance domains of physical fitness. Body mass index, percent body fat, serum vitamin D, geriatric depression scale (GDS), level of education, smoking, and history of cardiovascular or cerebrovascular disease were also assessed as covariates. Age, sex, GDS, and body fatness were negatively associated with MMSE-based cognitive performance. Serum vitamin D and physical fitness were positively associated with MMSE-based cognitive performance. Multivariate linear regression showed that agility (partial R2 = -0.184, p = 0.029) and endurance (partial R2 = 0.191, p = 0.022) domains of physical fitness along with serum vitamin D (partial R2 = 0.210, p = 0.012) were significant predictors for global cognitive performance after controlling for covariates (i.e., age, sex, education, GDS, body fatness, and comorbidity index). The current findings of the study suggest that promotion of physical fitness and vitamin D supplementation should be key components of interventions to prevent cognitive decline with normal aging. Key points Cognitive declines are associated with normal aging as well as modifiable lifestyle risk factors, and there is an increasing need to identify the modifiable risk factors for the onset of cognitive declines and to provide evidence-based strategies for healthy and successful aging. In Korea, little is known about the relationships of physical fitness and serum vitamin D with cognitive function in older adults, and we determined the associations between a) serum vitamin D levels and cognitive function and b) physical fitness and cognitive function among community-dwelling elderly Koreans. The current findings of the study suggest that agility and endurance domains of physical fitness along with serum vitamin D were significant predictors for global cognitive performance after controlling for covariates. PMID:26664270

Disentangling cognition and emotion in older adults: the role of cognitive control and mental health in emotional conflict adaptation.

PubMed

Hantke, Nathan C; Gyurak, Anett; Van Moorleghem, Katie; Waring, Jill D; Adamson, Maheen M; O'Hara, Ruth; Beaudreau, Sherry A

2017-08-01

Recent research suggests cognition has a bidirectional relationship with emotional processing in older adults, yet the relationship is still poorly understood. We aimed to examine a potential relationship between late-life cognitive function, mental health symptoms, and emotional conflict adaptation. We hypothesized that worse cognitive control abilities would be associated with poorer emotional conflict adaptation. We further hypothesized that a higher severity of mental health symptoms would be associated with poorer emotional conflict adaptation. Participants included 83 cognitively normal community-dwelling older adults who completed a targeted mental health and cognitive battery, and emotion and gender conflict-adaptation tasks. Consistent with our hypothesis, poorer performance on components of cognitive control, specifically attention and working memory, was associated with poorer emotional conflict adaptation. This association with attention and working memory was not observed in the non-affective-based gender conflict adaptation task. Mental health symptoms did not predict emotional conflict adaptation, nor did performance on other cognitive measures. Our findings suggest that emotion conflict adaptation is disrupted in older individuals who have poorer attention and working memory. Components of cognitive control may therefore be an important potential source of inter-individual differences in late-life emotion regulation and cognitive affective deficits. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The iconic memory skills of brain injury survivors and non-brain injured controls after visual scanning training.

PubMed

McClure, J T; Browning, R T; Vantrease, C M; Bittle, S T

1994-01-01

Previous research suggests that traumatic brain injury (TBI) results in impairment of iconic memory abilities.We would like to acknowledge the contribution of Jeffrey D. Vantrease, who wrote the software program for the Iconic Memory procedure and measurement. This raises serious implications for brain injury rehabilitation. Most cognitive rehabilitation programs do not include iconic memory training. Instead it is common for cognitive rehabilitation programs to focus on attention and concentration skills, memory skills, and visual scanning skills.This study compared the iconic memory skills of brain-injury survivors and control subjects who all reached criterion levels of visual scanning skills. This involved previous training for the brain-injury survivors using popular visual scanning programs that allowed them to visually scan with response time and accuracy within normal limits. Control subjects required only minimal training to reach normal limits criteria. This comparison allows for the dissociation of visual scanning skills and iconic memory skills.The results are discussed in terms of their implications for cognitive rehabilitation and the relationship between visual scanning training and iconic memory skills.

Contribution of four lifelong factors of cognitive reserve on late cognition in normal aging and Parkinson's disease.

PubMed

Rouillard, Maud; Audiffren, Michel; Albinet, Cédric; Ali Bahri, Mohamed; Garraux, Gaëtan; Collette, Fabienne

2017-03-01

Cognitive reserve (CR) was proposed to explain how individual differences in brain function help to cope with the effects of normal aging and neurodegenerative diseases. Education, professional solicitations, and engagement in leisure and physical activities across the lifetime are considered as major determinants of this reserve. Using multiple linear regression analyses, we tested separately in healthy elderly and Parkinson's disease (PD) populations to what extent cognitive performance in several domains was explained by (a) any of these four environmental lifespan variables; (b) demographic and clinical variables (age, gender, depression score, and, for the PD group, duration of disease and dopaminergic drugs). We also tested for an interaction, if any, between these lifespan variables and brain pathology indexed by global atrophy measured from high-resolution anatomical magnetic resonance imaging. Age was negatively associated with cognitive performance in the PD group. In healthy elderly participants, we observed significant positive associations between cognitive performance and (a) education, (b) leisure activities, and (c) professional solicitation (decisional latitude). Furthermore, participants with greater brain atrophy benefited more from CR. In PD patients, education and professional solicitations contributed to cognitive performance but to a lesser extent than in controls. CR factors modulated the relationship between cognition and brain atrophy only in patients with a slight or moderate brain atrophy. Education is the CR factor that contributed the most to late cognitive functioning in both groups, closely followed by leisure activity in normal aging and professional solicitations in PD. Our results also provide evidence suggesting that the effects of CR does not express similarly in normal aging and PD. From a broader perspective, these results seem to indicate that CR factors the most consistently practiced across lifespan (education and professional solicitation) are those that are the more strongly associated to late cognitive efficiency.

Two Different Populations within the Healthy Elderly: Lack of Conflict Detection in Those at Risk of Cognitive Decline

PubMed Central

Sánchez-Moguel, Sergio M.; Alatorre-Cruz, Graciela C.; Silva-Pereyra, Juan; González-Salinas, Sofía; Sanchez-Lopez, Javier; Otero-Ojeda, Gloria A.; Fernández, Thalía

2018-01-01

During healthy aging, inhibitory processing is affected at the sensorial, perceptual, and cognitive levels. The assessment of event-related potentials (ERPs) during the Stroop task has been used to study age-related decline in the efficiency of inhibitory processes. Studies using ERPs have found that the P300 amplitude increases and the N500 amplitude is attenuated in healthy elderly adults compared to those in young adults. On the other hand, it has been reported that theta excess in resting EEG with eyes closed is a good predictor of cognitive decline during aging 7 years later, while a normal EEG increases the probability of not developing cognitive decline. The behavioral and ERP responses during a Counting-Stroop task were compared between 22 healthy elderly subjects with normal EEG (Normal-EEG group) and 22 healthy elderly subjects with an excess of EEG theta activity (Theta-EEG group). Behaviorally, the Normal-EEG group showed a higher behavioral interference effect than the Theta-EEG group. ERP patterns were different between the groups, and two facts are highlighted: (a) the P300 amplitude was higher in the Theta-EEG group, with both groups showing a P300 effect in almost all electrodes, and (b) the Theta-EEG group did not show an N500 effect. These results suggest that the diminishment in inhibitory control observed in the Theta-EEG group may be compensated by different processes in earlier stages, which would allow them to perform the task with similar efficiency to that of participants with a normal EEG. This study is the first to show that healthy elderly subjects with an excess of theta EEG activity not only are at risk of developing cognitive decline but already have a cognitive impairment. PMID:29375352

Two Different Populations within the Healthy Elderly: Lack of Conflict Detection in Those at Risk of Cognitive Decline.

PubMed

Sánchez-Moguel, Sergio M; Alatorre-Cruz, Graciela C; Silva-Pereyra, Juan; González-Salinas, Sofía; Sanchez-Lopez, Javier; Otero-Ojeda, Gloria A; Fernández, Thalía

2017-01-01

During healthy aging, inhibitory processing is affected at the sensorial, perceptual, and cognitive levels. The assessment of event-related potentials (ERPs) during the Stroop task has been used to study age-related decline in the efficiency of inhibitory processes. Studies using ERPs have found that the P300 amplitude increases and the N500 amplitude is attenuated in healthy elderly adults compared to those in young adults. On the other hand, it has been reported that theta excess in resting EEG with eyes closed is a good predictor of cognitive decline during aging 7 years later, while a normal EEG increases the probability of not developing cognitive decline. The behavioral and ERP responses during a Counting-Stroop task were compared between 22 healthy elderly subjects with normal EEG (Normal-EEG group) and 22 healthy elderly subjects with an excess of EEG theta activity (Theta-EEG group). Behaviorally, the Normal-EEG group showed a higher behavioral interference effect than the Theta-EEG group. ERP patterns were different between the groups, and two facts are highlighted: (a) the P300 amplitude was higher in the Theta-EEG group, with both groups showing a P300 effect in almost all electrodes, and (b) the Theta-EEG group did not show an N500 effect. These results suggest that the diminishment in inhibitory control observed in the Theta-EEG group may be compensated by different processes in earlier stages, which would allow them to perform the task with similar efficiency to that of participants with a normal EEG. This study is the first to show that healthy elderly subjects with an excess of theta EEG activity not only are at risk of developing cognitive decline but already have a cognitive impairment.

Cognitive Fatigue Facilitates Procedural Sequence Learning.

PubMed

Borragán, Guillermo; Slama, Hichem; Destrebecqz, Arnaud; Peigneux, Philippe

2016-01-01

Enhanced procedural learning has been evidenced in conditions where cognitive control is diminished, including hypnosis, disruption of prefrontal activity and non-optimal time of the day. Another condition depleting the availability of controlled resources is cognitive fatigue (CF). We tested the hypothesis that CF, eventually leading to diminished cognitive control, facilitates procedural sequence learning. In a two-day experiment, 23 young healthy adults were administered a serial reaction time task (SRTT) following the induction of high or low levels of CF, in a counterbalanced order. CF was induced using the Time load Dual-back (TloadDback) paradigm, a dual working memory task that allows tailoring cognitive load levels to the individual's optimal performance capacity. In line with our hypothesis, reaction times (RT) in the SRTT were faster in the high- than in the low-level fatigue condition, and performance improvement was higher for the sequential than the motor components. Altogether, our results suggest a paradoxical, facilitating impact of CF on procedural motor sequence learning. We propose that facilitated learning in the high-level fatigue condition stems from a reduction in the cognitive resources devoted to cognitive control processes that normally oppose automatic procedural acquisition mechanisms.

Response-Conflict Moderates the Cognitive Control of Episodic and Contextual Load in Older Adults.

PubMed

Eich, Teal S; Rakitin, Brian C; Stern, Yaakov

2016-11-01

Decline in cognitive control is one of the primary cognitive changes in normal aging. Reaching a consensus regarding the nature of these age-related changes, however, is complicated by the complexity of cognitive control as a construct. Healthy older and younger adults participated in a multifactorial test of cognitive control. Within participants, the procedure varied as a function of the amount contextual load, episodic load, and response-conflict load present. We found that older adults showed impaired performance relative to younger adults. We also found, however, that the response selection process underlying the response-conflict manipulation was a major moderator of age-related differences in both the contextual and episodic load conditions-suggesting a hierarchical organization. These findings are consistent with previous findings, suggesting that deficits in cognitive control in older adults are directly related to the resolution of response-conflict and that other apparent deficits may be derivative upon the more basic response-conflict related deficit. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Using virtual reality to distinguish subjects with multiple- but not single-domain amnestic mild cognitive impairment from normal elderly subjects.

PubMed

Mohammadi, Alireza; Kargar, Mahmoud; Hesami, Ehsan

2018-03-01

Spatial disorientation is a hallmark of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease. Our aim was to use virtual reality to determine the allocentric and egocentric memory deficits of subjects with single-domain aMCI (aMCIsd) and multiple-domain aMCI (aMCImd). For this purpose, we introduced an advanced virtual reality navigation task (VRNT) to distinguish these deficits in mild Alzheimer's disease (miAD), aMCIsd, and aMCImd. The VRNT performance of 110 subjects, including 20 with miAD, 30 with pure aMCIsd, 30 with pure aMCImd, and 30 cognitively normal controls was compared. Our newly developed VRNT consists of a virtual neighbourhood (allocentric memory) and virtual maze (egocentric memory). Verbal and visuospatial memory impairments were also examined with Rey Auditory-Verbal Learning Test and Rey-Osterrieth Complex Figure Test, respectively. We found that miAD and aMCImd subjects were impaired in both allocentric and egocentric memory, but aMCIsd subjects performed similarly to the normal controls on both tasks. The miAD, aMCImd, and aMCIsd subjects performed worse on finding the target or required more time in the virtual environment than the aMCImd, aMCIsd, and normal controls, respectively. Our findings indicated the aMCImd and miAD subjects, as well as the aMCIsd subjects, were more impaired in egocentric orientation than allocentric orientation. We concluded that VRNT can distinguish aMCImd subjects, but not aMCIsd subjects, from normal elderly subjects. The VRNT, along with the Rey Auditory-Verbal Learning Test and Rey-Osterrieth Complex Figure Test, can be used as a valid diagnostic tool for properly distinguishing different forms of aMCI. © 2018 Japanese Psychogeriatric Society.

Combination of MRI hippocampal volumetry and arterial spin labeling MR perfusion at 3-Tesla improves the efficacy in discriminating Alzheimer's disease from cognitively normal elderly adults.

PubMed

Mak, Henry Ka-Fung; Qian, Wenshu; Ng, Kwok Sing; Chan, Queenie; Song, You-Qiang; Chu, Leung Wing; Yau, Kelvin Kai-Wing

2014-01-01

Structural magnetic resonance imaging has been employed for evaluation of medial temporal atrophy in patients with Alzheimer's disease (AD). Arterial spin labeling (ASL) technique could detect cerebral perfusion abnormalities in AD. We hypothesized that combination of hippocampal volumetry and cerebral blood flow yield higher accuracy than either method alone in discriminating AD patients from cognitively normal elderly adults. 13 AD patients and 15 healthy controls were studied using a 3-tesla scanner. Standardized T1W 3D volumetric Fast Field Echo and QUASAR ASL sequences were employed for cerebral volumetry and perfusion respectively. Manual Right and left hippocampal volumetry was performed manually by ANALYZE software, with total intracranial volume normalization. ASL data were analyzed by institutional specially-design software to calculate cerebral blood flow of region-of-interests placed at the middle and posterior cingulate gyri. Right and left hippocampal volumes and middle and posterior cingulate gyri cerebral blood flows were significantly lower in the patients than in the controls (independent-samples t-tests, p < 0.05), and prediction accuracies of 89.3%, 82.1%, 75.0% and 71.4% were achieved for each of the above parameters, respectively. In distinguishing patients from controls using corresponding optimized cut-off values, various combinations of these parameters were used to create the Receiver Operating Characteristic curves. The highest area under curve value was 0.944, by combining cerebral blood flow at the middle cingulate gyrus, normalized right and left hippocampal volumes. A 'one-stop-shop' magnetic resonance study of combined hippocampal volumetry and cerebral perfusion has improved efficacy in discriminating AD patients from cognitively normal elderly adults.

Graph Theory and Cognition: An Alternative Avenue for Examining Neuropsychological Status in Epilepsy

PubMed Central

Garcia-Ramos, Camille; Lin, Jack J; Kellermann, Tanja S; Bonilha, Leonardo; Prabhakaran, Vivek; Hermann, Bruce P

2016-01-01

The recent revision of the classification of the epilepsies released by the ILAE Commission on Classification and Terminology (2005–2009) has been a major development in the field. Papers in this section of the special issue were charged with examining the relevance of other techniques and approaches to examining, categorizing and classifying cognitive and behavioral comorbidities. In that light, we investigate the applicability of graph theory to understand the impact of epilepsy on cognition compared to controls, and then the patterns of cognitive development in normally developing children which would set the stage for prospective comparisons of children with epilepsy and controls. The overall goal is to examine the potential utility of other analytic tools and approaches to conceptualize the cognitive comorbidities in epilepsy. Given that the major cognitive domains representing cognitive function are interdependent, the associations between the neuropsychological abilities underlying these domains can be referred to as a cognitive network. Therefore, the architecture of this cognitive network can be quantified and assessed using graph theory methods, rendering a novel approach to the characterization of cognitive status. In this article we provide fundamental information about graph theory procedures, followed by application of these techniques to cross-sectional analysis of neuropsychological data in children with epilepsy compared to controls, finalizing with prospective analysis of neuropsychological development in younger and older healthy controls. PMID:27017326

Gait assessment in mild cognitive impairment and Alzheimer's disease: the effect of dual-task challenges across the cognitive spectrum.

PubMed

Muir, Susan W; Speechley, Mark; Wells, Jennie; Borrie, Michael; Gopaul, Karen; Montero-Odasso, Manuel

2012-01-01

Gait impairment is a prominent falls risk factor and a prevalent feature among older adults with cognitive impairment. However, there is a lack of comparative studies on gait performance and fall risk covering the continuum from normal cognition through mild cognitive impairment (MCI) to Alzheimer's disease (AD). We evaluated gait performance and the response to dual-task challenges in older adults with AD, MCI and normal cognition without a history of falls. We hypothesized that, in older people without history of falls, gait performance will deteriorate across the cognitive spectrum with changes being more evident under dual-tasking. Gait was assessed using an electronic walkway under single and three dual-tasks conditions. Gait velocity and stride time variability were not significantly different between the three groups under the single-task condition. By contrast, significant differences of decreasing velocity (p<0.0001), increasing stride time (p=0.0057) and increasing stride time variability (p=0.0037) were found under dual-task testing for people with MCI and AD. Less automatic and more complex dual-task tests, such as naming animals and serial subtraction by sevens from 100, created the greatest deterioration of gait performance. Gait changes under dual-tasking for the MCI and AD groups were statistically different from the cognitively normal controls. Dual-task assessment exposed gait impairments not obvious under a single-task test condition and may facilitate falls risk identification in cognitively impaired persons without a history of falls. Copyright © 2011 Elsevier B.V. All rights reserved.

Impaired math achievement in patients with acute vestibular neuritis.

PubMed

Moser, Ivan; Vibert, Dominique; Caversaccio, Marco D; Mast, Fred W

2017-12-01

Broad cognitive difficulties have been reported in patients with peripheral vestibular deficit, especially in the domain of spatial cognition. Processing and manipulating numbers relies on the ability to use the inherent spatial features of numbers. It is thus conceivable that patients with acute peripheral vestibular deficit show impaired numerical cognition. Using the number Stroop task and a short math achievement test, we tested 20 patients with acute vestibular neuritis and 20 healthy, age-matched controls. On the one hand, patients showed normal congruency and distance effects in the number Stroop task, which is indicative of normal number magnitude processing. On the other hand, patients scored lower than healthy controls in the math achievement test. We provide evidence that the lower performance cannot be explained by either differences in prior math knowledge (i.e., education) or slower processing speed. Our results suggest that peripheral vestibular deficit negatively affects numerical cognition in terms of the efficient manipulation of numbers. We discuss the role of executive functions in math performance and argue that previously reported executive deficits in patients with peripheral vestibular deficit provide a plausible explanation for the lower math achievement scores. In light of the handicapping effects of impaired numerical cognition in daily living, it is crucial to further investigate the mechanisms that cause mathematical deficits in acute PVD and eventually develop adequate means for cognitive interventions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Using Base Rate of Low Scores to Identify Progression from Amnestic Mild Cognitive Impairment to Alzheimer's Disease.

PubMed

Oltra-Cucarella, Javier; Sánchez-SanSegundo, Miriam; Lipnicki, Darren M; Sachdev, Perminder S; Crawford, John D; Pérez-Vicente, José A; Cabello-Rodríguez, Luis; Ferrer-Cascales, Rosario

2018-05-10

To investigate the implications of obtaining one or more low scores on a battery of cognitive tests on diagnosing mild cognitive impairment (MCI). Observational longitudinal study. Alzheimer's Disease Neuroimaging Initiative. Normal controls (NC, n = 280) and participants with MCI (n = 415) according to Petersen criteria were reclassified using the Jak/Bondi criteria and number of impaired tests (NIT) criteria. Diagnostic statistics and hazard ratios of progression to Alzheimer's disease (AD) were compared according to diagnostic criteria. The NIT criteria were a better predictor of progression to AD than the Petersen or Jak/Bondi criteria, with optimal sensitivity, specificity, and positive and negative predictive value. Considering normal variability in cognitive test performance when diagnosing MCI may help identify individuals at greatest risk of progression to AD with greater certainty. © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society.

Cognitive correlates of financial abilities in mild cognitive impairment.

PubMed

Okonkwo, Ozioma C; Wadley, Virginia G; Griffith, H Randall; Ball, Karlene; Marson, Daniel C

2006-11-01

To investigate the cognitive correlates of financial abilities in mild cognitive impairment (MCI). Controlled, matched-sample, cross-sectional analysis regressing five cognitive composites on financial performance measures. University medical and research centers. Forty-three persons with MCI and 43 normal controls. The Financial Capacity Instrument (FCI) and a comprehensive neurocognitive battery. Patients with MCI performed significantly worse than controls on cognitive domains of executive function, memory, and language and on FCI domains of financial conceptual knowledge, bank statement management, and bill payment. Patients with MCI also needed significantly more time to complete a multistep financial task and were significantly more likely than controls to make errors on this task. Stepwise regression models revealed that, within the MCI group, attention and executive function were significant correlates of FCI performance. Although impaired memory is the cardinal deficit in MCI, the neurocognitive basis of lower functional performance in MCI appears to be emergent declines in abilities to selectively attend, self-monitor, and temporally integrate information. Compromised performance on cognitive measures of attention and executive function may constitute clinical markers of lower financial abilities and should be evaluated for its relationship to functional ability in general. These cognitive domains may be appropriate targets of future intervention studies aimed at preservation of functional independence in people with MCI.

Temperature control can abolish anesthesia-induced tau hyperphosphorylation and partly reverse anesthesia-induced cognitive impairment in old mice.

PubMed

Xiao, Haibing; Run, Xiaoqin; Cao, Xu; Su, Ying; Sun, Zhou; Tian, Cheng; Sun, Shenggang; Liang, Zhihou

2013-11-01

Anesthesia is related to cognitive impairment and the risk for Alzheimer's disease. Hypothermia during anesthesia can lead to abnormal hyperphosphorylation of tau, which has been speculated to be involved in anesthesia-induced cognitive impairment. The aim of this study was to investigate whether maintenance of the tau phosphorylation level by body temperature control during anesthesia could reverse the cognitive dysfunction in C57BL/6 mice. Eighteen-month-old mice were repeatedly anesthetized during a 2-week period with or without maintenance of body temperature, control mice were treated with normal saline instead of anesthetics. Tau phosphorylation level in mice brain was detected on western blot, and cognitive performance was measured using the Morris water maze (MWM). After anesthesia-induced hypothermia in old mice, tau was hyperphosphorylated and the cognitive performance, measured on MWM, was impaired. When body temperature was controlled during anesthesia, however, the tau hyperphosphorylation was completely avoided, and there was partial recovery in cognitive impairment measured on the MWM. Hyperphosphorylation of tau in the brain after anesthesia is an important event, and it might be, although not solely, responsible for postoperative cognitive decline. © 2013 The Authors. Psychiatry and Clinical Neurosciences © 2013 Japanese Society of Psychiatry and Neurology.

Functional network integrity presages cognitive decline in preclinical Alzheimer disease.

PubMed

Buckley, Rachel F; Schultz, Aaron P; Hedden, Trey; Papp, Kathryn V; Hanseeuw, Bernard J; Marshall, Gad; Sepulcre, Jorge; Smith, Emily E; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Chhatwal, Jasmeer P

2017-07-04

To examine the utility of resting-state functional connectivity MRI (rs-fcMRI) measurements of network integrity as a predictor of future cognitive decline in preclinical Alzheimer disease (AD). A total of 237 clinically normal older adults (aged 63-90 years, Clinical Dementia Rating 0) underwent baseline β-amyloid (Aβ) imaging with Pittsburgh compound B PET and structural and rs-fcMRI. We identified 7 networks for analysis, including 4 cognitive networks (default, salience, dorsal attention, and frontoparietal control) and 3 noncognitive networks (primary visual, extrastriate visual, motor). Using linear and curvilinear mixed models, we used baseline connectivity in these networks to predict longitudinal changes in preclinical Alzheimer cognitive composite (PACC) performance, both alone and interacting with Aβ burden. Median neuropsychological follow-up was 3 years. Baseline connectivity in the default, salience, and control networks predicted longitudinal PACC decline, unlike connectivity in the dorsal attention and all noncognitive networks. Default, salience, and control network connectivity was also synergistic with Aβ burden in predicting decline, with combined higher Aβ and lower connectivity predicting the steepest curvilinear decline in PACC performance. In clinically normal older adults, lower functional connectivity predicted more rapid decline in PACC scores over time, particularly when coupled with increased Aβ burden. Among examined networks, default, salience, and control networks were the strongest predictors of rate of change in PACC scores, with the inflection point of greatest decline beyond the fourth year of follow-up. These results suggest that rs-fcMRI may be a useful predictor of early, AD-related cognitive decline in clinical research settings. © 2017 American Academy of Neurology.

The value of P300 event related potentials in the assessment of cognitive function in subclinical hypothyroidism.

PubMed

Dejanović, Mirjana; Ivetić, Vesna; Nestorović, Vojkan; Milanović, Zvezdan; Erić, Mirela

2017-03-01

Mild hypothyroidism (thyroid stimulating hormone [TSH] less than 10 mIU/L) induces reversible cognitive dysfunction, which can be evaluated by event related potentials (ERP). So far, only little is known about the impact of subclinical hypothyroidism on ERP as electrophysiological markers of cognitive activity. The aim of this study was to follow-up P300 latencies and amplitudes in patients with subclinical hypothyroidism and to evaluate the influence of thyroxine treatment which led to the normalization of TSH level in serum. We recorded the P300 wave using an auditory oddball paradigm in 60 patients (mean age 51.1±6.2 years, range 40-62 years), with subclinical hypothyroidism (normal mean value of FT4, with elevated TSH levels) at baseline, after 3 months, after 6 months and in 30 healthy control subjects. 30 patients treated six months with L-thyroxine until the normalization of TSH and 30 patients received placebo. The P300 latencies in patients with subclinical hypothyroidism were significantly longer, and the P300 amplitudes were significantly smaller than those of the control group. In the thyroxine treated patients P300 latency continuously decreased over the observation period with a significant difference after 6 months compared to baseline (P<0.01). The amplitude P300 showed no significant changes over time. Our results show the importance of P300 event related potentials in the detection of cognitive changes in patients with hypothyroidism. The P300 latency stands out as a marker for cognitive function recovery during treatment with thyroxine.

Exercise and Parkinson's: benefits for cognition and quality of life.

PubMed

Cruise, K E; Bucks, R S; Loftus, A M; Newton, R U; Pegoraro, R; Thomas, M G

2011-01-01

The benefits of physical exercise for psychological aspects of quality of life (QoL) are well established in normally ageing adults, yet potential benefits for people with Parkinson's disease (PD) have received limited attention. This study evaluated the benefits of exercise for cognitive functioning, mood and disease-specific QoL for people with PD. Twenty-eight individuals with PD were allocated to an exercise intervention program (EIP, n = 15) or control group (n = 13). The EIP group undertook a programme of progressive anabolic and aerobic exercise twice weekly for 12 weeks. The control group maintained their usual lifestyle. Exercise was shown to have selective benefits for cognitive functioning by improving frontal lobe based executive function. No significant effects were demonstrated for mood or disease-specific QoL. These results are consistent with previous research demonstrating selective benefits of exercise for executive function among normal ageing adults and PD. Copyright © 2010 The Authors. Journal compilation © 2010 Blackwell Munksgaard.

Cognitive Addition: Comparison of Learning Disabled and Academically Normal Children.

ERIC Educational Resources Information Center

Geary, David C.; And Others

To isolate the process deficits underlying a specific learning disability in mathematics achievement, 77 academically normal and 46 learning disabled (LD) students in second, fourth or sixth grade were presented 140 simple addition problems using a true-false reaction time verification paradigm. (The problems were on a video screen controlled by…

Graph theory and cognition: A complementary avenue for examining neuropsychological status in epilepsy.

PubMed

Garcia-Ramos, Camille; Lin, Jack J; Kellermann, Tanja S; Bonilha, Leonardo; Prabhakaran, Vivek; Hermann, Bruce P

2016-11-01

The recent revision of the classification of the epilepsies released by the ILAE Commission on Classification and Terminology (2005-2009) has been a major development in the field. Papers in this section of the special issue explore the relevance of other techniques to examine, categorize, and classify cognitive and behavioral comorbidities in epilepsy. In this review, we investigate the applicability of graph theory to understand the impact of epilepsy on cognition compared with controls and, then, the patterns of cognitive development in normally developing children which would set the stage for prospective comparisons of children with epilepsy and controls. The overall goal is to examine the potential utility of this analytic tool and approach to conceptualize the cognitive comorbidities in epilepsy. Given that the major cognitive domains representing cognitive function are interdependent, the associations between neuropsychological abilities underlying these domains can be referred to as a cognitive network. Therefore, the architecture of this cognitive network can be quantified and assessed using graph theory methods, rendering a novel approach to the characterization of cognitive status. We first provide fundamental information about graph theory procedures, followed by application of these techniques to cross-sectional analysis of neuropsychological data in children with epilepsy compared with that of controls, concluding with prospective analysis of neuropsychological development in younger and older healthy controls. This article is part of a Special Issue entitled "The new approach to classification: Rethinking cognition and behavior in epilepsy". Copyright © 2016 Elsevier Inc. All rights reserved.

Cognitive, emotional and social markers of serial murdering.

PubMed

Angrilli, Alessandro; Sartori, Giuseppe; Donzella, Giovanna

2013-01-01

Although criminal psychopathy is starting to be relatively well described, our knowledge of the characteristics and scientific markers of serial murdering is still very poor. A serial killer who murdered more than five people, KT, was administered a battery of standardized tests aimed at measuring neuropsychological impairment and social/emotional cognition deficits. KT exhibited a striking dissociation between a high level of emotional detachment and a low score on the antisocial behavior scale on the Psychopathy Checklist-Revised (PCL-R). The Minnesota Multiphasic Personality Inventory-2 showed a normal pattern with the psychotic triad at borderline level. KT had a high intelligence score and showed almost no impairment in cognitive tests sensitive to frontal lobe dysfunction (Wisconsin Card Sorting Test, Theory of Mind, Tower of London, this latter evidenced a mild impairment in planning performance). In the tests on moral, emotional and social cognition, his patterns of response differed from matched controls and from past reports on criminal psychopaths as, unlike these individuals, KT exhibited normal recognition of fear and a relatively intact knowledge of moral rules but he was impaired in the recognition of anger, embarrassment and conventional social rules. The overall picture of KT suggests that serial killing may be closer to normality than psychopathy defined according to either the DSM IV or the PCL-R, and it would be characterized by a relatively spared moral cognition and selective deficits in social and emotional cognition domains.

Multimodal imaging of the self-regulating developing brain.

PubMed

Fjell, Anders M; Walhovd, Kristine Beate; Brown, Timothy T; Kuperman, Joshua M; Chung, Yoonho; Hagler, Donald J; Venkatraman, Vijay; Roddey, J Cooper; Erhart, Matthew; McCabe, Connor; Akshoomoff, Natacha; Amaral, David G; Bloss, Cinnamon S; Libiger, Ondrej; Darst, Burcu F; Schork, Nicholas J; Casey, B J; Chang, Linda; Ernst, Thomas M; Gruen, Jeffrey R; Kaufmann, Walter E; Kenet, Tal; Frazier, Jean; Murray, Sarah S; Sowell, Elizabeth R; van Zijl, Peter; Mostofsky, Stewart; Jernigan, Terry L; Dale, Anders M

2012-11-27

Self-regulation refers to the ability to control behavior, cognition, and emotions, and self-regulation failure is related to a range of neuropsychiatric problems. It is poorly understood how structural maturation of the brain brings about the gradual improvement in self-regulation during childhood. In a large-scale multicenter effort, 735 children (4-21 y) underwent structural MRI for quantification of cortical thickness and surface area and diffusion tensor imaging for quantification of the quality of major fiber connections. Brain development was related to a standardized measure of cognitive control (the flanker task from the National Institutes of Health Toolbox), a critical component of self-regulation. Ability to inhibit responses and impose cognitive control increased rapidly during preteen years. Surface area of the anterior cingulate cortex accounted for a significant proportion of the variance in cognitive performance. This finding is intriguing, because characteristics of the anterior cingulum are shown to be related to impulse, attention, and executive problems in neurodevelopmental disorders, indicating a neural foundation for self-regulation abilities along a continuum from normality to pathology. The relationship was strongest in the younger children. Properties of large-fiber connections added to the picture by explaining additional variance in cognitive control. Although cognitive control was related to surface area of the anterior cingulate independently of basic processes of mental speed, the relationship between white matter quality and cognitive control could be fully accounted for by speed. The results underscore the need for integration of different aspects of brain maturation to understand the foundations of cognitive development.

Transcranial direct current stimulation in mild cognitive impairment: Behavioral effects and neural mechanisms.

PubMed

Meinzer, Marcus; Lindenberg, Robert; Phan, Mai Thy; Ulm, Lena; Volk, Carina; Flöel, Agnes

2015-09-01

The long preclinical phase of Alzheimer's disease provides opportunities for potential disease-modifying interventions in prodromal stages such as mild cognitive impairment (MCI). Anodal transcranial direct current stimulation (anodal-tDCS), with its potential to enhance neuroplasticity, may allow improving cognition in MCI. In a double-blind, cross-over, sham-controlled study, anodal-tDCS was administered to the left inferior frontal cortex during task-related and resting-state functional magnetic resonance imaging (fMRI) to assess its impact on cognition and brain functions in MCI. During sham stimulation, MCI patients produced fewer correct semantic-word-retrieval responses than matched healthy controls, which was associated with hyperactivity in bilateral prefrontal regions. Anodal-tDCS significantly improved performance to the level of controls, reduced task-related prefrontal hyperactivity and resulted in "normalization" of abnormal network configuration during resting-state fMRI. Anodal-tDCS exerts beneficial effects on cognition and brain functions in MCI, thereby providing a framework to test whether repeated stimulation sessions may yield sustained reversal of cognitive deficits. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Normal people working in normal organizations with normal equipment: system safety and cognition in a mid-air collision.

PubMed

de Carvalho, Paulo Victor Rodrigues; Gomes, José Orlando; Huber, Gilbert Jacob; Vidal, Mario Cesar

2009-05-01

A fundamental challenge in improving the safety of complex systems is to understand how accidents emerge in normal working situations, with equipment functioning normally in normally structured organizations. We present a field study of the en route mid-air collision between a commercial carrier and an executive jet, in the clear afternoon Amazon sky in which 154 people lost their lives, that illustrates one response to this challenge. Our focus was on how and why the several safety barriers of a well structured air traffic system melted down enabling the occurrence of this tragedy, without any catastrophic component failure, and in a situation where everything was functioning normally. We identify strong consistencies and feedbacks regarding factors of system day-to-day functioning that made monitoring and awareness difficult, and the cognitive strategies that operators have developed to deal with overall system behavior. These findings emphasize the active problem-solving behavior needed in air traffic control work, and highlight how the day-to-day functioning of the system can jeopardize such behavior. An immediate consequence is that safety managers and engineers should review their traditional safety approach and accident models based on equipment failure probability, linear combinations of failures, rules and procedures, and human errors, to deal with complex patterns of coincidence possibilities, unexpected links, resonance among system functions and activities, and system cognition.

Co-segregation of social cognition, executive function and local processing style in children with ASD, their siblings and normal controls.

PubMed

Oerlemans, Anoek M; Droste, Katharina; van Steijn, Daphne J; de Sonneville, Leo M J; Buitelaar, Jan K; Rommelse, Nanda N J

2013-12-01

Cognitive research proposes that social cognition (SC), executive functions (EF) and local processing style (weak CC) may be fruitful areas for research into the familial-genetic underpinnings of Autism Spectrum Disorders (ASD). The performance of 140 children with ASD, 172 siblings and 127 controls on tasks measuring SC (face recognition, affective prosody, and facial emotion recognition), EF (inhibition, cognitive flexibility, and verbal working memory) and local processing style was assessed. Compelling evidence was found for the interrelatedness of SC and EF, but not local processing style, within individuals and within families, suggesting that these domains tend to co-segregate in ASD. Using the underlying shared variance of these constructs in genetic research may increase the power for detecting susceptibility genes for ASD.

Neuropsychological function in relation to dysmenorrhea in adolescents.

PubMed

Bahrami, Afsane; Sadeghnia, Hamidreza; Avan, Amir; Mirmousavi, Seyed Jamal; Moslem, Alireza; Eslami, Saeed; Heshmati, Masoud; Bahrami-Taghanaki, Hamidreza; Ferns, Gordon A; Ghayour-Mobarhan, Majid

2017-08-01

Hormonal variations during the menstrual cycle may affect emotional regulation. We aimed to investigate the association between dysmenorrhea (the severe abdominal pain and cramps associated with menstruation) and cognitive abilities, emotional function and sleep patterns in adolescent girls. Moreover, we evaluated the frequency of premenstrual syndrome (PMS) in our population and then divided them into 4 groups: subjects with only PMS; subjects with only dysmenorrhea; individuals with both PMS and dysmenorrhea and normal subjects. In this cross sectional study, 897 adolescent girls who had entered menarche were recruited. Of these, 35.9% had only dysmenorrhea, 14.9% had only PMS, 32.7% had both PMS and dysmenorrhea while 16.5% had no PMS and/or dysmenorrhea (Normal). We assessed the tests for cognitive, emotional function and sleep patterns were compared for these groups. Individuals in the dysmenorrhea group had significantly higher depression, aggression, insomnia, daytime sleepiness and sleep apnea scores compared to normal controls and the PMS group, but did not have significantly different cognitive ability (P value <0.05). These differences were strongly correlated to pain intensity (P<0.001). However, there were no significant differences between those with only PMS and control subjects with regard to cognitive ability, emotional function and sleep pattern tests. Dysmenorrhea is highly prevalent among adolescents and appears to be associated with depressive mood, a tendency to aggressive behavior and sleep disorders among adolescent girls. Copyright © 2017 Elsevier B.V. All rights reserved.

Perforant path synaptic loss correlates with cognitive impairment and Alzheimer's disease in the oldest-old.

PubMed

Robinson, John L; Molina-Porcel, Laura; Corrada, Maria M; Raible, Kevin; Lee, Edward B; Lee, Virginia M-Y; Kawas, Claudia H; Trojanowski, John Q

2014-09-01

Alzheimer's disease, which is defined pathologically by abundant amyloid plaques and neurofibrillary tangles concurrent with synaptic and neuronal loss, is the most common underlying cause of dementia in the elderly. Among the oldest-old, those aged 90 and older, other ageing-related brain pathologies are prevalent in addition to Alzheimer's disease, including cerebrovascular disease and hippocampal sclerosis. Although definite Alzheimer's disease pathology can distinguish dementia from normal individuals, the pathologies underlying cognitive impairment, especially in the oldest-old, remain poorly understood. We therefore conducted studies to determine the relative contributions of Alzheimer's disease pathology, cerebrovascular disease, hippocampal sclerosis and the altered expression of three synaptic proteins to cognitive status and global cognitive function. Relative immunohistochemistry intensity measures were obtained for synaptophysin, Synaptic vesicle transporter Sv2 (now known as SV2A) and Vesicular glutamate transporter 1 in the outer molecular layer of the hippocampal dentate gyrus on the first 157 participants of 'The 90+ Study' who came to autopsy, including participants with dementia (n = 84), those with cognitive impairment but no dementia (n = 37) and those with normal cognition (n = 36). Thal phase, Braak stage, cerebrovascular disease, hippocampal sclerosis and Pathological 43-kDa transactive response sequence DNA-binding protein (TDP-43) were also analysed. All measures were obtained blind to cognitive diagnosis. Global cognition was tested by the Mini-Mental State Examinaton. Logistic regression analysis explored the association between the pathological measures and the odds of being in the different cognitive groups whereas multiple regression analyses explored the association between pathological measures and global cognition scores. No measure clearly distinguished the control and cognitive impairment groups. Comparing the cognitive impairment and dementia groups, synaptophysin and SV2 were reduced, whereas Braak stage, TDP-43 and hippocampal sclerosis frequency increased. Thal phase and VGLUT1 did not distinguish the cognitive impairment and dementia groups. All measures distinguished the dementia and control groups and all markers associated with the cognitive test scores. When all markers were analysed simultaneously, a reduction in synaptophysin, a high Braak stage and the presence of TDP-43 and hippocampal sclerosis associated with global cognitive function. These findings suggest that tangle pathology, hippocampal sclerosis, TDP-43 and perforant pathway synaptic loss are the major contributors to dementia in the oldest-old. Although an increase in plaque pathology and glutamatergic synaptic loss may be early events associated with cognitive impairment, we conclude that those with cognitive impairment, but no dementia, are indistinguishable from cognitively normal subjects based on the measures reported here. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effect of Mild Cognitive Impairment and Alzheimer Disease on Auditory Steady-State Responses

PubMed Central

Shahmiri, Elaheh; Jafari, Zahra; Noroozian, Maryam; Zendehbad, Azadeh; Haddadzadeh Niri, Hassan; Yoonessi, Ali

2017-01-01

Introduction: Mild Cognitive Impairment (MCI), a disorder of the elderly people, is difficult to diagnose and often progresses to Alzheimer Disease (AD). Temporal region is one of the initial areas, which gets impaired in the early stage of AD. Therefore, auditory cortical evoked potential could be a valuable neuromarker for detecting MCI and AD. Methods: In this study, the thresholds of Auditory Steady-State Response (ASSR) to 40 Hz and 80 Hz were compared between Alzheimer Disease (AD), MCI, and control groups. A total of 42 patients (12 with AD, 15 with MCI, and 15 elderly normal controls) were tested for ASSR. Hearing thresholds at 500, 1000, and 2000 Hz in both ears with modulation rates of 40 and 80 Hz were obtained. Results: Significant differences in normal subjects were observed in estimated ASSR thresholds with 2 modulation rates in 3 frequencies in both ears. However, the difference was significant only in 500 Hz in the MCI group, and no significant differences were observed in the AD group. In addition, significant differences were observed between the normal subjects and AD patients with regard to the estimated ASSR thresholds with 2 modulation rates and 3 frequencies in both ears. A significant difference was observed between the normal and MCI groups at 2000 Hz, too. An increase in estimated 40 Hz ASSR thresholds in patients with AD and MCI suggests neural changes in auditory cortex compared to that in normal ageing. Conclusion: Auditory threshold estimation with low and high modulation rates by ASSR test could be a potentially helpful test for detecting cognitive impairment. PMID:29158880

Cognitive Change Questionnaire as a method for cognitive impairment screening

PubMed Central

Damin, Antonio Eduardo; Nitrini, Ricardo; Brucki, Sonia Maria Dozzi

2015-01-01

The Cognitive Change Questionnaire (CCQ) was created as an effective measure of cognitive change that is easy to use and suitable for application in Brazil. Objective To evaluate whether the CCQ can accurately distinguish normal subjects from individuals with Mild Cognitive Impairment (MCI) and/or early stage dementia and to develop a briefer questionnaire, based on the original 22-item CCQ (CCQ22), that contains fewer questions. Methods A total of 123 individuals were evaluated: 42 healthy controls, 40 patients with MCI and 41 with mild dementia. The evaluation was performed using cognitive tests based on individual performance and on questionnaires administered to informants. The CCQ22 was created based on a selection of questions that experts deemed useful in screening for early stage dementia. Results The CCQ22 showed good accuracy for distinguishing between the groups. Statistical models selected the eight questions with the greatest power to discriminate between the groups. The AUC ROC corresponding to the final version of the 8-item CCQ (CCQ8), demonstrated good accuracy in differentiating between groups, good correlation with the final diagnosis (r=0.861) and adequate internal consistency (Cronbach's α=0.876). Conclusion The CCQ8 can be used to accurately differentiate between normal subjects and individuals with cognitive impairment, constituting a brief and appropriate instrument for cognitive screening. PMID:29213967

Characterization of Disease-Related Covariance Topographies with SSMPCA Toolbox: Effects of Spatial Normalization and PET Scanners

PubMed Central

Peng, Shichun; Ma, Yilong; Spetsieris, Phoebe G; Mattis, Paul; Feigin, Andrew; Dhawan, Vijay; Eidelberg, David

2013-01-01

In order to generate imaging biomarkers from disease-specific brain networks, we have implemented a general toolbox to rapidly perform scaled subprofile modeling (SSM) based on principal component analysis (PCA) on brain images of patients and normals. This SSMPCA toolbox can define spatial covariance patterns whose expression in individual subjects can discriminate patients from controls or predict behavioral measures. The technique may depend on differences in spatial normalization algorithms and brain imaging systems. We have evaluated the reproducibility of characteristic metabolic patterns generated by SSMPCA in patients with Parkinson's disease (PD). We used [18F]fluorodeoxyglucose PET scans from PD patients and normal controls. Motor-related (PDRP) and cognition-related (PDCP) metabolic patterns were derived from images spatially normalized using four versions of SPM software (spm99, spm2, spm5 and spm8). Differences between these patterns and subject scores were compared across multiple independent groups of patients and control subjects. These patterns and subject scores were highly reproducible with different normalization programs in terms of disease discrimination and cognitive correlation. Subject scores were also comparable in PD patients imaged across multiple PET scanners. Our findings confirm a very high degree of consistency among brain networks and their clinical correlates in PD using images normalized in four different SPM platforms. SSMPCA toolbox can be used reliably for generating disease-specific imaging biomarkers despite the continued evolution of image preprocessing software in the neuroimaging community. Network expressions can be quantified in individual patients independent of different physical characteristics of PET cameras. PMID:23671030

Characterization of disease-related covariance topographies with SSMPCA toolbox: effects of spatial normalization and PET scanners.

PubMed

Peng, Shichun; Ma, Yilong; Spetsieris, Phoebe G; Mattis, Paul; Feigin, Andrew; Dhawan, Vijay; Eidelberg, David

2014-05-01

To generate imaging biomarkers from disease-specific brain networks, we have implemented a general toolbox to rapidly perform scaled subprofile modeling (SSM) based on principal component analysis (PCA) on brain images of patients and normals. This SSMPCA toolbox can define spatial covariance patterns whose expression in individual subjects can discriminate patients from controls or predict behavioral measures. The technique may depend on differences in spatial normalization algorithms and brain imaging systems. We have evaluated the reproducibility of characteristic metabolic patterns generated by SSMPCA in patients with Parkinson's disease (PD). We used [(18) F]fluorodeoxyglucose PET scans from patients with PD and normal controls. Motor-related (PDRP) and cognition-related (PDCP) metabolic patterns were derived from images spatially normalized using four versions of SPM software (spm99, spm2, spm5, and spm8). Differences between these patterns and subject scores were compared across multiple independent groups of patients and control subjects. These patterns and subject scores were highly reproducible with different normalization programs in terms of disease discrimination and cognitive correlation. Subject scores were also comparable in patients with PD imaged across multiple PET scanners. Our findings confirm a very high degree of consistency among brain networks and their clinical correlates in PD using images normalized in four different SPM platforms. SSMPCA toolbox can be used reliably for generating disease-specific imaging biomarkers despite the continued evolution of image preprocessing software in the neuroimaging community. Network expressions can be quantified in individual patients independent of different physical characteristics of PET cameras. Copyright © 2013 Wiley Periodicals, Inc.

Concepts, Control, and Context: A Connectionist Account of Normal and Disordered Semantic Cognition

PubMed Central

2018-01-01

Semantic cognition requires conceptual representations shaped by verbal and nonverbal experience and executive control processes that regulate activation of knowledge to meet current situational demands. A complete model must also account for the representation of concrete and abstract words, of taxonomic and associative relationships, and for the role of context in shaping meaning. We present the first major attempt to assimilate all of these elements within a unified, implemented computational framework. Our model combines a hub-and-spoke architecture with a buffer that allows its state to be influenced by prior context. This hybrid structure integrates the view, from cognitive neuroscience, that concepts are grounded in sensory-motor representation with the view, from computational linguistics, that knowledge is shaped by patterns of lexical co-occurrence. The model successfully codes knowledge for abstract and concrete words, associative and taxonomic relationships, and the multiple meanings of homonyms, within a single representational space. Knowledge of abstract words is acquired through (a) their patterns of co-occurrence with other words and (b) acquired embodiment, whereby they become indirectly associated with the perceptual features of co-occurring concrete words. The model accounts for executive influences on semantics by including a controlled retrieval mechanism that provides top-down input to amplify weak semantic relationships. The representational and control elements of the model can be damaged independently, and the consequences of such damage closely replicate effects seen in neuropsychological patients with loss of semantic representation versus control processes. Thus, the model provides a wide-ranging and neurally plausible account of normal and impaired semantic cognition. PMID:29733663

Are Prescription Stimulants "Smart Pills"? The Epidemiology and Cognitive Neuroscience of Prescription Stimulant Use by Normal Healthy Individuals

ERIC Educational Resources Information Center

Smith, M. Elizabeth; Farah, Martha J.

2011-01-01

Use of prescription stimulants by normal healthy individuals to enhance cognition is said to be on the rise. Who is using these medications for cognitive enhancement, and how prevalent is this practice? Do prescription stimulants in fact enhance cognition for normal healthy people? We review the epidemiological and cognitive neuroscience…

Cognitive levels of performance account for hemispheric lateralisation effects in dyslexic and normally reading children.

PubMed

Heim, Stefan; Grande, Marion; Meffert, Elisabeth; Eickhoff, Simon B; Schreiber, Helen; Kukolja, Juraj; Shah, Nadim Jon; Huber, Walter; Amunts, Katrin

2010-12-01

Recent theories of developmental dyslexia explain reading deficits in terms of deficient phonological awareness, attention, visual and auditory processing, or automaticity. Since dyslexia has a neurobiological basis, the question arises how the reader's proficiency in these cognitive variables affects the brain regions involved in visual word recognition. This question was addressed in two fMRI experiments with 19 normally reading children (Experiment 1) and 19 children with dyslexia (Experiment 2). First, reading-specific brain activation was assessed by contrasting the BOLD signal for reading aloud words vs. overtly naming pictures of real objects. Next, ANCOVAs with brain activation during reading the individuals' scores for all five cognitive variables assessed outside the scanner as covariates were performed. Whereas the normal readers' brain activation during reading showed co-variation effects predominantly in the right hemisphere, the reverse pattern was observed for the dyslexics. In particular, middle frontal gyrus, inferior parietal cortex, and precuneus showed contralateral effects for controls as compared to dyslexics. In line with earlier findings in the literature, these data hint at a global change in hemispheric asymmetry during cognitive processing in dyslexic readers, which, in turn, might affect reading proficiency. Copyright © 2010 Elsevier Inc. All rights reserved.

[Cognitive functions of school children with normal IQ and histories of severe and early malnutrition].

PubMed

Perales, C G; Heresi, E; Pizarro, F; Colombo, M

1996-12-01

This is a cross section study designed to evaluate the long lasting consequences of early and severe undernutrition on the development of basic cognitive functions. Attention, memory and problem-solving capacity were assessed in a group of 16 school children, who were severely undernourished during the first two years of age. They were compared with a group of 16 children with a normal growth. All subjects, age 8 to 10, had a normal intellectual coefficient and they belonged to the me same socioeconomical level. Memory was measured with a modified version of subtest of digits from WISC; attention was evaluated with a modified version of the Continuous Performance Task and problem-solving was measured with the Anstey Domino Test. A personal computer was used to assess the cognitive functions. The children who were undernourished during infancy presented lower scores in memory (number of the digits) and in problems solving (number of correct answers). They also had a worse performance than the control group in the same response time, when attention was evaluated. These results suggest that early severe undernutrition had deletereous effects on basic cognitive functions.

Social cognition and metacognition in obsessive-compulsive disorder: an explorative pilot study.

PubMed

Mavrogiorgou, Paraskevi; Bethge, Mareike; Luksnat, Stefanie; Nalato, Fabio; Juckel, Georg; Brüne, Martin

2016-04-01

Obsessive-compulsive disorder (OCD) is a severe psychiatric condition that is, among other features, characterized by marked impairment in social functioning. Although theoretically plausible with regard to neurobiological underpinnings of OCD, there is little research about possible impairments in social cognitive and meta-cognitive abilities and their connections with social functioning in patients with OCD. Accordingly, we sought to examine social cognitive skills and metacognition in OCD. Twenty OCD patients and age-, sex-, and education-matched 20 healthy controls were assessed using neurocognitive and diverse social cognitive skills including the Ekman 60 Faces test, the Hinting Task, the faux pas test, and a proverb test. In addition, the Metacognition Questionnaire-30 was administered to both the OCD and the control groups. Social functioning was measured using the Personal and Social Performance Scale. Symptom severity in patients was determined by the Yale-Brown Obsessive-Compulsive Scale and the Maudsley Obsessive-Compulsive Inventory. No group differences emerged in basic social cognitive abilities. In contrast, compared to controls, OCD patients scored higher on all MCQ dimensions, particularly negative beliefs about worry, uncontrollability, and danger; beliefs about need to control thoughts; and cognitive self-consciousness. There were no significant correlations between social or metacognitive parameters and OCD symptom severity. However, in the patient group, depression and metacognition predicted social functioning. OCD patients show normal basal social cognitive abilities, but dysfunctional metacognitive profiles, which may contribute to their psychosocial impairment.

Neurocognitive functions and brain atrophy after proven neuroborreliosis: a case-control study.

PubMed

Schmidt, Holger; Djukic, Marija; Jung, Klaus; Holzgraefe, Manfred; Dechent, Peter; von Steinbüchel, Nicole; Blocher, Joachim; Eiffert, Helmut; Schmidt-Samoa, Carsten

2015-08-19

Patients often report neurocognitive difficulties after neuroborreliosis (NB). The frequency and extent of cognitive problems in European patients have been studied incompletely. Sixty patients received a neurological and neuropsychological work-up 6 months or longer after treatment for proven NB. Quality of life, psychiatric symptom load, and brain atrophy were measured. All results were compared with a group of 30 healthy control persons adapted for age, gender and education being serologically negative for Borrelia burgdorferi senso latu. A cognitive sum score and a global sum score including cognitive, psychological results and quality of life data was calculated for both groups. Patients after NB showed a lower (i.e. more impaired) score on the Scripps Neurological rating scale (SNRS), but the observed neurological deficits were generally mild (mean ± SD: 97.1 ± 4.7 vs. 99.1 ± 2.4, p = 0.02). The mean neuropsychological domain results of the NB group were all within the normal range. However, a lower performance was found for the frontal executive function z-values (mean ± SD -0.29 ± 0.60 vs. 0.09 ± 0.60; p = 0.0059) of NB patients. Comparing the global sum score (mean ± SD 11.3 ± 4.2 NB vs. 14.3 ± 2.9 control , p = 0.001) and the cognitive sum score of the NB group with those of the control group (mean ± SD -0.15 ± 0.42 NB vs. 0.08 ± 0.31 control , p = 0.0079), both differences were statistically different. The frequencies of impaired global sum scores and those of the pathological cognitive sum scores (p = 0.07) did not differ statistically. No significant differences were found for health-related quality of life (hrQoL), sleep, psychiatric symptom load, or brain atrophy. The mean cognitive functions of patients after proven NB were in the normal range. However, we were able to demonstrate a lower performance for the domain of frontal executive functions, for the mean cognitive sum score and the global sum score as a sign of subtle but measurable sequelae of neuroborreliosis. Brain atrophy is not a common consequence of neuroborreliosis.

Analysis of the Substantia Innominata Volume in Patients with Parkinson’s Disease with Dementia, Dementia with Lewy Bodies, and Alzheimer’s Disease

PubMed Central

Kim, Hee Jin; Lee, Ji Eun; Shin, Soo Jeong; Sohn, Young Ho; Lee, Phil Hyu

2011-01-01

Background and Purpose The substantia innominata (SI) contains the nucleus basalis of Meynert, which is the major source of cholinergic input to the cerebral cortex. We hypothesized that degeneration of the SI and its relationship to general cognitive performance differs in amyloidopathy and synucleinopathy. Methods We used magnetic resonance imaging (MRI)-based volumetric analysis to evaluate the SI volume in patients with amnestic mild cognitive impairment (aMCI), Alzheimer’s disease (AD), Parkinson’s disease-mild cognitive impairment (PD-MCI), PD with dementia (PDD), dementia with Lewy bodies (DLB), and healthy elderly controls. The correlation between SI volume and general cognitive performance, measured using the Korean version of the Mini-Mental State Examination (K-MMSE), was examined. Results Compared to control subjects, the mean normalized SI volume was significantly decreased in all of the other groups. The normalized SI volume did not differ between the subjects with PDD and DLB, whereas it was significantly smaller in subjects with PDD (p = 0.029) and DLB (p = 0.011) compared with AD. In subjects with PD-related cognitive impairment (PD-MCI, PDD, or DLB), there was a significant positive correlation between the SI volume and K-MMSE score (r = 0.366, p < 0.001), whereas no correlation was seen in subjects with AD-related cognitive impairment (aMCI or AD). Conclusions Our data suggest that the SI loss is greater in synucleinopathy-related dementia (PDD or DLB) than in AD and that the contribution of the SI to cognitive performance is greater in synucleinopathy than in amyloidopathy. PMID:24868398

First-degree relatives of suicide completers may have impaired decision-making but functional cognitive control.

PubMed

Hoehne, A; Richard-Devantoy, S; Ding, Y; Turecki, G; Jollant, F

2015-09-01

The heritability of suicide is well established. Transmission of risk appears to follow traits more than disorders like depression. In the present project, we aimed at investigating the potential for transmission of cognitive deficits previously observed in suicide attempters, specifically impaired decision-making and cognitive control. Seventeen healthy first-degree relatives of suicide completers with no personal history of suicidal act were compared to 18 first-degree relatives of individuals with major depressive disorder but no family history of suicidal act, and 19 healthy controls. Decision-making was assessed with the Iowa Gambling Task, and cognitive control with the Stroop Task, the Hayling Sentence Completion Test, and the Trail-Making Test. Both suicide and depressed relatives showed lower gambling task net scores than healthy controls. However, there were trends toward lower learning abilities in suicide than depressed relatives (interaction: p = 0.07), with more risky choices at the end of the test. Suicide relatives also showed a higher number of self-corrected errors relative to the total number of errors in the Stroop colour test compared to both control groups, with no difference in interference scores. There was no group-difference for any other cognitive tests. Our findings suggest that decision-making impairment may be found in healthy relatives of suicides and represent a cognitive endophenotype of suicidal behaviour. Normal cognitive control (or self-corrected deficits) may protect relatives against suicidal acts. Impairments in value-based and control processes may, therefore, be part of the suicide vulnerability and represent potential targets of preventative interventions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cognitive functions in Parkinson's disease: relation to disease severity and hallucination.

PubMed

Wakamori, Takaaki; Agari, Takashi; Yasuhara, Takao; Kameda, Masahiro; Kondo, Akihiko; Shinko, Aiko; Sasada, Susumu; Sasaki, Tatsuya; Furuta, Tomohisa; Date, Isao

2014-04-01

We wished to relate severity of Parkinson's disease (PD) with cognitive function in relation to cerebral blood flow (CBF). Eighty-one consecutive PD patients were enrolled in this study. We used Mini-Mental State Examination (MMSE) and Wechsler Adult Intelligence Scale-Third edition (WAIS-III) to evaluate cognitive functions, and three-dimensional stereotactic ROI template (3DSRT) and Statistical Parametric Mapping (SPM) 8 to evaluate single photon emission CT (SPECT) recordings of regional CBF. The mean MMSE score of PD patients was 27.4 ± 2.4. The scores of most patients were higher than 23/30. On the other hand, the mean Full-scale IQ of PD patients was 88.4 ± 17.3 in WAIS-III, which was lower than that of normal controls. In particular, visuospatial function score of most patients was lower. There was significant correlation between cognitive scores and Hoehn & Yahr stage and hallucinatory episodes. PD Patients with stage III and IV showed significant deterioration in cognitive functions compared to stage II patients. Analysis of CBF revealed relative reductions in perfusion in the cerebral cortex relative to that in normal control. SPM 8 showed that cognitive functions in PD patients were positively correlated with rCBF in the thalamus and cingulate gyrus. This is the study to demonstrate the cognitive impairments in PD patients using WAIS-III. Visuospatial dysfunction might be caused by decrease in rCBF in the parietal and occipital lobes and dorsolateral prefrontal cortex. The severity of cognitive impairments in PD patients was correlated with disease severity and hallucinatory episodes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task.

PubMed

Goldstein, Rita Z; Woicik, Patricia A; Maloney, Thomas; Tomasi, Dardo; Alia-Klein, Nelly; Shan, Juntian; Honorio, Jean; Samaras, Dimitris; Wang, Ruiliang; Telang, Frank; Wang, Gene-Jack; Volkow, Nora D

2010-09-21

Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function) in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.

Oral methylphenidate normalizes cingulate activity in cocaine addiction during a salient cognitive task

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldstein, R.Z.; Goldstein, R.Z.; Woicik, P.A.

Anterior cingulate cortex (ACC) hypoactivations during cognitive demand are a hallmark deficit in drug addiction. Methylphenidate (MPH) normalizes cortical function, enhancing task salience and improving associated cognitive abilities, in other frontal lobe pathologies; however, in clinical trials, MPH did not improve treatment outcome in cocaine addiction. We hypothesized that oral MPH will attenuate ACC hypoactivations and improve associated performance during a salient cognitive task in individuals with cocaine-use disorders (CUD). In the current functional MRI study, we used a rewarded drug cue-reactivity task previously shown to be associated with hypoactivations in both major ACC subdivisions (implicated in default brain function)more » in CUD compared with healthy controls. The task was performed by 13 CUD and 14 matched healthy controls on 2 d: after ingesting a single dose of oral MPH (20 mg) or placebo (lactose) in a counterbalanced fashion. Results show that oral MPH increased responses to this salient cognitive task in both major ACC subdivisions (including the caudal-dorsal ACC and rostroventromedial ACC extending to the medial orbitofrontal cortex) in the CUD. These functional MRI results were associated with reduced errors of commission (a common impulsivity measure) and improved task accuracy, especially during the drug (vs. neutral) cue-reactivity condition in all subjects. The clinical application of such MPH-induced brain-behavior enhancements remains to be tested.« less

Changes in running pattern due to fatigue and cognitive load in orienteering.

PubMed

Millet, Guillaume Y; Divert, Caroline; Banizette, Marion; Morin, Jean-Benoit

2010-01-01

The aim of this study was to examine the influence of fatigue on running biomechanics in normal running, in normal running with a cognitive task, and in running while map reading. Nineteen international and less experienced orienteers performed a fatiguing running exercise of duration and intensity similar to a classic distance orienteering race on an instrumented treadmill while performing mental arithmetic, an orienteering simulation, and control running at regular intervals. Two-way repeated-measures analysis of variance did not reveal any significant difference between mental arithmetic and control running for any of the kinematic and kinetic parameters analysed eight times over the fatiguing protocol. However, these parameters were systematically different between the orienteering simulation and the other two conditions (mental arithmetic and control running). The adaptations in orienteering simulation running were significantly more pronounced in the elite group when step frequency, peak vertical ground reaction force, vertical stiffness, and maximal downward displacement of the centre of mass during contact were considered. The effects of fatigue on running biomechanics depended on whether the orienteers read their map or ran normally. It is concluded that adding a cognitive load does not modify running patterns. Therefore, all changes in running pattern observed during the orienteering simulation, particularly in elite orienteers, are the result of adaptations to enable efficient map reading and/or potentially prevent injuries. Finally, running patterns are not affected to the same extent by fatigue when a map reading task is added.

Does a functional activity programme improve function, quality of life, and falls for residents in long term care? Cluster randomised controlled trial

PubMed Central

Peri, Kathy; Robinson, Elizabeth; Wilkinson, Tim; von Randow, Martin; Kiata, Liz; Parsons, John; Latham, Nancy; Parsons, Matthew; Willingale, Jane; Brown, Paul; Arroll, Bruce

2008-01-01

Objective To assess the effectiveness of an activity programme in improving function, quality of life, and falls in older people in residential care. Design Cluster randomised controlled trial with one year follow-up. Setting 41 low level dependency residential care homes in New Zealand. Participants 682 people aged 65 years or over. Interventions 330 residents were offered a goal setting and individualised activities of daily living activity programme by a gerontology nurse, reinforced by usual healthcare assistants; 352 residents received social visits. Main outcome measures Function (late life function and disability instruments, elderly mobility scale, FICSIT-4 balance test, timed up and go test), quality of life (life satisfaction index, EuroQol), and falls (time to fall over 12 months). Secondary outcomes were depressive symptoms and hospital admissions. Results 473 (70%) participants completed the trial. The programme had no impact overall. However, in contrast to residents with impaired cognition (no differences between intervention and control group), those with normal cognition in the intervention group may have maintained overall function (late life function and disability instrument total function, P=0.024) and lower limb function (late life function and disability instrument basic lower extremity, P=0.015). In residents with cognitive impairment, the likelihood of depression increased in the intervention group. No other outcomes differed between groups. Conclusion A programme of functional rehabilitation had minimal impact for elderly people in residential care with normal cognition but was not beneficial for those with poor cognition. Trial registration Australian Clinical Trials Register ACTRN12605000667617. PMID:18845605

Diagnostic Validity of an Automated Probabilistic Tractography in Amnestic Mild Cognitive Impairment

PubMed Central

Jung, Won Sang; Um, Yoo Hyun; Kang, Dong Woo; Lee, Chang Uk; Woo, Young Sup; Bahk, Won-Myong

2018-01-01

Objective Although several prior works showed the white matter (WM) integrity changes in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease, it is still unclear the diagnostic accuracy of the WM integrity measurements using diffusion tensor imaging (DTI) in discriminating aMCI from normal controls. The aim of this study is to explore diagnostic validity of whole brain automated probabilistic tractography in discriminating aMCI from normal controls. Methods One hundred-two subjects (50 aMCI and 52 normal controls) were included and underwent DTI scans. Whole brain WM tracts were reconstructed with automated probabilistic tractography. Fractional anisotropy (FA) and mean diffusivity (MD) values of the memory related WM tracts were measured and compared between the aMCI and the normal control groups. In addition, the diagnostic validities of these WM tracts were evaluated. Results Decreased FA and increased MD values of memory related WM tracts were observed in the aMCI group compared with the control group. Among FA and MD value of each tract, the FA value of left cingulum angular bundle showed the highest area under the curve (AUC) of 0.85 with a sensitivity of 88.2%, a specificity of 76.9% in differentiating MCI patients from control subjects. Furthermore, the combination FA values of WM integrity measures of memory related WM tracts showed AUC value of 0.98, a sensitivity of 96%, a specificity of 94.2%. Conclusion Our results with good diagnostic validity of WM integrity measurements suggest DTI might be promising neuroimaging tool for early detection of aMCI and AD patients. PMID:29739127

Response Inhibition Is Associated with White Matter Microstructure in Children

ERIC Educational Resources Information Center

Madsen, Kathrine Skak; Baare, William F. C.; Vestergaard, Martin; Skimminge, Arnold; Ejersbo, Lisser Rye; Ramsoy, Thomas Z.; Gerlach, Christian; Akeson, Per; Paulson, Olaf B.; Jernigan, Terry L.

2010-01-01

Cognitive control of thoughts, actions and emotions is important for normal behaviour and the development of such control continues throughout childhood and adolescence. Several lines of evidence suggest that response inhibition is primarily mediated by a right-lateralized network involving inferior frontal gyrus (IFG), presupplementary motor…

Diffusion tensor imaging of normal-appearing white matter in mild cognitive impairment and early Alzheimer disease: preliminary evidence of axonal degeneration in the temporal lobe.

PubMed

Huang, J; Friedland, R P; Auchus, A P

2007-01-01

Diffusion tensor imaging (DTI) is a sensitive technique for studying cerebral white matter. We used DTI to characterize microstructural white matter changes and their associations with cognitive dysfunction in Alzheimer disease (AD) and mild cognitive impairment (MCI). We studied elderly subjects with mild AD (n = 6), MCI (n = 11), or normal cognition (n = 8). A standardized clinical and neuropsychological evaluation was conducted on each subject. DTI images were acquired, and fractional anisotropy (FA), axial diffusivity (DA), and radial diffusivity (DR) of normal-appearing white matter (NAWM) in frontal, temporal, parietal, and occipital lobes were determined. These diffusion measurements were compared across the 3 groups, and significant differences were further examined for correlations with tests of cognitive function. Compared with normal controls, AD subjects demonstrated decreased FA and increased DR in the temporal, parietal, and frontal NAWM and decreased DA in temporal NAWM. MCI subjects also showed decreased FA and decreased DA in temporal NAWM, with decreased FA and increased DR in parietal NAWM. Diffusion measurements showed no differences in occipital NAWM. Across all subjects, temporal lobe FA and DR correlated with episodic memory, frontal FA and DR correlated with executive function, and parietal DR significantly correlated with visuospatial ability. We found evidence for functionally relevant microstructural changes in the NAWM of patients with AD and MCI. These changes were present in brain regions serving higher cortical functions, but not in regions serving primary functions, and are consistent with a hypothesized loss of axonal processes in the temporal lobe.

Cerebrospinal Fluid Amyloid-β 42, Total Tau and Phosphorylated Tau are Low in Patients with Normal Pressure Hydrocephalus: Analogies and Differences with Alzheimer's Disease.

PubMed

Santangelo, Roberto; Cecchetti, Giordano; Bernasconi, Maria Paola; Cardamone, Rosalinda; Barbieri, Alessandra; Pinto, Patrizia; Passerini, Gabriella; Scomazzoni, Francesco; Comi, Giancarlo; Magnani, Giuseppe

2017-01-01

Co-existence of Alzheimer's disease (AD) in normal pressure hydrocephalus (NPH) is a frequent finding, thus a common pathophysiological basis between AD and NPH has been postulated. We measured CSF amyloid-β 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) concentrations in a sample of 294 patients with different types of dementia and 32 subjects without dementia. We then compared scores on neuropsychological tests of NPH patients with pathological and normal CSF Aβ42 values. Aβ42 levels were significantly lower in NPH than in control patients, with no significant differences between AD and NPH. On the contrary, t-tau and p-tau levels were significantly lower in NPH than in AD, with no differences between NPH and controls. NPH patients with pathological Aβ42 levels did not perform worse than NPH patients with normal Aβ42 levels in any cognitive domains. Our data seem to support the hypothesis of amyloid accumulation in brains of NPH patients. Nevertheless, amyloid does not seem to play a pathogenetic role in the development of cognitive deficits in NPH.

Brain network connectivity in individuals with schizophrenia and their siblings.

PubMed

Repovs, Grega; Csernansky, John G; Barch, Deanna M

2011-05-15

Research on brain activity in schizophrenia has shown that changes in the function of any single region cannot explain the range of cognitive and affective impairments in this illness. Rather, neural circuits that support sensory, cognitive, and emotional processes are now being investigated as substrates for cognitive and affective impairments in schizophrenia, a shift in focus consistent with long-standing hypotheses about schizophrenia as a disconnection syndrome. Our goal was to further examine alterations in functional connectivity within and between the default mode network and three cognitive control networks (frontal-parietal, cingulo-opercular, and cerebellar) as a basis for such impairments. Resting state functional magnetic resonance imaging was collected from 40 individuals with DSM-IV-TR schizophrenia, 31 siblings of individuals with schizophrenia, 15 healthy control subjects, and 18 siblings of healthy control subjects while they rested quietly with their eyes closed. Connectivity metrics were compared between patients and control subjects for both within- and between-network connections and were used to predict clinical symptoms and cognitive function. Individuals with schizophrenia showed reduced distal and somewhat enhanced local connectivity between the cognitive control networks compared with control subjects. Additionally, greater connectivity between the frontal-parietal and cerebellar regions was robustly predictive of better cognitive performance across groups and predictive of fewer disorganization symptoms among patients. These results are consistent with the hypothesis that impairments of executive function and cognitive control result from disruption in the coordination of activity across brain networks and additionally suggest that these might reflect impairments in normal pattern of brain connectivity development. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Lower-extremity function in cognitively healthy aging, mild cognitive impairment, and Alzheimer's disease.

PubMed

Eggermont, Laura H; Gavett, Brandon E; Volkers, Karin M; Blankevoort, Christiaan G; Scherder, Erik J; Jefferson, Angela L; Steinberg, Eric; Nair, Anil; Green, Robert C; Stern, Robert A

2010-04-01

To examine differences in lower-extremity function in cognitive healthy older persons, older persons with mild cognitive impairment (MCI), and older persons with Alzheimer's disease (AD). Descriptive study. University Alzheimer's disease clinical and research program. Older persons (N=66) were studied (mean age, 76.7y); 22 were cognitively normal, 22 were diagnosed with probable MCI, 22 were diagnosed with probable AD. Not applicable. Lower-extremity function was assessed by the four-meter walk test (4MWT), Timed Up & Go (TUG) test, and sit-to-stand (STS) test. Analysis of variance, adjusting for covariates, revealed that performance on the 4MWT was significantly lower in the MCI and AD groups as compared with controls. TUG test performance was worse in the AD group compared with controls. No significant group differences were found for STS performance. These results suggest an association between cognitive impairment and lower-limb function in older persons. Walking speed could be evaluated for its possible utility in screening older persons at risk for cognitive impairment and falls. Copyright 2010 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The narcoleptic cognitive pupillary response.

PubMed

O'Neill, W D; Trick, K P

2001-09-01

It has been reported that narcoleptics exhibit deficits in short-term memory, list recall, and stimulus frequency estimation compared with control subjects. It is also well-known that pupil dilation during cognitive tasks is a measure of subject attention state. Here we present results from six narcoleptics and six controls, a total of 360 experimental records in which pupillograms were made during cognitive tests, which indicate that narcoleptics begin pupillary dilations at a smaller diameter, begin dilating earlier poststimulus, attain higher pupillary diameter velocities, yet achieve the same equilibrium dilation diameter as controls. These findings are derived from statistical tests performed on the parameters of a nonlinear regression model of pupillary cognitive dilation as a function of time. In our experiments, the standard 1-s interdigit time between cognitive stimuli was increased to 2.3 s, which yielded pupillographic time records showing that the process of short-term memory overload sets in gradually at about four memory digits for controls and three memory digits for narcoleptics. We suggest our results can be partially explained by a narcoleptic stimulus-encoding deficit, which limits the time available for subjects to rehearse cognitive tasks. However, we also report the unexpected finding that the inferred encoding deficit is a transient one in that repeated tasks at the same memory load elicit a near normal naroleptic pupillary dilation.

Meta-Analysis of Functional Neuroimaging and Cognitive Control Studies in Schizophrenia: Preliminary Elucidation of a Core Dysfunctional Timing Network

PubMed Central

Alústiza, Irene; Radua, Joaquim; Albajes-Eizagirre, Anton; Domínguez, Manuel; Aubá, Enrique; Ortuño, Felipe

2016-01-01

Timing and other cognitive processes demanding cognitive control become interlinked when there is an increase in the level of difficulty or effort required. Both functions are interrelated and share neuroanatomical bases. A previous meta-analysis of neuroimaging studies found that people with schizophrenia had significantly lower activation, relative to normal controls, of most right hemisphere regions of the time circuit. This finding suggests that a pattern of disconnectivity of this circuit, particularly in the supplementary motor area, is a trait of this mental disease. We hypothesize that a dysfunctional temporal/cognitive control network underlies both cognitive and psychiatric symptoms of schizophrenia and that timing dysfunction is at the root of the cognitive deficits observed. The goal of our study was to look, in schizophrenia patients, for brain structures activated both by execution of cognitive tasks requiring increased effort and by performance of time perception tasks. We conducted a signed differential mapping (SDM) meta-analysis of functional neuroimaging studies in schizophrenia patients assessing the brain response to increasing levels of cognitive difficulty. Then, we performed a multimodal meta-analysis to identify common brain regions in the findings of that SDM meta-analysis and our previously-published activation likelihood estimate (ALE) meta-analysis of neuroimaging of time perception in schizophrenia patients. The current study supports the hypothesis that there exists an overlap between neural structures engaged by both timing tasks and non-temporal cognitive tasks of escalating difficulty in schizophrenia. The implication is that a deficit in timing can be considered as a trait marker of the schizophrenia cognitive profile. PMID:26925013

A new EEG synchronization strength analysis method: S-estimator based normalized weighted-permutation mutual information.

PubMed

Cui, Dong; Pu, Weiting; Liu, Jing; Bian, Zhijie; Li, Qiuli; Wang, Lei; Gu, Guanghua

2016-10-01

Synchronization is an important mechanism for understanding information processing in normal or abnormal brains. In this paper, we propose a new method called normalized weighted-permutation mutual information (NWPMI) for double variable signal synchronization analysis and combine NWPMI with S-estimator measure to generate a new method named S-estimator based normalized weighted-permutation mutual information (SNWPMI) for analyzing multi-channel electroencephalographic (EEG) synchronization strength. The performances including the effects of time delay, embedding dimension, coupling coefficients, signal to noise ratios (SNRs) and data length of the NWPMI are evaluated by using Coupled Henon mapping model. The results show that the NWPMI is superior in describing the synchronization compared with the normalized permutation mutual information (NPMI). Furthermore, the proposed SNWPMI method is applied to analyze scalp EEG data from 26 amnestic mild cognitive impairment (aMCI) subjects and 20 age-matched controls with normal cognitive function, who both suffer from type 2 diabetes mellitus (T2DM). The proposed methods NWPMI and SNWPMI are suggested to be an effective index to estimate the synchronization strength. Copyright © 2016 Elsevier Ltd. All rights reserved.

Visual cognition in amnesic H.M.: selective deficits on the What's-Wrong-Here and Hidden-Figure tasks.

PubMed

MacKay, Donald G; James, Lori E

2009-10-01

Two experiments compared the visual cognition performance of amnesic H.M. and memory-normal controls matched for age, background, intelligence, and education. In Experiment 1 H.M. exhibited deficits relative to the controls in detecting "erroneous objects" in complex visual scenes--for example, a bird flying inside a fishbowl. In Experiment 2 H.M. exhibited deficits relative to the controls in standard Hidden-Figure tasks when detecting unfamiliar targets but not when detecting familiar targets--for example, circles, squares, and right-angle triangles. H.M.'s visual cognition deficits were not due to his well-known problems in explicit learning and recall, inability to comprehend or remember the instructions, general slowness, motoric difficulties, low motivation, low IQ relative to the controls, or working-memory limitations. Parallels between H.M.'s selective deficits in visual cognition, language, and memory are discussed. These parallels contradict the standard "systems theory" account of H.M.'s condition but comport with the hypothesis that H.M. has difficulty representing unfamiliar but not familiar information in visual cognition, language, and memory. Implications of our results are discussed for binding theory and the ongoing debate over what counts as "memory" versus "not-memory."

The utility of the Dementia Severity Rating Scale in differentiating mild cognitive impairment and Alzheimer disease from controls.

PubMed

Mitchell, Joel C; Dick, Malcolm B; Wood, Amanda E; Tapp, Andre M; Ziegler, Raphael

2015-01-01

The current study investigated the utility of the Dementia Severity Rating Scale (DSRS) total score to identify individuals at the earliest stage of impairment (ie, mild cognitive impairment/MCI). In addition, the authors sought to investigate how well the measure correlates with an expanded battery of cognitive tests and other measures of functional abilities. Of the 320 participants included in this study, 85 were normal controls, 96 had single-domain or multiple-domain amnestic MCI, and 139 had possible or probable Alzheimer disease (AD). Each participant underwent a thorough cognitive, neurological, and physical examination. Results from this study indicated that the DSRS total scores differed significantly between the 3 groups (P<0.001) and accurately identified 81% of the control group, 60% of the MCI group, and 78% of the AD group in a post hoc discriminant analysis. When combined with a brief cognitive measure (ie, Consortium to Establish a Registry for Alzheimer's Disease Word List 5 min recall test), the DSRS accurately identified 98% of the control group, 76% of the MCI group, and 82% of the AD group. Implications for clinical practice and proposed areas of future research are discussed.

The Effect of Participation in a Resource Room Enrichment Program on the Cognition Skills of Fourth Through Sixth Graders of High Academic Standing or Potential.

ERIC Educational Resources Information Center

Lym, C. LaVor; Rick, Pamela J.

A study of the effects of a resource room enrichment program was field tested on academically gifted fourth, fifth, and sixth grade students in 65 elementary schools. The Ss were pre- and posttested on the Cognitive Abilities Test. A norm referenced research design was used to control for normal development. Findings indicated that participation…

Neuropsychological Performance in Advanced Age- Influences of Demographic Factors and Apolipoprotein E: Findings from the Cache County Memory Study

PubMed Central

Welsh-Bohmer, Katheen A.; Østbye, Truls; Sanders, Linda; Pieper, Carl F.; Hayden, Kathleen M.; Tschanz, JoAnn T.; Norton, Maria C.

2009-01-01

The Cache County Study of Memory in Aging (CCMS) is an epidemiological study of Alzheimer’s disease (AD), mild cognitive disorders, and aging in a population of exceptionally long-lived individuals (7th to 11th decade). Observation of population members without dementia provides an opportunity for establishing the range of normal neurocognitive performance in a representative sample of the very old. We examined neurocognitive performance of the normal participants undergoing full clinical evaluations (n=507) and we tested the potential modifying effects of APOE genotype, a known genetic risk factor for the later development of AD. The results indicate that advanced age and low education are related to lower test scores across nearly all of the neurocognitive measures. Gender and APOE ε4 both had negligible and inconsistent influences, affecting only isolated measures of memory and expressive speech (in case of gender). The gender and APOE effects disappeared once age and education were controlled. The study of this exceptionally long-lived population provides useful normative information regarding the broad range of “normal” cognition seen in advanced age. Among elderly without dementia or other cognitive impairment, APOE does not appear to exert any major effects on cognition once other demographic influences are controlled. PMID:18609337

Training on Movement Figure-Ground Discrimination Remediates Low-Level Visual Timing Deficits in the Dorsal Stream, Improving High-Level Cognitive Functioning, Including Attention, Reading Fluency, and Working Memory.

PubMed

Lawton, Teri; Shelley-Tremblay, John

2017-01-01

The purpose of this study was to determine whether neurotraining to discriminate a moving test pattern relative to a stationary background, figure-ground discrimination, improves vision and cognitive functioning in dyslexics, as well as typically-developing normal students. We predict that improving the speed and sensitivity of figure-ground movement discrimination ( PATH to Reading neurotraining) acts to remediate visual timing deficits in the dorsal stream, thereby improving processing speed, reading fluency, and the executive control functions of attention and working memory in both dyslexic and normal students who had PATH neurotraining more than in those students who had no neurotraining. This prediction was evaluated by measuring whether dyslexic and normal students improved on standardized tests of cognitive skills following neurotraining exercises, more than following computer-based guided reading ( Raz-Kids ( RK )). The neurotraining used in this study was visually-based training designed to improve magnocellular function at both low and high levels in the dorsal stream: the input to the executive control networks coding working memory and attention. This approach represents a paradigm shift from the phonologically-based treatment for dyslexia, which concentrates on high-level speech and reading areas. This randomized controlled-validation study was conducted by training the entire second and third grade classrooms (42 students) for 30 min twice a week before guided reading. Standardized tests were administered at the beginning and end of 12-weeks of intervention training to evaluate improvements in academic skills. Only movement-discrimination training remediated both low-level visual timing deficits and high-level cognitive functioning, including selective and sustained attention, reading fluency and working memory for both dyslexic and normal students. Remediating visual timing deficits in the dorsal stream revealed the causal role of visual movement discrimination training in improving high-level cognitive functions such as attention, reading acquisition and working memory. This study supports the hypothesis that faulty timing in synchronizing the activity of magnocellular with parvocellular visual pathways in the dorsal stream is a fundamental cause of dyslexia and being at-risk for reading problems in normal students, and argues against the assumption that reading deficiencies in dyslexia are caused by phonological or language deficits, requiring a paradigm shift from phonologically-based treatment of dyslexia to a visually-based treatment. This study shows that visual movement-discrimination can be used not only to diagnose dyslexia early, but also for its successful treatment, so that reading problems do not prevent children from readily learning.

Training on Movement Figure-Ground Discrimination Remediates Low-Level Visual Timing Deficits in the Dorsal Stream, Improving High-Level Cognitive Functioning, Including Attention, Reading Fluency, and Working Memory

PubMed Central

Lawton, Teri; Shelley-Tremblay, John

2017-01-01

The purpose of this study was to determine whether neurotraining to discriminate a moving test pattern relative to a stationary background, figure-ground discrimination, improves vision and cognitive functioning in dyslexics, as well as typically-developing normal students. We predict that improving the speed and sensitivity of figure-ground movement discrimination (PATH to Reading neurotraining) acts to remediate visual timing deficits in the dorsal stream, thereby improving processing speed, reading fluency, and the executive control functions of attention and working memory in both dyslexic and normal students who had PATH neurotraining more than in those students who had no neurotraining. This prediction was evaluated by measuring whether dyslexic and normal students improved on standardized tests of cognitive skills following neurotraining exercises, more than following computer-based guided reading (Raz-Kids (RK)). The neurotraining used in this study was visually-based training designed to improve magnocellular function at both low and high levels in the dorsal stream: the input to the executive control networks coding working memory and attention. This approach represents a paradigm shift from the phonologically-based treatment for dyslexia, which concentrates on high-level speech and reading areas. This randomized controlled-validation study was conducted by training the entire second and third grade classrooms (42 students) for 30 min twice a week before guided reading. Standardized tests were administered at the beginning and end of 12-weeks of intervention training to evaluate improvements in academic skills. Only movement-discrimination training remediated both low-level visual timing deficits and high-level cognitive functioning, including selective and sustained attention, reading fluency and working memory for both dyslexic and normal students. Remediating visual timing deficits in the dorsal stream revealed the causal role of visual movement discrimination training in improving high-level cognitive functions such as attention, reading acquisition and working memory. This study supports the hypothesis that faulty timing in synchronizing the activity of magnocellular with parvocellular visual pathways in the dorsal stream is a fundamental cause of dyslexia and being at-risk for reading problems in normal students, and argues against the assumption that reading deficiencies in dyslexia are caused by phonological or language deficits, requiring a paradigm shift from phonologically-based treatment of dyslexia to a visually-based treatment. This study shows that visual movement-discrimination can be used not only to diagnose dyslexia early, but also for its successful treatment, so that reading problems do not prevent children from readily learning. PMID:28555097

Age-Related Decline in Anticipatory Motor Planning and Its Relation to Cognitive and Motor Skill Proficiency.

PubMed

Stöckel, Tino; Wunsch, Kathrin; Hughes, Charmayne M L

2017-01-01

Anticipatory motor planning abilities mature as children grow older, develop throughout childhood and are likely to be stable till the late sixties. In the seventh decade of life, motor planning performance dramatically declines, with anticipatory motor planning abilities falling to levels of those exhibited by children. At present, the processes enabling successful anticipatory motor planning in general, as do the cognitive processes mediating these age-related changes, remain elusive. Thus, the aim of the present study was (a) to identify cognitive and motor functions that are most affected by normal aging and (b) to elucidate key (cognitive and motor) factors that are critical for successful motor planning performance in young ( n = 40, mean age = 23.1 ± 2.6 years) and older adults ( n = 37, mean age = 73.5 ± 7.1 years). Results indicate that normal aging is associated with a marked decline in all aspects of cognitive and motor functioning tested. However, age-related declines were more apparent for fine motor dexterity, processing speed and cognitive flexibility. Furthermore, up to 64% of the variance in motor planning performance across age groups could be explained by the cognitive functions processing speed, response planning and cognitive flexibility. It can be postulated that anticipatory motor planning abilities are strongly influenced by cognitive control processes, which seem to be key mechanisms to compensate for age-related decline. These findings support the general therapeutic and preventive value of cognitive-motor training programs to reduce adverse effects associated with high age.

Detecting At-Risk Alzheimer's Disease Cases.

PubMed

Fladby, Tormod; Pålhaugen, Lene; Selnes, Per; Waterloo, Knut; Bråthen, Geir; Hessen, Erik; Almdahl, Ina Selseth; Arntzen, Kjell-Arne; Auning, Eirik; Eliassen, Carl Fredrik; Espenes, Ragna; Grambaite, Ramune; Grøntvedt, Gøril Rolfseng; Johansen, Krisztina Kunszt; Johnsen, Stein Harald; Kalheim, Lisa Flem; Kirsebom, Bjørn-Eivind; Müller, Kai Ivar; Nakling, Arne Exner; Rongve, Arvid; Sando, Sigrid Botne; Siafarikas, Nikias; Stav, Ane Løvli; Tecelao, Sandra; Timon, Santiago; Bekkelund, Svein Ivar; Aarsland, Dag

2017-01-01

While APOEɛ4 is the major genetic risk factor for Alzheimer's disease (AD), amyloid dysmetabolism is an initial or early event predicting clinical disease and is an important focus for secondary intervention trials. To improve identification of cases with increased AD risk, we evaluated recruitment procedures using pathological CSF concentrations of Aβ42 (pAβ) and APOEɛ4 as risk markers in a multi-center study in Norway. In total, 490 subjects aged 40-80 y were included after response to advertisements and media coverage or memory clinics referrals. Controls (n = 164) were classified as normal controls without first-degree relatives with dementia (NC), normal controls with first-degree relatives with dementia (NCFD), or controls scoring below norms on cognitive screening. Patients (n = 301) were classified as subjective cognitive decline or mild cognitive impairment. Subjects underwent a clinical and cognitive examination and MRI according to standardized protocols. Core biomarkers in CSF from 411 and APOE genotype from 445 subjects were obtained. Cases (both self-referrals (n = 180) and memory clinics referrals (n = 87)) had increased fractions of pAβ and APOEɛ4 frequency compared to NC. Also, NCFD had higher APOEɛ4 frequencies without increased fraction of pAβ compared to NC, and cases recruited from memory clinics had higher fractions of pAβ and APOEɛ4 frequency than self-referred. This study shows that memory clinic referrals are pAβ enriched, whereas self-referred and NCFD cases more frequently are pAβ negative but at risk (APOEɛ4 positive), suitable for primary intervention.

Controlled Antenatal Thyroid Screening II: effect of treating maternal sub-optimal thyroid function on child cognition.

PubMed

Hales, Charlotte; Taylor, Peter N; Channon, Sue; Paradice, Ruth; McEwan, Kirsten; Zhang, Lei; Gyedu, Michael; Bakhsh, Ameen; Okosieme, Onyebuchi; Muller, Ilaria; Draman, Mohd S; Gregory, John W; Dayan, Colin; Lazarus, John H; Rees, D Aled; Ludgate, Marian

2018-01-15

The Controlled Antenatal Thyroid Screening (CATS) study investigated treatment for suboptimal gestational thyroid function (SGTF) on childhood cognition and found no difference in IQ at 3 years between children of treated and untreated SGTF mothers. We have measured IQ in the same children at age 9.5-years and included children from normal-GTF mothers. One examiner, blinded to participant group, assessed children's IQ (WISC-IV), long-term memory and motor function (NEPSY-II) from children of 119 treated and 98 untreated SGTF mothers plus children of 232 mothers with normal-GTF. Logistic regression explored the odds and percentages of IQ<85 in the groups. There was no difference in IQ<85 between children of mothers with normal-GTF and combined SGTF i.e. treated and untreated (fully adjusted OR=1.15 (95% CI 0.52, 2.51) p=0.731). Furthermore, there was no significant effect of treatment (untreated OR=1.33 (95% CI 0.53, 3.34), treated OR=0.75 (95% CI 0.27, 2.06) p=0.576). IQ< 85 was 6.03% in normal-GTF, 7.56% in treated and 11.22% in untreated groups. Analyses accounting for treated-SGTF women with FT4 >97.5th centile of the entire CATS-I cohort revealed no significant effect on child's IQ<85 in CATS-II. IQ at age 3 predicted IQ at age 9.5 (p<0.0001) and accounted for 45% of the variation. Maternal thyroxine during pregnancy did not improve child cognition at age 9.5 years. Our findings confirmed CATS-I and suggest that the lack of treatment effect may be due to the similar proportion of IQ<85 in children of women with normal-GTF and SGTF. Copyright © 2018 Endocrine Society

Detecting navigational deficits in cognitive aging and Alzheimer disease using virtual reality

PubMed Central

Cushman, Laura A.; Stein, Karen; Duffy, Charles J.

2008-01-01

Background: Older adults get lost, in many cases because of recognized or incipient Alzheimer disease (AD). In either case, getting lost can be a threat to individual and public safety, as well as to personal autonomy and quality of life. Here we compare our previously described real-world navigation test with a virtual reality (VR) version simulating the same navigational environment. Methods: Quantifying real-world navigational performance is difficult and time-consuming. VR testing is a promising alternative, but it has not been compared with closely corresponding real-world testing in aging and AD. We have studied navigation using both real-world and virtual environments in the same subjects: young normal controls (YNCs, n = 35), older normal controls (ONCs, n = 26), patients with mild cognitive impairment (MCI, n = 12), and patients with early AD (EAD, n = 14). Results: We found close correlations between real-world and virtual navigational deficits that increased across groups from YNC to ONC, to MCI, and to EAD. Analyses of subtest performance showed similar profiles of impairment in real-world and virtual testing in all four subject groups. The ONC, MCI, and EAD subjects all showed greatest difficulty in self-orientation and scene localization tests. MCI and EAD patients also showed impaired verbal recall about both test environments. Conclusions: Virtual environment testing provides a valid assessment of navigational skills. Aging and Alzheimer disease (AD) share the same patterns of difficulty in associating visual scenes and locations, which is complicated in AD by the accompanying loss of verbally mediated navigational capacities. We conclude that virtual navigation testing reveals deficits in aging and AD that are associated with potentially grave risks to our patients and the community. GLOSSARY AD = Alzheimer disease; EAD = early Alzheimer disease; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; ONC = older normal control; std. wt. = standardized weight; THSD = Tukey honestly significant difference; VR = virtual reality; YNC = young normal control. PMID:18794491

Assessment of executive functioning in binge-eating disorder independent of weight status.

PubMed

Eneva, Kalina T; Arlt, Jean M; Yiu, Angelina; Murray, Susan M; Chen, Eunice Y

2017-08-01

Executive functioning (EF) problems may serve as vulnerability or maintenance factors for Binge-Eating Disorder (BED). However, it is unclear if EF problems observed in BED are related to overweight status or BED status. The current study extends this literature by examining EF in overweight and normal-weight BED compared to weight-matched controls. Participants were normal-weight women with BED (n = 23), overweight BED (n = 32), overweight healthy controls (n = 48), and normal-weight healthy controls (n = 29). The EF battery utilized tests from the National Institutes of Health (NIH) Toolbox and Delis-Kaplan Executive Function System (D-KEFS). After controlling for years of education and minority status, overweight individuals performed more poorly than normal-weight individuals on a task of cognitive flexibility requiring generativity (p < .01), and speed on psychomotor performance tasks (p = .01). Normal-weight and overweight BED performed worse on working memory tasks compared to controls (p = .04). Unexpectedly, normal-weight BED individuals out-performed all other groups on an inhibitory control task (p < .01). No significant differences were found between the four groups on tasks of planning. Regardless of weight status, BED is associated with working memory problems. Replication of the finding that normal-weight BED is associated with enhanced inhibitory control is needed. © 2017 Wiley Periodicals, Inc.

Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification1234

PubMed Central

Morris, Martha Savaria; Jacques, Paul F; Rosenberg, Irwin H; Selhub, Jacob

2007-01-01

Background Historic reports on the treatment of pernicious anemia with folic acid suggest that high-level folic acid fortification delays the diagnosis of or exacerbates the effects of vitamin B-12 deficiency, which affects many seniors. This idea is controversial, however, because observational data are few and inconclusive. Furthermore, experimental investigation is unethical. Objective We examined the relations between serum folate and vitamin B-12 status relative to anemia, macrocytosis, and cognitive impairment (ie, Digit Symbol-Coding score <34) in senior participants in the 1999–2002 US National Health and Nutrition Examination Survey. Design The subjects had normal serum creatinine concentrations and reported no history of stroke, alcoholism, recent anemia therapy, or diseases of the liver, thyroid, or coronary arteries (n = 1459). We defined low vitamin B-12 status as a serum vitamin B-12 concentration <148 pmol/L or a serum methylmalonic acid concentration >210 nmol/L—the maximum of the reference range for serum vitamin B-12–replete participants with normal creatinine. Results After control for demographic characteristics, cancer, smoking, alcohol intake, serum ferritin, and serum creatinine, low versus normal vitamin B-12 status was associated with anemia [odds ratio (OR): 2.7; 95% CI: 1.7, 4.2], macrocytosis (OR: 1.8; 95% CI: 1.01, 3.3), and cognitive impairment (OR: 2.5; 95% CI: 1.6, 3.8). In the group with a low vitamin B-12 status, serum folate ≤59 nmol/L (80th percentile), as opposed to ≤59 nmol/L, was associated with anemia (OR: 3.1; 95% CI: 1.5, 6.6) and cognitive impairment (OR: 2.6; 95% CI: 1.1, 6.1). In the normal vitamin B-12 group, ORs relating high versus normal serum folate to these outcomes were <1.0 (Pinteraction <0.05), but significantly <1.0 only for cognitive impairment (0.4; 95% CI: 0.2, 0.9). Conclusion In seniors with low vitamin B-12 status, high serum folate was associated with anemia and cognitive impairment. When vitamin B-12 status was normal, however, high serum folate was associated with protection against cognitive impairment. PMID:17209196

Low empathy in deaf and hard of hearing (pre)adolescents compared to normal hearing controls.

PubMed

Netten, Anouk P; Rieffe, Carolien; Theunissen, Stephanie C P M; Soede, Wim; Dirks, Evelien; Briaire, Jeroen J; Frijns, Johan H M

2015-01-01

The purpose of this study was to examine the level of empathy in deaf and hard of hearing (pre)adolescents compared to normal hearing controls and to define the influence of language and various hearing loss characteristics on the development of empathy. The study group (mean age 11.9 years) consisted of 122 deaf and hard of hearing children (52 children with cochlear implants and 70 children with conventional hearing aids) and 162 normal hearing children. The two groups were compared using self-reports, a parent-report and observation tasks to rate the children's level of empathy, their attendance to others' emotions, emotion recognition, and supportive behavior. Deaf and hard of hearing children reported lower levels of cognitive empathy and prosocial motivation than normal hearing children, regardless of their type of hearing device. The level of emotion recognition was equal in both groups. During observations, deaf and hard of hearing children showed more attention to the emotion evoking events but less supportive behavior compared to their normal hearing peers. Deaf and hard of hearing children attending mainstream education or using oral language show higher levels of cognitive empathy and prosocial motivation than deaf and hard of hearing children who use sign (supported) language or attend special education. However, they are still outperformed by normal hearing children. Deaf and hard of hearing children, especially those in special education, show lower levels of empathy than normal hearing children, which can have consequences for initiating and maintaining relationships.

Speed of processing and reading disability: a cross-linguistic investigation of dyslexia and borderline intellectual functioning.

PubMed

Bonifacci, Paola; Snowling, Margaret J

2008-06-01

English and Italian children with dyslexia were compared with children with reading difficulties associated with low-IQ on tests of simple and choice RT, and in number and symbol scanning tasks. On all four speed-of-processing tasks, children with low-IQ responded more slowly than children with dyslexia and age-controls. In the choice RT task, the performance of children with low-IQ was also less accurate than that of children of normal IQ, consistent with theories linking processing speed limitations with low-IQ. These findings support the hypothesis that dyslexia is a specific cognitive deficit that can arise in the context of normal IQ and normal speed of processing. The same cognitive phenotype was observed in readers of a deep (English) and a shallow (Italian) orthography.

A randomised controlled intervention trial evaluating the efficacy of a Mediterranean dietary pattern on cognitive function and psychological wellbeing in healthy older adults: the MedLey study.

PubMed

Knight, Alissa; Bryan, Janet; Wilson, Carlene; Hodgson, Jonathan; Murphy, Karen

2015-04-28

The incidence of age-related cognitive decline is rising considerably around the world. There is evidence from a number of recent cross-sectional and prospective studies indicating positive associations between the Mediterranean dietary pattern (MedDiet) and improved cognitive outcomes among the elderly including, reduced age-related cognitive decline and enhanced age-related cognitive performance. However, to date no study has validated these associations in healthy older adult populations (≥65 years and above) with randomised evidence. The main aim of the present study is to provide justified evidence regarding the efficacy of a MedDiet approach to safely reduce the onset of cognitive decline, and promote optimal cognitive performance among healthy older adults using rigorous, randomised intervention methodology. MedLey is a 6-month, randomised controlled 2-cohort parallel group intervention trial, with initial assessment at baseline and repeated every three months. A sample of 166 healthy Australian men and women aged 65 years and above, with normal cognitive function and proficient in English language were recruited from metropolitan Adelaide, South Australia for the study. Participants randomly allocated to the experimental group are required to maintain an intervention dietary pattern based from the traditional Cretan MedDiet (i.e. vegetables, fruits, olive oil, legumes, fish, whole grain cereals, nuts and seeds and low consumption of processed foods, dairy products, red meat and vegetable oils) for six months, while those participants allocated to the control group are asked to maintain their customary lifestyle and diet. The primary outcome of interest is the quantitative difference in age-related cognitive performance, as measured by latent variables (cognitive constructs) sensitive to normal ageing and diet (i.e. speed of processing, memory, attention, executive functions, visual spatial and visuomotor ability). Secondary outcomes include change in biomarkers of inflammation, oxidative stress, lipid metabolism, glucose, insulin, blood flow velocity, and psychological well-being factors (i.e. stress, sleep, anxiety, depression). To our knowledge this will be one of the first randomised clinical trials worldwide to provide evidence for the cause-effect relationship between the MedDiet and age-related cognitive function in a healthy older adult population (≥65 years and over). Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12613000602729.

Protocol for Fit Bodies, Fine Minds: a randomized controlled trial on the affect of exercise and cognitive training on cognitive functioning in older adults

PubMed Central

O'Dwyer, Siobhan T; Burton, Nicola W; Pachana, Nancy A; Brown, Wendy J

2007-01-01

Background Declines in cognitive functioning are a normal part of aging that can affect daily functioning and quality of life. This study will examine the impact of an exercise training program, and a combined exercise and cognitive training program, on the cognitive and physical functioning of older adults. Methods/Design Fit Bodies, Fine Minds is a randomized, controlled trial. Community-dwelling adults, aged between 65 and 75 years, are randomly allocated to one of three groups for 16 weeks. The exercise-only group do three 60-minute exercise sessions per week. The exercise and cognitive training group do two 60-minute exercise sessions and one 60-minute cognitive training session per week. A no-training control group is contacted every 4 weeks. Measures of cognitive functioning, physical fitness and psychological well-being are taken at baseline (0 weeks), post-test (16 weeks) and 6-month follop (40 weeks). Qualitative responses to the program are taken at post-test. Discussion With an increasingly aged population, interventions to improve the functioning and quality of life of older adults are particularly important. Exercise training, either alone or in combination with cognitive training, may be an effective means of optimizing cognitive functioning in older adults. This study will add to the growing evidence base on the effectiveness of these interventions. Trial Registration Australian Clinical Trials Register: ACTRN012607000151437 PMID:17915035

Effects of education on aging-related cortical thinning among cognitively normal individuals.

PubMed

Kim, Jun Pyo; Seo, Sang Won; Shin, Hee Young; Ye, Byoung Seok; Yang, Jin-Ju; Kim, Changsoo; Kang, Mira; Jeon, Seun; Kim, Hee Jin; Cho, Hanna; Kim, Jung-Hyun; Lee, Jong-Min; Kim, Sung Tae; Na, Duk L; Guallar, Eliseo

2015-09-01

We aimed to investigate the relationship between education and cortical thickness in cognitively normal individuals to determine whether education attenuated the association of advanced aging and cortical thinning. A total of 1,959 participants, in whom education levels were available, were included in the final analysis. Cortical thickness was measured on high-resolution MRIs using a surface-based method. Multiple linear regression analysis was performed for education level and cortical thickness, after controlling for possible confounders. High levels of education were correlated with increased mean cortical thickness throughout the entire cortex (p = 0.003). This association persisted after controlling for vascular risk factors. Statistical maps of cortical thickness showed that the high levels of education were correlated with increased cortical thickness in the bilateral premotor areas, anterior cingulate cortices, perisylvian areas, right superior parietal lobule, left lingual gyrus, and occipital pole. There were also interactive effects of age and education on the mean cortical thickness (p = 0.019). Our findings suggest the protective effect of education on cortical thinning in cognitively normal older individuals, regardless of vascular risk factors. This effect was found only in the older participants, suggesting that the protective effects of education on cortical thickness might be achieved by increased resistance to structural loss from aging rather than by simply providing a fixed advantage in the brain. © 2015 American Academy of Neurology.

Reading deficits in very low birthweight children are associated with vocabulary and attention issues at the age of seven.

PubMed

Leijon, Ingemar; Ingemansson, Fredrik; Nelson, Nina; Wadsby, Marie; Samuelsson, Stefan

2016-01-01

This Swedish study compared reading skills between seven-year-old children with a very low birthweight (VLBW) and controls with a normal birthweight, exploring associations between reading variables and cognition, parent-rated behaviour, perinatal factors and family factors. We studied 51 VLBW children, with no major neurodevelopmental impairments and attending their first year at a regular school, and compared them with the 51 sex- and age-matched controls. The test battery, carried out at 7.8 ± 0.4 years of age, included reading skills, the Wechsler Intelligence Scale for Children - III and the Child Behaviour Checklist. Very low birthweight children with a mean birthweight of 1105 g (± 291 g) and a gestational age of 28.8 (± 2.2) weeks scored significantly lower in all reading subtests and cognition and demonstrated more behavioural problems than normal birthweight controls. We also found significant associations between poor vocabulary, combined with attention problems, and phonological awareness, rapid naming and spelling control. Perinatal factors had no association with reading function, and socio-economic factors had very few. Very low birthweight children demonstrated deficits in all reading domains and had poorer cognition and more behavioural problems at the age of seven, with reading ability related to vocabulary and attention. ©2015 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.

Group Cognitive Behavioural Therapy and Group Recreational Activity for Adults with Autism Spectrum Disorders: A Preliminary Randomized Controlled Trial

ERIC Educational Resources Information Center

Hesselmark, Eva; Plenty, Stephanie; Bejerot, Susanne

2014-01-01

Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This "preliminary" randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive…

Rapid Automatized Naming in Children with Dyslexia: Is Inhibitory Control Involved?

PubMed

Bexkens, Anika; van den Wildenberg, Wery P M; Tijms, Jurgen

2015-08-01

Rapid automatized naming (RAN) is widely seen as an important indicator of dyslexia. The nature of the cognitive processes involved in rapid naming is however still a topic of controversy. We hypothesized that in addition to the involvement of phonological processes and processing speed, RAN is a function of inhibition processes, in particular of interference control. A total 86 children with dyslexia and 31 normal readers were recruited. Our results revealed that in addition to phonological processing and processing speed, interference control predicts rapid naming in dyslexia, but in contrast to these other two cognitive processes, inhibition is not significantly associated with their reading and spelling skills. After variance in reading and spelling associated with processing speed, interference control and phonological processing was partialled out, naming speed was no longer consistently associated with the reading and spelling skills of children with dyslexia. Finally, dyslexic children differed from normal readers on naming speed, literacy skills, phonological processing and processing speed, but not on inhibition processes. Both theoretical and clinical interpretations of these results are discussed. Copyright © 2014 John Wiley & Sons, Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elman, Jeremy A.; Madison, Cindee M.; Baker, Suzanne L.

In Alzheimer's disease (AD), Beta-amyloid (Aβ) deposition is one of the hallmarks. However, it is also present in some cognitively normal elderly adults and may represent a preclinical disease state. While AD patients exhibit disrupted functional connectivity (FC) both within and between resting-state networks, studies of preclinical cases have focused primarily on the default mode network (DMN). The extent to which Aβ-related effects occur outside of the DMN and between networks remains unclear. In the present study, we examine how within- and between-network FC are related to both global and regional Aβ deposition as measured by [ 11 C]PIB-PET inmore » 92 cognitively normal older people. We found that within-network FC changes occurred in multiple networks, including the DMN. Changes of between-network FC were also apparent, suggesting that regions maintaining connections to multiple networks may be particularly susceptible to Aβ-induced alterations. Cortical regions showing altered FC clustered in parietal and temporal cortex, areas known to be susceptible to AD pathology. These results likely represent a mix of local network disruption, compensatory reorganization, and impaired control network function. They indicate the presence of Aβ-related dysfunction of neural systems in cognitively normal people well before these areas become hypometabolic with the onset of cognitive decline.« less

Decision-making in frontotemporal dementia: clinical, theoretical and legal implications.

PubMed

Manes, Facundo; Torralva, Teresa; Ibáñez, Agustín; Roca, María; Bekinschtein, Tristán; Gleichgerrcht, Ezequiel

2011-01-01

The behavioral variant of frontotemporal dementia (bvFTD) is characterized by progressive changes in personality and social interaction, loss of empathy, disinhibition and impulsivity, most of which generally precede the onset of cognitive deficits. In this study, we investigated decision-making cognition in a group of patients with an early bvFTD diagnosis whose standard neuropsychological performance was within normal range for all variables. The Iowa Gambling Task was administered to this group of early bvFTD patients, to a group of early bvFTD patients who had shown impaired performance on the classical neuropsychological battery and to healthy controls. Decision-making was impaired in both bvFTD patient groups, whether they had shown impaired or normal performance in the classical neuropsychological evaluation. Patients with early bvFTD may perform normally on standard cognitive tests, and yet develop severe deficits in judgment and decision-making. In many current legal systems, early bvFTD patients showing preserved cognitive functioning who commit unlawful acts run the risk of not being able to plead insane or not guilty on the grounds of diminished responsibility beyond reasonable doubt. This represents a unique legal and ethical dilemma. Our findings have important implications for medicolegal decisions relating to capacity and culpability, and regarding the philosophical concept of 'free will'. 2011 S. Karger AG, Basel.

The Earliest Stage of Cognitive Impairment in Transition From Normal Aging to Alzheimer Disease Is Marked By Prominent RNA Oxidation in Vulnerable Neurons

PubMed Central

Nunomura, Akihiko; Tamaoki, Toshio; Motohashi, Nobutaka; Nakamura, Masao; McKeel, Daniel W.; Tabaton, Massimo; Lee, Hyoung-gon; Smith, Mark A.; Perry, George; Zhu, Xiongwei

2012-01-01

Although neuronal RNA oxidation is a prominent and established feature in age-associated neurodegenerative disorders such as Alzheimer disease (AD), oxidative damage to neuronal RNA in aging and in the transitional stages from normal elderly to the onset of AD has not been fully examined. In this study, we used an in situ approach to identify an oxidized RNA nucleoside 8-hydroxyguanosine (8OHG) in the cerebral cortex of 65 individuals without dementia ranging in age from 0.3 to 86 years. We also examined brain samples from 20 elderly who were evaluated for their premortem clinical dementia rating score and postmortem brain pathological diagnoses to investigate preclinical AD and mild cognitive impairment. Relative density measurements of 8OHG-immunoreactivity revealed a statistically significant increase in neuronal RNA oxidation during aging in the hippocampus and the temporal neocortex. In subjects with mild cognitive impairment but not preclinical AD, neurons of the temporal cortex showed a higher burden of oxidized RNA compared to age-matched controls. These results indicate that although neuronal RNA oxidation fundamentally occurs as an age-associated phenomenon, more prominent RNA damage than in normal aging correlates with the onset of cognitive impairment in the prodromal stage of AD. PMID:22318126

EEG Analysis of the Effects of Therapeutic Cooling on the Cognitive Performance of Multiple Sclerosis Patients

NASA Technical Reports Server (NTRS)

Montgomery, Leslie D.; Montgomery, Richard W.; Ku, Yu-Tsuan E.; Luna, Bernadette; Lee, Hank C.; Kliss, Mark; Webbon, Bruce; Mead, Susan C. (Technical Monitor)

1999-01-01

The objective of this project was to determine whether a controlled period of head and torso cooling would enhance the cognitive performance of multiple sclerosis patients. Nineteen MS patients (11 men and 8 women) participated in the study. Control data were taken from nineteen healthy volunteers (12 men and 7 women). All but six of nineteen MS patients tested improved their cognitive performance, as measured by their scores on the Rao test battery. A second objective was to gain insight into the neurological effects of cooling. Visual evoked potentials (VEPs) stimulated by a reversing checkerboard pattern were recorded before and after cooling. We found that cooling selectively benefited the cognitive performance of those MS patients whose pre-cooling VEPs were abnormally shaped (which is an indication of visual pathway impairment due to demyelinization). Moreover, for female MS patients, the degree of cognitive performance improvement following cooling was correlated with a change in the shape of their VEPs toward a more normal shape following cooling.

Is impaired cerebral vasoreactivity an early marker of cognitive decline in multiple sclerosis patients?

PubMed

Metzger, Aude; Le Bars, Emmanuelle; Deverdun, Jeremy; Molino, François; Maréchal, Bénédicte; Picot, Marie-Christine; Ayrignac, Xavier; Carra, Clarisse; Bauchet, Luc; Krainik, Alexandre; Labauge, Pierre; Menjot de Champfleur, Nicolas

2018-03-01

The link between cerebral vasoreactivity and cognitive status in multiple sclerosis remains unclear. The aim of the present study was to investigate a potential decrease of cerebral vasoreactivity in multiple sclerosis patients and correlate it with cognitive status. Thirty-three patients with multiple sclerosis (nine progressive and 24 remitting forms, median age: 39 years, 12 males) and 22 controls underwent MRI with a hypercapnic challenge to assess cerebral vasoreactivity and a neuropsychological assessment. Cerebral vasoreactivity, measured as the cerebral blood flow percent increase normalised by end-tidal carbon dioxide variation, was assessed globally and by regions of interest using the blood oxygen level-dependent technique. Non-parametric statistics tests were used to assess differences between groups, and associations were estimated using linear models. Cerebral vasoreactivity was lower in patients with cognitive impairment than in cognitively normal patients (p=0.004) and was associated with education level in patients (R 2 = 0.35; p = 0.047). There was no decrease in cerebral vasoreactivity between patients and controls. Cognitive impairment in multiple sclerosis may be mediated through decreased cerebral vasoreactivity. Cerebral vasoreactivity could therefore be considered as a marker of cognitive decline in multiple sclerosis. • Cerebral vasoreactivity does not differ between multiple sclerosis patients and controls. • Cerebral vasoreactivity measure is linked to cognitive impairment in multiple sclerosis. • Cerebral vasoreactivity is linked to level of education in multiple sclerosis.

Proton Pump Inhibitors and Risk of Mild Cognitive Impairment and Dementia.

PubMed

Goldstein, Felicia C; Steenland, Kyle; Zhao, Liping; Wharton, Whitney; Levey, Allan I; Hajjar, Ihab

2017-09-01

To examine the risk associated with the use of proton pump inhibitors (PPIs) of conversion to mild cognitive impairment (MCI), dementia, and specifically Alzheimer's disease (AD). Observational, longitudinal study. Tertiary academic Alzheimer's Disease Centers funded by the National Institute on Aging. Research volunteers aged 50 and older with two to six annual visits; 884 were taking PPIs at every visit, 1,925 took PPIs intermittently, and 7,677 never reported taking PPIs. All had baseline normal cognition or MCI. Multivariable Cox regression analyses evaluated the association between PPI use and annual conversion of baseline normal cognition to MCI or dementia or annual conversion of baseline MCI to dementia, controlling for demographic characteristics, vascular comorbidities, mood, and use of anticholinergics and histamine-2 receptor antagonists. Continuous (always vs never) PPI use was associated with lower risk of decline in cognitive function (hazard ratio (HR) = 0.78, 95% confidence interval (CI) =0.66-0.93, P = .005) and lower risk of conversion to MCI or AD (HR = 0.82, 95% CI = 0.69-0.98, P = .03). Intermittent use was also associated with lower risk of decline in cognitive function (HR = 0.84, 95% CI = 0.76-0.93, P = .001) and risk of conversion to MCI or AD (HR = 0.82, 95% CI = 0.74-0.91, P = .001). This lower risk was found for persons with normal cognition or MCI. Proton pump inhibitors were not associated with greater risk of dementia or of AD, in contrast to recent reports. Study limitations include reliance on self-reported PPI use and lack of dispensing data. Prospective studies are needed to confirm these results to guide empirically based clinical treatment recommendations. © 2017, Copyright the Authors Journal compilation © 2017, The American Geriatrics Society.

Emotional instability but intact spatial cognition in adenosine receptor 1 knock out mice.

PubMed

Lang, Undine E; Lang, Florian; Richter, Kerstin; Vallon, Volker; Lipp, Hans-Peter; Schnermann, Jürgen; Wolfer, David P

2003-10-17

Several lines of evidence point to the involvement of adenosine in the regulation of important central mechanisms such as cognition, arousal, aggression and anxiety. In order to elucidate the involvement of the adenosine A1 receptor (A1AR) in spatial learning and the control of exploratory behaviour, we assessed A1AR knockout mice (A1AR-/-) and their wild-type littermates (A1AR+/+) in a place navigation task in the water maze and in a battery of forced and free exploration tests. In the water maze, A1AR-/- mice showed normal escape latencies and were indistinguishable from controls with respect to measures of spatial performance during both training and probe trial. But despite normal performance they showed increased wall hugging, most prominently after the relocation of the goal platform for reversal training. Quantitative analysis of strategy choices indicated that wall hugging was increased mainly at the expense of chaining and passive floating, whereas the frequency of trials characterised as direct swims or focal searching was normal in A1AR-/- mice. These results indicate intact spatial cognition, but mildly altered emotional reactions to the water maze environment. In line with this interpretation, A1AR-/- mice showed normal levels and patterns of activity, but a mild increase of some measures of anxiety in our battery of forced and free exploration paradigms. These results are in line with findings published using a genetically similar line, but demonstrate that the magnitude of the changes and the range of affected behavioural measures may vary considerably depending on the environmental conditions during testing.

Terminal decline and practice effects in older adults without dementia: the MoVIES project.

PubMed

Dodge, Hiroko H; Wang, Chia-Ning; Chang, Chung-Chou H; Ganguli, Mary

2011-08-23

To track cognitive change over time in dementia-free older adults and to examine terminal cognitive decline. A total of 1,230 subjects who remained free from dementia over 14 years of follow-up were included in a population-based epidemiologic cohort study. First, we compared survivors and decedents on their trajectories of 5 cognitive functions (learning, memory, language, psychomotor speed, executive functions), dissociating practice effects which can mask clinically significant decline from age-associated cognitive decline. We used longitudinal mixed-effects models with penalized linear spline. Second, limiting the sample to 613 subjects who died during follow-up, we identified the inflection points at which the rate of cognitive decline accelerated, in relation to time of death, controlling for practice effects. We used mixed-effects model with a change point. Age-associated cognitive trajectories were similar between decedents and survivors without dementia. However, substantial differences were observed between the trajectories of practice effects of survivors and decedents, resembling those usually observed between normal and mildly cognitively impaired elderly. Executive and language functions showed the earliest terminal declines, more than 9 years prior to death, independent of practice effects. Terminal cognitive decline in older adults without dementia may reflect presymptomatic disease which does not cross the clinical threshold during life. Alternatively, cognitive decline attributed to normal aging may itself represent underlying neurodegenerative or vascular pathology. Although we cannot conclude definitively from this study, the separation of practice effects from age-associated decline could help identify preclinical dementia.

Similar profile of cognitive impairment and recovery for Aboriginal Australians in treatment for episodic or chronic alcohol use.

PubMed

Dingwall, Kylie M; Maruff, Paul; Cairney, Sheree

2011-08-01

The cognitive impairment and recovery associated with chronic alcohol abuse and subsequent abstinence is well understood. However, the recovery profile following heavy episodic or 'binge' use, which is common among some Australian Aboriginal users, has not been investigated thoroughly and no empirical studies have examined chronic use in this population. The aim of this study was to identify and compare cognitive impairment and recovery associated with chronic and episodic alcohol use among Aboriginal Australians. Longitudinal case-control design. Residential alcohol treatment programmes in northern Australia. Forty chronic alcohol users, 24 episodic users and 41 healthy controls [mean age = 34.24; standard deviation (SD) = 9.73]. Cognitive assessments of visual motor, attention, memory, learning and executive functions at baseline (start of treatment), then 4 weeks and 8 weeks later. Reassessment of 31% of participants an average of 11 months later (SD = 4.4) comparing those who remained abstinent (n = 5), those who relapsed (n = 11) and healthy controls (n = 19). At baseline, chronic and episodic alcohol users showed impaired visual motor, learning, memory and executive functions. With the exception of visual motor impairment, all deficits had improved to normal levels within 4 weeks. Visual motor deficits had normalized within 11 months. Performances did not differ at any time between chronic and episodic alcohol groups. In Aboriginal Australians, episodic drinking is associated with similar patterns of impairment and recovery as chronic alcohol use. Most cognitive deficits appear to recover within the first month of abstinence, while persisting visual motor problems recover within 1 year. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

Interaction between personality traits and cerebrospinal fluid biomarkers of Alzheimer's disease pathology modulates cognitive performance.

PubMed

Tautvydaitė, Domilė; Kukreja, Deepti; Antonietti, Jean-Philippe; Henry, Hugues; von Gunten, Armin; Popp, Julius

2017-02-02

During adulthood, personality characteristics may contribute to the individual capacity to compensate the impact of developing cerebral Alzheimer's disease (AD) pathology on cognitive impairment in later life. In this study we aimed to investigate whether and how premorbid personality traits interact with cerebrospinal fluid (CSF) markers of AD pathology to predict cognitive performance in subjects with mild cognitive impairment or mild AD dementia and in participants with normal cognition. One hundred and ten subjects, of whom 66 were patients with mild cognitive impairment or mild AD dementia and 44 were healthy controls, had a comprehensive medical and neuropsychological examination as well as lumbar puncture to measure CSF biomarkers of AD pathology (amyloid beta 1-42 , phosphorylated tau and total-tau). Participants' proxies completed the Revised NEO Personality Inventory, Form R to retrospectively assess subjects' premorbid personality. In hierarchical multivariate regression analyses, including age, gender, education, APOEε4 status and cognitive level, premorbid neuroticism, conscientiousness and agreeableness modulated the effect of CSF biomarkers on cognitive performance. Low premorbid openness independently predicted lower levels of cognitive functioning after controlling for biomarker concentrations. Our findings suggest that specific premorbid personality traits are associated with cerebral AD pathology and modulate its impact on cognitive performance. Considering personality characteristics may help to appraise a person's cognitive reserve and the risk of cognitive decline in later life.

Association of body mass index with amnestic and non-amnestic mild cognitive impairment risk in elderly.

PubMed

Wang, Feng; Zhao, Minghui; Han, Zhaoli; Li, Dai; Zhang, Shishuang; Zhang, Yongqiang; Kong, Xiaodong; Sun, Ning; Zhang, Qiang; Lei, Ping

2017-09-15

Previous studies focused on the relationship between body mass index and cognitive disorder and obtained many conflicting results. This study explored the potential effects of body mass index on the risk of mild cognitive impairment (amnestic and non-amnestic) in the elderly. The study enrolled 240 amnestic mild cognitive impairment patients, 240 non-amnestic mild cognitive impairment patients and 480 normal cognitive function controls. Data on admission and retrospective data at baseline (6 years ago) were collected from their medical records. Cognitive function was evaluated using Mini-Mental State Examination and Montreal Cognitive Assessment. Being underweight, overweight or obese at baseline was associated with an increased risk of amnestic mild cognitive impairment (OR: 2.30, 95%CI: 1.50 ~ 3.52; OR: 1.74, 95%CI: 1.36 ~ 2.20; OR: 1.71, 95%CI: 1.32 ~ 2.22, respectively). Being overweight or obese at baseline was also associated with an increased risk of non-amnestic mild cognitive impairment (OR: 1.51, 95%CI: 1.20 ~ 1.92; OR: 1.52, 95%CI: 1.21 ~ 1.97, respectively). In subjects with normal weights at baseline, an increased or decreased body mass index at follow-up was associated with an elevated risk of amnestic mild cognitive impairment (OR: 1.80, 95%CI: 1.10 ~ 3.05; OR: 3.96, 95%CI: 2.88 ~ 5.49, respectively), but only an increased body mass index was associated with an elevated risk of non-amnestic mild cognitive impairment (OR: 1.71, 95%CI: 1.16 ~ 2.59). Unhealthy body mass index levels at baseline and follow-up might impact the risk of both types of mild cognitive impairment (amnestic and non-amnestic).

Specific interference between a cognitive task and sensory organization for stance balance control in healthy young adults: visuospatial effects.

PubMed

Chong, Raymond K Y; Mills, Bradley; Dailey, Leanna; Lane, Elizabeth; Smith, Sarah; Lee, Kyoung-Hyun

2010-07-01

We tested the hypothesis that a computational overload results when two activities, one motor and the other cognitive that draw on the same neural processing pathways, are performed concurrently. Healthy young adult subjects carried out two seemingly distinct tasks of maintaining standing balance control under conditions of low (eyes closed), normal (eyes open) or high (eyes open, sway-referenced surround) visuospatial processing load while concurrently performing a cognitive task of either subtracting backwards by seven or generating words of the same first letter. A decrease in the performance of the balance control task and a decrement in the speed and accuracy of responses were noted during the subtraction but not the word generation task. The interference in the subtraction task was isolated to the first trial of the high but not normal or low visuospatial conditions. Balance control improvements with repeated exposures were observed only in the low visuospatial conditions while performance in the other conditions remained compromised. These results suggest that sensory organization for balance control appear to draw on similar visuospatial computational resources needed for the subtraction but not the word generation task. In accordance with the theory of modularity in human performance, the contrast in results between the subtraction and word generation tasks suggests that the neural overload is related to competition for similar visuospatial processes rather than limited attentional resources. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Association of Higher Cortical Amyloid Burden With Loneliness in Cognitively Normal Older Adults.

PubMed

Donovan, Nancy J; Okereke, Olivia I; Vannini, Patrizia; Amariglio, Rebecca E; Rentz, Dorene M; Marshall, Gad A; Johnson, Keith A; Sperling, Reisa A

2016-12-01

Emotional and behavioral symptoms in cognitively normal older people may be direct manifestations of Alzheimer disease (AD) pathophysiology at the preclinical stage, prior to the onset of mild cognitive impairment. Loneliness is a perceived state of social and emotional isolation that has been associated with cognitive and functional decline and an increased risk of incident AD dementia. We hypothesized that loneliness might occur in association with elevated cortical amyloid burden, an in vivo research biomarker of AD. To determine whether cortical amyloid burden is associated with greater loneliness in cognitively normal older adults. Cross-sectional analyses using data from the Harvard Aging Brain Study of 79 cognitively normal, community-dwelling participants. A continuous, aggregate measure of cortical amyloid burden, determined by Pittsburgh Compound B-positron emission tomography (PiB-PET), was examined in association with loneliness in linear regression models adjusting for age, sex, apolipoprotein E ε4 (APOEε4), socioeconomic status, depression, anxiety, and social network (without and with the interaction of amyloid and APOEε4). We also quantified the association of high amyloid burden (amyloid-positive group) to loneliness (lonely group) using logistic regression, controlling for the same covariates, with the amyloid-positive group and the lonely group, each composing 32% of the sample (n = 25). Loneliness, as determined by the 3-item UCLA Loneliness Scale (possible range, 3-12, with higher score indicating greater loneliness). The 79 participants included 43 women and 36 men with a mean (SD) age of 76.4 (6.2) years. Mean (SD) cortical amyloid burden via PiB-PET was 1.230 (0.209), and the mean (SD) UCLA-3 loneliness score was 5.3 (1.8). Twenty-two (28%) had positive APOEε4 carrier status, and 25 (32%) were in the amyloid-positive group with cortical PiB distribution volume ratio greater than 1.2. Controlling for age, sex, APOEε4, socioeconomic status, depression, anxiety, and social network, we found that higher amyloid burden was significantly associated with greater loneliness: compared with individuals in the amyloid-negative group, those in the amyloid-positive group were 7.5-fold (95% CI, 1.7-fold to 34.0-fold) more likely to be classified as lonely than nonlonely (β = 3.3, partial r = 0.4, P = .002). Furthermore, the association of high amyloid burden and loneliness was stronger in APOEε4 carriers than in noncarriers. We report a novel association of loneliness with cortical amyloid burden in cognitively normal older adults, suggesting that loneliness is a neuropsychiatric symptom relevant to preclinical AD. This work will inform new research into the neural underpinnings and disease mechanisms involved in loneliness and may enhance early detection and intervention research in AD.

Executive functions in adolescents with binge-eating disorder and obesity.

PubMed

Kittel, Rebekka; Schmidt, Ricarda; Hilbert, Anja

2017-08-01

Binge-eating disorder (BED) in adults is associated with alterations in executive functions (EF) and obesity. Much less is known about these relationships in adolescents, including whether poor EF are associated with eating disorder psychopathology and/or elevated body mass index. This study examined EF in response to neutral stimuli in youth with BED. Adolescents with BED and obesity (n = 22), individually matched adolescents with obesity (n = 22), and normal weight (n = 22) completed neuropsychological tests targeting inhibition (Color-Word Interference Test), sustained attention (D2 Concentration Endurance Test), cognitive flexibility (Comprehensive Trail Making Test), and decision-making (Iowa Gambling Task). Adolescents with BED and obesity displayed significantly poorer inhibitory control compared to normal-weight adolescents. This effect persisted after controlling for the level of secondary education. However, initial differences between adolescents with obesity and normal-weight controls regarding inhibitory control and sustained attention vanished after controlling for education. The three groups did not differ regarding cognitive flexibility and decision-making. Moreover, adolescents with BED and obesity did not perform worse than adolescents with obesity on any of the neuropsychological tests. Overall, our results indicate that adolescent BED is associated with only a few alterations in general EF, specifically inhibitory control, and underline BED and educational level as confounding factors in neuropsychological research on obesity. To further delineate EF profiles of adolescents with BED, future research should focus on EF in response to disorder-related stimuli and experimental settings with high ecological validity. © 2017 Wiley Periodicals, Inc.

A validation study of the Hong Kong version of Montreal Cognitive Assessment (HK-MoCA) in Chinese older adults in Hong Kong.

PubMed

Yeung, P Y; Wong, L L; Chan, C C; Leung, Jess L M; Yung, C Y

2014-12-01

To validate the Hong Kong version of Montreal Cognitive Assessment (HK-MoCA) in identification of mild cognitive impairment and dementia in Chinese older adults. Cross-sectional study. Cognition clinic and memory clinic of a public hospital in Hong Kong. A total of 272 participants (dementia, n=130; mild cognitive impairment, n=93; normal controls, n=49) aged 60 years or above were assessed using HK-MoCA. The HK-MoCA scores were validated against expert diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed) criteria for dementia and Petersen's criteria for mild cognitive impairment. Statistical analysis was performed using receiver operating characteristic curve and regression analyses. Additionally, comparison was made with the Cantonese version of Mini-Mental State Examination and Global Deterioration Scale. The optimal cutoff score for the HK-MoCA to differentiate cognitive impaired persons (mild cognitive impairment and dementia) from normal controls was 21/22 after adjustment of education level, giving a sensitivity of 0.928, specificity of 0.735, and area under the curve of 0.920. Moreover, the cutoff to detect mild cognitive impairment was 21/22 with a sensitivity of 0.828, specificity of 0.735, and area under the curve of 0.847. Score of the Cantonese version of the Mini-Mental State Examination to detect mild cognitive impairment was 26/27 with a sensitivity of 0.785, specificity of 0.816, and area under the curve of 0.857. At the optimal cutoff of 18/19, HK-MoCA identified dementia from controls with a sensitivity of 0.923, specificity of 0.918, and area under the curve of 0.971. The HK-MoCA is a useful cognitive screening instrument for use in Chinese older adults in Hong Kong. A score of less than 22 should prompt further diagnostic assessment. It has comparable sensitivity with the Cantonese version of Mini-Mental State Examination for detection of mild cognitive impairment. It is brief and feasible to conduct in the clinical setting, and can be completed in less than 15 minutes. Thus, HK-MoCA provides an attractive alternative screening instrument to Mini-Mental State Examination which has ceiling effect (ie may fail to detect mild/moderate cognitive impairment in people with high education level or premorbid intelligence) and needs to be purchased due to copyright issues.

[Cognitive function in patients with systemic sclerosis].

PubMed

Straszecka, J; Jonderko, G; Kucharz, E J; Brzezińska-Wcisło, L; Kotulska, A; Bogdanowski, T

1997-09-01

Central nervous system involvement is seldom reported in patients with systemic sclerosis (SSc). Cognitive functions were determined in 21 patients with definite SSc and 42 healthy controls. Thyroid function was also measured in order to eliminate the effect of hypothyroidism on cognitive functioning. It was found that the SSc patients with normal thyroid function showed defective long-term and recent memory, learning ability, criticism, perception and visuo-perceptual skills, their simple reaction time was prolonged. Similar but less advanced cognitive defects were shown in the SSc patients with overt or latent hypothyroidism. The obtained results indicate that the central nervous system involvement is more common in patients with SSc than it has been reported earlier.

Non-Pharmacologic Interventions for Older Adults with Subjective Cognitive Decline: Systematic Review, Meta-Analysis, and Preliminary Recommendations.

PubMed

Smart, Colette M; Karr, Justin E; Areshenkoff, Corson N; Rabin, Laura A; Hudon, Carol; Gates, Nicola; Ali, Jordan I; Arenaza-Urquijo, Eider M; Buckley, Rachel F; Chetelat, Gael; Hampel, Harald; Jessen, Frank; Marchant, Natalie L; Sikkes, Sietske A M; Tales, Andrea; van der Flier, Wiesje M; Wesselman, Linda

2017-09-01

In subjective cognitive decline (SCD), older adults present with concerns about self-perceived cognitive decline but are found to have clinically normal function. However, a significant proportion of those adults are subsequently found to develop mild cognitive impairment, Alzheimer's dementia or other neurocognitive disorder. In other cases, SCD may be associated with mood, personality, and physical health concerns. Regardless of etiology, adults with SCD may benefit from interventions that could enhance current function or slow incipient cognitive decline. The objective of this systematic review and meta-analysis, conducted in accordance with the PRISMA guidelines, is to examine the benefits of non-pharmacologic intervention (NPI) in persons with SCD. Inclusion criteria were studies of adults aged 55 + with SCD defined using published criteria, receiving NPI or any control condition, with cognitive, behavioural, or psychological outcomes in controlled trails. Published empirical studies were obtained through a standardized search of CINAHL Complete, Cochrane Central Register of Controlled Trials, MEDLINE with Full Text, PsycINFO, and PsycARTICLES, supplemented by a manual retrieval of relevant articles. Study quality and bias was determined using PEDro. Nine studies were included in the review and meta-analysis. A wide range of study quality was observed. Overall, a small effect size was found on cognitive outcomes, greater for cognitive versus other intervention types. The available evidence suggests that NPI may benefit current cognitive function in persons with SCD. Recommendations are provided to improve future trials of NPI in SCD.

Late-onset multiple sclerosis presenting with cognitive dysfunction and severe cortical/infratentorial atrophy.

PubMed

Calabrese, Massimiliano; Gajofatto, Alberto; Gobbin, Francesca; Turri, Giulia; Richelli, Silvia; Matinella, Angela; Oliboni, Eugenio Simone; Benedetti, Maria Donata; Monaco, Salvatore

2015-04-01

Although cognitive dysfunction is a relevant aspect of multiple sclerosis (MS) from the earliest disease phase, cognitive onset is unusual thus jeopardizing early and accurate diagnosis. Here we describe 12 patients presenting with cognitive dysfunction as primary manifestation of MS with either mild or no impairment in non-cognitive neurological domains. Twelve patients with cognitive onset who were subsequently diagnosed with MS (CI-MS) were included in this retrospective study. Twelve cognitively normal MS patients (CN-MS), 12 healthy controls and four patients having progressive supranuclear palsy (PSP) served as the reference population. Ten CI-MS patients had progressive clinical course and all patients had late disease onset (median age = 49 years; range = 40-58 years). Among cognitive functions, frontal domains were the most involved. Compared to CN-MS and healthy controls, significant cortical and infratentorial atrophy characterized CI-MS patients. Selective atrophy of midbrain tegmentum with relative sparing of pons, known as "The Hummingbird sign," was observed in eight CI-MS and in three PSP patients. Our observation suggests that MS diagnosis should be taken into consideration in case of cognitive dysfunction, particularly when associated with slowly progressive disease course and severe cortical, cerebellar and brainstem atrophy even in the absence of other major neurological symptoms and signs. © The Author(s), 2014.

Cognitive and meta-cognitive dimensions of psychoses.

PubMed

O'Connor, Kieron

2009-03-01

This paper outlines cognitive approaches to understanding and treating positive psychotic symptoms, such as hallucinations, delusions, and dissociations. Recent cognitive accounts of psychosis are reviewed along with the claim that it is not the symptoms themselves but cognitive and meta-cognitive appraisals (attributions and beliefs) about the significance of the symptoms that cause distress and dysfunction. Psychotic symptoms do lie on a continuum with normal experience. Cognitive appraisal dimensions may interact with reasoning styles such as inferential confusion, cognitive slippage, fantasy proneness, and perceptual immersion (styles also normally distributed in the population) and together persuade the person with psychosis to live in fictional narratives as if they were real. Recent clinical studies suggest that addressing beliefs about symptoms modifying inferential styles and normalizing experiences may help symptom management.

Working memory span in mild cognitive impairment. Influence of processing speed and cognitive reserve.

PubMed

Facal, David; Juncos-Rabadán, Onésimo; Pereiro, Arturo X; Lojo-Seoane, Cristina

2014-04-01

Mild cognitive impairment (MCI) often includes episodic memory impairment, but can also involve other types of cognitive decline. Although previous studies have shown poorer performance of MCI patients in working memory (WM) span tasks, different MCI subgroups were not studied. In the present exploratory study, 145 participants underwent extensive cognitive evaluation, which included three different WM span tasks, and were classified into the following groups: multiple-domain amnestic MCI (mda-MCI), single-domain amnestic MCI (sda-MCI), and controls. General linear model was conducted by considering the WM span tasks as the within-subject factor; the group (mda-MCI, sda-MCI, and controls) as the inter-subject factor; and processing speed, vocabulary and age as covariates. Multiple linear regression models were also used to test the influence of processing speed, vocabulary, and other cognitive reserve (CR) proxies. Results indicate different levels of impairment of WM, with more severe impairment in mda-MCI patients. The differences were still present when processing resources and CR were controlled. Between-group differences can be understood as a manifestation of the greater severity and widespread memory impairment in mda-MCI patients and may contribute to a better understanding of continuum from normal controls to mda-MCI patients. Processing speed and CR have a limited influence on WM scores, reducing but not removing differences between groups.

Alzheimer Disease Cerebrospinal Fluid Biomarkers Moderate Baseline Differences and Predict Longitudinal Change in Attentional Control and Episodic Memory Composites in the Adult Children Study

PubMed Central

Aschenbrenner, Andrew J.; Balota, David A.; Fagan, Anne M.; Duchek, Janet M.; Benzinger, Tammie L.S.; Morris, John C.

2015-01-01

Objective Cognitive measures that are sensitive to biological markers of Alzheimer disease (AD) pathology are needed in order to (a) facilitate preclinical staging, (b) identify individuals who are at the highest risk for developing clinical symptoms and (c) serve as endpoints for evaluating the efficacy of interventions. The present study assesses the utility of two cognitive composite scores of attentional control and episodic memory as markers for preclinical AD pathology in a group of cognitively normal older adults (N = 238), as part of the Adult Children Study. Method All participants were given a baseline cognitive assessment and follow-up assessments every 3 years over an 8-year period, as well as a lumbar puncture within two years of the initial assessment to collect cerebrospinal fluid (CSF) and a PET-PIB scan for amyloid imaging. Results Results indicated that attentional control was correlated with levels of Aβ42 at the initial assessment whereas episodic memory was not. Longitudinally, individuals with high CSF tau exhibited a decline in both attention and episodic memory over the course of the study. Conclusion These results indicate that measures of attentional control and episodic memory can be utilized to evaluate cognitive decline in preclinical AD and provide support that CSF tau may be a key mechanism driving longitudinal cognitive change. PMID:26416094

Cognitive Alexithymia Is Associated with the Degree of Risk for Psychosis

PubMed Central

van der Velde, Jorien; Swart, Marte; van Rijn, Sophie; van der Meer, Lisette; Wunderink, Lex; Wiersma, Durk; Krabbendam, Lydia; Bruggeman, Richard; Aleman, André

2015-01-01

Alexithymia is a personality construct denoting emotion processing problems. It has been suggested to encompass two dimensions: a cognitive and affective dimension. The cognitive dimension is characterized by difficulties in identifying, verbalizing and analyzing emotions, while the affective dimension reflects the level of emotional arousal and imagination. Alexithymia has been previously proposed as a risk factor for developing psychosis. More specifically, the two alexithymia dimensions might be differentially related to the vulnerability for psychosis. Therefore, we examined the two dimensions of alexithymia, measured with the BVAQ in 94 siblings of patients with schizophrenia, 52 subjects at ultra-high risk (UHR) for developing psychosis, 38 patients with schizophrenia and 109 healthy controls. The results revealed that siblings and patients had higher levels of cognitive alexithymia compared to controls. In addition, subjects at UHR for psychosis had even higher levels of cognitive alexithymia compared to the siblings. The levels of affective alexithymia in siblings and patients were equal to controls. However, UHR individuals had significantly lower levels of affective alexithymia (i.e. higher levels of emotional arousal and fantasizing) compared to controls. Alexithymia was further related to subclinical levels of negative and depressive symptoms. These findings indicate that alexithymia varies parametrically with the degree of risk for psychosis. More specifically, a type-II alexithymia pattern, with high levels of cognitive alexithymia and normal or low levels of affective alexithymia, might be a vulnerability factor for psychosis. PMID:26030357

Alzheimer Disease Cerebrospinal Fluid Biomarkers Moderate Baseline Differences and Predict Longitudinal Change in Attentional Control and Episodic Memory Composites in the Adult Children Study.

PubMed

Aschenbrenner, Andrew J; Balota, David A; Fagan, Anne M; Duchek, Janet M; Benzinger, Tammie L S; Morris, John C

2015-09-01

Cognitive measures that are sensitive to biological markers of Alzheimer disease (AD) pathology are needed to (a) facilitate preclinical staging, (b) identify individuals who are at the highest risk for developing clinical symptoms, and (c) serve as endpoints for evaluating the efficacy of interventions. The present study assesses the utility of two cognitive composite scores of attentional control and episodic memory as markers for preclinical AD pathology in a group of cognitively normal older adults (N = 238), as part of the Adult Children Study. All participants were given a baseline cognitive assessment and follow-up assessments every 3 years over an 8-year period, as well as a lumbar puncture within 2 years of the initial assessment to collect cerebrospinal fluid (CSF) and amyloid tracer Pittsburgh compound-B scan for amyloid imaging. Results indicated that attentional control was correlated with levels of Aβ42 at the initial assessment whereas episodic memory was not. Longitudinally, individuals with high CSF tau exhibited a decline in both attention and episodic memory over the course of the study. These results indicate that measures of attentional control and episodic memory can be used to evaluate cognitive decline in preclinical AD and provide support that CSF tau may be a key mechanism driving longitudinal cognitive change.

Clinical symptoms and cognitive impairment associated with male schizophrenia relate to plasma manganese superoxide dismutase activity: a case-control study.

PubMed

Zhang, Xiang Yang; Chen, Da Chun; Xiu, Mei Hong; Tan, Yun Long; Yang, Fu De; Zhang, Laurence Y; Zhang, Laura Y; Haile, Colin N; Kosten, Thomas R

2013-08-01

Several lines of evidence suggest that excessive reactive oxygen species-induced oxidative damage may underlie cognitive impairment in psychiatric disorders. A growing body of evidence show that oxidative damage may relate to the range of cognitive deficits associated with schizophrenia. In this study we examine one of the primary antioxidant defense enzymes manganese superoxide dismutase (MnSOD), and whether it relates to cognitive deficits in schizophrenia. We recruited 185 chronic male schizophrenia patients and 132 male controls and compared results from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and plasma MnSOD activity between groups. Symptom severity in patients with schizophrenia was assessed with the Positive and Negative Syndrome Scale (PANSS). Our results showed that MnSOD activities were significantly lower in patients than controls (p<0.05). Cognitive scores on the RBANS and nearly all of its five subscales (all p<0.001) except for the Visuospatial/Constructional index were significantly lower in schizophrenia patients than normal controls. MnSOD was negatively correlated with the general psychopathology subscale of PANSS, PANSS total score, positive symptoms and RBANS total score in patients with schizophrenia. Our findings add to growing evidence that oxidative stress may be involved in the psychopathology of male schizophrenia, and its associated cognitive impairment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Age-Related Decline in Anticipatory Motor Planning and Its Relation to Cognitive and Motor Skill Proficiency

PubMed Central

Stöckel, Tino; Wunsch, Kathrin; Hughes, Charmayne M. L.

2017-01-01

Anticipatory motor planning abilities mature as children grow older, develop throughout childhood and are likely to be stable till the late sixties. In the seventh decade of life, motor planning performance dramatically declines, with anticipatory motor planning abilities falling to levels of those exhibited by children. At present, the processes enabling successful anticipatory motor planning in general, as do the cognitive processes mediating these age-related changes, remain elusive. Thus, the aim of the present study was (a) to identify cognitive and motor functions that are most affected by normal aging and (b) to elucidate key (cognitive and motor) factors that are critical for successful motor planning performance in young (n = 40, mean age = 23.1 ± 2.6 years) and older adults (n = 37, mean age = 73.5 ± 7.1 years). Results indicate that normal aging is associated with a marked decline in all aspects of cognitive and motor functioning tested. However, age-related declines were more apparent for fine motor dexterity, processing speed and cognitive flexibility. Furthermore, up to 64% of the variance in motor planning performance across age groups could be explained by the cognitive functions processing speed, response planning and cognitive flexibility. It can be postulated that anticipatory motor planning abilities are strongly influenced by cognitive control processes, which seem to be key mechanisms to compensate for age-related decline. These findings support the general therapeutic and preventive value of cognitive-motor training programs to reduce adverse effects associated with high age. PMID:28928653

The normalities and abnormalities associated with speech in psychometrically-defined schizotypy.

PubMed

Cohen, Alex S; Auster, Tracey L; McGovern, Jessica E; MacAulay, Rebecca K

2014-12-01

Speech deficits are thought to be an important feature of schizotypy--defined as the personality organization reflecting a putative liability for schizophrenia. There is reason to suspect that these deficits manifest as a function of limited cognitive resources. To evaluate this idea, we examined speech from individuals with psychometrically-defined schizotypy during a low cognitively-demanding task versus a relatively high cognitively-demanding task. A range of objective, computer-based measures of speech tapping speech production (silence, number and length of pauses, number and length of utterances), speech variability (global and local intonation and emphasis) and speech content (word fillers, idea density) were employed. Data for control (n=37) and schizotypy (n=39) groups were examined. Results did not confirm our hypotheses. While the cognitive-load task reduced speech expressivity for subjects as a group for most variables, the schizotypy group was not more pathological in speech characteristics compared to the control group. Interestingly, some aspects of speech in schizotypal versus control subjects were healthier under high cognitive load. Moreover, schizotypal subjects performed better, at a trend level, than controls on the cognitively demanding task. These findings hold important implications for our understanding of the neurocognitive architecture associated with the schizophrenia-spectrum. Of particular note concerns the apparent mismatch between self-reported schizotypal traits and objective performance, and the resiliency of speech under cognitive stress in persons with high levels of schizotypy. Copyright © 2014 Elsevier B.V. All rights reserved.

Reduced Structural Connectivity in Frontostriatal White Matter Tracts in the Associative Loop in Schizophrenia.

PubMed

Levitt, James J; Nestor, Paul G; Levin, Laura; Pelavin, Paula; Lin, Pan; Kubicki, Marek; McCarley, Robert W; Shenton, Martha E; Rathi, Yogesh

2017-11-01

The striatum receives segregated and integrative white matter tracts from the cortex facilitating information processing in the cortico-basal ganglia network. The authors examined both types of input tracts in the striatal associative loop in chronic schizophrenia patients and healthy control subjects. Structural and diffusion MRI scans were acquired on a 3-T system from 26 chronic schizophrenia patients and 26 matched healthy control subjects. Using FreeSurfer, the associative cortex was parcellated into ventrolateral prefrontal cortex and dorsolateral prefrontal cortex subregions. The striatum was manually parcellated into its associative and sensorimotor functional subregions. Fractional anisotropy and normalized streamlines, an estimate of fiber counts, were assessed in four frontostriatal tracts (dorsolateral prefrontal cortex-associative striatum, dorsolateral prefrontal cortex-sensorimotor striatum, ventrolateral prefrontal cortex-associative striatum, and ventrolateral prefrontal cortex-sensorimotor striatum). Furthermore, these measures were correlated with a measure of cognitive control, the Trail-Making Test, Part B. Results showed reduced fractional anisotropy and fewer streamlines in chronic schizophrenia patients for all four tracts, both segregated and integrative. Post hoc t tests showed reduced fractional anisotropy in the left ventrolateral prefrontal cortex-associative striatum and left ventrolateral prefrontal cortex-sensorimotor striatum and fewer normalized streamlines in the right dorsolateral prefrontal cortex-sensorimotor striatum and in the left and right ventrolateral prefrontal cortex-sensorimotor striatum in chronic schizophrenia patients. Furthermore, normalized streamlines in the right dorsolateral prefrontal cortex-sensorimotor striatum negatively correlated with Trail-Making Test, Part B, time spent in healthy control subjects but not in chronic schizophrenia patients. These findings demonstrated that structural connectivity is reduced in both segregated and integrative tracts in the striatal associative loop in chronic schizophrenia and that reduced normalized streamlines in the right-hemisphere dorsolateral prefrontal cortex-sensorimotor striatum predicted worse cognitive control in healthy control subjects but not in chronic schizophrenia patients, suggesting a loss of a "normal" brain-behavior correlation in chronic schizophrenia.

Childhood cognitive development in 22q11.2 deletion syndrome: case-control study.

PubMed

Chawner, Samuel J R A; Doherty, Joanne L; Moss, Hayley; Niarchou, Maria; Walters, James T R; Owen, Michael J; van den Bree, Marianne B M

2017-10-01

Background 22q11.2 deletion syndrome (22q11.2DS) is associated with a high risk of childhood as well as adult psychiatric disorders, in particular schizophrenia. Childhood cognitive deterioration in 22q11.2DS has previously been reported, but only in studies lacking a control sample. Aims To compare cognitive trajectories in children with 22q11.2DS and unaffected control siblings. Method A longitudinal study of neurocognitive functioning (IQ, executive function, processing speed and attention) was conducted in children with 22q11.2DS ( n = 75, mean age time 1 ( T 1 ) 9.9, time 2 ( T 2 ) 12.5) and control siblings ( n = 33, mean age T 1 10.6, T 2 13.4). Results Children with 22q11.2DS exhibited deficits in all cognitive domains. However, mean scores did not indicate deterioration. When individual trajectories were examined, some participants showed significant decline over time, but the prevalence was similar for 22q11.2DS and control siblings. Findings are more likely to reflect normal developmental fluctuation than a 22q11.2DS-specific abnormality. Conclusions Childhood cognitive deterioration is not associated with 22q11.2DS. Contrary to previous suggestions, we believe it is premature to recommend repeated monitoring of cognitive function for identifying individual children with 22q11.2DS at high risk of developing schizophrenia. © The Royal College of Psychiatrists 2017.

Aerobic Exercise Improves Mood, Cognition, and Language Function in Parkinson's Disease: Results of a Controlled Study.

PubMed

Altmann, Lori J P; Stegemöller, Elizabeth; Hazamy, Audrey A; Wilson, Jonathan P; Bowers, Dawn; Okun, Michael S; Hass, Chris J

2016-10-01

Parkinson's disease (PD) results in a range of non-motor deficits that can affect mood, cognition, and language, and many of these issues are unresponsive to pharmacological intervention. Aerobic exercise can improve mood and cognition in healthy older adults, although only a few studies have examined exercise effects on these domains in PD. The current study assesses the effects of aerobic exercise on aspects of cognition, mood, and language production in people with PD. This study compares the effects of aerobic exercise to stretch-balance training and a no-contact control group in participants with idiopathic PD. The aerobic and stretch-balance groups trained three times a week for 16 weeks, while controls continued normal activities. Outcome measures included disease severity, mood, cognition (speed of processing, memory, and executive function), and language production (picture descriptions). Cognition and language were assessed in single and dual task conditions. Depressive symptoms increased only in the control group (p<.02). Executive function improved in the aerobic exercise group only in the single task (p=.007) and declined in controls in the dual task. Completeness of picture descriptions improved significantly more in the aerobic group than in the stretch-balance group (p<.02). Aerobic exercise is a viable intervention for PD that can be protective against increased depressive symptoms, and can improve several non-motor domains, including executive dysfunction and related aspects of language production. (JINS, 2016, 22, 878-889).

Functional decline in the elderly with MCI: Cultural adaptation of the ADCS-ADL scale.

PubMed

Cintra, Fabiana Carla Matos da Cunha; Cintra, Marco Túlio Gualberto; Nicolato, Rodrigo; Bertola, Laiss; Ávila, Rafaela Teixeira; Malloy-Diniz, Leandro Fernandes; Moraes, Edgar Nunes; Bicalho, Maria Aparecida Camargos

2017-07-01

Translate, transcultural adaptation and application to Brazilian Portuguese of the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale as a cognitive screening instrument. We applied the back translation added with pretest and bilingual methods. The sample was composed by 95 elderly individuals and their caregivers. Thirty-two (32) participants were diagnosed as mild cognitive impairment (MCI) patients, 33 as Alzheimer's disease (AD) patients and 30 were considered as cognitively normal individuals. There were only little changes on the scale. The Cronbach alpha coefficient was 0.89. The scores were 72.9 for control group, followed by MCI (65.1) and by AD (55.9), with a p-value < 0.001. The ROC curve value was 0.89. We considered a cut point of 72 and we observed a sensibility of 86.2%, specificity of 70%, positive predictive value of 86.2%, negative predictive value of 70%, positive likelihood ratio of 2.9 and negative likelihood ratio of 0.2. ADCS-ADL scale presents satisfactory psychometric properties to discriminate between MCI, AD and normal cognition.

Cognitive stimulation intervention for elders with mild cognitive impairment compared with normal aged subjects: preliminary results.

PubMed

Wenisch, Emilie; Cantegreil-Kallen, Inge; De Rotrou, Jocelyne; Garrigue, Pia; Moulin, Florence; Batouche, Fériel; Richard, Aurore; De Sant'Anna, Martha; Rigaud, Anne Sophie

2007-08-01

Cognitive training programs have been developed for Alzheimer's disease patients and the healthy elderly population. Collective cognitive stimulation programs have been shown to be efficient for subjects with memory complaint. The aim of this study was to evaluate the benefit of such cognitive programs in populations with Mild Cognitive Impairment (MCI). Twelve patients with MCI and twelve cognitively normal elders were administered a cognitive stimulation program. Cognitive performance (Logical Memory, Word paired associative learning task, Trail Making Test, verbal fluency test) were collected before and after the intervention. A gain score [(post-score - pre-score)/ pre-score] was calculated for each variable and compared between groups. The analysis revealed a larger intervention size effect in MCI than in normal elders' performances on the associative learning task (immediate recall: p<0.05, delayed recall: p<0.01). The intervention was more beneficial in improving associative memory abilities in MCI than in normal subjects. At the end of the intervention, the MCI group had lower results than the normal group only for the delayed recall of Logical Memory. Although further studies are needed for more details on the impact of cognitive stimulation programs on MCI patients, this intervention is effective in compensating associative memory difficulties of these patients. Among non-pharmacological interventions, cognitive stimulation therapy is a repeatable and inexpensive collective method that can easily be provided to various populations with the aim of slowing down the rate of decline in elderly persons with cognitive impairment.

Normal Vitamin Levels and Nutritional Indices in Alzheimer's Disease Patients with Mild Cognitive Impairment or Dementia with Normal Body Mass Indexes.

PubMed

Ulstein, Ingun; Bøhmer, Thomas

2017-01-01

Evidence supports an association between vitamin deficiencies and cognitive decline in Alzheimer's disease (AD). If vitamin deficiencies are causative for AD development, they should be detectable during very early stages of AD. Here we investigated nutritional factors among home-living patients diagnosed with mild cognitive impairment (MCI) or mild dementia due to AD, compared to healthy controls. Our study included 73 patients with AD (25 with MCI, 48 with dementia) and 63 cognitively intact age-matched controls. All participants underwent cognitive testing, somatic examination, and measurements of vitamins A, B1, B6, folate, B12, C, D, and E, and F2-α-isoprostane. Results are given as mean (SD). MMSE scores were 29.1 (1.0) for healthy controls, 27.4 (1.8) for patients with MCI, and 24.3 (3.2) for patients with dementia. Vitamin concentrations for the these groups, respectively, were as follows: B1 (nmol/l), 157 (29), 161 (35), and 161 (32); B6 (nmol/l), 57 (63), 71 (104), and 58 (44); folate (mmol/l), 23 (9), 26 (10), and 23 (11); B12 (pmol/l), 407 (159), 427 (116), and 397 (204); C (μmol/l), 63 (18), 61 (16), and 63 (29); A (μmol/l), 2.3 (0.6), 2.2 (0.5), and 2.3 (0.5); E (μmol/l), 36 (6.3), 36 (6.9), and 36 (8.2); 25-OH vitamin D (nmol/l), 65 (18), 61 (19), and 65 (20); and 8-iso-PGFα (pg/ml), 64 (27); 60 (19), and 66 (51). These concentrations did not significantly differ (p≤0.05) between the three groups. Our results do not support the hypothesis that vitamin deficiencies play a causative role in the development of early cognitive impairment.

Cellular, synaptic and biochemical features of resilient cognition in Alzheimer’s disease

PubMed Central

Arnold, Steven. E.; Louneva, Natalia; Cao, Kajia; Wang, Li-San; Han, Li-Ying; Wolk, David A.; Negash, Selamawit; Leurgans, Sue E.; Schneider, Julie A.; Buchman, Aron S.; Wilson, Robert S.; Bennett, David A.

2012-01-01

While neuritic plaques and neurofibrillary tangles in older adults are correlated with cognitive impairment and severity of dementia, it has long been recognized that the relationship is imperfect as some people exhibit normal cognition despite high levels of AD pathology. We compared the cellular, synaptic and biochemical composition of midfrontal cortices in female subjects from the Religious Orders Study who were stratified into three subgroups: 1) pathological AD with normal cognition (“AD-Resilient”), 2) pathological AD with AD-typical dementia (“AD-Dementia)” and 3) pathologically normal with normal cognition (“Normal Comparison”). The AD-Resilient group exhibited preserved densities of synaptophysin-labeled presynaptic terminals and synaptopodin-labeled dendritic spines compared to the AD-Dementia group, and increased densities of GFAP astrocytes compared to both the AD-Dementia and Normal Comparison group. Further, in a discovery antibody microarray protein analysis we identified a number of candidate protein abnormalities that were associated with diagnostic group. These data characterize cellular and synaptic features and identify novel biochemical targets that may be associated with resilient cognitive brain aging in the setting of pathological AD. PMID:22554416

Color discrimination performance in patients with Alzheimer's disease.

PubMed

Salamone, Giovanna; Di Lorenzo, Concetta; Mosti, Serena; Lupo, Federica; Cravello, Luca; Palmer, Katie; Musicco, Massimo; Caltagirone, Carlo

2009-01-01

Visual deficits are frequent in Alzheimer's disease (AD), yet little is known about the nature of these disturbances. The aim of the present study was to investigate color discrimination in patients with AD to determine whether impairment of this visual function is a cognitive or perceptive/sensory disturbance. A cross-sectional clinical study was conducted in a specialized dementia unit on 20 patients with mild/moderate AD and 21 age-matched normal controls. Color discrimination was measured by the Farnsworth-Munsell 100 hue test. Cognitive functioning was measured with the Mini-Mental State Examination (MMSE) and a comprehensive battery of neuropsychological tests. The scores obtained on the color discrimination test were compared between AD patients and controls adjusting for global and domain-specific cognitive performance. Color discrimination performance was inversely related to MMSE score. AD patients had a higher number of errors in color discrimination than controls (mean +/- SD total error score: 442.4 +/- 84.5 vs. 304.1 +/- 45.9). This trend persisted even after adjustment for MMSE score and cognitive performance on specific cognitive domains. A specific reduction of color discrimination capacity is present in AD patients. This deficit does not solely depend upon cognitive impairment, and involvement of the primary visual cortex and/or retinal ganglionar cells may be contributory.

A comparative study on long-term evoked auditory and visual potential responses between Schizophrenic patients and normal subjects

PubMed Central

2011-01-01

Background The electrical signals measuring method is recommended to examine the relationship between neuronal activities and measure with the event related potentials (ERPs) during an auditory and a visual oddball paradigm between schizophrenic patients and normal subjects. The aim of this study is to discriminate the activation changes of different stimulations evoked by auditory and visual ERPs between schizophrenic patients and normal subjects. Methods Forty-three schizophrenic patients were selected as experimental group patients, and 40 healthy subjects with no medical history of any kind of psychiatric diseases, neurological diseases, or drug abuse, were recruited as a control group. Auditory and visual ERPs were studied with an oddball paradigm. All the data were analyzed by SPSS statistical software version 10.0. Results In the comparative study of auditory and visual ERPs between the schizophrenic and healthy patients, P300 amplitude at Fz, Cz, and Pz and N100, N200, and P200 latencies at Fz, Cz, and Pz were shown significantly different. The cognitive processing reflected by the auditory and the visual P300 latency to rare target stimuli was probably an indicator of the cognitive function in schizophrenic patients. Conclusions This study shows the methodology of application of auditory and visual oddball paradigm identifies task-relevant sources of activity and allows separation of regions that have different response properties. Our study indicates that there may be slowness of automatic cognitive processing and controlled cognitive processing of visual ERPs compared to auditory ERPs in schizophrenic patients. The activation changes of visual evoked potentials are more regionally specific than auditory evoked potentials. PMID:21542917

The influence of risperidone on attentional functions in children and adolescents with attention-deficit/hyperactivity disorder and co-morbid disruptive behavior disorder.

PubMed

Günther, Thomas; Herpertz-Dahlmann, Beate; Jolles, Jellemer; Konrad, Kerstin

2006-12-01

This study aims to examine the influence of risperidone on various attentional functions, including intensity and selectivity aspects of attention plus inhibitory control in children with attention deficit/hyperactivity disorder (ADHD) with co-morbid Disruptive Behavior Disorders (DBD) and normal IQ. Children with ADHD and DBD, aged 8-15 years, were treated with risperidone (mean daily dose: 1.5 mg; n = 23) and examined with three attentional paradigms before and after a 4-week treatment period. Age- and IQ-matched normal controls (n = 23) were also tested without medication on the same two occasions. No influence of the medication could be detected for any neuropsychological variable, neither as a positive enhancement nor as adverse side effects. However, clinical symptoms of ADHD and DBD assessed on the IOWA Conners Scale significantly improved after the 4-week treatment period. Divergent behavioral and cognitive effects of risperidone on ADHD symptoms were observed, with a significant reduction in behavioral symptoms, whereas no positive treatment effects were found on laboratory tasks of impulsivity. Thus, the cognitive effects of risperidone seem to differ from the cognitive effects of stimulant treatments in children with ADHD + DBD. However, no negative impact of risperidone was observed on attentional functions either, i.e., there was no slowing of cognitive speed.

Overweight and obese infants present lower cognitive and motor development scores than normal-weight peers.

PubMed

Camargos, Ana Cristina Resende; Mendonça, Vanessa Amaral; Andrade, Camila Alves de; Oliveira, Katherine Simone Caires; Lacerda, Ana Cristina Rodrigues

2016-12-01

Compare the cognitive and motor development in overweight/obese infants versus normal-weight peers and investigate the correlation of body weight, body length and body mass index with cognitive and motor development. We conducted a cross-sectional study with 28 overweight/obese infants and 28 normal-weight peers between 6 and 24 months of age. Both groups were evaluated with cognitive and motor scales of the Bayley-III infant development test. The t-test for independent samples was performed to compare the groups, and the Spearman correlation was used to verify the association between variables. Overweight/obese infants showed lower cognitive and motor composite scores than their normal-weight peers. A significant negative association was found of body weight and body length with cognitive development and of body mass index with motor development. This is the first study that found an effect on both cognitive and motor development in overweight/obese infants when compared with normal-weight peers between 6 and 24 months of age. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reduced prefrontal activation during working and long-term memory tasks and impaired patient-reported cognition among cancer survivors postchemotherapy compared with healthy controls.

PubMed

Wang, Lei; Apple, Alexandra C; Schroeder, Matthew P; Ryals, Anthony J; Voss, Joel L; Gitelman, Darren; Sweet, Jerry J; Butt, Zeeshan A; Cella, David; Wagner, Lynne I

2016-01-15

Patients who receive adjuvant chemotherapy have reported cognitive impairments that may last for years after the completion of treatment. Working memory-related and long-term memory-related changes in this population are not well understood. The objective of this study was to demonstrate that cancer-related cognitive impairments are associated with the under recruitment of brain regions involved in working and recognition memory compared with controls. Oncology patients (n = 15) who were receiving adjuvant chemotherapy and had evidence of cognitive impairment according to neuropsychological testing and self-report and a group of age-matched, education group-matched, cognitively normal control participants (n = 14) underwent functional magnetic resonance imaging. During functional magnetic resonance imaging, participants performed a nonverbal n-back working memory task and a visual recognition task. On the working memory task, when 1-back and 2-back data were averaged and contrasted with 0-back data, significantly reduced activation was observed in the right dorsolateral prefrontal cortex for oncology patients versus controls. On the recognition task, oncology patients displayed decreased activity of the left-middle hippocampus compared with controls. Neuroimaging results were not associated with patient-reported cognition. Decreased recruitment of brain regions associated with the encoding of working memory and recognition memory was observed in the oncology patients compared with the control group. These results suggest that there is a reduction in neural functioning postchemotherapy and corroborate patient-reported cognitive difficulties after cancer treatment, although a direct association was not observed. Cancer 2016;122:258-268. © 2015 American Cancer Society. © 2015 American Cancer Society.

Low Empathy in Deaf and Hard of Hearing (Pre)Adolescents Compared to Normal Hearing Controls

PubMed Central

Netten, Anouk P.; Rieffe, Carolien; Theunissen, Stephanie C. P. M.; Soede, Wim; Dirks, Evelien; Briaire, Jeroen J.; Frijns, Johan H. M.

2015-01-01

Objective The purpose of this study was to examine the level of empathy in deaf and hard of hearing (pre)adolescents compared to normal hearing controls and to define the influence of language and various hearing loss characteristics on the development of empathy. Methods The study group (mean age 11.9 years) consisted of 122 deaf and hard of hearing children (52 children with cochlear implants and 70 children with conventional hearing aids) and 162 normal hearing children. The two groups were compared using self-reports, a parent-report and observation tasks to rate the children’s level of empathy, their attendance to others’ emotions, emotion recognition, and supportive behavior. Results Deaf and hard of hearing children reported lower levels of cognitive empathy and prosocial motivation than normal hearing children, regardless of their type of hearing device. The level of emotion recognition was equal in both groups. During observations, deaf and hard of hearing children showed more attention to the emotion evoking events but less supportive behavior compared to their normal hearing peers. Deaf and hard of hearing children attending mainstream education or using oral language show higher levels of cognitive empathy and prosocial motivation than deaf and hard of hearing children who use sign (supported) language or attend special education. However, they are still outperformed by normal hearing children. Conclusions Deaf and hard of hearing children, especially those in special education, show lower levels of empathy than normal hearing children, which can have consequences for initiating and maintaining relationships. PMID:25906365

MRI-based comparative study of different mild cognitive impairment subtypes: protocol for an observational case-control study.

PubMed

Yu, Yang; Zhao, Weina; Li, Siou; Yin, Changhao

2017-03-08

Amnestic mild cognitive impairment (aMCI) and vascular mild cognitive impairment (VaMCI) comprise the 2 main types of mild cognitive impairment (MCI). The first condition generally progresses to Alzheimer's disease, whereas the second is likely to develop into vascular dementia (VD). The brain structure and function of patients with MCI differ from those of normal elderly individuals. However, whether brain structures or functions differ between these 2 MCI subtypes has not been studied. This study is designed to analyse neuroimages of brain in patients with VaMCI and aMCI using multimodality MRI (structural MRI (sMRI), functional MRI and diffusion tensor imaging (DTI)). In this study, 80 participants diagnosed with aMCI, 80 participants diagnosed with VaMCI, and 80 age-matched, gender-matched and education-matched normal controls (NCs) will be recruited to the Hongqi Hospital of Mudanjiang Medical University, Heilongjiang, China. All participants will undergo neuroimaging and neuropsychological evaluations. The primary outcome measures will be (1) microstructural alterations revealed by multimodal MRIs, including sMRI, resting-state functional MRI and DTI; and (2) a neuropsychological evaluation, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Auditory Verbal Learning Test (AVLT), Memory and Executive Screening (MES), trail making test, Stroop colour naming condition and Clinical Dementia Rating (CDR) scale, to evaluate global cognition, memory function, attention, visuospatial skills, processing speed, executive function and emotion, respectively. NCT02706210; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Cognitive behavior therapy for eating disorders versus normalization of eating behavior.

PubMed

Södersten, P; Bergh, C; Leon, M; Brodin, U; Zandian, M

2017-05-15

We examine the science and evidence supporting cognitive behavior therapy (CBT) for the treatment of bulimia nervosa and other eating disorders. Recent trials focusing on the abnormal cognitive and emotional aspects of bulimia have reported a remission rate of about 45%, and a relapse rate of about 30% within one year. However, an early CBT trial that emphasized the normalization of eating behavior had a better outcome than treatment that focused on cognitive intervention. In support of this finding, another treatment, that restores a normal eating behavior using mealtime feedback, has an estimated remission rate of about 75% and a relapse rate of about 10% over five years. Moreover, when eating behavior was normalized, cognitive and emotional abnormalities were resolved at remission without cognitive therapy. The critical aspect of the CBT treatment of bulimia nervosa therefore may actually have been the normalization of eating behavior. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Sleep deprivation impairs inhibitory control during wakefulness in adult sleepwalkers.

PubMed

Labelle, Marc-Antoine; Dang-Vu, Thien Thanh; Petit, Dominique; Desautels, Alex; Montplaisir, Jacques; Zadra, Antonio

2015-12-01

Sleepwalkers often complain of excessive daytime somnolence. Although excessive daytime somnolence has been associated with cognitive impairment in several sleep disorders, very few data exist concerning sleepwalking. This study aimed to investigate daytime cognitive functioning in adults diagnosed with idiopathic sleepwalking. Fifteen sleepwalkers and 15 matched controls were administered the Continuous Performance Test and Stroop Colour-Word Test in the morning after an overnight polysomnographic assessment. Participants were tested a week later on the same neuropsychological battery, but after 25 h of sleep deprivation, a procedure known to precipitate sleepwalking episodes during subsequent recovery sleep. There were no significant differences between sleepwalkers and controls on any of the cognitive tests administered under normal waking conditions. Testing following sleep deprivation revealed significant impairment in sleepwalkers' executive functions related to inhibitory control, as they made more errors than controls on the Stroop Colour-Word Test and more commission errors on the Continuous Performance Test. Sleepwalkers' scores on measures of executive functions were not associated with self-reported sleepiness or indices of sleep fragmentation from baseline polysomnographic recordings. The results support the idea that sleepwalking involves daytime consequences and suggest that these may also include cognitive impairments in the form of disrupted inhibitory control following sleep deprivation. These disruptions may represent a daytime expression of sleepwalking's pathophysiological mechanisms. © 2015 European Sleep Research Society.

Cognitive symptoms facilitatory for diagnoses in neuropsychiatric disorders: executive functions and locus of control.

PubMed

Archer, Trevor; Kostrzewa, Richard M; Beninger, Richard J; Palomo, Tomas

2008-10-01

Cognitive symptoms, considered in conjunction both with their regional brain and biomarkers as well as affective, attributional and neurodevelopmental components, demonstrate ever-increasing complexity to facilitate conceptualization yet, unavoidably, bedevil diagnosis in neuropsychiatry even before considerations of the enigmatic processes in memory, such as executive function and working memory, are drawn into the myriads of equations that await remedial interpretations. Prefrontal and limbic regions of the brain are involved in a diversity of expressions of cognition, normal or dysfunctional, at synaptic, intracellular and molecular levels that mobilize a concatenation of signaling entities. Serotoninergic neurotransission at prefrontal regions directs cognitive-affective entities that mediate decision-making and goal-directed behaviour. Clinical, non-clinical and basic studies challenge attempts to consolidate the multitude of evidence in order to obtain therapeutic notions to alleviate the disordered status of the diagnosed and yet-to-be diagnosed individuals. Locus of control, a concept of some utility in health-seeking procedures, is examined in three self-report studies from the perspective of a cognitive-emotional situation through observations of ordinary, 'healthy' young and middle-aged individuals, to assess the predictors of internal and external locus of control. A notion based on high level executive functioning in the dorsolateral prefrontal cortex (DLPFC) in individuals characterised by internal locus of control is contrasted with a hypofunctional executive DLPFC, characterising individuals that express an external locus of control, is discussed.

[Dyslexia as a disfunction in successive processing].

PubMed

Pérez-Alvarez, F; Timoneda-Gallart, C

We present a study on reading and writing difficulties after normal instruction during a year. Verifying if these patients showed a specific pattern of PASS (Planning, Attention, Sequential and Simultaneous) cognitive processing; if so, it allows us a rapid diagnosis and a useful cognitive remediation according to the PASS theory of intelligence. Thirty patients were selected from neuropediatric patients because of learning disability. They were selected according to their performance on several tests of phonological aware and a test of writing to discover errors in spelling. Patients with verbal language problems, as in dysphasia, and patients with learning difficulty not determined by reading or writing were ruled out. A control group of 300 scholars was used. The translated DN:CAS battery was administered to the study group and the control group for assessing the PASS cognitive processing. Statistical factorial analysis of the control group was performed as a validity confirmation to discriminate the four PASS cognitive processes. Cluster analysis of the study group was performed to discriminate its homogeneity. Differences between means were tested with the t-Student. The four PASS cognitive processes were identified in the control group. The study group scored less than minus 1 SD in successive processing, the rest of the processes being clearly higher than minus 1 SD, and the mean of study group was inferior to control group (p = 0.001). A kind of dyslexia may be defined by disfunction in PASS successive processing.

Hypothetical Preclinical Alzheimer Disease Groups and Longitudinal Cognitive Change.

PubMed

Soldan, Anja; Pettigrew, Corinne; Cai, Qing; Wang, Mei-Cheng; Moghekar, Abhay R; O'Brien, Richard J; Selnes, Ola A; Albert, Marilyn S

2016-06-01

Clinical trials testing treatments for Alzheimer disease (AD) are increasingly focused on cognitively normal individuals in the preclinical phase of the disease. To optimize observing a treatment effect, such trials need to enroll cognitively normal individuals likely to show cognitive decline over the duration of the trial. To identify which group of cognitively normal individuals shows the greatest cognitive decline over time based on their cerebrospinal fluid biomarker profile. In this cohort study, cognitively normal participants were classified into 1 of the following 4 hypothetical preclinical AD groups using baseline cerebrospinal fluid levels of Aβ and tau or Aβ and phosphorylated tau (p-tau): stage 0 (high Aβ and low tau), stage 1 (low Aβ and low tau), stage 2 (low Aβ and high tau), and suspected non-AD pathology (SNAP) (high Aβ and high tau). The data presented herein were collected between August 1995 and August 2014. An a priori cognitive composite score based on the following 4 tests previously shown to predict progression from normal cognition to symptom onset of mild cognitive impairment or dementia: Paired Associates immediate recall, Logical Memory delayed recall, Boston Naming, and Digit-Symbol Substitution. Linear mixed-effects models were used to compare the cognitive composite scores across the 4 groups over time, adjusting for baseline age, sex, education, and their interactions with time. Two hundred twenty-two cognitively normal participants were included in the analyses (mean follow-up, 11.0 years [range, 0-18.3 years] and mean baseline age, 56.9 years [range, 22.1-85.8 years]). Of these, 102 were stage 0, 46 were stage 1, 28 were stage 2, and 46 were SNAP. Individuals in stage 2 (low Aβ and high tau [or p-tau]) had lower baseline cognitive scores and a greater decline in the cognitive composite score relative to the other 3 groups (β ≤ -0.06 for all and P ≤ .001 for the rate of decline for all). Individuals in stage 0, stage 1, and SNAP did not differ from one another in cognitive performance at baseline or over time (11.0 years) and showed practice-related improvement in performance. The APOE ε4 genotype was not associated with baseline cognitive composite score or the rate of change in the cognitive composite score. These results suggest that, to optimize observing a treatment effect, clinical trials enrolling cognitively normal individuals should selectively recruit participants with abnormal levels of both amyloid and tau (ie, stage 2) because this group would be expected to show the greatest cognitive decline over time if untreated.

Cerebral glucose uptake in patients with chronic mental and cognitive sequelae following a single blunt mild TBI without visible brain lesions.

PubMed

Komura, Akifumi; Kawasaki, Tomohiro; Yamada, Yuichi; Uzuyama, Shiho; Asano, Yoshitaka; Shinoda, Jun

2018-06-19

The aim of this study is to investigate glucose uptake on FDG-PET in patients with chronic mental and cognitive symptoms following a single blunt mild traumatic brain injury (TBI) and without visible brain lesions on CT/MRI. Eighty-nine consecutive patients (mean age 43.8±10.75) who had a single blunt mild TBI from a traffic accident and suffering from chronic mental and cognitive symptoms without visible brain lesions on CT/MRI were enrolled in the study. Patients underwent FDG-PET imaging, and the mean interval between the TBI and FDG-PET was 50.0 months. The Wechsler Adult Intelligence Scale version III testing was performed within one month of the FDG-PET. A control group consisting of 93 healthy adult volunteers (mean age 42.2±14.3 years) also underwent FDG-PET. The glucose uptake pattern from FDG-PET in the patient group was compared to that from normal controls using statistical parametric mapping. Glucose uptake was significantly decreased in the bilateral prefrontal area and significantly increased around the limbic system in the patient group compared to normal controls. This topographical pattern of glucose uptake is different from that reported previously in patients with diffuse axonal injury (DAI), but may be similar to that seen in patients with major depression disorder. These results suggest that the pathological mechanism causing chronic mental and cognitive symptoms in patients with a single blunt mild TBI and without visible brain lesions might be different from that due to primary axonopathy in patients with DAI.

Normal IQ is possible in Smith-Lemli-Opitz syndrome.

PubMed

Eroglu, Yasemen; Nguyen-Driver, Mina; Steiner, Robert D; Merkens, Louise; Merkens, Mark; Roullet, Jean-Baptiste; Elias, Ellen; Sarphare, Geeta; Porter, Forbes D; Li, Chumei; Tierney, Elaine; Nowaczyk, Małgorzata J; Freeman, Kurt A

2017-08-01

Children with Smith-Lemli-Opitz syndrome (SLOS) are typically reported to have moderate to severe intellectual disability. This study aims to determine whether normal cognitive function is possible in this population and to describe clinical, biochemical and molecular characteristics of children with SLOS and normal intelligent quotient (IQ). The study included children with SLOS who underwent cognitive testing in four centers. All children with at least one IQ composite score above 80 were included in the study. Six girls, three boys with SLOS were found to have normal or low-normal IQ in a cohort of 145 children with SLOS. Major/multiple organ anomalies and low serum cholesterol levels were uncommon. No correlation with IQ and genotype was evident and no specific developmental profile were observed. Thus, normal or low-normal cognitive function is possible in SLOS. Further studies are needed to elucidate factors contributing to normal or low-normal cognitive function in children with SLOS. © 2017 Wiley Periodicals, Inc.

Altered Odor-Induced Brain Activity as an Early Manifestation of Cognitive Decline in Patients With Type 2 Diabetes.

PubMed

Zhang, Zhou; Zhang, Bing; Wang, Xin; Zhang, Xin; Yang, Qing X; Qing, Zhao; Lu, Jiaming; Bi, Yan; Zhu, Dalong

2018-05-01

Type 2 diabetes is reported to be associated with olfactory dysfunction and cognitive decline. However, whether and how olfactory neural circuit abnormalities involve cognitive impairment in diabetes remains uncovered. This study thus aimed to investigate olfactory network alterations and the associations of odor-induced brain activity with cognitive and metabolic parameters in type 2 diabetes. Participants with normal cognition, including 51 patients with type 2 diabetes and 41 control subjects without diabetes, underwent detailed cognitive assessment, olfactory behavior tests, and odor-induced functional MRI measurements. Olfactory brain regions showing significantly different activation between the two groups were selected for functional connectivity analysis. Compared with the control subjects, patients with diabetes demonstrated significantly lower olfactory threshold score, decreased brain activation, and disrupted functional connectivity in the olfactory network. Positive associations of the disrupted functional connectivity with decreased neuropsychology test scores and reduced pancreatic function were observed in patients with diabetes. Notably, the association between pancreatic function and executive function was mediated by olfactory behavior and olfactory functional connectivity. Our results suggested the alteration of olfactory network is present before clinically measurable cognitive decrements in type 2 diabetes, bridging the gap between the central olfactory system and cognitive decline in diabetes. © 2018 by the American Diabetes Association.

Distributive justice and cognitive enhancement in lower, normal intelligence.

PubMed

Dunlop, Mikael; Savulescu, Julian

2014-01-01

There exists a significant disparity within society between individuals in terms of intelligence. While intelligence varies naturally throughout society, the extent to which this impacts on the life opportunities it affords to each individual is greatly undervalued. Intelligence appears to have a prominent effect over a broad range of social and economic life outcomes. Many key determinants of well-being correlate highly with the results of IQ tests, and other measures of intelligence, and an IQ of 75 is generally accepted as the most important threshold in modern life. The ability to enhance our cognitive capacities offers an exciting opportunity to correct disabling natural variation and inequality in intelligence. Pharmaceutical cognitive enhancers, such as modafinil and methylphenidate, have been shown to have the capacity to enhance cognition in normal, healthy individuals. Perhaps of most relevance is the presence of an 'inverted U effect' for most pharmaceutical cognitive enhancers, whereby the degree of enhancement increases as intelligence levels deviate further below the mean. Although enhancement, including cognitive enhancement, has been much debated recently, we argue that there are egalitarian reasons to enhance individuals with low but normal intelligence. Under egalitarianism, cognitive enhancement has the potential to reduce opportunity inequality and contribute to relative income and welfare equality in the lower, normal intelligence subgroup. Cognitive enhancement use is justifiable under prioritarianism through various means of distribution; selective access to the lower, normal intelligence subgroup, universal access, or paradoxically through access primarily to the average and above average intelligence subgroups. Similarly, an aggregate increase in social well-being is achieved through similar means of distribution under utilitarianism. In addition, the use of cognitive enhancement within the lower, normal intelligence subgroup negates, or at the very least minimises, several common objections to cognitive enhancement. Subsequently, this paper demonstrates that there is a compelling case for cognitive enhancement use in individuals with lower, normal intelligence.

A STUDY OF COGNITIVE DEVELOPMENT AND PERFORMANCE IN CHILDREN WITH NORMAL AND DEFECTIVE HEARING.

ERIC Educational Resources Information Center

TEMPLIN, MILDRED C.

A COMPARATIVE, LONGITUDINAL STUDY WAS CONDUCTED TO EXAMINE SPECIFIC PERFORMANCE CHARACTERISTICS OF DEAF AND NORMAL CHILDREN ON SELECTED COGNITIVE TASKS. THE SAMPLE, DISTRIBUTED INTO 3 AGE CATEGORIES, CONSISTED OF 72 NORMAL AND 60 DEAF CHILDREN. MEASURES WERE SELECTED TO ASSESS THE PERFORMANCE OF SUBJECTS (1) IN DIFFERENT AREAS OF COGNITION, (2) BY…

Electroencephalogram complexity analysis in children with attention-deficit/hyperactivity disorder during a visual cognitive task.

PubMed

Zarafshan, Hadi; Khaleghi, Ali; Mohammadi, Mohammad Reza; Moeini, Mahdi; Malmir, Nastaran

2016-01-01

The aim of this study was to investigate electroencephalogram (EEG) dynamics using complexity analysis in children with attention-deficit/hyperactivity disorder (ADHD) compared with healthy control children when performing a cognitive task. Thirty 7-12-year-old children meeting Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) criteria for ADHD and 30 healthy control children underwent an EEG evaluation during a cognitive task, and Lempel-Ziv complexity (LZC) values were computed. There were no significant differences between ADHD and control groups on age and gender. The mean LZC of the ADHD children was significantly larger than healthy children over the right anterior and right posterior regions during the cognitive performance. In the ADHD group, complexity of the right hemisphere was higher than that of the left hemisphere, but the complexity of the left hemisphere was higher than that of the right hemisphere in the normal group. Although fronto-striatal dysfunction is considered conclusive evidence for the pathophysiology of ADHD, our arithmetic mental task has provided evidence of structural and functional changes in the posterior regions and probably cerebellum in ADHD.

Puppets, robots, critics, and actors within a taxonomy of attention for developmental disorders

PubMed Central

DENNIS, MAUREEN; SINOPOLI, KATIA J.; FLETCHER, JACK M.; SCHACHAR, RUSSELL

2008-01-01

This review proposes a new taxonomy of automatic and controlled attention. The taxonomy distinguishes among the role of the attendee (puppet and robot, critic and actor), the attention process (stimulus orienting vs. response control), and the attention operation (activation vs. inhibition vs. adjustment), and identifies cognitive phenotypes by which attention is overtly expressed. We apply the taxonomy to four childhood attention disorders: attention deficit hyperactivity disorder, spina bifida meningomyelocele, traumatic brain injury, and acute lymphoblastic leukemia. Variations in attention are related to specific brain regions that support normal attention processes when intact, and produce disordered attention when impaired. The taxonomy explains group differences in behavioral inattention, hyperactivity, and impulsiveness, as well as medication response. We also discuss issues relevant to theories of the cognitive and neural architecture of attention: functional dissociations within and between automatic and controlled attention; the relative importance of type of brain damage and developmental timing to attention profile; cognitive-energetic models of attention and white matter damage; temporal processing deficits, attention deficits and cerebellar damage; and the issue of cognitive phenotypes as candidate endophenotypes. PMID:18764966

Cognitive performance in multiple sclerosis: the contribution of intellectual enrichment and brain MRI measures.

PubMed

Santangelo, Gabriella; Bisecco, Alvino; Trojano, Luigi; Sacco, Rosaria; Siciliano, Mattia; d'Ambrosio, Alessandro; Della Corte, Marida; Lavorgna, Luigi; Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2018-05-26

Cognitive reserve (CR) is a construct that originates from the observation of poor correspondence between brain damage and clinical symptoms. The aim of the study was to investigate the association between cognitive reserve (CR), brain reserve (BR) and cognitive functions and to evaluate whether CR might attenuate/moderate the negative impact of brain atrophy and lesion load on cognitive functions in multiple sclerosis (MS). To achieve these aims, ninety-eight relapsing-remitting MS patients underwent the brief repeatable battery of neuropsychological tests and Stroop test (ST). CR was assessed by vocabulary-based estimate of lifetime intellectual enrichment. All patients underwent a 3T MRI to assess T2-lesion load and atrophy measures, including normalized gray matter and white matter (nWMV) volumes. The BR was evaluated by maximal lifetime brain volume expressed by intracranial volume (ICV). Hierarchical regressions were used to investigate whether higher BR and/or CR is related to better cognitive performances after controlling for potentially confounding factors. The ICV was not associated with any cognitive tests. Intellectual enrichment was positively associated with performance on tests assessing memory, attention and information processing speed, verbal fluency and inhibitory control. Significant relationship between nWMV and ST was moderated by intellectual enrichment. In conclusion, the findings suggested that CR seems to mitigate cognitive dysfunction in MS patients and can reduce the negative impact of brain atrophy on inhibitory control, relevant for integrity of instrumental activities of daily living.

Widespread Volumetric Reductions in Schizophrenia and Schizoaffective Patients Displaying Compromised Cognitive Abilities.

PubMed

Van Rheenen, Tamsyn E; Cropley, Vanessa; Zalesky, Andrew; Bousman, Chad; Wells, Ruth; Bruggemann, Jason; Sundram, Suresh; Weinberg, Danielle; Lenroot, Roshel K; Pereira, Avril; Shannon Weickert, Cynthia; Weickert, Thomas W; Pantelis, Christos

2018-04-06

Progress toward understanding brain mechanisms in psychosis is hampered by failures to account for within-group heterogeneity that exists across neuropsychological domains. We recently identified distinct cognitive subgroups that might assist in identifying more biologically meaningful subtypes of psychosis. In the present study, we examined whether underlying structural brain abnormalities differentiate these cognitively derived subgroups. 1.5T T1 weighted structural scans were acquired for 168 healthy controls and 220 patients with schizophrenia/schizoaffective disorder. Based on previous work, 47 patients were categorized as being cognitively compromised (impaired premorbid and current IQ), 100 as cognitively deteriorated (normal premorbid IQ, impaired current IQ), and 73 as putatively cognitively preserved (premorbid and current IQ within 1 SD of controls). Global, subcortical and cortical volume, thickness, and surface area measures were compared among groups. Whole cortex, subcortical, and regional volume and thickness reductions were evident in all subgroups compared to controls, with the largest effect sizes in the compromised group. This subgroup also showed abnormalities in regions not seen in the other patient groups, including smaller left superior and middle frontal areas, left anterior and inferior temporal areas and right lateral medial and inferior frontal, occipital lobe and superior temporal areas. This pattern of more prominent brain structural abnormalities in the group with the most marked cognitive impairments-both currently and putatively prior to illness onset, is consistent with the concept of schizophrenia as a progressive neurodevelopmental disorder. In this group, neurodevelopmental and neurodegenerative factors may be important for cognitive function.

Attribution of somatic symptoms in hypochondriasis.

PubMed

Neng, Julia M B; Weck, Florian

2015-01-01

The misinterpretation of bodily symptoms as an indicator of a serious illness is a key feature of the criteria and the cognitive-behavioural models of hypochondriasis. Previous research suggests that individuals suffering from health anxiety endorse attributions of physical disease, whereas persons with elevated general anxiety have the tendency to attribute psychological causes to their symptoms. However, whether a somatic attribution style is specific to patients with hypochondriasis, as opposed to those with anxiety disorders, has not yet been investigated and is therefore part of the present study. Fifty patients with hypochondriasis, 50 patients with a primary anxiety disorder and 50 healthy participants were presented with nine common bodily sensations and had to spontaneously attribute possible causes to the symptoms. Patients with hypochondriasis differed from patients with anxiety disorders and healthy controls in giving significantly fewer normalizing explanations, but attributing more often in terms of moderate or serious diseases. Patients with anxiety disorders also made significantly fewer normalizing attributions and more somatic attributions to a severe illness than healthy controls. There were no differences between the groups in the frequency of psychological attributions and somatic attributions concerning mild diseases. The present study demonstrates that hypochondriasis is associated with a disorder-specific attribution style connecting somatic symptoms primarily with moderate and serious diseases. By contrast, normalizing attributions are largely omitted from consideration by patients with hypochondriasis. The findings conform with the cognitive conception of hypochondriasis and support the strategy of modifying symptom attributions, as practiced in cognitive-behavioural therapy. Copyright © 2013 John Wiley & Sons, Ltd.

Cognitive and motor functions of iodine-deficient but euthyroid children in Bangladesh do not benefit from iodized poppy seed oil (Lipiodol).

PubMed

Huda, S N; Grantham-McGregor, S M; Tomkins, A

2001-01-01

Iodine supplementation before pregnancy in iodine-deficient women prevents cretinism and neuromotor deficits in their offspring. It is unclear whether iodine supplementation benefits cognitive function in iodine-deficient school-aged children. We therefore conducted a double-blind, randomized, controlled trial of the effects of iodized poppy seed oil (Lipiodol) on cognitive and motor function and weight gain of iodine-deficient school children. The study was conducted with 305 children in grades 1 and 2 from 10 primary schools in two iodine-deficient areas in Bangladesh. The children were stratified by school and grade and randomly assigned to receive 400 mg of oral Lipiodol or a placebo. All children were given a battery of cognitive and motor function tests and had their weights, serum thyroxine (T4) and thyroid-stimulating hormone (TSH) and urinary iodine levels measured before and 4 mo after the intervention. On enrollment, both groups were moderately iodine deficient (median urinary iodine values: placebo group = 3.3 micromol/L, n = 148; iodine group = 3.1 micromol/L, n = 152; goiter prevalence in both groups >95%). However, their T4 and TSH levels were within the normal range. After 4 mo, there was a significant treatment effect on urinary iodine levels (P < 0.0001), but the levels of the treated group were still below normal (median = 7.9 micromol/L). No significant differences were found in T4 and TSH levels, weight gain, cognitive or motor function. The findings suggest that Lipiodol supplementation in moderately iodine-deficient children with normal T4 levels is unlikely to benefit their cognitive function. However, it remains possible that other iodine preparations may have benefits.

Effects of Beta-Amyloid on Resting State Functional Connectivity Within and Between Networks Reflect Known Patterns of Regional Vulnerability

DOE PAGES

Elman, Jeremy A.; Madison, Cindee M.; Baker, Suzanne L.; ...

2014-11-07

In Alzheimer's disease (AD), Beta-amyloid (Aβ) deposition is one of the hallmarks. However, it is also present in some cognitively normal elderly adults and may represent a preclinical disease state. While AD patients exhibit disrupted functional connectivity (FC) both within and between resting-state networks, studies of preclinical cases have focused primarily on the default mode network (DMN). The extent to which Aβ-related effects occur outside of the DMN and between networks remains unclear. In the present study, we examine how within- and between-network FC are related to both global and regional Aβ deposition as measured by [ 11 C]PIB-PET inmore » 92 cognitively normal older people. We found that within-network FC changes occurred in multiple networks, including the DMN. Changes of between-network FC were also apparent, suggesting that regions maintaining connections to multiple networks may be particularly susceptible to Aβ-induced alterations. Cortical regions showing altered FC clustered in parietal and temporal cortex, areas known to be susceptible to AD pathology. These results likely represent a mix of local network disruption, compensatory reorganization, and impaired control network function. They indicate the presence of Aβ-related dysfunction of neural systems in cognitively normal people well before these areas become hypometabolic with the onset of cognitive decline.« less

The effects of apolipoprotein ε 4 on aging brain in cognitively normal Chinese elderly: a surface-based morphometry study.

PubMed

Lu, Hanna; Ma, Suk Ling; Chan, Sandra Sau Man; Lam, Linda Chiu Wa

2016-09-01

Default mode network (DMN) has been reported to be susceptible to APOE ε 4 genotype. However, the APOE ε 4-related brain changes in young carriers are different from the ones in elderly carriers. The current study aimed to evaluate the cortical morphometry of DMN subregions in cognitively normal elderly with APOE ε 4. 11 cognitively normal senior APOE ε 4 carriers and 27 matched healthy controls (HC) participated the neuropsychological tests, genotyping, and magnetic resonance imaging (MRI) scanning. Voxel-based morphometry (VBM) analysis was used to assess the global volumetric changes. Surface-based morphometry (SBM) analysis was performed to measure regional gray matter volume (GMV) and gray matter thickness (GMT). Advancing age was associated with decreased GMV of DMN subregions. Compared to HC, APOE ε 4 carriers presented cortical atrophy in right cingulate gyrus (R_CG) (GMV: APOE carriers: 8475.23 ± 1940.73 mm3, HC: 9727.34 ± 1311.57 mm3, t = 2.314, p = 0.026, corrected) and left insular (GMT: APOE ε 4 carriers: 3.83 ± 0.37 mm, HC: 4.05 ± 0.25 mm, t = 2.197, p = 0.033, corrected). Our results highlight the difference between different cortical measures and suggest that the cortical reduction of CG and insular maybe a potential neuroimaging marker for APOE 4 ε senior carriers, even in the context of relatively intact cognition.

Pericortical Enhancement on Delayed Postgadolinium Fluid-Attenuated Inversion Recovery Images in Normal Aging, Mild Cognitive Impairment, and Alzheimer Disease.

PubMed

Freeze, W M; Schnerr, R S; Palm, W M; Jansen, J F; Jacobs, H I; Hoff, E I; Verhey, F R; Backes, W H

2017-09-01

Breakdown of BBB integrity occurs in dementia and may lead to neurodegeneration and cognitive decline. We assessed whether extravasation of gadolinium chelate could be visualized on delayed postcontrast FLAIR images in older individuals with and without cognitive impairment. Seventy-four individuals participated in this study (15 with Alzheimer disease, 33 with mild cognitive impairment, and 26 with normal cognition). We assessed the appearance of pericortical enhancement after contrast administration, MR imaging markers of cerebrovascular damage, and medial temporal lobe atrophy. Three participants who were positive for pericortical enhancement (1 with normal cognition and 2 with mild cognitive impairment) were followed up for approximately 2 years. In vitro experiments with a range of gadolinium concentrations served to elucidate the mechanisms underlying the postcontrast FLAIR signals. Postcontrast pericortical enhancement was observed in 21 participants (28%), including 6 individuals with Alzheimer disease (40%), 10 with mild cognitive impairment (30%), and 5 with normal cognition (19%). Pericortical enhancement was positively associated with age ( P < .02) and ischemic stroke ( P < .05), but not with cognitive status ( P = .3). Foci with enhanced signal remained stable across time in all follow-up cases. The in vitro measurements confirmed that FLAIR imaging is highly sensitive for the detection of low gadolinium concentrations in CSF, but not in cerebral tissue. Postcontrast pericortical enhancement on FLAIR images occurs in older individuals with normal cognition, mild cognitive impairment, and dementia. It may represent chronic focal superficial BBB leakage. Future longitudinal studies are needed to determine its clinical significance. © 2017 by American Journal of Neuroradiology.

Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions.

PubMed

Biessels, Geert Jan; Strachan, Mark W J; Visseren, Frank L J; Kappelle, L Jaap; Whitmer, Rachel A

2014-03-01

Type 2 diabetes is associated with dementia, and also with more slight cognitive decrements. In this Review we discuss trajectories from normal cognition to dementia in people with type 2 diabetes, and explore opportunities for treatment. Slight diabetes-associated cognitive decrements and dementia affect different age groups and show a different evolution. These cognitive entities should therefore not be regarded as a continuum, although their effects might be additive. Vascular damage is a key underlying process in both entities. Glucose-mediated processes and other metabolic disturbances might also have a role. No treatment has been established, but management of vascular risk factors and optimisation of glycaemic control could have therapeutic benefit. We identify possible opportunities for intervention to improve cognitive outcomes in people with type 2 diabetes, and suggest how treatment can be tailored to individual risk profiles and comorbidities. Copyright © 2014 Elsevier Ltd. All rights reserved.

A cognitive account of belief: a tentative road map

PubMed Central

Connors, Michael H.; Halligan, Peter W.

2015-01-01

Over the past decades, delusions have become the subject of growing and productive research spanning clinical and cognitive neurosciences. Despite this, the nature of belief, which underpins the construct of delusions, has received little formal investigation. No account of delusions, however, would be complete without a cognitive level analysis of belief per se. One reason for this neglect is the assumption that, unlike more established and accessible modular psychological process (e.g., vision, audition, face-recognition, language-processing, and motor-control systems), beliefs comprise more distributed and therefore less accessible central cognitive processes. In this paper, we suggest some defining characteristics and functions of beliefs. Working back from cognitive accounts of delusions, we consider potential candidate cognitive processes that may be involved in normal belief formation. Finally, we advance a multistage account of the belief process that could provide the basis for a more comprehensive model of belief. PMID:25741291

Plasma apolipoprotein levels are associated with cognitive status and decline in a community cohort of older individuals.

PubMed

Song, Fei; Poljak, Anne; Crawford, John; Kochan, Nicole A; Wen, Wei; Cameron, Barbara; Lux, Ora; Brodaty, Henry; Mather, Karen; Smythe, George A; Sachdev, Perminder S

2012-01-01

Apolipoproteins have recently been implicated in the etiology of Alzheimer's disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals.

Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

PubMed Central

Song, Fei; Poljak, Anne; Crawford, John; Kochan, Nicole A.; Wen, Wei; Cameron, Barbara; Lux, Ora; Brodaty, Henry; Mather, Karen; Smythe, George A.; Sachdev, Perminder S.

2012-01-01

Objectives Apolipoproteins have recently been implicated in the etiology of Alzheimer’s disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort. Methods 664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique. Results At Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years. Conclusions Elderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals. PMID:22701550

Impact of monetary incentives on cognitive performance and error monitoring following sleep deprivation.

PubMed

Hsieh, Shulan; Li, Tzu-Hsien; Tsai, Ling-Ling

2010-04-01

To examine whether monetary incentives attenuate the negative effects of sleep deprivation on cognitive performance in a flanker task that requires higher-level cognitive-control processes, including error monitoring. Twenty-four healthy adults aged 18 to 23 years were randomly divided into 2 subject groups: one received and the other did not receive monetary incentives for performance accuracy. Both subject groups performed a flanker task and underwent electroencephalographic recordings for event-related brain potentials after normal sleep and after 1 night of total sleep deprivation in a within-subject, counterbalanced, repeated-measures study design. Monetary incentives significantly enhanced the response accuracy and reaction time variability under both normal sleep and sleep-deprived conditions, and they reduced the effects of sleep deprivation on the subjective effort level, the amplitude of the error-related negativity (an error-related event-related potential component), and the latency of the P300 (an event-related potential variable related to attention processes). However, monetary incentives could not attenuate the effects of sleep deprivation on any measures of behavior performance, such as the response accuracy, reaction time variability, or posterror accuracy adjustments; nor could they reduce the effects of sleep deprivation on the amplitude of the Pe, another error-related event-related potential component. This study shows that motivation incentives selectively reduce the effects of total sleep deprivation on some brain activities, but they cannot attenuate the effects of sleep deprivation on performance decrements in tasks that require high-level cognitive-control processes. Thus, monetary incentives and sleep deprivation may act through both common and different mechanisms to affect cognitive performance.

Impaired glucose tolerance in first-episode drug-naïve patients with schizophrenia: relationships with clinical phenotypes and cognitive deficits.

PubMed

Chen, D C; Du, X D; Yin, G Z; Yang, K B; Nie, Y; Wang, N; Li, Y L; Xiu, M H; He, S C; Yang, F D; Cho, R Y; Kosten, T R; Soares, J C; Zhao, J P; Zhang, X Y

2016-11-01

Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia. A total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids. They were also compared using a 75 g oral glucose tolerance test and the homeostasis model assessment of insulin resistance (HOMA-IR). Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Of the patients, 24.5% had IGT compared with none of the controls, and they also had significantly higher levels of fasting blood glucose and 2-h glucose after an oral glucose load, and were more insulin resistant. Compared with those patients with normal glucose tolerance, the IGT patients were older, had a later age of onset, higher waist or hip circumference and body mass index, higher levels of low-density lipoprotein and triglycerides and higher insulin resistance. Furthermore, IGT patients had higher PANSS total and negative symptom subscale scores, but no greater cognitive impairment except on the emotional intelligence index of the MCCB. IGT occurs with greater frequency in FEDN schizophrenia, and shows association with demographic and anthropometric parameters, as well as with clinical symptoms but minimally with cognitive impairment during the early course of the disorder.

EEG mapping and low-resolution brain electromagnetic tomography (LORETA) in diagnosis and therapy of psychiatric disorders: evidence for a key-lock principle.

PubMed

Saletu, Bernd; Anderer, Peter; Saletu-Zyhlarz, Gerda M; Pascual-Marqui, Roberto D

2005-04-01

Different psychiatric disorders, such as schizophrenia with predominantly positive and negative symptomatology, major depression, generalized anxiety disorder, agoraphobia, obsessive-compulsive disorder, multi-infarct dementia, senile dementia of the Alzheimer type and alcohol dependence, show EEG maps that differ statistically both from each other and from normal controls. Representative drugs of the main psychopharmacological classes, such as sedative and non-sedative neuroleptics and antidepressants, tranquilizers, hypnotics, psychostimulants and cognition-enhancing drugs, induce significant and typical changes to normal human brain function, which in many variables are opposite to the above-mentioned differences between psychiatric patients and normal controls. Thus, by considering these differences between psychotropic drugs and placebo in normal subjects, as well as between mental disorder patients and normal controls, it may be possible to choose the optimum drug for a specific patient according to a key-lock principle, since the drug should normalize the deviant brain function. This is supported by 3-dimensional low-resolution brain electromagnetic tomography (LORETA), which identifies regions within the brain that are affected by psychiatric disorders and psychopharmacological substances.

[Psychological research on the cognitive aspect of emotional processes in schizophrenia patients].

PubMed

Kurek, N S

1988-01-01

Cognitive aspects of emotionality were psychologically investigated in 250 patients with continuous and paroxysmal progredient schizophrenia and differently pronounced defect. The control group consisted of 100 normal subjects. A set of 7 techniques was applied. In cases of the patient's defect accentuated, cognitive emotional disorder was marked with the emotions and emotiogenic situations underestimation in dealing with other people and cognitive activities. This underestimation was not a uniform one concerning to a larger extent the strong emotions in other subjects, patients' own positive emotions, success in individual problem solving and degree of success in cooperative performance. Weak emotions, negative ones and failure situations were underestimated to a lesser degree, as was the success rating in competitive paradigms.

Molecular networks and the evolution of human cognitive specializations.

PubMed

Fontenot, Miles; Konopka, Genevieve

2014-12-01

Inroads into elucidating the origins of human cognitive specializations have taken many forms, including genetic, genomic, anatomical, and behavioral assays that typically compare humans to non-human primates. While the integration of all of these approaches is essential for ultimately understanding human cognition, here, we review the usefulness of coexpression network analysis for specifically addressing this question. An increasing number of studies have incorporated coexpression networks into brain expression studies comparing species, disease versus control tissue, brain regions, or developmental time periods. A clearer picture has emerged of the key genes driving brain evolution, as well as the developmental and regional contributions of gene expression patterns important for normal brain development and those misregulated in cognitive diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Is emotional memory enhancement preserved in amnestic mild cognitive impairment? Evidence from separating recollection and familiarity.

PubMed

Wang, Pengyun; Li, Juan; Li, Huijie; Li, Bing; Jiang, Yang; Bao, Feng; Zhang, Shouzi

2013-11-01

This study investigated whether the observed absence of emotional memory enhancement in recognition tasks in patients with amnestic mild cognitive impairment (aMCI) could be related to their greater proportion of familiarity-based responses for all stimuli, and whether recognition tests with emotional items had better discriminative power for aMCI patients than those with neutral items. In total, 31 aMCI patients and 30 healthy older adults participated in a recognition test followed by remember/know judgments. Positive, neutral, and negative faces were used as stimuli. For overall recognition performance, emotional memory enhancement was found only in healthy controls; they remembered more negative and positive stimuli than neutral ones. For "remember" responses, we found equivalent emotional memory enhancement in both groups, though a greater proportion of "remember" responses was observed in normal controls. For "know" responses, aMCI patients presented a larger proportion than normal controls did, and their "know" responses were not affected by emotion. A negative correlation was found between emotional enhancement effect and the memory performance related to "know" responses. In addition, receiver operating characteristic curve analysis revealed higher diagnostic accuracy for recognition test with emotional stimuli than with neutral stimuli. The present results implied that the absence of the emotional memory enhancement effect in aMCI patients might be related to their tendency to rely more on familiarity-based "know" responses for all stimuli. Furthermore, recognition memory tests using emotional stimuli may be better able than neutral stimuli to differentiate people with aMCI from cognitively normal older adults. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Assessing Mild Cognitive Impairment among Older African Americans

PubMed Central

Gamaldo, Alyssa A.; Allaire, Jason C.; Sims, Regina C.; Whitfield, Keith E.

2009-01-01

OBJECTIVES To examine the frequency of MCI in African American older adults. The study also plans to explore the specific cognitive domains of impairment as well as whether there are differences in demographics, health, and cognitive performance between MCI and normal participants. DESIGN Cross-sectional. SETTING Independent-living sample of urban dwelling elders in Baltimore, Maryland. PARTICIPANTS The sample consisted of 554 subjects ranging in age from 50 to 95 (mean = 68.79 ± 9.60). MEASUREMENTS Socio-demographics and health were assessed. Several cognitive measures were administered to assess inductive reasoning, declarative memory, perceptual speed, working memory, executive functioning, language, global cognitive functioning. RESULTS Approximately 22% of participants were considered MCI (i.e. 18% non-amnestic vs. 4% amnestic). A majority of the non-amnestic MCI participants had impairment in one cognitive domain, particularly language and executive function. Individuals classified as non-amnestic MCI were significantly older and had more years of education than normal individuals. The MCI groups were not significantly different than cognitively normal individuals on health factors. Individuals classified as MCI performed significantly worse on global cognitive measures as well as across specific cognitive domains than cognitively normal individuals. CONCLUSION This study demonstrates that impairment in a non-memory domain may be an early indicator of cognitive impairment, particularly among African Americans. PMID:20069588

Sex differences in obesity and cognitive function in a cognitively normal aging Chinese Han population.

PubMed

Li, Wei; Qiu, Qi; Sun, Lin; Yue, Ling; Wang, Tao; Li, Xia; Xiao, Shifu

2017-01-01

Sex differences in Alzheimer's disease and mild cognitive impairment have been well recognized. However, sex differences in cognitive function and obesity in cognitively normal aging Chinese Han population have not attracted much attention. The aim of this study was to investigate the relationship between sex, obesity, and cognitive function in an elderly Chinese population with normal cognitive function. A total of 228 cognitively normal aging participants (males/females =93/135) entered this study. Their general demographic information (sex, age, and education) was collected by standardized questionnaire. Apolipoprotein E (APOE) genotype and serum lipid levels were measured. The Montreal Cognitive Assessment (MoCA) was used to assess participants' cognitive function. The prevalence of obesity in elderly women (18/133, 13.5%) was significantly higher than that in men (5/92, 5.4%, P =0.009). Regression analyses showed that obesity was associated with drinking alcohol (OR =13.695, P =0.045) and triglyceride (OR =1.436, P =0.048) in women and limited to low-density lipoprotein (OR =11.829, P =0.023) in men. Women performed worse on the naming score for MoCA than men ( P <0.01). Stepwise linear regression analysis showed that education ( t =3.689, P <0.001) and smoking ( t =2.031, P =0.045) were related to the score of naming in female, while high-density lipoprotein ( t =-2.077, P =0.041) was related to the score of naming in male; however, no correlation was found between body mass index and cognitive function in both male and female ( P >0.05). Our finding suggests that there are significant sex differences in obesity and specific cognitive domains in aging Chinese Han population with normal cognitive function.

The Role of Episodic Memory in Controlled Evaluative Judgments about Attitudes: An Event-Related Potential Study

ERIC Educational Resources Information Center

Johnson, Ray, Jr.; Simon, Elizabeth J.; Henkell, Heather; Zhu, John

2011-01-01

Event-related potentials (ERPs) are unique in their ability to provide information about the timing of activity in the neural networks that perform complex cognitive processes. Given the dearth of extant data from normal controls on the question of whether attitude representations are stored in episodic or semantic memory, the goal here was to…

Inhibitory Control in Mind and Brain: An Interactive Race Model of Countermanding Saccades

ERIC Educational Resources Information Center

Boucher, Leanne; Palmeri, Thomas J.; Logan, Gordon D.; Schall, Jeffrey D.

2007-01-01

The stop-signal task has been used to study normal cognitive control and clinical dysfunction. Its utility is derived from a race model that accounts for performance and provides an estimate of the time it takes to stop a movement. This model posits a race between go and stop processes with stochastically independent finish times. However,…

Divided attention deficits in patients with chronic fatigue syndrome.

PubMed

Ross, S; Fantie, B; Straus, S F; Grafman, J

2001-01-01

Chronic fatigue syndrome (CFS) patients and controls were compared on a variety of mood state, personality, and neuropsychological measures, including memory, word finding, and attentional tasks that required participants to focus, sustain, or divide their attention, or to perform a combination of these functions. CFS patients demonstrated a selective deficit on 3 measures of divided attention. Their performance on the other neuropsychological tests of intelligence, fluency, and memory was no different than that of normal controls despite their reports of generally diminished cognitive capacity. There was an inverse relation between CFS patient fatigue severity and performance on 1 of the divided attention measures. Given these findings, it is probable that CFS patients will report more cognitive difficulties in real-life situations that cause them to divide their effort or rapidly reallocate cognitive resources between 2 response channels (vision and audition).

Correlation between Cognition and Function across the Spectrum of Alzheimer's Disease.

PubMed

Liu-Seifert, H; Siemers, E; Selzler, K; Sundell, K; Aisen, P; Cummings, J; Raskin, J; Mohs, R

2016-01-01

Both cognitive and functional deterioration are characteristic of the clinical progression of Alzheimer's disease (AD). To systematically assess correlations between widely used measures of cognition and function across the spectrum of AD. Spearman rank correlations were calculated for cognitive and functional measures across datasets from various AD patient populations. Post-hoc analysis from existing databases. Pooled data from placebo-treated patients with mild (MMSE score ≥20 and ≤26) and moderate (MMSE score ≥16 and ≤19) AD dementia from two Phase 3 solanezumab (EXPEDITION/2) and two semagecesatat (IDENTITY/2) studies and normal, late mild cognitive impairment (LMCI) and mild AD patients from the Alzheimer's Disease Neuroimaging Initiative 2-Grand Opportunity (ADNI-2/GO). Intervention (if any): Placebo (EXPEDITION/2 and IDENTITY/2 subjects). Cognitive and functional abilities were measured in all datasets. Data were collected at baseline and every three months for 18 months in EXPEDITION and IDENTITY studies; and at baseline, 6, 12, and 24 months in the ADNI dataset. The relationship of cognition and function became stronger over time as AD patients progressed from preclinical to moderate dementia disease stages, with the magnitude of correlations dependent on disease stage and the complexity of functional task. The correlations were minimal in the normal control population, but became stronger with disease progression. This analysis found that measures of cognition and function become more strongly correlated with disease progression from preclinical to moderate dementia across multiple datasets. These findings improve the understanding of the relationship between cognitive and functional clinical measures during the course of AD progression and how cognition and function measures relate to each other in AD clinical trials.

Alzheimer Disease Biomarkers, Attentional Control and Semantic Memory Retrieval: Synergistic and Mediational Effects of Biomarkers on a Sensitive Cognitive Measure

PubMed Central

Aschenbrenner, Andrew J.; Balota, David A.; Tse, Chi-Shing; Fagan, Anne M.; Holtzman, David M.; Benzinger, Tammie L.S.; Morris, John C.

2014-01-01

Objective Past studies have shown that measures of attentional control and semantic memory are sensitive markers of Alzheimer disease (AD). The effects of established biomarkers of AD (cerebrospinal fluid tau and amyloid-beta42, PET-PIB, and APOE genotype) on concurrent cognitive performance in cognitively normal individuals have been mixed. The present study examined the utility of combining attentional control with semantic retrieval as a sensitive correlate of AD biomarkers and used mediation analyses to examine possible mechanisms by which the biomarkers influence cognition. Method 363 participants completed a category verification task (CVT) and 113 of them concurrently underwent biomarker assessments. On each trial, participants viewed a category (e.g. “unit of time”) and verified whether a subsequent target item was an exemplar of the category (“hour”) or not (“clock”). Importantly, the nonmembers of the category were associatively related to the category (e.g., “clock” is not “a unit of time”, but is highly related), and demanded attentional control to reject. Results Accuracy to the foil items was the strongest discriminator between healthy aging and very mild symptomatic AD. CSF biomarkers had independent yet synergistic influence on CVT performance in cognitively healthy older adults. Furthermore, the influence of the biomarkers and APOE genotype was mediated primarily through increased levels of PIB. Conclusion The combined influence of attentional control with semantic retrieval is a marker of symptomatic AD and a sensitive correlate of established biomarkers for AD risk in cognitively healthy participants. The biomarkers influenced cognition primarily through increased levels of amyloid in the brain. PMID:25222200

Motivational Influences on Response Inhibition Measures

ERIC Educational Resources Information Center

Leotti, Lauren A.; Wager, Tor D.

2010-01-01

Psychological research has placed great emphasis on inhibitory control due to its integral role in normal cognition and clinical disorders. The stop-signal task and associated measure--stop-signal reaction time (SSRT)--provides a well-established paradigm for measuring response inhibition. However, motivational influences on stop-signal…

Conflict and performance monitoring throughout the lifespan: An event-related potential (ERP) and temporospatial component analysis.

PubMed

Clawson, Ann; Clayson, Peter E; Keith, Cierra M; Catron, Christina; Larson, Michael J

2017-03-01

Cognitive control includes higher-level cognitive processes used to evaluate environmental conflict. Given the importance of cognitive control in regulating behavior, understanding the developmental course of these processes may contribute to a greater understanding of normal and abnormal development. We examined behavioral (response times [RTs], error rates) and event-related potential data (N2, error-related negativity [ERN], correct-response negativity [CRN], error positivity [Pe]) during a flanker task in cross-sectional groups of 45 youth (ages 8-18), 52 younger adults (ages 20-28), and 58 older adults (ages 56-91). Younger adults displayed the most efficient processing, including significantly reduced CRN and N2 amplitude, increased Pe amplitude, and significantly better task performance than youth or older adults (e.g., faster RTs, fewer errors). Youth displayed larger CRN and N2, attenuated Pe, and significantly worse task performance than younger adults. Older adults fell either between youth and younger adults (e.g., CRN amplitudes, N2 amplitudes) or displayed neural and behavioral performance that was similar to youth (e.g., Pe amplitudes, error rates). These findings point to underdeveloped neural and cognitive processes early in life and reduced efficiency in older adulthood, contributing to poor implementation and modulation of cognitive control in response to conflict. Thus, cognitive control processing appears to reach peak performance and efficiency in younger adulthood, marked by improved task performance with less neural activation. Copyright © 2017 Elsevier B.V. All rights reserved.

Kinetics of the Tau PET Tracer 18F-AV-1451 (T807) in Subjects with Normal Cognitive Function, Mild Cognitive Impairment, and Alzheimer Disease.

PubMed

Shcherbinin, Sergey; Schwarz, Adam J; Joshi, Abhinay; Navitsky, Michael; Flitter, Matthew; Shankle, William R; Devous, Michael D; Mintun, Mark A

2016-10-01

We report kinetic modeling results of dynamic acquisition data from 0 to 100 min after injection with the tau PET tracer 18 F-AV-1451 in 19 subjects. Subjects were clinically diagnosed as 4 young cognitively normal, 5 old cognitively normal, 5 mild cognitive impairment, and 5 Alzheimer disease (AD). Kinetic modeling was performed using Logan graphical analysis with the cerebellum crus as a reference region. Voxelwise binding potential ([Formula: see text]) and SUV ratio ([Formula: see text]) images were compared. In AD subjects, slower and spatially nonuniform clearance from cortical regions was observed as compared with the controls, which led to focal uptake and elevated retention in the imaging data from 80 to 100 min after injection. BP from the dynamic data from 0 to 100 min correlated strongly (R 2 > 0.86) with corresponding regional [Formula: see text] values. In the putamen, the observed kinetics (positive [Formula: see text] at the tracer delivery stage and plateauing time-SUVR curves for all diagnostic categories) may suggest either additional off-target binding or a second binding site with different kinetics. The kinetics of the 18 F-AV-1451 tracer in cortical areas, as examined in this small group of subjects, differed by diagnostic stage. A delayed 80- to 100-min scan provided a reasonable substitute for a dynamic 0- to 100-min acquisition for cortical regions although other windows (e.g., 75-105 min) may be useful to evaluate. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Memory Binding Test Predicts Incident Amnestic Mild Cognitive Impairment.

PubMed

Mowrey, Wenzhu B; Lipton, Richard B; Katz, Mindy J; Ramratan, Wendy S; Loewenstein, David A; Zimmerman, Molly E; Buschke, Herman

2016-07-14

The Memory Binding Test (MBT), previously known as Memory Capacity Test, has demonstrated discriminative validity for distinguishing persons with amnestic mild cognitive impairment (aMCI) and dementia from cognitively normal elderly. We aimed to assess the predictive validity of the MBT for incident aMCI. In a longitudinal, community-based study of adults aged 70+, we administered the MBT to 246 cognitively normal elderly adults at baseline and followed them annually. Based on previous work, a subtle reduction in memory binding at baseline was defined by a Total Items in the Paired (TIP) condition score of ≤22 on the MBT. Cox proportional hazards models were used to assess the predictive validity of the MBT for incident aMCI accounting for the effects of covariates. The hazard ratio of incident aMCI was also assessed for different prediction time windows ranging from 4 to 7 years of follow-up, separately. Among 246 controls who were cognitively normal at baseline, 48 developed incident aMCI during follow-up. A baseline MBT reduction was associated with an increased risk for developing incident aMCI (hazard ratio (HR) = 2.44, 95% confidence interval: 1.30-4.56, p = 0.005). When varying the prediction window from 4-7 years, the MBT reduction remained significant for predicting incident aMCI (HR range: 2.33-3.12, p: 0.0007-0.04). Persons with poor performance on the MBT are at significantly greater risk for developing incident aMCI. High hazard ratios up to seven years of follow-up suggest that the MBT is sensitive to early disease.

Elevated cerebral glutamate and myo-inositol levels in cognitively normal middle-aged adults with metabolic syndrome.

PubMed

Haley, Andreana P; Gonzales, Mitzi M; Tarumi, Takashi; Miles, Steven C; Goudarzi, Katayoon; Tanaka, Hirofumi

2010-12-01

Metabolic syndrome (MetS) is a cluster of risk factors associated with significant cardiovascular morbidity and mortality and diminished cognitive function. Given that the cerebral mechanisms mediating the relationship between peripheral metabolic dysfunction and cognitive impairment are unknown, we set out to examine the relationship between diagnosis of metabolic syndrome and cerebral metabolism. Thirteen participants with MetS (aged 48 ± 6 years) and 25 healthy adults (aged 51 ± 6 years) underwent neuropsychological assessment, health screen and proton magnetic resonance spectroscopy ((1)H MRS) examining N-acetyl-aspartate (NAA), myo-inositol (mI), creatine (Cr), choline (Cho), and glutamate (Glu) concentrations in occipitoparietal grey matter. Cerebral metabolite ratios (NAA/Cr, Cho/Cr, mI/Cr, and Glu/Cr) of participants with MetS, defined by the International Diabetes Federation criteria, were compared with controls matched for age, education, cognition, and emotional function. There were no significant differences in global cognitive function, memory, language, and psychomotor performance between the groups. Diagnosis of MetS was associated with significantly higher mI/Cr (F(1,36) = 5.02, p = 0.031) and Glu/Cr ratio (F(1,36) = 4.81, p = 0.035). Even in cognitively normal adults, MetS is related to cerebral metabolic disturbances, a possible indication of early brain vulnerability. Longitudinal studies that begin in mid-life can help validate the use of (1)H MRS markers as indicators of long-term cognitive outcomes.

[Subjective cognitive impairment and Alzheimer's disease: a two year follow up of 51 subjects during two years].

PubMed

Sambuchi, Nathalie; Muraccioli, Isabelle; Alescio-Lautier, Béatrice; Paban, Véronique; Sambuc, Roland; Jouve, Élisabeth; Geda, Yonas Endale; Petersen, Ronald Karl; Michel, Bernard François

2015-12-01

Subjective cognitive impairment (SCI) is defined by a state of subjective complaint, without objective cognitive deterioration. Amnestic mild cognitive impairment (A-MCI), which characterizes a syndrome between normal cognitive aging and early Alzheimer's disease (E-AD), is preceded by A-MCI from many years. SCI expresses a metacognitive impairment. A cohort of 51 subjects [7 normal controls (NC), 28 SCI, 12 A-MCI and 5 E-AD] was followed up during 24 months, with a neuropsychological evaluation each 6 months during 1 year (V1, V2, V3), then 1 year later (V4). Among the 28 SCI, 6 converted to A-MCI at V4 (21.42%), 1 to A-MCI-A at V3, then to E-AD at V4. These results suggest a continuum from SCI to A-MCI, and E-AD. Progressive SCI differed from non-progressive SCI on verbal episodic memory and executive functions tests at the initial examination. MRI showed anterior cingular atrophy in all SCI patients but hippocampal atrophy was only observed in 20 patients. Our results suggest that metacognition impairment is the expression of a dysfunction in the anterior pre-frontal cortex, in correlation with a syndrome of hyper-attention.

Influence of population versus convenience sampling on sample characteristics in studies of cognitive aging.

PubMed

Brodaty, Henry; Mothakunnel, Annu; de Vel-Palumbo, Melissa; Ames, David; Ellis, Kathryn A; Reppermund, Simone; Kochan, Nicole A; Savage, Greg; Trollor, Julian N; Crawford, John; Sachdev, Perminder S

2014-01-01

We examined whether differences in findings of studies examining mild cognitive impairment (MCI) were associated with recruitment methods by comparing sample characteristics in two contemporaneous Australian studies, using population-based and convenience sampling. The Sydney Memory and Aging Study invited participants randomly from the electoral roll in defined geographic areas in Sydney. The Australian Imaging, Biomarkers and Lifestyle Study of Ageing recruited cognitively normal (CN) individuals via media appeals and MCI participants via referrals from clinicians in Melbourne and Perth. Demographic and cognitive variables were harmonized, and similar diagnostic criteria were applied to both samples retrospectively. CN participants recruited via convenience sampling were younger, better educated, more likely to be married and have a family history of dementia, and performed better cognitively than those recruited via population-based sampling. MCI participants recruited via population-based sampling had better memory performance and were less likely to carry the apolipoprotein E ε4 allele than clinically referred participants but did not differ on other demographic variables. A convenience sample of normal controls is likely to be younger and better functioning and that of an MCI group likely to perform worse than a purportedly random sample. Sampling bias should be considered when interpreting findings. Copyright © 2014 Elsevier Inc. All rights reserved.

Breakfast improves cognitive function in cirrhotic patients with cognitive impairment.

PubMed

Vaisman, Nachum; Katzman, Helena; Carmiel-Haggai, Michal; Lusthaus, Michal; Niv, Eva

2010-07-01

Cognitive disturbances are relatively common in patients with liver disease. High protein load precipitates hepatic encephalopathy in cirrhotic patients. Minimal hepatic encephalopathy (MHE) is a prevalent neurocognitive complication of cirrhosis. Because the influence of nutritional factors on the progression of cognitive impairment has not been explored in depth, this study aimed to investigate the effect on cognition of acute metabolic changes induced by breakfast consumption. Twenty-one subjects (10 women) with Child A cirrhosis and 21 age- and sex-matched healthy controls were enrolled. Patients and controls were divided into 2 groups: those receiving a breakfast of 500 kcal and 21 g protein and those receiving no breakfast. Serum ammonia concentrations and cognitive functions were studied (Mindstreams; NeuroTrax, Fresh Meadows, NY) before and 2 h after breakfast. A mixed model was used to analyze the data. At baseline, cirrhotic patients had significantly lower total scores and significantly lower subscores (P < 0.015 global cognitive score) in 4 of 7 cognitive categories, which is indicative of MHE. Patients with hyperammonemia (>85 mug/dL) scored significantly lower for attention than did patients with normal serum ammonia concentrations (P < 0.003). After 2 h, MHE patients and controls responded differently to breakfast consumption with regard to attention and executive functions (P < 0.003 and P < 0.04, respectively). Although patients' scores improved after breakfast consumption, despite an increase in serum ammonia, healthy controls who continued to fast performed better. Chronic hyperammonemia may negatively affect attention. Eating breakfast improves attention and executive functions of patients with MHE. Prolonged periods of starvation may be partly responsible for these changes. This trial was registered at clinicaltrials.gov as NCT01083446.

Cognitive deficits in obese persons with and without binge eating disorder. Investigation using a mental flexibility task.

PubMed

Mobbs, Olivia; Iglesias, Katia; Golay, Alain; Van der Linden, Martial

2011-08-01

Studies suggest that cognitive deficits and attentional biases play a role in the development and maintenance of obesity and eating disorders. In this study, we simultaneously examine attentional biases, as well as inhibitory control and mental flexibility, which are keys to controlling unwanted behaviors and thoughts in obese patients with and without binge eating disorder. 16 obese patients with binge eating disorder and 16 patients without binge eating disorder were compared with 16 normal-weight controls on a "food/body-mental flexibility task", which allows the investigation of inhibitory control, mental flexibility and attention for stimuli related to the body and food. All obese patients made significantly more errors (i.e., pressing a key when a distracter displayed) and more omissions (i.e., not pressing a key when a target displayed) than controls in both food and body sections of the task. Obese participants with binge eating disorder made significantly more errors and omissions than those without binge eating disorder. No difference between groups was found concerning mental flexibility and cognitive biases for food- and body-related targets. These results suggest that obese patients have a general inhibition problem and difficulty focusing attention, which do not depend on the types of stimuli processed. The results also suggest that these cognitive deficits are more severe in obese patients with binge eating disorder, which indicates that there is a continuum of increasing inhibition and cognitive problems with increasingly disordered eating. These cognitive deficits may contribute to problematic eating behaviors. Copyright © 2011 Elsevier Ltd. All rights reserved.

Certified Normal: Alzheimer’s Disease Biomarkers and Normative Estimates of Cognitive Functioning

PubMed Central

Hassenstab, Jason; Chasse, Rachel; Grabow, Perri; Benzinger, Tammie L.S.; Fagan, Anne M.; Xiong, Chengjie; Jasielec, Mateusz; Grant, Elizabeth; Morris, John C.

2016-01-01

Normative samples drawn from older populations may unintentionally include individuals with preclinical Alzheimer’s disease (AD) pathology, resulting in reduced means, increased variability, and overestimation of age-effects on cognitive performance. 264 cognitively normal (CDR=0) older adults were classified as biomarker-negative (“Robust Normal,” n=177) or biomarker-positive (“Preclinical Alzheimer’s Disease” (PCAD), n=87) based on amyloid imaging, cerebrospinal fluid biomarkers, and hippocampal volumes. PCAD participants performed worse than Robust Normals on nearly all cognitive measures. Removing PCAD participants from the normative sample yielded higher means and less variability on episodic memory, visuospatial ability, and executive functioning measures. These results were more pronounced in participants aged 75 and older. Notably, removing PCAD participants from the sample significantly reduced age effects across all cognitive domains. Applying norms from the Robust Normal sample to a separate cohort did not improve CDR classification when using standard deviation cutoff scores. Overall, removing individuals with biomarker evidence of preclinical AD improves normative sample quality and substantially reduces age-effects on cognitive performance, but provides no substantive benefit for diagnostic classifications. PMID:27255812

Cognitive Changes After Adjuvant Treatment in Older Adults with Early-Stage Breast Cancer.

PubMed

Lange, Marie; Heutte, Natacha; Noal, Sabine; Rigal, Olivier; Kurtz, Jean-Emmanuel; Lévy, Christelle; Allouache, Djelila; Rieux, Chantal; Lefel, Johan; Clarisse, Bénédicte; Leconte, Alexandra; Veyret, Corinne; Barthélémy, Philippe; Longato, Nadine; Tron, Laure; Castel, Hélène; Eustache, Francis; Giffard, Bénédicte; Joly, Florence

2018-06-22

Group-based trajectory modeling is particularly important to identify subgroups of patients with pathological cognitive changes after cancer treatment. To date, only one study has explored cognitive trajectories in older patients with cancer. The present article describes objective cognitive changes before to after adjuvant treatment in older adults with early-stage breast cancer (EBC) after adjuvant treatment compared with healthy controls. Participants were patients ≥65 years of age with newly diagnosed EBC and healthy controls (age-, sex-, and education-matched). The pretreatment assessment was conducted before adjuvant therapy, and the post-treatment assessment after the end of the first adjuvant treatment. Objective cognitive changes before to after treatment were evaluated based on the Reliable Change Index for cognitive decline accounting for cognitive impairment status. The sample consisted of women newly diagnosed with EBC ( n  = 118) and healthy controls ( n  = 62). Five patterns of changes before to after treatment were identified based on the presence of cognitive decline and cognitive impairment. The distribution of these five change patterns was statistically significant ( p  = .0001). Thirty-six percent of patients had phase shift changes, 31% without initial objective cognitive impairment developed impairment, 15% had a normal aging, 12% had a nonpathological decline, and 6% experienced accelerated cognitive decline. This study described for the first time objective cognitive changes before to after treatment of older adults with EBC immediately after the end of adjuvant treatment. A longer-term remote follow-up of adjuvant treatment is needed to better understand the cognitive trajectories of older patients with EBC. The Oncologist IMPLICATIONS FOR PRACTICE: After the end of adjuvant treatment, 31% of older adults with early-stage breast cancer without initial objective cognitive impairment developed impairment, and 6% experienced accelerated cognitive decline. Initial cognitive functioning should be included in the balance of benefits and harms of systemic therapy for patients who are likely to be at highest risk for cognitive decline after cancer treatments. Regular cognitive follow-up of patients who had cognitive impairment before cancer treatment should monitor symptoms suggestive of neurodegenerative disease and avert the effect of cognitive disorders on patients' autonomy. © AlphaMed Press 2018.

Lower cognitive performance in 81-year-old men with greater nocturnal blood pressure dipping

PubMed Central

Axelsson, Johan; Reinprecht, Faina; Siennicki-Lantz, Arkadiusz; Elmståhl, Sölve

2008-01-01

Abnormal day-to-night blood pressure (BP) pattern have been found to be associated with cerebrovascular damage, yet studies of the elderly 80 years of age and above, for whom the risk pattern may be different due to ageing and age-associated diseases, are lacking. Ninety-seven 81-year-old men underwent ambulatory BP monitoring and were given six cognitive tests, 79 of the men completing the cognitive test battery. The odds ratio (OR) for performing one standard deviation below the mean on any cognitive test was calculated using a forward stepwise logistic regression model, confounding factors being controlled for. Groups defined in terms of day-to-night changes in BP were compared in this respect. Cognitive performance was lower (OR 3.6; P = 0.017) in the group usually described as dippers (10%–20% nocturnal drop in systolic BP [SBP]) as compared with nondippers (<10% drop). The tertile with the greatest SBP fall (10.6%–19.8%, a range considered as normal among middle aged) showed lowest cognitive performance (OR 4.7; P = 0.008) as compared with the middle tertile (5.1%–10.5% drop). The mean nocturnal fall in SBP was 7.4%, significantly greater in those with lower rather than higher cognitive performance. A nocturnal drop in SBP of ≥10% was associated with lower cognitive performance in these elderly men. The limits to normal dipping appear to be shifted in the direction of a lesser drop in the very elderly. PMID:20428409

Type 2 diabetes and/or its treatment leads to less cognitive impairment in Alzheimer's disease patients.

PubMed

Domínguez, Raúl O; Marschoff, Enrique R; González, Silvia E; Repetto, Marisa G; Serra, Jorge A

2012-10-01

To evaluate the cognitive performance of a homogeneous population of Alzheimer's disease (AD), non-demented Type 2 Diabetes Mellitus (DIAB), demented with concomitant diseases (AD+DIAB) and healthy control subjects. AD is a progressive dementia disorder characterized clinically by impairment of memory, cognition and behavior. Recently, a major research interest in AD has been placed on early evaluation. Diabetes is one of the clinical conditions that represent the greatest risk of developing oxidative stress and dementia. Glucose overload, leading to the development of impaired-induced insulin secretion in DIAB and has been suggested to slow or deter AD pathogenesis. The degree of cognitive impairment was determined on the Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog) and the Folstein's Mini Mental State Examination (MMSE); the severity of dementia was quantified applying the Clinical Dementia Rating (CDR) test; the Hamilton test was employed to evaluate depressive conditions; the final population studied was 101 subjects. The cognitive deterioration is statistically significantly lower (p<0.05) in AD+DIAB patients as compared with AD patients. In this longitudinal study the superimposed diabetic condition was associated with a lower rate of cognitive decline, while diabetic non-demented patients and controls present normal scores. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Exploring social cognition in patients with apathy following acquired brain damage.

PubMed

Njomboro, Progress; Humphreys, Glyn W; Deb, Shoumitro

2014-01-23

Research on cognition in apathy has largely focused on executive functions. To the best of our knowledge, no studies have investigated the relationship between apathy symptoms and processes involved in social cognition. Apathy symptoms include attenuated emotional behaviour, low social engagement and social withdrawal, all of which may be linked to underlying socio-cognitive deficits. We compared patients with brain damage who also had apathy symptoms against similar patients with brain damage but without apathy symptoms. Both patient groups were also compared against normal controls on key socio-cognitive measures involving moral reasoning, social awareness related to making judgements between normative and non-normative behaviour, Theory of Mind processing, and the perception of facial expressions of emotion. We also controlled for the likely effects of executive deficits and depressive symptoms on these comparisons. Our results indicated that patients with apathy were distinctively impaired in making moral reasoning decisions and in judging the social appropriateness of behaviour. Deficits in Theory of Mind and perception of facial expressions of emotion did not distinguish patients with apathy from those without apathy. Our findings point to a possible socio-cognitive profile for apathy symptoms and provide initial insights into how socio-cognitive deficits in patients with apathy may affect social functioning.

Perceptual, Cognitive, and Personality Rigidity in Parkinson’s Disease

PubMed Central

Díaz-Santos, Mirella; Cao, Bo; Yazdanbakhsh, Arash; Norton, Daniel J.; Neargarder, Sandy; Cronin-Golomb, Alice

2015-01-01

Parkinson’s disease (PD) is associated with motor and non-motor rigidity symptoms (e.g., cognitive and personality). The question is raised as to whether rigidity in PD also extends to perception, and if so, whether perceptual, cognitive, and personality rigidities are correlated. Bistable stimuli were presented to 28 non-demented individuals with PD and 26 normal control adults (NC). Necker cube perception and binocular rivalry were examined during passive viewing, and the Necker cube was additionally used for two volitional-control conditions: Hold one percept in front, and Switch between the two percepts. Relative to passive viewing, PD were significantly less able than NC to reduce dominance durations in the Switch condition, indicating perceptual rigidity. Tests of cognitive flexibility and a personality questionnaire were administered to explore the association with perceptual rigidity. Cognitive flexibility was not correlated with perceptual rigidity for either group. Personality (novelty seeking) correlated with dominance durations on Necker passive viewing for PD but not NC. The results indicate the presence in mild-moderate PD of perceptual rigidity and suggest shared neural substrates with novelty seeking, but functional divergence from those supporting cognitive flexibility. The possibility is raised that perceptual rigidity may be a harbinger of cognitive inflexibility later in the disease course. PMID:25640973

Asenapine Effects on Cognitive and Monoamine Dysfunction Elicited by Subchronic Phencyclidine Administration

PubMed Central

Elsworth, John D.; Groman, Stephanie; Jentsch, J. David; Valles, Rodrigo; Shahid, Mohammed; Wong, Erik; Marston, Hugh; Roth, Robert H.

2013-01-01

Purpose Repeated, intermittent administration of the psychotropic NMDA antagonist phencyclidine (PCP) to laboratory animals causes impairment in cognitive and executive functions, modeling important sequelae of schizophrenia; these effects are thought to be due to a dysregulation of neurotransmission within the prefrontal cortex. Atypical antipsychotic drugs have been reported to have measurable, if incomplete, effects on cognitive dysfunction in this model, and these effects may be due to their ability to normalize a subset of the physiological deficits occurring within the prefrontal cortex. Asenapine is an atypical antipsychotic approved in the US for the treatment of schizophrenia and for the treatment, as monotherapy or adjunctive therapy to lithium or valproate, of acute manic or mixed episodes associated bipolar I disorder. To understand its cognitive and neurochemical actions more fully, we explored the effects of short- and long-term dosing with asenapine on measures of cognitive and motor function in normal monkeys and in those previously exposed for 2 weeks to PCP; we further studied the impact of treatment with asenapine on dopamine and serotonin turnover in discrete brain regions from the same cohort. Methods Monkeys were trained to perform reversal learning and object retrieval procedures before twice-daily administration of PCP (0.3 mg/kg intramuscular) or saline for 14 days. Tests confirmed cognitive deficits in PCP-exposed animals before beginning twice-daily administration of saline (control) or asenapine (50, 100, or 150 μg/kg, intramuscular). Dopamine and serotonin turnover were assessed in 15 specific brain regions by high-pressure liquid chromatography measures of the ratio of parent amine to its major metabolite. Results On average, PCP-treated monkeys made twice as many errors in the reversal task as did control monkeys. Asenapine facilitated reversal learning performance in PCP-exposed monkeys, with improvements at trend level after 1 week of administration and reaching significance after 2–4 weeks of dosing. In week 4, the improvement with asenapine 150 μg/kg (p=0.01) rendered the performance of PCP-exposed monkeys indistinguishable from that of normal monkeys without compromising fine motor function. Asenapine administration (150 μg/kg twice daily) produced an increase in dopamine and serotonin turnover in most brain regions of control monkeys and asenapine (50–150 μg/kg) increased dopamine and serotonin turnover in several brain regions of subchronic PCP-treated monkeys. No significant changes in the steady-state levels of dopamine or serotonin were observed in any brain region except for the central amygdala, in which a significant depletion of dopamine was observed in PCP-treated control monkeys; asenapine treatment reversed this dopamine depletion. A significant decrease in serotonin utilization was observed in the orbitofrontal cortex and nucleus accumbens in PCP monkeys, which may underlie poor reversal learning. In the same brain regions, dopamine utilization was not affected. Asenapine ameliorated this serotonin deficit in a dose-related manner that matched its efficacy for reversing the cognitive deficit. Conclusions In this model of cognitive dysfunction, asenapine produced substantial gains in executive functions that were maintained with long-term administration. The cognition-enhancing effects of asenapine and the neurochemical changes in serotonin and dopamine turnover seen in this study are hypothesized to be primarily related to its potent serotonergic and noradrenergic receptor binding properties, and support the potential for asenapine to reduce cognitive dysfunction in patients with schizophrenia and bipolar disorder. PMID:21875607

Unable or Unwilling to Exercise Self-control? The Impact of Neuroscience on Perceptions of Impulsive Offenders

PubMed Central

Blakey, Robert; Kremsmayer, Tobias P.

2018-01-01

In growing numbers of court cases, neuroscience is presented to document the mental state of the offender at the level of the brain. While a small body of research has documented the effects of describing the brain state of psychotic offenders, this study tested the impact of neuroscience that could apply to far more offenders; that is the neuroscience of impulse control. In this online vignette experiment, 759 participants sentenced a normally controlled or normally impulsive actor, who committed a violent offense on impulse, explained in either cognitive or neurobiological terms. Although participants considered the neurobiological actor less responsible for his impulsive disposition than the cognitive actor, the neuroscientific testimony did not affect attributions of choice, blame, dangerousness, or punishment for the criminal act. In fact, the neuroscientific testimony exacerbated the perception that the offender offended consciously and “really wanted” to offend. The described disposition of the actor was also influential: participants attributed more capacity for reform, more free choice and consequently, more blame to the normally controlled actor. Participants also attributed this actor's offending more to his social life experiences and less to his genes and brain. However, this shift in attributions was unable to explain the greater blame directed at this offender. Together, such findings suggest that even when neuroscience changes attributions for impulsive character, attributions for impulsive offending may remain unchanged. Hence this study casts doubt on the mitigating and aggravating potential of neuroscientific testimony in court. PMID:29354076

Altered Brain Connectivity in Early Postmenopausal Women with Subjective Cognitive Impairment

PubMed Central

Vega, Jennifer N.; Zurkovsky, Lilia; Albert, Kimberly; Melo, Alyssa; Boyd, Brian; Dumas, Julie; Woodward, Neil; McDonald, Brenna C.; Saykin, Andrew J.; Park, Joon H.; Naylor, Magdalena; Newhouse, Paul A.

2016-01-01

Cognitive changes after menopause are a common complaint, especially as the loss of estradiol at menopause has been hypothesized to contribute to the higher rates of dementia in women. To explore the neural processes related to subjective cognitive complaints, this study examined resting state functional connectivity in 31 postmenopausal women (aged 50–60) in relationship to cognitive complaints following menopause. A cognitive complaint index was calculated using responses to a 120-item questionnaire. Seed regions were identified for resting state brain networks important for higher-order cognitive processes and for areas that have shown differences in volume and functional activity associated with cognitive complaints in prior studies. Results indicated a positive correlation between the executive control network and cognitive complaint score, weaker negative functional connectivity within the frontal cortex, and stronger positive connectivity within the right middle temporal gyrus in postmenopausal women who report more cognitive complaints. While longitudinal studies are needed to confirm this hypothesis, these data are consistent with previous findings suggesting that high levels of cognitive complaints may reflect changes in brain connectivity and may be a potential marker for the risk of late-life cognitive dysfunction in postmenopausal women with otherwise normal cognitive performance. PMID:27721740

Cognition Enhancing Activity of Sulforaphane Against Scopolamine Induced Cognitive Impairment in Zebra Fish (Danio rerio).

PubMed

Rajesh, Venugopalan; Ilanthalir, Sakthivel

2016-10-01

Several epidemiological studies have shown that consumption of large quantities of vegetables especially cruciferous vegetables (Broccoli and Brussels sprouts) can protect against chronic diseases. Sulforaphane, an isothiocynate found in cruciferous vegetables has been demonstrated to have neuroprotective effects in several experimental paradigms. This study was undertaken to examine the effect of sulforaphane on cognitive impairment in zebra fish model using a novel method of fear conditioning. Initially, the normal behaviour of zebra fishes was studied in light-dark tank for 10 min daily for 10 days. Fishes were then divided into seven groups of twelve in each. Group I served as normal, group II served as fear conditioned control, group III and group IV were sulforaphane (25 µM/L) and piracetam (200 mg/L) treated respectively. Group V served as scopolamine (400 µM/L) induced memory impairment fishes. Group VI and VII were sulforaphane (25 µM/L) and piracetam (200 mg/L) treated scopolamine induced memory impairment groups respectively. In normal behavioural analysis, fishes preferred to stay in dark compartment. The average number of entries into the dark and time spent in dark were significantly more. Fishes in group II to VII were individually subjected to fear conditioning passive avoidance task and evaluated for learned task memory. It was observed that the average number of entries into dark and time spent in dark were significantly decreased. After exposure to respective treatment fishes in group III to VII were subjected to cognitive evaluation. There was no significant difference in cognition of group III and IV fishes exposed to sulforaphane and piracetam alone respectively. Fishes exposed to scopolamine showed a significant cognitive impairment. Sulforaphane exposure prior to scopolamine significantly retained the memory of learned task. These findings suggest that sulforaphane might be a promising therapeutic agent for cognitive enhancement in Alzheimer's disease.

Gait Pattern Alterations during Walking, Texting and Walking and Texting during Cognitively Distractive Tasks while Negotiating Common Pedestrian Obstacles

PubMed Central

Licence, Sammy; Smith, Robynne; McGuigan, Miranda P.; Earnest, Conrad P.

2015-01-01

Objectives Mobile phone texting is a common daily occurrence with a paucity of research examining corresponding gait characteristics. To date, most studies have participants walk in a straight line vs. overcoming barriers and obstacles that occur during regular walking. The aim of our study is to examine the effect of mobile phone texting during periods of cognitive distraction while walking and negotiating barriers synonymous with pedestrian traffic. Methods Thirty participants (18-50y) completed three randomized, counter-balanced walking tasks over a course during: (1) normal walking (control), (2) texting and walking, and (3) texting and walking whilst being cognitively distraction via a standard mathematical test performed while negotiating the obstacle course. We analyzed gait characteristics during course negotiation using a 3-dimensional motion analysis system and a general linear model and Dunnet-Hsu post-hoc procedure the normal walking condition to assess gait characteristic differences. Primary outcomes included the overall time to complete the course time and barrier contact. Secondary outcomes included obstacle clearance height, step frequency, step time, double support phase and lateral deviation. Results Participants took significantly longer (mean ± SD) to complete the course while texting (24.96±4.20 sec) and during cognitive distraction COG (24.09±3.36 sec) vs. normal walking (19.32±2.28 sec; all, P<0.001). No significant differences were noted for barrier contacts (P = 0.28). Step frequency, step time, double support phase and lateral deviation all increased in duration during the texting and cognitive distraction trial. Texting and being cognitively distracted also increased obstacle clearance versus the walking condition (all, P<0.02). Conclusions Texting while walking and/or being cognitively distracted significantly affect gait characteristics concordant to mobile phone usage resulting in a more cautious gate pattern. Future research should also examine a similar study in older participants who may be at a greater risk of tripping with such walking deviations. PMID:26222430

A high-glycemic diet is associated with cerebral amyloid burden in cognitively normal older adults.

PubMed

Taylor, Matthew K; Sullivan, Debra K; Swerdlow, Russell H; Vidoni, Eric D; Morris, Jill K; Mahnken, Jonathan D; Burns, Jeffrey M

2017-12-01

Background: Little is known about the relation between dietary intake and cerebral amyloid accumulation in aging. Objective: We assessed the association of dietary glycemic measures with cerebral amyloid burden and cognitive performance in cognitively normal older adults. Design: We performed cross-sectional analyses relating dietary glycemic measures [adherence to a high-glycemic-load diet (HGLDiet) pattern, intakes of sugar and carbohydrates, and glycemic load] with cerebral amyloid burden (measured by florbetapir F-18 positron emission tomography) and cognitive performance in 128 cognitively normal older adults who provided eligibility screening data for the University of Kansas's Alzheimer's Prevention through Exercise (APEX) Study. The study began in November 2013 and is currently ongoing. Results: Amyloid was elevated in 26% ( n = 33) of participants. HGLDiet pattern adherence ( P = 0.01), sugar intake ( P = 0.03), and carbohydrate intake ( P = 0.05) were significantly higher in participants with elevated amyloid burden. The HGLDiet pattern was positively associated with amyloid burden both globally and in all regions of interest independently of age, sex, and education (all P ≤ 0.001). Individual dietary glycemic measures (sugar intake, carbohydrate intake, and glycemic load) were also positively associated with global amyloid load and nearly all regions of interest independently of age, sex, and educational level ( P ≤ 0.05). Cognitive performance was associated only with daily sugar intake, with higher sugar consumption associated with poorer global cognitive performance (global composite measure and Mini-Mental State Examination) and performance on subtests of Digit Symbol, Trail Making Test B, and Block Design, controlling for age, sex, and education. Conclusion: A high-glycemic diet was associated with greater cerebral amyloid burden, which suggests diet as a potential modifiable behavior for cerebral amyloid accumulation and subsequent Alzheimer disease risk. This trial was registered at clinicaltrials.gov as NCT02000583. © 2017 American Society for Nutrition.

Cognition and event-related potentials in adult-onset non-demented myotonic dystrophy type 1.

PubMed

Tanaka, H; Arai, M; Harada, M; Hozumi, A; Hirata, K

2012-02-01

To clarify the cognitive and event-related potentials (ERPs) profiles of adult-onset genetically-proven non-demented myotonic dystrophy type 1 (DM1). Fourteen DM1 patients and matched 14 normal controls were enrolled. DM1 patients were compared with normal controls, using a variety of neuropsychological tests; an auditory "oddball" counting paradigm for the ERPs, and low-resolution brain electromagnetic tomography (LORETA). For patients, ERPs and neuropsychological parameters were correlated with CTG repeat size, duration of illness, grip strength, and arterial blood gas analysis. Frontal lobe dysfunction, prolonged N1 latency, and attenuated N2/P3 amplitudes were observed in DM1. Longer CTG repeat size was associated with fewer categories achieved on Wisconsin Card Sorting Test. Greater grip strength was associated with better scores on color-word "interference" of Stroop test. P3 latency was negatively correlated with PaO(2). LORETA revealed significant hypoactivities at the orbitofrontal and medial temporal lobe, cingulate, and insula. There was no correlation between ERPs and CTG expansion. Adult-onset non-demented DM1 presented frontal lobe dysfunction. Absence of correlations between CTG repeat size and objective ERP parameters suggested CTG expansion in lymphocytes does not directly contribute to cognitive dysfunction. CTG expansion in lymphocytes does not directly contribute to cognitive dysfunction of adult-onset non-demented DM1. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Evaluation of Cognitive Function of Children with Developmental Disabilities by means of Button-Press Task

NASA Astrophysics Data System (ADS)

Nakazono, Shogo; Kobori, Satoshi

The button-press task means that the subject observes a moving target and presses a button to stop it when the target enters a specified area on a computer display. Subjects perform normal task, suppressed task and delayed task. In the suppressed task, the moving target disappears at some point during the trial. In the delayed task, there is some lag time between the time of pressing button and of stopping target. In these tasks, subjects estimate the movement of the target, and press the button considering his/her own reaction time. In our previous study, we showed that cognitive and motor function was able to be evaluated by these tasks. In this study, we examined error data of children with developmental disabilities to evaluate the cognitive function, and investigated the learning processes. Moreover, we discussed the developmental stages by comparing the children with disabilities to normal control children, and we clarified the behavior characteristics of children with developmental disabilities. Asa result, it was shown that our evaluation method and system for the button-press task were effective to evaluate cognitive ability of children with developmental disabilities.

Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.

PubMed

Jansen, Willemijn J; Ossenkoppele, Rik; Tijms, Betty M; Fagan, Anne M; Hansson, Oskar; Klunk, William E; van der Flier, Wiesje M; Villemagne, Victor L; Frisoni, Giovanni B; Fleisher, Adam S; Lleó, Alberto; Mintun, Mark A; Wallin, Anders; Engelborghs, Sebastiaan; Na, Duk L; Chételat, Gäel; Molinuevo, José Luis; Landau, Susan M; Mattsson, Niklas; Kornhuber, Johannes; Sabri, Osama; Rowe, Christopher C; Parnetti, Lucilla; Popp, Julius; Fladby, Tormod; Jagust, William J; Aalten, Pauline; Lee, Dong Young; Vandenberghe, Rik; Resende de Oliveira, Catarina; Kapaki, Elisabeth; Froelich, Lutz; Ivanoiu, Adrian; Gabryelewicz, Tomasz; Verbeek, Marcel M; Sanchez-Juan, Páscual; Hildebrandt, Helmut; Camus, Vincent; Zboch, Marzena; Brooks, David J; Drzezga, Alexander; Rinne, Juha O; Newberg, Andrew; de Mendonça, Alexandre; Sarazin, Marie; Rabinovici, Gil D; Madsen, Karine; Kramberger, Milica G; Nordberg, Agneta; Mok, Vincent; Mroczko, Barbara; Wolk, David A; Meyer, Philipp T; Tsolaki, Magda; Scheltens, Philip; Verhey, Frans R J; Visser, Pieter Jelle; Aarsland, Dag; Alcolea, Daniel; Alexander, Myriam; Almdahl, Ina S; Arnold, Steven E; Baldeiras, Inês; Barthel, Henryk; van Berckel, Bart N M; Blennow, Kaj; van Buchem, Mark A; Cavedo, Enrica; Chen, Kewei; Chipi, Elena; Cohen, Ann D; Förster, Stefan; Fortea, Juan; Frederiksen, Kristian S; Freund-Levi, Yvonne; Gkatzima, Olymbia; Gordon, Mark Forrest; Grimmer, Timo; Hampel, Harald; Hausner, Lucrezia; Hellwig, Sabine; Herukka, Sanna-Kaisa; Johannsen, Peter; Klimkowicz-Mrowiec, Aleksandra; Köhler, Sebastian; Koglin, Norman; van Laere, Koen; de Leon, Mony; Lisetti, Viviana; Maier, Wolfgang; Marcusson, Jan; Meulenbroek, Olga; Møllergård, Hanne M; Morris, John C; Nordlund, Arto; Novak, Gerald P; Paraskevas, George P; Perera, Gayan; Peters, Oliver; Ramakers, Inez H G B; Rami, Lorena; Rodríguez-Rodríguez, Eloy; Roe, Catherine M; Rot, Uros; Rüther, Eckart; Santana, Isabel; Schröder, Johannes; Seo, Sang W; Soininen, Hilkka; Spiru, Luiza; Stomrud, Erik; Struyfs, Hanne; Teunissen, Charlotte E; Vos, Stephanie J B; van Waalwijk van Doorn, Linda J C; Waldemar, Gunhild; Wallin, Åsa K; Wiltfang, Jens; Zetterberg, Henrik

2018-01-01

Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials. To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia. This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017. Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype. Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P = .16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P < .001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P < .001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years. Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.

A novel biomarker of amnestic MCI based on dynamic cross-frequency coupling patterns during cognitive brain responses

PubMed Central

Dimitriadis, Stavros I.; Laskaris, Nikolaos A.; Bitzidou, Malamati P.; Tarnanas, Ioannis; Tsolaki, Magda N.

2015-01-01

The detection of mild cognitive impairment (MCI), the transitional stage between normal cognitive changes of aging and the cognitive decline caused by AD, is of paramount clinical importance, since MCI patients are at increased risk of progressing into AD. Electroencephalographic (EEG) alterations in the spectral content of brainwaves and connectivity at resting state have been associated with early-stage AD. Recently, cognitive event-related potentials (ERPs) have entered into the picture as an easy to perform screening test. Motivated by the recent findings about the role of cross-frequency coupling (CFC) in cognition, we introduce a relevant methodological approach for detecting MCI based on cognitive responses from a standard auditory oddball paradigm. By using the single trial signals recorded at Pz sensor and comparing the responses to target and non-target stimuli, we first demonstrate that increased CFC is associated with the cognitive task. Then, considering the dynamic character of CFC, we identify instances during which the coupling between particular pairs of brainwave frequencies carries sufficient information for discriminating between normal subjects and patients with MCI. In this way, we form a multiparametric signature of impaired cognition. The new composite biomarker was tested using data from a cohort that consists of 25 amnestic MCI patients and 15 age-matched controls. Standard machine-learning algorithms were employed so as to implement the binary classification task. Based on leave-one-out cross-validation, the measured classification rate was found reaching very high levels (95%). Our approach compares favorably with the traditional alternative of using the morphology of averaged ERP response to make the diagnosis and the usage of features from spectro-temporal analysis of single-trial responses. This further indicates that task-related CFC measurements can provide invaluable analytics in AD diagnosis and prognosis. PMID:26539070

Neurogranin as a predictor of memory and executive function decline in MCI patients.

PubMed

Headley, Alison; De Leon-Benedetti, Andres; Dong, Chuanhui; Levin, Bonnie; Loewenstein, David; Camargo, Christian; Rundek, Tatjana; Zetterberg, Henrik; Blennow, Kaj; Wright, Clinton B; Sun, Xiaoyan

2018-03-06

To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313, p = 0.0068 and β = -0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ 42 ) were controlled for in these analyses. High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ 42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD. © 2018 American Academy of Neurology.

Cognitive impairment in metabolically-obese, normal-weight rats: identification of early biomarkers in peripheral blood mononuclear cells.

PubMed

Cifre, Margalida; Palou, Andreu; Oliver, Paula

2018-03-22

Metabolically-obese, normal-weight (MONW) individuals are not obese in terms of weight and height but have a number of obesity-related features (e.g. greater visceral adiposity, insulin resistance, and increased risk of cardiovascular disease). The MONW phenotype is related to the intake of unbalanced diets, such as those rich in fat. Increasing evidence shows a relationship between high-fat diet consumption and mild cognitive impairment and dementia. Thus, MONW individuals could be at a greater risk of cognitive dysfunction. We aimed to evaluate whether MONW-like animals present gene expression alterations in the hippocampus associated with an increased risk of cognitive impairment, and to identify early biomarkers of cognitive dysfunction in peripheral blood mononuclear cells (PBMC). Wistar rats were chronically fed with a 60% (HF60) or a 45% (HF45) high-fat diet administered isocalorically to control animals to mimic MONW features. Expression analysis of cognitive decline-related genes was performed using RT-qPCR, and working memory was assessed using a T-maze. High-fat diet consumption altered the pattern of gene expression in the hippocampus, clearly pointing to cognitive decline, which was accompanied by a worse performance in the T-maze in HF60 animals. Remarkably, Syn1 and Sorl1 mRNA showed the same expression pattern in both the hippocampus and the PBMC obtained at different time-points in the HF60 group, even before other pathological signs were observed. Our results demonstrate that long-term intake of high-fat diets, even in the absence of obesity, leads to cognitive disruption that is reflected in PBMC transcriptome. Therefore, PBMC are revealed as a plausible, minimally-invasive source of early biomarkers of cognitive impairment associated with increased fat intake.

A pilot placebo-controlled, double-blind, and randomized study on the cognition-enhancing benefits of a proprietary chicken meat ingredient in healthy subjects.

PubMed

Azhar, Zain M; Zubaidah, Jamil O; Norjan, Khin O N; Zhuang, Candy Yi-Jing; Tsang, Fai

2013-08-15

It has long been postulated that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that could be responsible for the action of diet on brain health and cognitive function. Here, through a double-blind, randomized, placebo-controlled trial, we asked if the newly discovered chicken meat ingredient-168 (CMI-168) could be beneficial to the cognitive function in healthy adults. Normal, healthy subjects were supplemented with either placebo or CMI-168 for 6 weeks. The subjects were given a series of cognitive tests to examine their levels of cognitive functioning at the beginning and end of supplementation, as well as two weeks after termination of supplementation. The combination of these tests, namely Digit Span Backwards, Letter-Number Sequencing, and the Rey Auditory Verbal Learning Test (RAVLT), was used to assess the subjects' attention and working memory. For all comparisons, the probability level of p < 0.05 was taken as statistically significant using repeated measure 2-way ANOVA followed by Bonferroni post-hoc test. Overall, subjects supplemented with CMI-168 showed significantly (p < 0.01) better performance in all cognitive tests after 6 weeks' supplementation compared to control and such superior performance was maintained even 2 weeks after termination of supplementation. The present study reveals the cognition-enhancing properties of a recently developed chicken meat ingredient, likely arising from the promotion of attention and prefrontal cortex functions.

Altered Blood-Brain Barrier Permeability in Patients With Systemic Lupus Erythematosus: A Novel Imaging Approach.

PubMed

Gulati, Gaurav; Jones, Jordan T; Lee, Gregory; Altaye, Mekibib; Beebe, Dean W; Meyers-Eaton, Jamie; Wiley, Kasha; Brunner, Hermine I; DiFrancesco, Mark W

2017-02-01

To evaluate a safe, noninvasive magnetic resonance imaging (MRI) method to measure regional blood-brain barrier integrity and investigate its relationship with neurocognitive function and regional gray matter volume in juvenile-onset systemic lupus erythematosus (SLE). In this cross-sectional, case-control study, capillary permeability was measured as a marker of blood-brain barrier integrity in juvenile SLE patients and matched healthy controls, using a combination of arterial spin labeling and diffusion-weighted brain MRI. Regional gray matter volume was measured by voxel-based morphometry. Correlation analysis was done to investigate the relationship between regional capillary permeability and regional gray matter volume. Formal neurocognitive testing was completed (measuring attention, visuoconstructional ability, working memory, and psychomotor speed), and scores were regressed against regional blood-brain barrier integrity among juvenile SLE patients. Formal cognitive testing confirmed normal cognitive ability in all juvenile SLE subjects (n = 11) included in the analysis. Regional capillary permeability was negatively associated (P = 0.026) with neurocognitive performance concerning psychomotor speed in the juvenile SLE cohort. Compared with controls (n = 11), juvenile SLE patients had significantly greater capillary permeability involving Brodmann's areas 19, 28, 36, and 37 and caudate structures (P < 0.05 for all). There is imaging evidence of increased regional capillary permeability in juvenile SLE patients with normal cognitive performance using a novel noninvasive MRI technique. These blood-brain barrier outcomes appear consistent with functional neuronal network alterations and gray matter volume loss previously observed in juvenile SLE patients with overt neurocognitive deficits, supporting the notion that blood-brain barrier integrity loss precedes the loss of cognitive ability in juvenile SLE. Longitudinal studies are needed to confirm the findings of this pilot study. © 2016, American College of Rheumatology.

Subjective Cognitive Complaints and Objective Cognitive Impairment in Parkinson's Disease.

PubMed

Hong, Jin Yong; Lee, Yoonju; Sunwoo, Mun Kyung; Sohn, Young H; Lee, Phil Hyu

2018-01-01

Subjective cognitive complaints (SCCs) are very common in patients with Parkinson's disease (PD). However, the relationship between SCCs and objective cognitive impairment is still unclear. This study aimed to determine whether SCCs are correlated with objective cognitive performance in patients with PD. Totals of 148 cognitively normal patients, 71 patients with mild cognitive impairment (MCI), and 31 demented patients were recruited consecutively from a movement-disorders clinic. Their SCCs and cognitive performances were evaluated using the Cognitive Complaints Interview (CCI) and a comprehensive neuropsychological battery. The CCI score increased with age, duration of PD, and depression score, and was inversely correlated with cognitive performance. The association between CCI score and performance remained significant after adjustment for the depression score, age, and duration of PD. The CCI score could be used to discriminate patients with dementia from cognitively normal and MCI patients [area under the receiver operating characteristics curve (AUC) of 0.80], but not patients with MCI or dementia from cognitively normal patients (AUC of 0.67). SCCs as measured by the CCI are strongly correlated with objective cognitive performance in patients with PD. The CCI can also be used to screen for dementia in patients with PD. Copyright © 2018 Korean Neurological Association.

Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson's Disease.

PubMed

Harrington, Deborah L; Shen, Qian; Castillo, Gabriel N; Filoteo, J Vincent; Litvan, Irene; Takahashi, Colleen; French, Chelsea

2017-01-01

Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI) are common in Parkinson's disease (PD), but have largely been studied in a priori defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN) and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF) and regional homogeneity (ReHo), a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex), sensorimotor cortex (primary motor, pre/post-central gyrus), basal ganglia (putamen, caudate), and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a pathological, rather than compensatory influence on cognitive abilities tested in this study. Receiver operating curve analyses demonstrated excellent sensitivity (≥90%) of rsfMRI variables in distinguishing patients from controls, but poor accuracy for brain volume and cognitive variables. Altogether these results provide new insights into the topology, cognitive relevance, and sensitivity of aberrant intrinsic activity and connectivity that precedes clinically significant cognitive impairment. Longitudinal studies are needed to determine if these neurocognitive associations presage the development of future mild cognitive impairment or dementia.

Impaired Sleep Predicts Cognitive Decline in Old People: Findings from the Prospective KORA Age Study.

PubMed

Johar, Hamimatunnisa; Kawan, Rasmila; Emeny, Rebecca Thwing; Ladwig, Karl-Heinz

2016-01-01

To investigate the association between sleep-related characteristics and cognitive change over 3 years of follow up in an aged population. Sleep characteristics and covariates were assessed at baseline in a standardized interview and clinical examination of the population-based KORA Age Study (n = 740, mean age = 75 years). Cognitive score (determined by telephone interview for cognitive status, TICS-m) was recorded at baseline and 3 years later. At baseline, 82.83% (n = 613) of participants had normal cognitive status, 13.51% (n = 100) were classified with mild cognitive impairment (MCI), and 3.64% (n = 27) with probable dementia. The effect of three distinct patterns of poor sleep (difficulties initiating [DIS] or maintaining sleep [DMS], daytime sleepiness [DS] or sleep duration) were considered on a change in cognitive score with adjustments for potential confounders in generalized linear regression models. Cognitive decline was more pronounced in individuals with DMS compared to those with no DMS (β = 1.33, 95% CI = 0.41-2.24, P < 0.001). However, the predictive power of DMS was only significant in individuals with normal cognition and not impaired subjects at baseline. Prolonged sleep duration increased the risk for cognitive decline in cognitively impaired elderly (β = 1.86, 95% CI = 0.15-3.57, P = 0.03). Other sleep characteristics (DIS and DS) were not significantly associated with cognitive decline. DMS and long sleep duration were associated with cognitive decline in normal and cognitively impaired elderly, respectively. The identification of impaired sleep quality may offer intervention strategies to deter cognitive decline in the elderly with normal cognitive function. © 2016 Associated Professional Sleep Societies, LLC.

Patterns of verbal memory performance in mild cognitive impairment, Alzheimer disease, and normal aging.

PubMed

Greenaway, Melanie C; Lacritz, Laura H; Binegar, Dani; Weiner, Myron F; Lipton, Anne; Munro Cullum, C

2006-06-01

Individuals with mild cognitive impairment (MCI) typically demonstrate memory loss that falls between normal aging (NA) and Alzheimer disease (AD), but little is known about the pattern of memory dysfunction in MCI. To explore this issue, California Verbal Learning Test (CVLT) performance was examined across groups of MCI, AD, and NA. MCI subjects displayed a pattern of deficits closely resembling that of AD, characterized by reduced learning, rapid forgetting, increased recency recall, elevated intrusion errors, and poor recognition discriminability with increased false-positives. MCI performance was significantly worse than that of controls and better than that of AD patients across memory indices. Although qualitative analysis of CVLT profiles may be useful in individual cases, discriminant function analysis revealed that delayed recall and total learning were the best aspects of learning/memory on the CVLT in differentiating MCI, AD, and NA. These findings support the position that amnestic MCI represents an early point of decline on the continuum of AD that is different from normal aging.

Orexin-A is Associated with Increases in Cerebrospinal Fluid Phosphorylated-Tau in Cognitively Normal Elderly Subjects.

PubMed

Osorio, Ricardo S; Ducca, Emma L; Wohlleber, Margaret E; Tanzi, Emily B; Gumb, Tyler; Twumasi, Akosua; Tweardy, Samuel; Lewis, Clifton; Fischer, Esther; Koushyk, Viachaslau; Cuartero-Toledo, Maria; Sheikh, Mohammed O; Pirraglia, Elizabeth; Zetterberg, Henrik; Blennow, Kaj; Lu, Shou-En; Mosconi, Lisa; Glodzik, Lidia; Schuetz, Sonja; Varga, Andrew W; Ayappa, Indu; Rapoport, David M; de Leon, Mony J

2016-06-01

To evaluate the role of orexin-A with respect to cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers, and explore its relationship to cognition and sleep characteristics in a group of cognitively normal elderly individuals. Subjects were recruited from multiple community sources for National Institutes of Health supported studies on normal aging, sleep and CSF biomarkers. Sixty-three participants underwent home monitoring for sleep-disordered breathing, clinical, sleep and cognitive evaluations, as well as a lumbar puncture to obtain CSF. Individuals with medical history or with magnetic resonance imaging evidence of disorders that may affect brain structure or function were excluded. Correlation and linear regression analyses were used to assess the relationship between orexin-A and CSF AD-biomarkers controlling for potential sociodemographic and sleep confounders. Levels of orexin-A, amyloid beta 42 (Aβ42), phosphorylated-tau (P-Tau), total-tau (T-Tau), Apolipoprotein E4 status, age, years of education, reported total sleep time, number of awakenings, apnea-hypopnea indices (AHI), excessive daytime sleepiness, and a cognitive battery were analyzed. Subjects were 69.59 ± 8.55 years of age, 57.1% were female, and 30.2% were apolipoprotein E4+. Orexin-A was positively correlated with Aβ42, P-Tau, and T-Tau. The associations between orexin-A and the AD-biomarkers were driven mainly by the relationship between orexin-A and P-Tau and were not influenced by other clinical or sleep characteristics that were available. Orexin-A is associated with increased P-Tau in normal elderly individuals. Increases in orexin-A and P-Tau might be a consequence of the reduction in the proportion of the deeper, more restorative slow wave sleep and rapid eye movement sleep reported with aging. Clinicaltrials.gov registration number NCT01962779. © 2016 Associated Professional Sleep Societies, LLC.

Over-the-Counter Supplement Interventions to Prevent Cognitive Decline, Mild Cognitive Impairment, and Clinical Alzheimer-Type Dementia: A Systematic Review.

PubMed

Butler, Mary; Nelson, Victoria A; Davila, Heather; Ratner, Edward; Fink, Howard A; Hemmy, Laura S; McCarten, J Riley; Barclay, Terry R; Brasure, Michelle; Kane, Robert L

2018-01-02

Optimal interventions to prevent or delay cognitive decline, mild cognitive impairment (MCI), or dementia are uncertain. To summarize the evidence on efficacy and harms of over-the-counter (OTC) supplements to prevent or delay cognitive decline, MCI, or clinical Alzheimer-type dementia in adults with normal cognition or MCI but no dementia diagnosis. Multiple electronic databases from 2009 to July 2017 and bibliographies of systematic reviews. English-language trials of at least 6 months' duration that enrolled adults without dementia and compared cognitive outcomes with an OTC supplement versus placebo or active controls. Extraction performed by a single reviewer and confirmed by a second reviewer; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence. Thirty-eight trials with low to medium risk of bias compared ω-3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin D plus calcium, vitamin C or β-carotene, multi-ingredient supplements, or other OTC interventions with placebo or other supplements. Few studies examined effects on clinical Alzheimer-type dementia or MCI, and those that did suggested no benefit. Daily folic acid plus vitamin B12 was associated with improvements in performance on some objectively measured memory tests that were statistically significant but of questionable clinical significance. Moderate-strength evidence showed that vitamin E had no benefit on cognition. Evidence about effects of ω-3 fatty acids, soy, ginkgo biloba, folic acid alone or with other B vitamins, β-carotene, vitamin C, vitamin D plus calcium, and multivitamins or multi-ingredient supplements was either insufficient or low-strength, suggesting that these supplements did not reduce risk for cognitive decline. Adverse events were rarely reported. Studies had high attrition and short follow-up and used a highly variable set of cognitive outcome measures. Evidence is insufficient to recommend any OTC supplement for cognitive protection in adults with normal cognition or MCI. Agency for Healthcare Research and Quality.

Orexin-A is Associated with Increases in Cerebrospinal Fluid Phosphorylated-Tau in Cognitively Normal Elderly Subjects

PubMed Central

Osorio, Ricardo S.; Ducca, Emma L.; Wohlleber, Margaret E.; Tanzi, Emily B.; Gumb, Tyler; Twumasi, Akosua; Tweardy, Samuel; Lewis, Clifton; Fischer, Esther; Koushyk, Viachaslau; Cuartero-Toledo, Maria; Sheikh, Mohammed O.; Pirraglia, Elizabeth; Zetterberg, Henrik; Blennow, Kaj; Lu, Shou-En; Mosconi, Lisa; Glodzik, Lidia; Schuetz, Sonja; Varga, Andrew W.; Ayappa, Indu; Rapoport, David M.; de Leon, Mony J.

2016-01-01

Study Objectives: To evaluate the role of orexin-A with respect to cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers, and explore its relationship to cognition and sleep characteristics in a group of cognitively normal elderly individuals. Methods: Subjects were recruited from multiple community sources for National Institutes of Health supported studies on normal aging, sleep and CSF biomarkers. Sixty-three participants underwent home monitoring for sleep-disordered breathing, clinical, sleep and cognitive evaluations, as well as a lumbar puncture to obtain CSF. Individuals with medical history or with magnetic resonance imaging evidence of disorders that may affect brain structure or function were excluded. Correlation and linear regression analyses were used to assess the relationship between orexin-A and CSF AD-biomarkers controlling for potential sociodemographic and sleep confounders. Results: Levels of orexin-A, amyloid beta 42 (Aβ42), phosphorylated-tau (P-Tau), total-tau (T-Tau), Apolipoprotein E4 status, age, years of education, reported total sleep time, number of awakenings, apnea-hypopnea indices (AHI), excessive daytime sleepiness, and a cognitive battery were analyzed. Subjects were 69.59 ± 8.55 years of age, 57.1% were female, and 30.2% were apolipoprotein E4+. Orexin-A was positively correlated with Aβ42, P-Tau, and T-Tau. The associations between orexin-A and the AD-biomarkers were driven mainly by the relationship between orexin-A and P-Tau and were not influenced by other clinical or sleep characteristics that were available. Conclusions: Orexin-A is associated with increased P-Tau in normal elderly individuals. Increases in orexin-A and P-Tau might be a consequence of the reduction in the proportion of the deeper, more restorative slow wave sleep and rapid eye movement sleep reported with aging. Clinical Trial Registration: Clinicaltrials.gov registration number NCT01962779. Citation: Osorio RS, Ducca EL, Wohlleber ME, Tanzi EB, Gumb T, Twumasi A, Tweardy S, Lewis C, Fischer E, Koushyk V, Cuartero-Toledo M, Sheikh MO, Pirraglia E, Zetterberg H, Blennow K, Lu SE, Mosconi L, Glodzik L, Schuetz S, Varga AW, Ayappa I, Rapoport DM, de Leon MJ. Orexin-A is associated with increases in cerebrospinal fluid phosphorylated-tau in cognitively normal elderly subjects. SLEEP 2016;39(6):1253–1260. PMID:26951396

Intrinsic Brain Activity of Cognitively Normal Older Persons Resembles More That of Patients Both with and at Risk for Alzheimer's Disease Than That of Healthy Younger Persons

PubMed Central

Pasquini, Lorenzo; Tonch, Annika; Plant, Claudia; Zherdin, Andrew; Ortner, Marion; Kurz, Alexander; Förstl, Hans; Zimmer, Claus; Grimmer, Timo; Wohlschäger, Afra; Riedl, Valentin

2014-01-01

Abstract In Alzheimer's disease (AD), recent findings suggest that amyloid-β (Aβ)-pathology might start 20–30 years before first cognitive symptoms arise. To account for age as most relevant risk factor for sporadic AD, it has been hypothesized that lifespan intrinsic (i.e., ongoing) activity of hetero-modal brain areas with highest levels of functional connectivity triggers Aβ-pathology. This model induces the simple question whether in older persons without any cognitive symptoms intrinsic activity of hetero-modal areas is more similar to that of symptomatic patients with AD or to that of younger healthy persons. We hypothesize that due to advanced age and therefore potential impact of pre-clinical AD, intrinsic activity of older persons resembles more that of patients than that of younger controls. We tested this hypothesis in younger (ca. 25 years) and older healthy persons (ca. 70 years) and patients with mild cognitive impairment and AD-dementia (ca. 70 years) by the use of resting-state functional magnetic resonance imaging, distinct measures of intrinsic brain activity, and different hierarchical clustering approaches. Independently of applied methods and involved areas, healthy older persons' intrinsic brain activity was consistently more alike that of patients than that of younger controls. Our result provides evidence for larger similarity in intrinsic brain activity between healthy older persons and patients with or at-risk for AD than between older and younger ones, suggesting a significant proportion of pre-clinical AD cases in the group of cognitively normal older people. The observed link of aging and AD with intrinsic brain activity supports the view that lifespan intrinsic activity may contribute critically to the pathogenesis of AD. PMID:24689864

Cognitive computer training in children with attention deficit hyperactivity disorder (ADHD) versus no intervention: study protocol for a randomized controlled trial.

PubMed

Bikic, Aida; Leckman, James F; Lindschou, Jane; Christensen, Torben Ø; Dalsgaard, Søren

2015-10-24

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder characterized by symptoms of inattention and impulsivity and/or hyperactivity and a range of cognitive dysfunctions. Pharmacological treatment may be beneficial; however, many affected individuals continue to have difficulties with cognitive functions despite medical treatment, and up to 30 % do not respond to pharmacological treatment. Inadequate medical compliance and the long-term effects of treatment make it necessary to explore nonpharmacological and supplementary treatments for ADHD. Treatment of cognitive dysfunctions may prove particularly important because of the impact of these dysfunctions on the ability to cope with everyday life. Lately, several trials have shown promising results for cognitive computer training, often referred to as cognitive training, which focuses on particular parts of cognition, mostly on the working memory or attention but with poor generalization of training on other cognitive functions and functional outcome. Children with ADHD have a variety of cognitive dysfunctions, and it is important that cognitive training target multiple cognitive functions. This multicenter randomized clinical superiority trial aims to investigate the effect of "ACTIVATE™," a computer program designed to improve a range of cognitive skills and ADHD symptoms. A total of 122 children with ADHD, aged 6 to 13 years, will be randomized to an intervention or a control group. The intervention group will be asked to use ACTIVATE™ at home 40 minutes per day, 6 days per week for 8 weeks. Both intervention and control group will receive treatment as usual. Outcome measures will assess cognitive functions, symptoms, and behavioral and functional measures before and after the 8 weeks of training and in a 12- and 24-week follow-up. Results of this trial will provide useful information on the effectiveness of computer training focusing on several cognitive functions. Cognitive training has the potential to reduce cognitive dysfunctions and to become a new treatment option, which can promote a more normal neural development in young children with ADHD and thus reduce cognitive dysfunctions and symptoms. This could help children with ADHD to perform better in everyday life and school. ClinicalTrials.gov: NCT01752530 , date of registration: 10 December 2012.

The Relationship between Speech Production and Speech Perception Deficits in Parkinson's Disease

ERIC Educational Resources Information Center

De Keyser, Kim; Santens, Patrick; Bockstael, Annelies; Botteldooren, Dick; Talsma, Durk; De Vos, Stefanie; Van Cauwenberghe, Mieke; Verheugen, Femke; Corthals, Paul; De Letter, Miet

2016-01-01

Purpose: This study investigated the possible relationship between hypokinetic speech production and speech intensity perception in patients with Parkinson's disease (PD). Method: Participants included 14 patients with idiopathic PD and 14 matched healthy controls (HCs) with normal hearing and cognition. First, speech production was objectified…

Empathy in Boys with Disruptive Behavior Disorders

ERIC Educational Resources Information Center

de Wied, Minet; Goudena, Paul P.; Matthys, Walter

2005-01-01

Background: The present study examined empathy in 8- to 12-year-old clinically referred boys with disruptive behavior disorders (DBD) (n = 25) and age-matched normal controls (n = 24). Method: Situational empathy was assessed by children's emotional and cognitive responses to six empathy-inducing vignettes (displaying sadness, anger or happiness).…

Pragmatic Competency and Obsessive-Compulsive Disorder: A Comparative Assessment with Normal Controls

ERIC Educational Resources Information Center

Ghahari, Shima; Hassani, Hamidreza; Purmofrad, Maryam

2017-01-01

Unlike such cognitive impairments as autism and schizophrenia, the speech pattern in obsessive-compulsive disorder (OCD) has largely remained underrepresented. We examined the pragmatic competence of OCD-affected individuals under two variant modes: pragmatic recognition and pragmatic production. In the recognition phase, the informants completed…

Daily supplementation with mushroom (Agaricus bisporus) improves balance and working memory in aged rats

USDA-ARS?s Scientific Manuscript database

Animals and humans show decrements in motor control, cognition, and brain function during normal aging, partly due to the long-term effects of oxidative stress and inflammation. Recent studies have identified a number of fruits and vegetables, whose phytochemical make-up contains potent antioxidant ...

Subjective cognitive complaints, personality and brain amyloid-beta in cognitively normal older adults

PubMed Central

Snitz, Beth E.; Weissfeld, Lisa A.; Cohen, Ann D.; Lopez, Oscar L.; Nebes, Robert D.; Aizenstein, Howard J.; McDade, Eric; Price, Julie C.; Mathis, Chester A.; Klunk, William E.

2015-01-01

Objectives Subjective cognitive complaints in otherwise normal aging are common but may be associated with preclinical Alzheimer Disease in some individuals. Little is known about who is mostly likely to show associations between cognitive complaints and preclinical Alzheimer pathology. We sought to 1) demonstrate associations between subjective complaints and brain amyloid-β in cognitively normal older adults; 2) to explore personality factors as potential moderators of this association. Design Cross-sectional observational study. Setting Clinical neuroimaging research center. Participants Community volunteer sample of 92 healthy older adults, screened for normal cognition with comprehensive neuropsychological evaluation. Measurements Subjective cognitive self-report measures included the Memory Functioning Questionnaire, Cognitive Failures Questionnaire, and the Subjective Cognitive Complaint Scale. Personality was measured with the NEO Five Factor Inventory. Brain amyloid-β deposition was assessed with Pittsburgh compound B (PiB)-PET imaging. Results One of three cognitive complaint measures, the Memory Functioning Questionnaire, was associated with global PiB retention (standardized beta =−.230, p=.046, adjusting for age, sex and depressive symptoms). Neuroticism moderated this association such that only high neuroticism individuals showed the predicted pattern of high complaint – high amyloid-β association. Conclusions Evidence for association between subjective cognition and brain amyloid-β deposition in healthy older adults is demonstrable but measure-specific. Neuroticism may moderate the MFQ – amyloid-β association such that it is observed in the context of higher trait neuroticism. Subjective cognitive complaints and neuroticism may reflect a common susceptibility toward psychological distress and negative affect, which are in turn risk factors for cognitive decline in aging and incident Alzheimer Disease. PMID:25746485

Certified normal: Alzheimer's disease biomarkers and normative estimates of cognitive functioning.

PubMed

Hassenstab, Jason; Chasse, Rachel; Grabow, Perri; Benzinger, Tammie L S; Fagan, Anne M; Xiong, Chengjie; Jasielec, Mateusz; Grant, Elizabeth; Morris, John C

2016-07-01

Normative samples drawn from older populations may unintentionally include individuals with preclinical Alzheimer's disease (AD) pathology, resulting in reduced means, increased variability, and overestimation of age effects on cognitive performance. A total of 264 cognitively normal (Clinical Dementia Rating = 0) older adults were classified as biomarker negative ("Robust Normal," n = 177) or biomarker positive ("Preclinical Alzheimer's Disease" [PCAD], n = 87) based on amyloid imaging, cerebrospinal fluid biomarkers, and hippocampal volumes. PCAD participants performed worse than robust normals on nearly all cognitive measures. Removing PCAD participants from the normative sample yielded higher means and less variability on episodic memory, visuospatial ability, and executive functioning measures. These results were more pronounced in participants aged 75 years and older. Notably, removing PCAD participants from the sample significantly reduced age effects across all cognitive domains. Applying norms from the robust normal sample to a separate cohort did not improve Clinical Dementia Rating classification when using standard deviation cutoff scores. Overall, removing individuals with biomarker evidence of preclinical AD improves normative sample quality and substantially reduces age effects on cognitive performance but provides no substantive benefit for diagnostic classifications. Copyright © 2016 Elsevier Inc. All rights reserved.

The Gesture Imitation in Alzheimer's Disease Dementia and Amnestic Mild Cognitive Impairment.

PubMed

Li, Xudong; Jia, Shuhong; Zhou, Zhi; Hou, Chunlei; Zheng, Wenjing; Rong, Pei; Jiao, Jinsong

2016-07-14

Alzheimer's disease dementia (ADD) has become an important health problem in the world. Visuospatial deficits are considered to be an early symptom besides memory disorder. The gesture imitation test was devised to detect ADD and amnestic mild cognitive impairment (aMCI). A total of 117 patients with ADD, 118 with aMCI, and 95 normal controls were included in this study. All participants were administered our gesture imitation test, the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Clock Drawing Test (CDT), and the Clinical Dementia Rating Scale (CDR). Patients with ADD performed worse than normal controls on global scores and had a lower success rate on every item (p < 0.001). The area under the curve (AUC) for the global scores when comparing the ADD and control groups was 0.869 (p < 0.001). Item 4 was a better discriminator with a sensitivity of 84.62% and a specificity of 67.37%. The AUC for the global scores decreased to 0.621 when applied to the aMCI and control groups (p = 0.002). After controlling for age and education, the gesture imitation test scores were positively correlated with the MMSE (r = 0.637, p < 0.001), the MoCA (r = 0.572, p < 0.001), and the CDT (r = 0.514, p < 0.001) and were negatively correlated with the CDR scores (r = -0.558, p < 0.001). The gesture imitation test is an easy, rapid tool for detecting ADD, and is suitable for the patients suspected of mild ADD and aMCI in outpatient clinics.

Does Cognitive Impairment Affect Rehabilitation Outcome in Parkinson’s Disease?

PubMed Central

Ferrazzoli, Davide; Ortelli, Paola; Maestri, Roberto; Bera, Rossana; Giladi, Nir; Ghilardi, Maria Felice; Pezzoli, Gianni; Frazzitta, Giuseppe

2016-01-01

Background: The cognitive status is generally considered as a major determinant of rehabilitation outcome in Parkinson’s disease (PD). No studies about the effect of cognitive impairment on motor rehabilitation outcomes in PD have been performed before. Objective: This study is aimed to evaluate the impact of cognitive decline on rehabilitation outcomes in patients with PD. Methods: We retrospectively identified 485 patients with PD hospitalized for a 4-week Multidisciplinary Intensive Rehabilitation Treatment (MIRT) between January 2014 and September 2015. According to Mini Mental State Examination (MMSE), patients were divided into: group 1—normal cognition (score 27–30), group 2—mild cognitive impairment (score 21–26), group 3—moderate or severe cognitive impairment (score ≤ 20). According to Frontal Assessment Battery (FAB), subjects were divided into patients with normal (score ≥13.8) and pathological (score <13.8) executive functions. The outcome measures were: Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Disability Scale (PDDS), Six Minutes Walking Test (6MWT), Timed Up and Go Test (TUG) and Berg Balance Scale (BBS). Results: All scales had worse values with the increase of cognitive impairment and passing from normal to pathological executive functions. After rehabilitation, all the outcome measures improved in all groups (p < 0.0001). Between groups, the percentage of improvement was significantly different for total UPDRS (p = 0.0009, best improvement in normal MMSE group; p = 0.019, best improvement in normal FAB group), and BBS (p < 0.0001, all pairwise comparisons significant, best improvement in patients with worse MMSE score; p < 0.0001, best improvement in patients with pathological FAB). TUG (p = 0.006) and BBS (p < 0.0001) improved in patients with pathological FAB score, more than in those with normal FAB score. Conclusions: Patients gain benefit in the rehabilitative outcomes, regardless of cognition. Our data suggest that rehabilitation could be effective also in Parkinsonian subjects with cognitive impairment, as well as with dysexecutive syndrome. PMID:27563290

Personality and complex brain networks: The role of openness to experience in default network efficiency

PubMed Central

Kaufman, Scott Barry; Benedek, Mathias; Jung, Rex E.; Kenett, Yoed N.; Jauk, Emanuel; Neubauer, Aljoscha C.; Silvia, Paul J.

2015-01-01

Abstract The brain's default network (DN) has been a topic of considerable empirical interest. In fMRI research, DN activity is associated with spontaneous and self‐generated cognition, such as mind‐wandering, episodic memory retrieval, future thinking, mental simulation, theory of mind reasoning, and creative cognition. Despite large literatures on developmental and disease‐related influences on the DN, surprisingly little is known about the factors that impact normal variation in DN functioning. Using structural equation modeling and graph theoretical analysis of resting‐state fMRI data, we provide evidence that Openness to Experience—a normally distributed personality trait reflecting a tendency to engage in imaginative, creative, and abstract cognitive processes—underlies efficiency of information processing within the DN. Across two studies, Openness predicted the global efficiency of a functional network comprised of DN nodes and corresponding edges. In Study 2, Openness remained a robust predictor—even after controlling for intelligence, age, gender, and other personality variables—explaining 18% of the variance in DN functioning. These findings point to a biological basis of Openness to Experience, and suggest that normally distributed personality traits affect the intrinsic architecture of large‐scale brain systems. Hum Brain Mapp 37:773–779, 2016. © 2015 Wiley Periodicals, Inc. PMID:26610181

Prediction of conversion from mild cognitive impairment to dementia with neuronally derived blood exosome protein profile.

PubMed

Winston, Charisse N; Goetzl, Edward J; Akers, Johnny C; Carter, Bob S; Rockenstein, Edward M; Galasko, Douglas; Masliah, Eliezer; Rissman, Robert A

2016-01-01

Levels of Alzheimer's disease (AD)-related proteins in plasma neuronal derived exosomes (NDEs) were quantified to identify biomarkers for prediction and staging of mild cognitive impairment (MCI) and AD. Plasma exosomes were extracted, precipitated, and enriched for neuronal source by anti-L1CAM antibody absorption. NDEs were characterized by size (Nanosight) and shape (TEM) and extracted NDE protein biomarkers were quantified by ELISAs. Plasma NDE cargo was injected into normal mice, and results were characterized by immunohistochemistry to determine pathogenic potential. Plasma NDE levels of P-T181-tau, P-S396-tau, and Aβ1-42 were significantly higher, whereas those of neurogranin (NRGN) and the repressor element 1-silencing transcription factor (REST) were significantly lower in AD and MCI converting to AD (ADC) patients compared to cognitively normal controls (CNC) subjects and stable MCI patients. Mice injected with plasma NDEs from ADC patients displayed increased P-tau (PHF-1 antibody)-positive cells in the CA1 region of the hippocampus compared to plasma NDEs from CNC and stable MCI patients. Abnormal plasma NDE levels of P-tau, Aβ1-42, NRGN, and REST accurately predict conversion of MCI to AD dementia. Plasma NDEs from demented patients seeded tau aggregation and induced AD-like neuropathology in normal mouse CNS.

Normalizing memory recall in fibromyalgia with rehearsal: a distraction-counteracting effect.

PubMed

Leavitt, Frank; Katz, Robert S

2009-06-15

To examine the impact of distraction on the retention of rehearsed information in patients with fibromyalgia syndrome (FMS). Data refer to the neurocognitive examination of 134 patients (91 with FMS and 43 control subjects) presenting with memory loss. Four neurocognitive measures free of distraction, along with 2 measures with added distraction, were completed. Differences in the retention of rehearsed and unrehearsed information with a source of distraction present were calculated. Patients with FMS showed normal cognitive functioning on verbal memory tests free of distraction. Adding a source of distraction caused unrefreshed information to be lost at a disproportionate rate in patients with FMS. Over 87% of patients with FMS scored in the impaired range on a task of unrehearsed verbal memory. Adding a source of distraction to well-rehearsed information produced a normal rate of recall in FMS. Rehearsal mechanisms are intact in patients with FMS and play beneficial roles in managing interference from a source of distraction. In the absence of rehearsal, a source of distraction added to unrefreshed information signals a remarkable level of cognitive deficit in FMS that goes undetected by conventionally relied-upon neurocognitive measures. We present a theory to promote understanding of the cognitive deficit of people with FMS based on reduced speed of lexical activation and poor recall after distraction.

Subtle changes in daily functioning predict conversion from normal to mild cognitive impairment or dementia: an analysis of the NACC database

PubMed Central

Nowrangi, Milap A.; Rosenberg, Paul B.; Leoutsakos, Jeannie-Marie S.

2017-01-01

Background There are relatively small but observable changes in functional ability in those without Mild cognitive impairment (MCI) or dementia. The present study seeks to understand whether these individuals go on to develop MCI or dementia by assessing the association between baseline Functional Activities Questionnaire (FAQ) and conversion independent and after adjustment for cognitive tests. Methods The NACC database was used to conduct the analysis of which 7,625 participants were initially identified as having more than one visit and who were cognitively normal at their first visit. Cox proportional hazards were used to fit three models that controlled for executive and non-executive cognitive domains. A similar model was used to assess the effect of FAQ subcategories on conversion. Results Of these individuals, 1,328 converted to either MCI or dementia by visit 10. Converters had a total visit 1 FAQ score significantly higher than non-converters indicating more functional impairment at baseline. After adjustment for cognitive tests, the association between visit 1 FAQ and subsequent conversion was not attenuated. Doing taxes, remembering dates, and traveling were individually identified as significant predictors of conversion. Conclusions The FAQ can be used as an indirect measure of functional ability and is associated with conversion to MCI or dementia. There is a selective and significant association between changes in financial ability and conversion that is in accordance with other research of financial capacity. PMID:27585497

Association of cerebrospinal fluid Aβ42 with A2M gene in cognitively normal subjects

PubMed Central

Millard, Steven P.; Lutz, Franziska; Li, Ge; Galasko, Douglas R.; Farlow, Martin R.; Quinn, Joseph F.; Kaye, Jeffrey A.; Leverenz, James B.; Tsuang, Debby; Yu, Chang-En; Peskind, Elaine R.; Bekris, Lynn M.

2013-01-01

Low cerebrospinal fluid (CSF) Aβ42 levels correlate with increased brain Aβ deposition in Alzheimer’s disease (AD), which suggests a disruption in the degradation and clearance of Aβ from the brain. In addition, APOE ε4 carriers have lower CSF Aβ42 levels than non-carriers. The hypothesis of this investigation was that CSF Aβ42 levels correlate with regulatory region variation in genes that are biologically associated with degradation or clearance of Aβ from the brain. CSF Aβ42 levels were tested for associations with Aβ degradation and clearance genes and APOE ε4. Twenty-four SNPs located within the 5′ and 3′ regions of 12 genes were analyzed. The study sample consisted of 99 AD patients and 168 cognitively normal control subjects. CSF Aβ42 levels were associated with APOE ε4 status in controls but not in AD patients; A2M regulatory region SNPs were also associated with CSF Aβ42 levels in controls, but not in AD patients, even after adjusting for APOE ε4. These results suggest that genetic variation within the A2M gene influences CSF Aβ42 levels. PMID:24011543

Reaction times of normal listeners to laryngeal, alaryngeal, and synthetic speech.

PubMed

Evitts, Paul M; Searl, Jeff

2006-12-01

The purpose of this study was to compare listener processing demands when decoding alaryngeal compared to laryngeal speech. Fifty-six listeners were presented with single words produced by 1 proficient speaker from 5 different modes of speech: normal, tracheosophageal (TE), esophageal (ES), electrolaryngeal (EL), and synthetic speech (SS). Cognitive processing load was indexed by listener reaction time (RT). To account for significant durational differences among the modes of speech, an RT ratio was calculated (stimulus duration divided by RT). Results indicated that the cognitive processing load was greater for ES and EL relative to normal speech. TE and normal speech did not differ in terms of RT ratio, suggesting fairly comparable cognitive demands placed on the listener. SS required greater cognitive processing load than normal and alaryngeal speech. The results are discussed relative to alaryngeal speech intelligibility and the role of the listener. Potential clinical applications and directions for future research are also presented.

NESSTI: Norms for Environmental Sound Stimuli

PubMed Central

Hocking, Julia; Dzafic, Ilvana; Kazovsky, Maria; Copland, David A.

2013-01-01

In this paper we provide normative data along multiple cognitive and affective variable dimensions for a set of 110 sounds, including living and manmade stimuli. Environmental sounds are being increasingly utilized as stimuli in the cognitive, neuropsychological and neuroimaging fields, yet there is no comprehensive set of normative information for these type of stimuli available for use across these experimental domains. Experiment 1 collected data from 162 participants in an on-line questionnaire, which included measures of identification and categorization as well as cognitive and affective variables. A subsequent experiment collected response times to these sounds. Sounds were normalized to the same length (1 second) in order to maximize usage across multiple paradigms and experimental fields. These sounds can be freely downloaded for use, and all response data have also been made available in order that researchers can choose one or many of the cognitive and affective dimensions along which they would like to control their stimuli. Our hope is that the availability of such information will assist researchers in the fields of cognitive and clinical psychology and the neuroimaging community in choosing well-controlled environmental sound stimuli, and allow comparison across multiple studies. PMID:24023866

Cortical Cerebral Microinfarcts on 3 Tesla MRI in Patients with Vascular Cognitive Impairment.

PubMed

Ferro, Doeschka A; van Veluw, Susanne J; Koek, Huiberdina L; Exalto, Lieza G; Biessels, Geert Jan

2017-01-01

Cerebral microinfarcts (CMIs) are small ischemic lesions that are a common neuropathological finding in patients with stroke or dementia. CMIs in the cortex can now be detected in vivo on 3 Tesla MRI. To determine the occurrence of CMIs and associated clinical features in patients with possible vascular cognitive impairment (VCI). 182 memory-clinic patients (mean age 71.4±10.6, 55% male) with vascular injury on brain MRI (i.e., possible VCI) underwent a standardized work-up including 3 Tesla MRI and cognitive assessment. A control group consisted of 70 cognitively normal subjects (mean age 70.6±4.7, 60% male). Cortical CMIs and other neuroimaging markers of vascular brain injury were rated according to established criteria. Occurrence of CMIs was higher (20%) in patients compared to controls (10%). Among patients, the presence of CMIs was associated with male sex, history of stroke, infarcts, and white matter hyperintensities. CMI presence was also associated with a diagnosis of vascular dementia and reduced performance in multiple cognitive domains. CMIs on 3 Tesla MRI are common in patients with possible VCI and co-occur with imaging markers of small and large vessel disease, likely reflecting a heterogeneous etiology. CMIs are associated with worse cognitive performance, independent of other markers of vascular brain injury.

What success can teach us about failure: the plasma metabolome of older adults with superior memory and lessons for Alzheimer's disease.

PubMed

Mapstone, Mark; Lin, Feng; Nalls, Mike A; Cheema, Amrita K; Singleton, Andrew B; Fiandaca, Massimo S; Federoff, Howard J

2017-03-01

As the world population ages, primary prevention of age-related cognitive decline and disability will become increasingly important. Prevention strategies are often developed from an understanding of disease pathobiology, but models of biological success may provide additional useful insights. Here, we studied 224 older adults, some with superior memory performance (n = 41), some with normal memory performance (n = 109), and some with mild cognitive impairment or Alzheimer's disease (AD; n = 74) to understand metabolomic differences which might inform future interventions to promote cognitive health. Plasma metabolomics revealed significant differential abundance of 12 metabolites in those with superior memory relative to controls (receiver operating characteristic area under the curve [AUC] = 0.89) and the inverse abundance pattern in the mild cognitive impairment, AD (AUC = 1.0) and even preclinical AD groups relative to controls (AUC = 0.97). The 12 metabolites are components of key metabolic pathways regulating oxidative stress, inflammation, and nitric oxide bioavailability. These findings from opposite ends of the cognitive continuum highlight the role of these pathways in superior memory abilities and whose failure may contribute to age-related memory impairment. These pathways may be targeted to promote successful cognitive aging. Copyright © 2016 Elsevier Inc. All rights reserved.

Robonaut 2 and Watson: Cognitive Dexterity for Future Exploration

NASA Technical Reports Server (NTRS)

Badger, Julia M.; Strawser, Philip; Farrell, Logan; Goza, S. Michael; Claunch, Charles A.; Chancey, Raphael; Potapinski, Russell

2018-01-01

Future exploration missions will dictate a level of autonomy never before experienced in human spaceflight. Mission plans involving the uncrewed phases of complex human spacecraft in deep space will require a coordinated autonomous capability to be able to maintain the spacecraft when ground control is not available. One promising direction involves embedding intelligence into the system design both through the employment of state-of-the-art system engineering principles as well as through the creation of a cognitive network between a smart spacecraft or habitat and embodiments of cognitive agents. The work described here details efforts to integrate IBM's Watson and other cognitive computing services into NASA Johnson Space Center (JSC)'s Robonaut 2 (R2) anthropomorphic robot. This paper also discusses future directions this work will take. A cognitive spacecraft management system that is able to seamlessly collect data from subsystems, determine corrective actions, and provide commands to enable those actions is the end goal. These commands could be to embedded spacecraft systems or to a set of robotic assets that are tied into the cognitive system. An exciting collaboration with Woodside provides a promising Earth-bound testing analog, as controlling and maintaining not normally manned off-shore platforms have similar constraints to the space missions described.

Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder

PubMed Central

Bilder, Robert M.; Loo, Sandra; McGough, James J.; Whelan, Fiona; Hellemann, Gerhard; Sugar, Catherine; Del’Homme, Melissa; Sturm, Alexandra; Cowen, Jennifer; Hanada, Grant; McCracken, James T.

2016-01-01

Objective Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD. Method Children with ADHD (n = 182; age 7–14 years) completed an eight-week double blind randomized controlled trial with three arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A non-clinical comparison group (n = 93) had baseline testing, and a subset was re-tested 8 weeks later (n = 38). Analyses examined treatment effects in four cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables. Results The ADHD group showed impaired working memory relative to the non-clinical comparison group (effect size = −0.53 SD units). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN, but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group. Conclusion Combined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone, and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear necessary to achieve normalization of cognitive function in ADHD. Clinical trial registration information Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273 PMID:27453080

Relationship between Cognitive Performance and Measures of Neurodegeneration among Hispanic and White Non-Hispanic Individuals with Normal Cognition, Mild Cognitive Impairment, and Dementia.

PubMed

Burke, Shanna L; Rodriguez, Miriam J; Barker, Warren; Greig-Custo, Maria T; Rosselli, Monica; Loewenstein, David A; Duara, Ranjan

2018-02-01

The aim of this study was to determine the presence and severity of potential cultural and language bias in widely used cognitive and other assessment instruments, using structural MRI measures of neurodegeneration as biomarkers of disease stage and severity. Hispanic (n=75) and White non-Hispanic (WNH) (n=90) subjects were classified as cognitively normal (CN), amnestic mild cognitive impairment (aMCI) and mild dementia. Performance on the culture-fair and educationally fair Fuld Object Memory Evaluation (FOME) and Clinical Dementia Rating Scale (CDR) between Hispanics and WNHs was equivalent, in each diagnostic group. Volumetric and visually rated measures of the hippocampus entorhinal cortex, and inferior lateral ventricles (ILV) were measured on structural MRI scans for all subjects. A series of analyses of covariance, controlling for age, depression, and education, were conducted to compare the level of neurodegeneration on these MRI measures between Hispanics and WNHs in each diagnostic group. Among both Hispanics and WNH groups there was a progressive decrease in volume of the hippocampus and entorhinal cortex, and an increase in volume of the ILV (indicating increasing atrophy in the regions surrounding the ILV) from CN to aMCI to mild dementia. For equivalent levels of performance on the FOME and CDR, WNHs had greater levels of neurodegeneration than did Hispanic subjects. Atrophy in medial temporal regions was found to be greater among WNH than Hispanic diagnostic groups, despite the lack of statistical differences in cognitive performance between these two ethnic groups. Presumably, unmeasured factors result in better cognitive performance among WNH than Hispanics for a given level of neurodegeneration. (JINS, 2018, 24, 176-187).

Can performance of daily activities discriminate between older adults with normal cognitive function and those with Mild Cognitive Impairment?

PubMed Central

Rodakowski, Juleen; Skidmore, Elizabeth R.; Reynolds, Charles F.; Dew, Mary Amanda; Butters, Meryl A.; Holm, Margo B.; Lopez, Oscar L.; Rogers, Joan C.

2014-01-01

OBJECTIVES Our primary aim was to examine whether preclinical disability in performance of cognitively-focused instrumental activities of daily living (C-IADL) tasks can discriminate between older adults with normal cognitive function and those with Mild Cognitive Impairment (MCI). The secondary purpose was to determine the two tasks with the strongest psychometric properties and assess their discriminative ability. Our goal was to generate diagnosis-relevant information about cognitive changes associated with MCI and DSM-5 Mild Neurocognitive Disorder. DESIGN Secondary analyses of cross-sectional data from a cohort of individuals diagnosed with normal cognitive function or MCI. SETTING Private home locations in Pittsburgh, PA. PARTICIPANTS Older adults with remitted major depression (N=157). MEASUREMENTS Diagnosis of cognitive status was made by the Alzheimer’s Disease Research Center at the University of Pittsburgh. Performance of 8 C-IADL was measured using the criterion-referenced, observation-based Performance Assessment of Self-Care Skills (PASS). RESULTS A total of 96 older adults with normal cognitive function (mean age=72.5, SD=5.9) and 61 older adults with MCI (mean age=75.5, SD=6.3) participated. The 8 C-IADL demonstrated 81% accuracy in discriminating cognitive status (area under curve 0.81, p<0.001). Two tasks (shopping and checkbook balancing) were the most discriminating (area under curve 0.80, p<0.001); they demonstrated similar ability, as the 8 C-IADL, to discriminate cognitive status. Assessing performance on these two C-IADL takes 10–15 minutes. CONCLUSION This is the first demonstration of the discriminative ability of preclinical disability in distinguishing MCI from cognitively normal older adults. These findings highlight potential tasks, when measured with the observation-based PASS, which demonstrate increased effort for individuals with MCI. These tasks may be considered when attempting to diagnose MCI or Mild Neurocognitive Disorder in clinical practice and research. PMID:24890517

Semantic error patterns on the Boston Naming Test in normal aging, amnestic mild cognitive impairment, and mild Alzheimer's disease: is there semantic disruption?

PubMed

Balthazar, Marcio Luiz Figueredo; Cendes, Fernando; Damasceno, Benito Pereira

2008-11-01

Naming difficulty is common in Alzheimer's disease (AD), but the nature of this problem is not well established. The authors investigated the presence of semantic breakdown and the pattern of general and semantic errors in patients with mild AD, patients with amnestic mild cognitive impairment (aMCI), and normal controls by examining their spontaneous answers on the Boston Naming Test (BNT) and verifying whether they needed or were benefited by semantic and phonemic cues. The errors in spontaneous answers were classified in four mutually exclusive categories (semantic errors, visual paragnosia, phonological errors, and omission errors), and the semantic errors were further subclassified as coordinate, superordinate, and circumlocutory. Patients with aMCI performed normally on the BNT and needed fewer semantic and phonemic cues than patients with mild AD. After semantic cues, subjects with aMCI and control subjects gave more correct answers than patients with mild AD, but after phonemic cues, there was no difference between the three groups, suggesting that the low performance of patients with AD cannot be completely explained by semantic breakdown. Patterns of spontaneous naming errors and subtypes of semantic errors were similar in the three groups, with decreasing error frequency from coordinate to superordinate to circumlocutory subtypes.

Fibrinogen gamma-A chain precursor in CSF: a candidate biomarker for Alzheimer's disease

PubMed Central

Lee, Joung Wook; Namkoong, Hong; Kim, Hyun Kee; Kim, Sanghee; Hwang, Dong Whi; Na, Hae Ri; Ha, Seon-Ah; Kim, Jae-Ryong; Kim, Jin Woo

2007-01-01

Background Cerebrospinal fluid (CSF) may be valuable for exploring protein markers for the diagnosis of Alzheimer's disease (AD). The prospect of early detection and treatment, to slow progression, holds hope for aging populations with increased average lifespan. The aim of the present study was to investigate candidate CSF biological markers in patients with mild cognitive impairment (MCI) and AD and compare them with age-matched normal control subjects. Methods We applied proteomics approaches to analyze CSF samples derived from 27 patients with AD, 3 subjects with MCI and 30 controls. The AD group was subdivided into three groups by clinical severity according to clinical dementia rating (CDR), a well known clinical scale for dementia. Results We demonstrated an elevated level of fibrinogen gamma-A chain precursor protein in CSF from patients with mild cognitive impairment and AD compared to the age-matched normal subjects. Moreover, its expression was more prominent in the AD group than in the MCI and correlated with disease severity and progression. In contrast, fibrinogen gamma-A chain precursor protein was detected very low in the age-matched normal group. Conclusion These findings suggest that the CSF level of fibrinogen gamma-A chain precursor may be a candidate biomarker for AD. PMID:17565664

[Cognitive event-related brain potentials (P300) in patients with normal pressure hydrocephalus. Results of a prospective study].

PubMed

de la Calzada, M D; Poca, M A; Sahuquillo, J; Matarín, M; Mataró, M; Solana, E

2010-01-01

To determine the response to cognitive event-related potentials (P300) in patients with normal-pressure hydrocephalus (NPH) and their relationship with clinical and cognitive status before and after shunt surgery. We performed a prospective study in a series of 26 patients with NPH who underwent clinical and cognitive assessment before surgery and 6 months afterwards. Visual P300 potentials obtained before and after treatment were also compared with those obtained in 18 healthy volunteers. Before shunting, the P300 wave was detected in 11 (42.3%) NPH patients, compared with the 18 (100%) volunteers. Six months after shunting, the P300 wave was found in 20 (76.9%) NPH patients. P300 latency was significantly longer in NPH patients than in the control group before surgery, but not at 6 months after surgery. No significant differences in neuropsychological studies or in the level of dependence for daily life activities were found between the subgroups of NPH patients with and without pre-surgical P300 waves, or between changes in P300 parameters and clinical and cognitive changes. The P300 wave was delayed or undetectable in a substantial percentage of patients with NPH before surgery. These alterations can be reversed by shunting. P300 analysis and neuropsychological tests could be complementary measures to evaluate functional status in patients with NPH.

Cognitive-behavioral therapy induces sensorimotor and specific electrocortical changes in chronic tic and Tourette's disorder.

PubMed

Morand-Beaulieu, Simon; O'Connor, Kieron P; Sauvé, Geneviève; Blanchet, Pierre J; Lavoie, Marc E

2015-12-01

Tic disorders, such as the Gilles de la Tourette syndrome and persistent tic disorder, are neurodevelopmental movement disorders involving impaired motor control. Hence, patients show repetitive unwanted muscular contractions in one or more parts of the body. A cognitive-behavioral therapy, with a particular emphasis on the psychophysiology of tic expression and sensorimotor activation, can reduce the frequency and intensity of tics. However, its impact on motor activation and inhibition is not fully understood. To study the effects of a cognitive-behavioral therapy on electrocortical activation, we recorded the event-related potentials (ERP) and lateralized readiness potentials (LRP), before and after treatment, of 20 patients with tic disorders and 20 healthy control participants (matched on age, sex and intelligence), during a stimulus-response compatibility inhibition task. The cognitive-behavioral therapy included informational, awareness training, relaxation, muscle discrimination, cognitive restructuration and relapse prevention strategies. Our results revealed that prior to treatment; tic patients had delayed stimulus-locked LRP onset latency, larger response-locked LRP peak amplitude, and a frontal overactivation during stimulus inhibition processing. Both stimulus-locked LRP onset latency and response-locked LRP peak amplitude normalized after the cognitive behavioral therapy completion. However, the frontal overactivation related to inhibition remained unchanged following therapy. Our results showed that P300 and reaction times are sensitive to stimulus-response compatibility, but are not related to tic symptoms. Secondly, overactivity of the frontal LPC and impulsivity in TD patients were not affected by treatment. Finally, CBT had normalizing effects on the activation of the pre-motor and motor cortex in TD patients. These results imply specific modifications of motor processes following therapy, while inhibition processes remained unchanged. Given that LRPs are partially generated within the sensorimotor and supplementary motor area, the reported reduction in tic frequency and improvements of LRPs components suggest that CBT induced a physiological change in patients' motor area. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dopaminergic Therapy Increases Go Timeouts in the Go/No-Go Task in Patients with Parkinson’s Disease

PubMed Central

Yang, Xue Q.; Lauzon, Brian; Seergobin, Ken N.; MacDonald, Penny A.

2018-01-01

Parkinson’s disease (PD) is characterized by resting tremor, rigidity and bradykinesia. Dopaminergic medications such as L-dopa treat these motor symptoms, but can have complex effects on cognition. Impulse control is an essential cognitive function. Impulsivity is multifaceted in nature. Motor impulsivity involves the inability to withhold pre-potent, automatic, erroneous responses. In contrast, cognitive impulsivity refers to improper risk-reward assessment guiding behavior. Informed by our previous research, we anticipated that dopaminergic therapy would decrease motor impulsivity though it is well known to enhance cognitive impulsivity. We employed the Go/No-go paradigm to assess motor impulsivity in PD. Patients with PD were tested using a Go/No-go task on and off their normal dopaminergic medication. Participants completed cognitive, mood, and physiological measures. PD patients on medication had a significantly higher proportion of Go trial Timeouts (i.e., trials in which Go responses were not completed prior to a deadline of 750 ms) compared to off medication (p = 0.01). No significant ON-OFF differences were found for Go trial or No-go trial response times (RTs), or for number of No-go errors. We interpret that dopaminergic therapy induces a more conservative response set, reflected in Go trial Timeouts in PD patients. In this way, dopaminergic therapy decreased motor impulsivity in PD patients. This is in contrast to the widely recognized effects of dopaminergic therapy on cognitive impulsivity leading in some patients to impulse control disorders. Understanding the nuanced effects of dopaminergic treatment in PD on cognitive functions such as impulse control will clarify therapeutic decisions. PMID:29354045

Enhancing Innovation and Underlying Neural Mechanisms Via Cognitive Training in Healthy Older Adults

PubMed Central

Chapman, Sandra B.; Spence, Jeffrey S.; Aslan, Sina; Keebler, Molly W.

2017-01-01

Non-invasive interventions, such as cognitive training (CT) and physical exercise, are gaining momentum as ways to augment both cognitive and brain function throughout life. One of the most fundamental yet little studied aspects of human cognition is innovative thinking, especially in older adults. In this study, we utilize a measure of innovative cognition that examines both the quantity and quality of abstracted interpretations. This randomized pilot trial in cognitively normal adults (56–75 years) compared the effect of cognitive reasoning training (SMART) on innovative cognition as measured by Multiple Interpretations Measure (MIM). We also examined brain changes in relation to MIM using two MRI-based measurement of arterial spin labeling (ASL) to measure cerebral blood flow (CBF) and functional connectivity MRI (fcMRI) to measure default mode and central executive network (CEN) synchrony at rest. Participants (N = 58) were randomized to the CT, physical exercise (physical training, PT) or control (CN) group where CT and PT groups received training for 3 h/week over 12 weeks. They were assessed at baseline-, mid- and post-training using innovative cognition and MRI measures. First, the CT group showed significant gains pre- to post-training on the innovation measure whereas the physical exercise and control groups failed to show significant gains. Next, the CT group showed increased CBF in medial orbitofrontal cortex (mOFC) and bilateral posterior cingulate cortex (PCC), two nodes within the Default Mode Network (DMN) compared to physical exercise and control groups. Last, significant correlations were found between innovation performance and connectivity of two major networks: CEN (positive correlation) and DMN (negative correlation). These results support the view that both the CEN and DMN are important for enhancement of innovative cognition. We propose that neural mechanisms in healthy older adults can be modified through reasoning training to better subserve enhanced innovative cognition. PMID:29062276

Aerobic Physical Exercise Improved the Cognitive Function of Elderly Males but Did Not Modify Their Blood Homocysteine Levels

PubMed Central

Antunes, Hanna Karen M.; De Mello, Marco Túlio; de Aquino Lemos, Valdir; Santos-Galduróz, Ruth Ferreira; Camargo Galdieri, Luciano; Amodeo Bueno, Orlando Francisco; Tufik, Sergio; D'Almeida, Vânia

2015-01-01

Background Physical exercise influences homocysteine (Hcy) concentrations, cognitive function and the metabolic profile. The purpose of this study was to investigate the influence of regular physical exercise on Hcy levels, the metabolic profile and cognitive function in healthy elderly males before and after an endurance exercise program. Methods Forty-five healthy and sedentary volunteers were randomized into 2 groups: (1) a control group asked not to change their normal everyday activities and not to start any regular physical exercise program and (2) an experimental group trained at a heart rate intensity corresponding to ventilatory threshold 1 (VT-1) for 60 min/day 3 times weekly on alternate days for 6 months using a cycle ergometer. All volunteers underwent cognitive evaluations, blood sample analyses and ergospirometric assessments. Results A significant improvement in cognitive function was observed in the experimental group compared with the control group (p < 0.05). No significant changes in Hcy levels were observed in the experimental group (p > 0.05), but there was a significant increase in peak oxygen consumption and workload at VT-1 as well as a significant improvement in cholesterol, triglycerides, HDL, glucose, alkaline phosphatase, urea, T3, T4 and prostate-specific antigen compared with the control group (p < 0.05). Conclusion The data suggest that a physical exercise program does not reduce Hcy levels in healthy elderly males, although it improves the cardiovascular and metabolic profile as well as cognitive function. PMID:25759715

Gender difference in association of cognition with BDNF in chronic schizophrenia.

PubMed

Zhang, Xiang Yang; Chen, Da-Chun; Tan, Yun-Long; Tan, Shu-Ping; Wang, Zhi-Ren; Yang, Fu-De; Xiu, Mei-Hong; Hui, Li; Lv, Meng-Han; Zunta-Soares, Giovana B; Soares, Jair C

2014-10-01

While numerous studies have reported that brain-derived neurotrophic factor (BDNF) may be involved in the pathophysiology of schizophrenia, very few studies have explored its association with cognitive impairment or gender differences in schizophrenia which we explored. We compared gender differences in 248 chronic schizophrenic patients (male/female=185/63) to 188 healthy controls (male/female=98/90) on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and serum BDNF. Schizophrenic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). Our results showed that schizophrenic patients performed worse than normals on most of the cognitive tasks, and male patients had significantly lower immediate memory and delayed memory scores than female patients. BDNF levels were significantly lower in patients than controls, and male patients had significantly lower BDNF levels than female patients. For the patients, BDNF was positively associated with immediate memory and the RBANS total score. Furthermore, these associations were only observed in female not male patients. Among healthy controls, no gender difference was observed in cognitive domains and BDNF levels, or in the association between BDNF and cognition. Our results suggest gender differences in cognitive impairments, BDNF levels and their association in chronic patients with schizophrenia. However, the findings should be regarded as preliminary due to the cross-sectional design and our chronic patients, which need replication in a first-episode and drug naïve patients using a longitudinal study. Copyright © 2014 Elsevier Ltd. All rights reserved.

Confirmatory factor analysis reveals a latent cognitive structure common to bipolar disorder, schizophrenia, and normal controls.

PubMed

Schretlen, David J; Peña, Javier; Aretouli, Eleni; Orue, Izaskun; Cascella, Nicola G; Pearlson, Godfrey D; Ojeda, Natalia

2013-06-01

We sought to determine whether a single hypothesized latent factor structure would characterize cognitive functioning in three distinct groups. We assessed 576 adults (340 community controls, 126 adults with bipolar disorder, and 110 adults with schizophrenia) using 15 measures derived from nine cognitive tests. Confirmatory factor analysis (CFA) was conducted to examine the fit of a hypothesized six-factor model. The hypothesized factors included attention, psychomotor speed, verbal memory, visual memory, ideational fluency, and executive functioning. The six-factor model provided an excellent fit for all three groups [for community controls, root mean square error of approximation (RMSEA) <0.048 and comparative fit index (CFI) = 0.99; for adults with bipolar disorder, RMSEA = 0.071 and CFI = 0.99; and for adults with schizophrenia, RMSEA = 0.06 and CFI = 0.98]. Alternate models that combined fluency with processing speed or verbal and visual memory reduced the goodness of fit. Multi-group CFA results supported factor invariance across the three groups. Confirmatory factor analysis supported a single six-factor structure of cognitive functioning among patients with schizophrenia or bipolar disorder and community controls. While the three groups clearly differ in level of performance, they share a common underlying architecture of information processing abilities. These cognitive factors could provide useful targets for clinical trials of treatments that aim to enhance information processing in persons with neurological and neuropsychiatric disorders. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Plasma tau in Alzheimer disease.

PubMed

Mattsson, Niklas; Zetterberg, Henrik; Janelidze, Shorena; Insel, Philip S; Andreasson, Ulf; Stomrud, Erik; Palmqvist, Sebastian; Baker, David; Tan Hehir, Cristina A; Jeromin, Andreas; Hanlon, David; Song, Linan; Shaw, Leslie M; Trojanowski, John Q; Weiner, Michael W; Hansson, Oskar; Blennow, Kaj

2016-10-25

To test whether plasma tau is altered in Alzheimer disease (AD) and whether it is related to changes in cognition, CSF biomarkers of AD pathology (including β-amyloid [Aβ] and tau), brain atrophy, and brain metabolism. This was a study of plasma tau in prospectively followed patients with AD (n = 179), patients with mild cognitive impairment (n = 195), and cognitive healthy controls (n = 189) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and cross-sectionally studied patients with AD (n = 61), mild cognitive impairment (n = 212), and subjective cognitive decline (n = 174) and controls (n = 274) from the Biomarkers for Identifying Neurodegenerative Disorders Early and Reliably (BioFINDER) study at Lund University, Sweden. A total of 1284 participants were studied. Associations were tested between plasma tau and diagnosis, CSF biomarkers, MRI measures, 18 fluorodeoxyglucose-PET, and cognition. Higher plasma tau was associated with AD dementia, higher CSF tau, and lower CSF Aβ 42 , but the correlations were weak and differed between ADNI and BioFINDER. Longitudinal analysis in ADNI showed significant associations between plasma tau and worse cognition, more atrophy, and more hypometabolism during follow-up. Plasma tau partly reflects AD pathology, but the overlap between normal aging and AD is large, especially in patients without dementia. Despite group-level differences, these results do not support plasma tau as an AD biomarker in individual people. Future studies may test longitudinal plasma tau measurements in AD. © 2016 American Academy of Neurology.

Cognitive deficits in recent-onset and chronic schizophrenia☆

PubMed Central

Sponheim, S.R.; Jung, R.E.; Seidman, L.J.; Mesholam-Gately, R.I.; Manoach, D.S.; O'Leary, D.S.; Ho, B.C.; Andreasen, N.C.; Lauriello, J.; Schulz, S.C.

2014-01-01

Although cognitive dysfunction is a primary characteristic of schizophrenia, only recently have investigations begun to pinpoint when the dysfunction develops in the individual afflicted by the disorder. Research to date provides evidence for significant cognitive impairments prior to disorder onset. Less is known about the course of cognitive dysfunction from onset to the chronic phase of schizophrenia. Although longitudinal studies are optimal for assessing stability of cognitive deficits, practice effects often confound assessments, and large and representative subject samples have not been followed over long periods of time. We report results of a cross-sectional study of cognitive deficits early and late in the course of schizophrenia carried out at four different geographic locations to increase sample size and generalizability of findings. We examined a broad set of cognitive functions in 41 recent-onset schizophrenia patients and 106 chronic schizophrenia patients. The study included separate groups of 43 matched controls for the recent-onset sample and 105 matched controls for the chronic schizophrenia sample in order to evaluate the effects of cohort (i.e., age) and diagnosis (i.e., schizophrenia) on cognitive functions. All measures of cognitive function showed effects of diagnosis; however, select time-based measures of problem solving and fine motor dexterity exhibited interactions of diagnosis and cohort indicating that these deficits may progress beyond what is expected with normal aging. Also, worse recall of material in episodic memory was associated with greater length of illness. Nevertheless, findings indicate that nearly all cognitive deficits are comparably impaired across recent-onset and chronic schizophrenia. PMID:19878956

Cognitive deficits in recent-onset and chronic schizophrenia.

PubMed

Sponheim, S R; Jung, R E; Seidman, L J; Mesholam-Gately, R I; Manoach, D S; O'Leary, D S; Ho, B C; Andreasen, N C; Lauriello, J; Schulz, S C

2010-05-01

Although cognitive dysfunction is a primary characteristic of schizophrenia, only recently have investigations begun to pinpoint when the dysfunction develops in the individual afflicted by the disorder. Research to date provides evidence for significant cognitive impairments prior to disorder onset. Less is known about the course of cognitive dysfunction from onset to the chronic phase of schizophrenia. Although longitudinal studies are optimal for assessing stability of cognitive deficits, practice effects often confound assessments, and large and representative subject samples have not been followed over long periods of time. We report results of a cross-sectional study of cognitive deficits early and late in the course of schizophrenia carried out at four different geographic locations to increase sample size and generalizability of findings. We examined a broad set of cognitive functions in 41 recent-onset schizophrenia patients and 106 chronic schizophrenia patients. The study included separate groups of 43 matched controls for the recent-onset sample and 105 matched controls for the chronic schizophrenia sample in order to evaluate the effects of cohort (i.e., age) and diagnosis (i.e., schizophrenia) on cognitive functions. All measures of cognitive function showed effects of diagnosis; however, select time-based measures of problem solving and fine motor dexterity exhibited interactions of diagnosis and cohort indicating that these deficits may progress beyond what is expected with normal aging. Also, worse recall of material in episodic memory was associated with greater length of illness. Nevertheless, findings indicate that nearly all cognitive deficits are comparably impaired across recent-onset and chronic schizophrenia. Published by Elsevier Ltd.

Associations between Markers of Glucose and Insulin Function and Cognitive Function in Healthy African American Elders

PubMed Central

Skinner, Jeannine S.; Morgan, Amy; Hernandez-Saucedo, Hector; Hansen, Angela; Corbett, Selena; Arbuckle, Matthew; Leverenz, James BA; Wilkins, Consuelo H.; Craft, Suzanne; Baker, Laura D.

2015-01-01

Background Glucose and insulin are important moderators of cognitive function. African Americans have poorer glycemic control across the glycemic spectrum and are at increased risk for type 2 diabetes and poor cognitive health. It is unclear which glucoregulatory markers predict cognitive function in this at-risk population. The purpose of this study was to examine the association between cognitive function and common markers of glucoregulation in non-diabetic African Americans elders. Methods Thirty-four, community-dwelling African Americans, aged 50-75 years completed cognitive testing and blood collection as part of a health screening assessment. Cognitive outcomes were composite scores derived from neuropsychological tests of executive function and verbal memory. Linear regression was used to examine relationships between cognitive composite scores and fasting blood levels of glucose, insulin, and hemoglobin A1C, with adjustments for age, education, body mass index, and antihypertensive medication use. Results Fasting plasma glucose was negatively associated with executive function (β=−0.41, p=0.03). There was a trend of an association between fasting plasma glucose and verbal memory (β=−0.34, p=0.06). Fasting insulin and hemoglobin A1c were not associated with cognitive function. Conclusion High non-diabetic fasting glucose levels were associated with poorer executive function and verbal memory. These results provide preliminary support for proactive glucose control in older African Americans even before glycemic criteria for type 2 diabetes are met. Our findings suggests that high-normal FPG levels may represent an early red-flag to signify increased risk of cognitive impairment or decline. PMID:26798567

Cytokine Response, Tract-Specific Fractional Anisotropy, and Brain Morphometry in Post-Stroke Cognitive Impairment.

PubMed

Kulesh, Aleksey; Drobakha, Viktor; Kuklina, Elena; Nekrasova, Irina; Shestakov, Vladimir

2018-07-01

Post-stroke cognitive impairment is a clinically heterogeneous condition and its types have a different course and prognosis. The aim of the present study is to address the roles of inflammation, white matter pathology, and brain atrophy in different neuropsychological types of cognitive impairment in the acute period of ischemic stroke. In 92 patients, we performed an assessment of the cognitive status and measured concentrations of cytokines (interleukin [IL]-1β, IL-6, tumor necrosis factor-alpha, IL-10) in liquor and serum, as well as a number of magnetic resonance imaging (MRI) morphometric parameters and fractional anisotropy. The control group consisted of 14 individuals without cerebrovascular disease. All patients had a higher level of IL-10 in serum than the control group. Patients with dysexecutive cognitive impairment had a higher concentration of IL-1β and IL-10 in liquor, IL-6 level in serum, and a lower fractional anisotropy of the ipsilateral thalamus than patients with normal cognition. Patients with mixed cognitive impairment were characterized by a lower fractional anisotropy of contralateral fronto-occipital fasciculus, compared with patients with dysexecutive cognitive impairment. Patients with both dysexecutive and mixed cognitive deficit had a wide area of leukoaraiosis and a reduced fractional anisotropy of the contralateral cingulum, compared with patients without cognitive impairment. Also, we found numerous correlations between cognitive status and levels of cytokines, MRI morphometric parameters, and fractional anisotropy of certain regions of the brain. The concentrations of cytokines in serum and cerebrospinal fluid studied in combination with MRI morphometric parameters and fractional anisotropy appear to be informative biomarkers of clinical types of post-stroke cognitive impairment. Copyright © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved.

A pilot placebo-controlled, double-blind, and randomized study on the cognition-enhancing benefits of a proprietary chicken meat ingredient in healthy subjects

PubMed Central

2013-01-01

Background It has long been postulated that the relative abundance of specific nutrients can affect cognitive processes and emotions. Newly described influences of dietary factors on neuronal function and synaptic plasticity have revealed some of the vital mechanisms that could be responsible for the action of diet on brain health and cognitive function. Here, through a double-blind, randomized, placebo-controlled trial, we asked if the newly discovered chicken meat ingredient-168 (CMI-168) could be beneficial to the cognitive function in healthy adults. Methods Normal, healthy subjects were supplemented with either placebo or CMI-168 for 6 weeks. The subjects were given a series of cognitive tests to examine their levels of cognitive functioning at the beginning and end of supplementation, as well as two weeks after termination of supplementation. The combination of these tests, namely Digit Span Backwards, Letter-Number Sequencing, and the Rey Auditory Verbal Learning Test (RAVLT), was used to assess the subjects’ attention and working memory. For all comparisons, the probability level of p < 0.05 was taken as statistically significant using repeated measure 2-way ANOVA followed by Bonferroni post-hoc test. Results Overall, subjects supplemented with CMI-168 showed significantly (p < 0.01) better performance in all cognitive tests after 6 weeks’ supplementation compared to control and such superior performance was maintained even 2 weeks after termination of supplementation. Conclusions The present study reveals the cognition-enhancing properties of a recently developed chicken meat ingredient, likely arising from the promotion of attention and prefrontal cortex functions. PMID:23945213

Cortical thickness in neuropsychologically near-normal schizophrenia.

PubMed

Cobia, Derin J; Csernansky, John G; Wang, Lei

2011-12-01

Schizophrenia is a severe psychiatric illness with widespread impairments of cognitive functioning; however, a certain percentage of subjects are known to perform in the normal range on neuropsychological measures. While the cognitive profiles of these individuals have been examined, there has been relatively little attention to the neuroanatomical characteristics of this important subgroup. The aims of this study were to statistically identify schizophrenia subjects with relatively normal cognition, examine their neuroanatomical characteristics relative to their more impaired counterparts using cortical thickness mapping, and to investigate relationships between these characteristics and demographic variables to better understand the nature of cognitive heterogeneity in schizophrenia. Clinical, neuropsychological, and MRI data were collected from schizophrenia (n = 79) and healthy subjects (n = 65). A series of clustering algorithms on neuropsychological scores was examined, and a 2-cluster solution that separated subjects into neuropsychologically near-normal (NPNN) and neuropsychologically impaired (NPI) groups was determined most appropriate. Surface-based cortical thickness mapping was utilized to examine differences in thinning among schizophrenia subtypes compared with the healthy participants. A widespread cortical thinning pattern characteristic of schizophrenia emerged in the NPI group, while NPNN subjects demonstrated very limited thinning relative to healthy comparison subjects. Analysis of illness duration indicated minimal effects on subtype classification and cortical thickness results. Findings suggest a strong link between cognitive impairment and cortical thinning in schizophrenia, where subjects with near-normal cognitive abilities also demonstrate near-normal cortical thickness patterns. While generally supportive of distinct etiological processes for cognitive subtypes, results provide direction for further examination of additional neuroanatomical differences. Copyright © 2011 Elsevier B.V. All rights reserved.

Multichannel linear descriptors analysis for event-related EEG of vascular dementia patients during visual detection task.

PubMed

Lou, Wutao; Xu, Jin; Sheng, Hengsong; Zhao, Songzhen

2011-11-01

Multichannel EEG recorded in a task condition could contain more information about cognition. However, that has not been widely investigated in the vascular-dementia (VaD)- related studies. The purpose of this study was to explore the differences of brain functional states between VaD patients and normal controls while performing a detection task. Three multichannel linear descriptors, i.e. spatial complexity (Ω), field strength (Σ) and frequency of field changes (Φ), were applied to analyse four frequency bands (delta, theta, alpha and beta) of multichannel event-related EEG signals for 12 VaD patients (mean age ± SD: 69.25 ± 10.56 years ; MMSE score ± SD: 22.58 ± 4.42) and 12 age-matched healthy subjects (mean age ± SD: 67.17 ± 5.97 years ; MMSE score ± SD: 29.08 ± 0.9). The correlations between the three measures and MMSE scores were also analysed. VaD patients showed a significant higher Ω value in the delta (p = 0.013) and theta (p = 0.021) frequency bands, a lower Σ value (p = 0.011) and a higher Φ (p = 0.008) value in the delta frequency band compared with normal controls. The MMSE scores were negatively correlated with the Ω (r = -0.52, p = 0.01) and Φ (r = -0.47, p = 0.02) values in the delta frequency band. The results indicated the VaD patients presented a reduction of synchronization in the slow frequency band during target detection, and suggested more neurons might be activated in VaD patients compared with normal controls. The Ω and Φ measures in the delta frequency band might be used to evaluate the degree of cognitive dysfunction. The multichannel linear descriptors are promising measures to reveal the differences in brain functions between VaD patients and normal subjects, and could potentially be used to evaluate the degree of cognitive dysfunction in VaD patients. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

A randomized controlled trial of brain training with non-action video games in older adults: results of the 3-month follow-up

PubMed Central

Ballesteros, Soledad; Mayas, Julia; Prieto, Antonio; Toril, Pilar; Pita, Carmen; Laura, Ponce de León; Reales, José M.; Waterworth, John A.

2015-01-01

This randomized controlled study (ClinicalTrials.gov NCT02007616) investigated the maintenance of training effects of 20 1-hr non-action video game training sessions with selected games from a commercial package on several age-declining cognitive functions and subjective wellbeing after a 3-month no-contact period. Two groups of cognitively normal older adults participated in both the post-training (posttest) and the present follow-up study, the experimental group who received training and the control group who attended several meetings with the research team during the study but did not receive training. Groups were similar at baseline on demographics, vocabulary, global cognition, and depression status. Significant improvements in the trained group, and no variation in the control group had been previously found at posttest, in processing speed, attention and visual recognition memory, as well as in two dimensions of subjective wellbeing. In the current study, improvement from baseline to 3 months follow-up was found only in wellbeing (Affection and Assertivity dimensions) in the trained group whereas there was no change in the control group. Previous significant improvements in processing speed, attention and spatial memory become non-significant after the 3-month interval. Training older adults with non-action video games enhanced aspects of cognition just after training but this effect disappeared after a 3-month no-contact follow-up period. Cognitive plasticity can be induced in older adults by training, but to maintain the benefits periodic boosting sessions would be necessary. PMID:25926790

A randomized controlled trial of brain training with non-action video games in older adults: results of the 3-month follow-up.

PubMed

Ballesteros, Soledad; Mayas, Julia; Prieto, Antonio; Toril, Pilar; Pita, Carmen; Laura, Ponce de León; Reales, José M; Waterworth, John A

2015-01-01

This randomized controlled study (ClinicalTrials.gov NCT02007616) investigated the maintenance of training effects of 20 1-hr non-action video game training sessions with selected games from a commercial package on several age-declining cognitive functions and subjective wellbeing after a 3-month no-contact period. Two groups of cognitively normal older adults participated in both the post-training (posttest) and the present follow-up study, the experimental group who received training and the control group who attended several meetings with the research team during the study but did not receive training. Groups were similar at baseline on demographics, vocabulary, global cognition, and depression status. Significant improvements in the trained group, and no variation in the control group had been previously found at posttest, in processing speed, attention and visual recognition memory, as well as in two dimensions of subjective wellbeing. In the current study, improvement from baseline to 3 months follow-up was found only in wellbeing (Affection and Assertivity dimensions) in the trained group whereas there was no change in the control group. Previous significant improvements in processing speed, attention and spatial memory become non-significant after the 3-month interval. Training older adults with non-action video games enhanced aspects of cognition just after training but this effect disappeared after a 3-month no-contact follow-up period. Cognitive plasticity can be induced in older adults by training, but to maintain the benefits periodic boosting sessions would be necessary.

Boosting Cognition With Music in Patients With Disorders of Consciousness.

PubMed

Castro, Maïté; Tillmann, Barbara; Luauté, Jacques; Corneyllie, Alexandra; Dailler, Frédéric; André-Obadia, Nathalie; Perrin, Fabien

2015-09-01

Music listening conveys beneficial effects on cognitive processes in both normal and pathologic cerebral functioning. Surprisingly, no quantitative study has evaluated the potential effects of music on cognition and consciousness in patients with disorders of consciousness. The aim of the present study was to evaluate the effect of music on cerebral processing in patients with disorders of consciousness. Using bedside electroencephalographic recording, we acquired in 13 patients with disorders of consciousness event-related potentials to the patient's first name after either an excerpt of the patient's preferred music (music condition) or a continuous sound (control condition). The cerebral response to the patient's first name was more often observed in the music condition, than in the control condition. Furthermore, the presence or absence of a discriminative response in the music condition seemed to be associated with a favorable or unfavorable outcome, respectively. These findings demonstrate for the first time that music has a beneficial effect on cognitive processes of patients with disorders of consciousness. The autobiographical characteristics of music, that is, its emotional and personal relevance, probably increase arousal and/or awareness. © The Author(s) 2015.

Impaired ability to organize information in individuals with autism spectrum disorders and their siblings.

PubMed

Sumiyoshi, Chika; Kawakubo, Yuki; Suga, Motomu; Sumiyoshi, Tomiki; Kasai, Kiyoto

2011-03-01

Despite rigorous research on disturbances of executive function and social cognition in autism spectrum disorders (ASD), little information has been available concerning higher cognitive functions, such as the ability to focus and associate relevant features to form categories, or 'organizing of information'. The purpose of this study was to investigate this issue by using the Wisconsin Card Sorting Test (WCST) and the Verbal Learning Task (VLT). Cognitive assessments were conducted in 22 individuals with ASD, 14 non-affected siblings, and 15 age-matched control subjects. Overall, individuals with ASD performed significantly worse on the WCST and VLT compared to their siblings and normal control subjects. Although siblings performed generally well on both tasks, they exhibited similar degree of perseverative responses in the WCST compared to the probands. A linear increase of the memory organization score in the VLT was also absent in siblings as well as the ASD group. These results suggest an impaired ability to organize information is one of the cognitive endophenotypes for ASD. Copyright © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Reduced Empathy Scores in Patients with Parkinson's Disease: A Non-Motor Symptom Associated with Advanced Disease Stages.

PubMed

Schmidt, Nele; Paschen, Laura; Deuschl, Günther; Witt, Karsten

2017-01-01

Empathy describes the ability to infer and share emotional experiences of other people and is a central component of normal social functioning. Impaired empathy might be a non-motor symptom in Parkinson's disease (PD). To examine empathic abilities and their relationship to clinical and cognitive functioning in PD patients. Empathy was measured in 75 non-demented PD patients and 34 age-matched healthy controls using a German version of the Interpersonal Reactivity Index. Moreover, we collected demographic and clinical data and conducted a comprehensive neuropsychological test battery. PD patients had a significant lower global empathy score than healthy controls. Furthermore, we found significant group differences for the cognitive empathy scales but not for the scales which are sensitive for affective empathy components. The empathy decrease was significantly higher in advanced Hoehn & Yahr stages. There were only sporadic significant correlations between empathy scores and cognitive variables. PD patients show a stage dependent empathy score decrease which is driven mainly by cognitive aspects of empathy. However, emotional empathy aspects are not reduced.

Numerical and arithmetical cognition: a longitudinal study of process and concept deficits in children with learning disability.

PubMed

Geary, D C; Hamson, C O; Hoard, M K

2000-11-01

Based on the stability and level of performance on standard achievement tests in first and second grade (mean age in first grade = 82 months), children with IQ scores in the low-average to high-average range were classified as learning disabled (LD) in mathematics (MD), reading (RD), or both (MD/RD). These children (n = 42), a group of children who showed variable achievement test performance across grades (n = 16), and a control group of academically normal peers (n = 35) were administered a series of experimental and psychometric tasks. The tasks assessed number comprehension and production skills, counting knowledge, arithmetic skills, working memory, the ease of activation of phonetic representations of words and numbers, and spatial abilities. The children with variable achievement test performance did not differ from the academically normal children in any cognitive domain, whereas the children in the LD groups showed specific patterns of cognitive deficit, above and beyond the influence of IQ. Discussion focuses on the similarities and differences across the groups of LD children. Copyright 2000 Academic Press.

Cognitive and emotional functioning in binge-eating disorder: A systematic review.

PubMed

Kittel, Rebekka; Brauhardt, Anne; Hilbert, Anja

2015-09-01

Binge-eating disorder (BED) is characterized by recurrent episodes of binge eating and is associated with eating disorder and general psychopathology and overweight/obesity. Deficits in cognitive and emotional functioning for eating disorders or obesity have been reported. However, a systematic review on cognitive and emotional functioning for individuals with BED is lacking. A systematic literature search was conducted across three databases (Medline, PubMed, and PsycINFO). Overall, n = 57 studies were included in the present review. Regarding cognitive functioning (CoF), individuals with BED consistently demonstrated higher information processing biases compared to obese and normal-weight controls in the context of disorder-related stimuli (i.e., food and body cues), whereas CoF in the context of neutral stimuli appeared to be less affected. Thus, results suggest disorder-related rather than general difficulties in CoF in BED. With respect to emotional functioning (EmF), individuals with BED reported difficulties similar to individuals with other eating disorders, with a tendency to show less severe difficulties in some domains. In addition, individuals with BED reported greater emotional deficits when compared to obese and normal-weight controls. Findings suggest general difficulties in EmF in BED. Thus far, however, investigations of EmF in disorder-relevant situations are lacking. Overall, the cross-sectional findings indicate BED to be associated with difficulties in CoF and EmF. Future research should determine the nature of these difficulties, in regards to general and disorder-related stimuli, and consider interactions of both domains to foster the development and improvement of appropriate interventions in BED. © 2015 Wiley Periodicals, Inc.

White matter lesion severity is associated with reduced cognitive performances in patients with normal CSF Abeta42 levels.

PubMed

Stenset, V; Hofoss, D; Johnsen, L; Skinningsrud, A; Berstad, A E; Negaard, A; Reinvang, I; Gjerstad, L; Fladby, T

2008-12-01

To identify possible associations between white matter lesions (WML) and cognition in patients with memory complaints, stratified in groups with normal and low cerebrospinal fluid (CSF) Abeta42 values. 215 consecutive patients with subjective memory complaints were retrospectively included. Patients were stratified into two groups with normal (n = 127) or low (n = 88) CSF Abeta42 levels (cut-off is 450 ng/l). Cognitive scores from the Mini-Mental State Examination (MMSE) and the Neurobehavioral Cognitive Status Examination (Cognistat) were used as continuous dependent variables in linear regression. WML load was used as a continuous independent variable and was scored with a visual rating scale. The regression model was corrected for possible confounding factors. WML were significantly associated with MMSE and all Cognistat subscores except language (repetition and naming) and attention in patients with normal CSF Abeta42 levels. No significant associations were observed in patients with low CSF Abeta42. WML were associated with affection of multiple cognitive domains, including delayed recall and executive functions, in patients with normal CSF Abeta42 levels. The lack of such associations for patients with low CSF Abeta42 (i.e. with evidence for amyloid deposition), suggests that amyloid pathology may obscure cognitive effects of WML.

Effect of cognitive challenge on the postural control of patients with ACL reconstruction under visual and surface perturbations.

PubMed

Lion, Alexis; Gette, Paul; Meyer, Christophe; Seil, Romain; Theisen, Daniel

2018-02-01

Our study aimed to evaluate the effect of cognitive challenge on double-leg postural control under visual and surface perturbations of patients with anterior cruciate ligament reconstruction (ACLR) cleared to return to sport. Double-leg stance postural control of 19 rehabilitated patients with ACLR (age: 24.8 ± 6.7 years, time since surgery: 9.2 ± 1.6 months) and 21 controls (age: 24.9 ± 3.7 years) was evaluated in eight randomized situations combining two cognitive (with and without silent backward counting in steps of seven), two visual (eyes open, eyes closed) and two surface (stable support, foam support) conditions. Sway area and sway path of the centre of foot pressure were measured during three 20-s recordings for each situation. Higher values indicated poorer postural control. Generally, postural control of patients with ACLR and controls was similar for sway area and sway path (p > 0.05). The lack of visual anchorage and the disturbance of the plantar input by the foam support increased sway area and sway path (p < 0.001) similarly in both groups. The addition of the cognitive task decreased sway area and sway path (p < 0.001) similarly in both groups. Patients with ACLR who recently completed their rehabilitation have normalized postural control during double-leg stance tests. The use of a dual task paradigm under increased task complexity modified postural control, but in a similar way in patients with ACLR than in healthy controls. Double-leg stance tests, even under challenging conditions, are not sensitive enough to reveal postural control differences between rehabilitated patients with ACLR and controls. Copyright © 2017 Elsevier B.V. All rights reserved.

Longitudinal change of biomarkers in cognitive decline.

PubMed

Lo, Raymond Y; Hubbard, Alan E; Shaw, Leslie M; Trojanowski, John Q; Petersen, Ronald C; Aisen, Paul S; Weiner, Michael W; Jagust, William J

2011-10-01

To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Cohort study. The 59 study sites for the Alzheimer's Disease Neuroimaging Initiative. A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease's Assessment Scale-cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease's Assessment Scale-cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent.

The Effects of Congenital Heart Disease on Cognitive Development, Illness Causality Concepts, and Vulnerability.

ERIC Educational Resources Information Center

Myers-Vando, Rosemary; And Others

1979-01-01

It was found, among other things, that Ss with cardiac disease responded at lower levels of development on attainment of conservation tasks than did normal controls, and that cardiac Ss appeared to feel somewhat more vulnerable to illness in general, especially when projecting to adult health status. (DLS)

Cerebellum, Language, and Cognition in Autism and Specific Language Impairment

ERIC Educational Resources Information Center

Hodge, Steven M.; Makris, Nikos; Kennedy, David N.; Caviness, Verne S., Jr.; Howard, James; McGrath, Lauren; Steele, Shelly; Frazier, Jean A.; Tager-Flusberg, Helen; Harris, Gordon J.

2010-01-01

We performed cerebellum segmentation and parcellation on magnetic resonance images from right-handed boys, aged 6-13 years, including 22 boys with autism [16 with language impairment (ALI)], 9 boys with Specific Language Impairment (SLI), and 11 normal controls. Language-impaired groups had reversed asymmetry relative to unimpaired groups in…

Mental state attribution in schizophrenia: what distinguishes patients with "poor" from patients with "fair" mentalising skills?

PubMed

Brüne, M; Schaub, D

2012-07-01

Although many patients with schizophrenia are impaired in mental states attribution abilities, a significant number perform within normal or near-normal ranges in mental state attribution tasks. No studies have analysed cognitive or behavioural differences between patients with - to some extent - preserved mental state attribution skills and those with poor mentalising abilities. To examine characteristics of "poor" and "fair" mentalisers, 58 patients with schizophrenia performed a mental state attribution task, a test of general intelligence, and two executive functioning tests. "Poor" and "fair" mentalising skills were defined according to a median-split procedure; the median score in the patient group was also within two standard deviations of the control group. In addition, patients' social behavioural skills and psychopathological profiles were rated. Patients performing within normal or near normal ranges on the mental state attribution task had fewer social behavioural abnormalities than patients with poor mentalising abilities (even when controlled for intelligence), but did not differ in executive functioning. Fair mental state performers showed less disorganisation and excitement symptoms than poor performers. The degree of disorganisation mediated the influence of mental state attribution on social behavioural skills. Schizophrenia patients with (partially) preserved mentalising skills have fewer behavioural problems in the social domain than patients with poor mentalising abilities. Conceptual disorganisation mediates the prediction of social behavioural skills through mentalising skills, suggesting that disorganised patients may require special attention regarding social-cognitive skills training. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Analysis of collaborative communication for linguistic cues of cognitive load.

PubMed

Khawaja, M Asif; Chen, Fang; Marcus, Nadine

2012-08-01

Analyses of novel linguistic and grammatical features, extracted from transcribed speech of people working in a collaborative environment, were performed for cognitive load measurement Prior studies have attempted to assess users' cognitive load with several measures, but most of them are intrusive and disrupt normal task flow. An effective measurement of people's cognitive load can help improve their performance by deploying appropriate output and support strategies accordingly. The authors studied 33 members of bushfire management teams working collaboratively in computerized incident control rooms and involved in complex bushfire management tasks. The participants' communication was analyzed for some novel linguistic features as potential indices of cognitive load, which included sentence length, use of agreement and disagreement phrases, and use of personal pronouns, including both singular and plural pronoun types. Results showed users' different linguistic and grammatical patterns with various cognitive load levels. Specifically, with high load, people spoke more and used longer sentences, used more words that indicated disagreement with other team members, and exhibited increased use of plural personal pronouns and decreased use of singular pronouns. The article provides encouraging evidence for the use of linguistic and grammatical analysis for measuring users' cognitive load and proposes some novel features as cognitive load indices. The proposed approach may be applied to many data-intense and safety-critical task scenarios, such as emergency management departments, for example, bushfire or traffic incident management centers; air traffic control rooms; and call centers, where speech is used as part of everyday tasks.

The Bank of Standardized Stimuli (BOSS), a New Set of 480 Normative Photos of Objects to Be Used as Visual Stimuli in Cognitive Research

PubMed Central

Brodeur, Mathieu B.; Dionne-Dostie, Emmanuelle; Montreuil, Tina; Lepage, Martin

2010-01-01

There are currently stimuli with published norms available to study several psychological aspects of language and visual cognitions. Norms represent valuable information that can be used as experimental variables or systematically controlled to limit their potential influence on another experimental manipulation. The present work proposes 480 photo stimuli that have been normalized for name, category, familiarity, visual complexity, object agreement, viewpoint agreement, and manipulability. Stimuli are also available in grayscale, blurred, scrambled, and line-drawn version. This set of objects, the Bank Of Standardized Stimuli (BOSS), was created specifically to meet the needs of scientists in cognition, vision and psycholinguistics who work with photo stimuli. PMID:20532245

The Bank of Standardized Stimuli (BOSS), a new set of 480 normative photos of objects to be used as visual stimuli in cognitive research.

PubMed

Brodeur, Mathieu B; Dionne-Dostie, Emmanuelle; Montreuil, Tina; Lepage, Martin

2010-05-24

There are currently stimuli with published norms available to study several psychological aspects of language and visual cognitions. Norms represent valuable information that can be used as experimental variables or systematically controlled to limit their potential influence on another experimental manipulation. The present work proposes 480 photo stimuli that have been normalized for name, category, familiarity, visual complexity, object agreement, viewpoint agreement, and manipulability. Stimuli are also available in grayscale, blurred, scrambled, and line-drawn version. This set of objects, the Bank Of Standardized Stimuli (BOSS), was created specifically to meet the needs of scientists in cognition, vision and psycholinguistics who work with photo stimuli.

Long-term functional outcome of patients with cerebellar pilocytic astrocytoma surgically treated in childhood.

PubMed

Ait Khelifa-Gallois, N; Laroussinie, F; Puget, S; Sainte-Rose, C; Dellatolas, G

2015-01-01

Abstract Purpose: A number of studies report neurological and cognitive deficits and behavioural disorders in children after surgical treatment for a benign cerebellar tumour. The present study explores functional outcome in adolescents and adults treated for a low-grade cerebellar astrocytoma in childhood. Participants were 18 adolescents and 46 adults treated for low-grade astrocytoma in childhood. Academic achievement, professional status and neurological, cognitive and behavioural disturbances were collected using self-completed and parental questionnaires for adolescents and phone interview for adults. For the adolescent group, a control group filled in the same questionnaires. Mean time lapse from surgery was 7.8 years for adolescents and 12.9 years for adults. Five adults (11%) had major sequelae related to post-operative complications, post-operative mutism and/or brain stem involvement. All the other participants presented close-to-normal academic achievement and normal autonomy, despite a high rate of reported cognitive difficulties and difficulties related to mild neurological sequelae (fine motor skills, balance). The long-term functional outcome of low-grade cerebellar astrocytoma is generally favourable, in the absence of post-operative complications and brain stem involvement. No major impact of neurological deficits, cognitive problems and emotional disorders on academic achievement and independent functioning was observed.

Characteristics associated with willingness to participate in a randomized controlled behavioral clinical trial using home-based personal computers and a webcam.

PubMed

Dodge, Hiroko H; Katsumata, Yuriko; Zhu, Jian; Mattek, Nora; Bowman, Molly; Gregor, Mattie; Wild, Katherine; Kaye, Jeffrey A

2014-12-23

Trials aimed at preventing cognitive decline through cognitive stimulation among those with normal cognition or mild cognitive impairment are of significant importance in delaying the onset of dementia and reducing dementia prevalence. One challenge in these prevention trials is sample recruitment bias. Those willing to volunteer for these trials could be socially active, in relatively good health, and have high educational levels and cognitive function. These participants' characteristics could reduce the generalizability of study results and, more importantly, mask trial effects. We developed a randomized controlled trial to examine whether conversation-based cognitive stimulation delivered through personal computers, a webcam and the internet would have a positive effect on cognitive function among older adults with normal cognition or mild cognitive impairment. To examine the selectivity of samples, we conducted a mass mail-in survey distribution among community-dwelling older adults, assessing factors associated with a willingness to participate in the trial. Two thousand mail-in surveys were distributed to retirement communities in order to collect data on demographics, the nature and frequency of social activities, personal computer use and additional health-related variables, and interest in the prevention study. We also asked for their contact information if they were interested in being contacted as potential participants in the trial. Of 1,102 surveys returned (55.1% response rate), 983 surveys had complete data for all the variables of interest. Among them, 309 showed interest in the study and provided their contact information (operationally defined as the committed with interest group), 74 provided contact information without interest in the study (committed without interest group), 66 showed interest, but provided no contact information (interest only group), and 534 showed no interest and provided no contact information (no interest group). Compared with the no interest group, the committed with interest group were more likely to be personal computer users (odds ratio (OR) = 2.78), physically active (OR = 1.03) and had higher levels of loneliness (OR = 1.16). Increasing potential participants' familiarity with a personal computer and the internet before trial recruitment could increase participation rates and improve the generalizability of future studies of this type. The trial was registered on 29 March 2012 at ClinicalTirals.gov (ID number NCT01571427).

Common and Distinctive Patterns of Cognitive Dysfunction in Children With Benign Epilepsy Syndromes.

PubMed

Cheng, Dazhi; Yan, Xiuxian; Gao, Zhijie; Xu, Keming; Zhou, Xinlin; Chen, Qian

2017-07-01

Childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes are the most common forms of benign epilepsy syndromes. Although cognitive dysfunctions occur in children with both childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes, the similarity between their patterns of underlying cognitive impairments is not well understood. To describe these patterns, we examined multiple cognitive functions in children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes. In this study, 43 children with childhood absence epilepsy, 47 children with benign childhood epilepsy with centrotemporal spikes, and 64 control subjects were recruited; all received a standardized assessment (i.e., computerized test battery) assessing processing speed, spatial skills, calculation, language ability, intelligence, visual attention, and executive function. Groups were compared in these cognitive domains. Simple regression analysis was used to analyze the effects of epilepsy-related clinical variables on cognitive test scores. Compared with control subjects, children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes showed cognitive deficits in intelligence and executive function, but performed normally in language processing. Impairment in visual attention was specific to patients with childhood absence epilepsy, whereas impaired spatial ability was specific to the children with benign childhood epilepsy with centrotemporal spikes. Simple regression analysis showed syndrome-related clinical variables did not affect cognitive functions. This study provides evidence of both common and distinctive cognitive features underlying the relative cognitive difficulties in children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes. Our data suggest that clinicians should pay particular attention to the specific cognitive deficits in children with childhood absence epilepsy and benign childhood epilepsy with centrotemporal spikes, to allow for more discriminative and potentially more effective interventions. Copyright © 2017 Elsevier Inc. All rights reserved.

Shunting for normal pressure hydrocephalus (NPH).

PubMed

Esmonde, T; Cooke, S

2002-01-01

Since the condition was first described in 1965, the syndrome of normal pressure hydrocephalus (NPH) has conventionally been managed by placement of a cerebrospinal fluid (CSF) shunt. To determine the effectiveness of shunting procedures in promoting stability or improvement in the neurological symptoms and signs of NPH. The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 26 June 2001 using the terms 'shunt*' and 'normal pressure hydrocephalus'. Studies included for analysis were those involving the placement of a CSF shunt for the treatment of NPH as part of a randomized controlled trial. No data matching the selection criteria were found. No randomized controlled trials of shunt placement versus no shunt were found. There is no evidence to indicate whether placement of a shunt is effective in the management of NPH.

Cognitive profiles in euthymic patients with bipolar disorders: results from the FACE-BD cohort.

PubMed

Roux, Paul; Raust, Aurélie; Cannavo, Anne Sophie; Aubin, Valérie; Aouizerate, Bruno; Azorin, Jean-Michel; Bellivier, Frank; Belzeaux, Raoul; Bougerol, Thierry; Cussac, Iréna; Courtet, Philippe; Etain, Bruno; Gard, Sébastien; Job, Sophie; Kahn, Jean-Pierre; Leboyer, Marion; Olié, Emilie; Henry, Chantal; Passerieux, Christine

2017-03-01

Although cognitive deficits are a well-established feature of bipolar disorders (BD), even during periods of euthymia, little is known about cognitive phenotype heterogeneity among patients with BD. We investigated neuropsychological performance in 258 euthymic patients with BD recruited via the French network of expert centers for BD. We used a test battery assessing six domains of cognition. Hierarchical cluster analysis of the cross-sectional data was used to determine the optimal number of subgroups and to assign each patient to a specific cognitive cluster. Subsequently, subjects from each cluster were compared on demographic, clinical functioning, and pharmacological variables. A four-cluster solution was identified. The global cognitive performance was above normal in one cluster and below normal in another. The other two clusters had a near-normal cognitive performance, with above and below average verbal memory, respectively. Among the four clusters, significant differences were observed in estimated intelligence quotient and social functioning, which were lower for the low cognitive performers compared to the high cognitive performers. These results confirm the existence of several distinct cognitive profiles in BD. Identification of these profiles may help to develop profile-specific cognitive remediation programs, which might improve functioning in BD. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of Delay Duration on the WMS Logical Memory Performance of Older Adults with Probable Alzheimer's Disease, Probable Vascular Dementia, and Normal Cognition.

PubMed

Montgomery, Valencia; Harris, Katie; Stabler, Anthony; Lu, Lisa H

2017-05-01

To examine how the duration of time delay between Wechsler Memory Scale (WMS) Logical Memory I and Logical Memory II (LM) affected participants' recall performance. There are 46,146 total Logical Memory administrations to participants diagnosed with either Alzheimer's disease (AD), vascular dementia (VaD), or normal cognition in the National Alzheimer's Disease Coordinating Center's Uniform Data Set. Only 50% of the sample was administered the standard 20-35 min of delay as specified by WMS-R and WMS-III. We found a significant effect of delay time duration on proportion of information retained for the VaD group compared to its control group, which remained after adding LMI raw score as a covariate. There was poorer retention of information with longer delay for this group. This association was not as strong for the AD and cognitively normal groups. A 24.5-min delay was most optimal for differentiating AD from VaD participants (47.7% classification accuracy), an 18.5-min delay was most optimal for differentiating AD versus normal participants (51.7% classification accuracy), and a 22.5-min delay was most optimal for differentiating VaD versus normal participants (52.9% classification accuracy). Considering diagnostic implications, our findings suggest that test administration should incorporate precise tracking of delay periods. We recommend a 20-min delay with 18-25-min range. Poor classification accuracy based on LM data alone is a reminder that story memory performance is only one piece of data that contributes to complex clinical decisions. However, strict adherence to the recommended range yields optimal data for diagnostic decisions. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Study of Spirituality in Elderly With Subjective Memory Complaints.

PubMed

Trivedi, Surbhi C; Subramanyam, Alka A; Kamath, Ravindra M; Pinto, Charles

2016-01-01

Subjective memory complaints are very common among elderly. They can be due to depression, cognitive decline, or be a part of normal aging process. Spirituality is another important dimension in elderly, and it is believed to help them cope with various adversities. This study was done to find out whether any relation exists between these 2 variables in elderly. A total of 120 elderly individuals, presenting with subjective memory complaints, were divided into 3 groups - controls, elderly with depression, and elderly with mild cognitive impairment (MCI). Spirituality in them was studied by dividing it into the subdomains of self-transcendence, presence of meaning in life, search for meaning in life, and locus of control. Spirituality was the highest in controls, followed by MCI group, and then depression group. Spirituality had a direct negative relationship with severity of depression, while relationship of spirituality with severity of cognitive decline was more complex. Relationship of spirituality with mental health status in elderly patients seemed bidirectional, that is, cause as well as effect relationship. © The Author(s) 2015.

Fast decay of iconic memory in observers with mild cognitive impairments.

PubMed

Lu, Zhong-Lin; Neuse, James; Madigan, Stephen; Dosher, Barbara Anne

2005-02-01

In a previous clinical report, unusually fast decay of iconic memory was obtained from a subject who later developed Alzheimer's disease. By using the partial-report paradigm, iconic memory (a form of visual sensory memory) in a group of observers with mild cognitive impairments (MCI) was characterized and compared with that of young college-age adults and older controls. Relatively long stimulus exposures were used for all three groups to ensure that older observers could perceive the stimuli. A set of conventional neuropsychological tests assessed cognitive functions of the MCI and older control groups. We found that iconic memory decayed much faster for observers with MCI than for normal controls, old or young, although the two groups of older observers performed at equivalent levels in precue tests (assay of visibility) and tests cued at long delays (assay of short-term memory). The result suggests that fast decay of iconic memory might be a general characteristic of observers with MCI who are at much higher than average risk of developing Alzheimer's disease later in life.

Fast decay of iconic memory in observers with mild cognitive impairments

PubMed Central

Lu, Zhong-Lin; Neuse, James; Madigan, Stephen; Dosher, Barbara Anne

2005-01-01

In a previous clinical report, unusually fast decay of iconic memory was obtained from a subject who later developed Alzheimer's disease. By using the partial-report paradigm, iconic memory (a form of visual sensory memory) in a group of observers with mild cognitive impairments (MCI) was characterized and compared with that of young college-age adults and older controls. Relatively long stimulus exposures were used for all three groups to ensure that older observers could perceive the stimuli. A set of conventional neuropsychological tests assessed cognitive functions of the MCI and older control groups. We found that iconic memory decayed much faster for observers with MCI than for normal controls, old or young, although the two groups of older observers performed at equivalent levels in precue tests (assay of visibility) and tests cued at long delays (assay of short-term memory). The result suggests that fast decay of iconic memory might be a general characteristic of observers with MCI who are at much higher than average risk of developing Alzheimer's disease later in life. PMID:15665101

X Chromosome Abnormalities and Cognitive Development: Implications for Understanding Normal Human Development.

ERIC Educational Resources Information Center

Walzer, Stanley

1985-01-01

Argues that knowledge from studies of individuals with sex chromosome abnormalities can further understanding of aspects of normal human development. Studies of XO girls, XXY boys, XXX girls, and males with a fragile X chromosome are summarized to demonstrate how results contribute to knowledge about normal cognitive development and about…

Word Recognition and Basic Cognitive Processes among Reading-Disabled and Normal Readers in Arabic.

ERIC Educational Resources Information Center

Abu-Rabia, Salim; Share, David; Mansour, Maysaloon Said

2003-01-01

Investigates word identification in Arabic and basic cognitive processes in reading-disabled (RD) and normal level readers of the same chronological age, and in younger normal readers at the same reading level. Indicates significant deficiencies in morphology, working memory, and syntactic and visual processing, with the most severe deficiencies…

Cognitive Enhancement and Education

ERIC Educational Resources Information Center

Buchanan, Allen

2011-01-01

Cognitive enhancement--augmenting normal cognitive capacities--is not new. Literacy, numeracy, computers, and the practices of science are all cognitive enhancements. Science is now making new cognitive enhancements possible. Biomedical cognitive enhancements (BCEs) include the administration of drugs, implants of genetically engineered or…

Mild Cognitive Impairment (MCI)

MedlinePlus

Mild cognitive impairment (MCI) Overview Mild cognitive impairment (MCI) is an intermediate stage between the expected cognitive decline of normal aging and the more-serious decline of dementia. It ...

APOE, MAPT, and COMT and Parkinson's Disease Susceptibility and Cognitive Symptom Progression.

PubMed

Paul, Kimberly C; Rausch, Rebecca; Creek, Michelle M; Sinsheimer, Janet S; Bronstein, Jeff M; Bordelon, Yvette; Ritz, Beate

2016-04-02

Cognitive decline is well recognized in Parkinson's disease (PD) and a major concern for patients and caregivers. Apolipoprotein E (APOE), catechol-O-methyl transferase (COMT), and microtubule-associated protein tau (MAPT) are of interest related to their contributions to cognitive decline or dementia in PD. Here, we investigate whether APOE, COMT, or MAPT influence the rate of cognitive decline in PD patients. We relied on 634 PD patients and 879 controls to examine gene-PD susceptibility associations, and nested longitudinal cohort of 246 patients from the case-control study, which followed patients on average 5 years and 7.5 years into disease. We repeatedly assessed cognitive symptom progression with the MMSE and conducted a full neuropsychological battery on a subset of 183 cognitively normal patients. We used repeated-measures regression analyses to assess longitudinal associations between genotypes and cognitive progression scores. The MAPT H1 haplotype was associated with PD susceptibility. APOE 4 carriers (ɛ4+) (p = 0.03) and possibly COMT Met/Met (p = 0.06) carriers exhibited faster annual decline on the MMSE. Additionally, APOEɛ4+ carriers showed faster decline in many of the neuropsychological test scores. No such differences in neuropsychological outcomes were seen for the COMT genotypes. This work supports a growing set of research identifying overlapping etiology and pathology between synucleinopathies, such as PD, Alzheimer's disease, and tauopathies, especially in the context of cognitive dysfunction in PD. We provide support for the argument that APOE ɛ4+ and COMT Met/Met genotypes can be used as predictors of faster cognitive decline in PD.

Cognitive functioning in the first-episode of major depressive disorder: A systematic review and meta-analysis.

PubMed

Ahern, Elayne; Semkovska, Maria

2017-01-01

Cognitive deficits are frequently observed in major depression. Yet, when these deficits emerge and how they relate to the depressed state is unclear. The aim of this 2-part systematic review and meta-analysis is to determine the pattern and extent of cognitive deficits during a first-episode of depression (FED) and their persistence following FED remission. Published, peer-reviewed articles on cognitive function in FED patients through October 2015 were searched. Meta-analyses with random-effects modeling were conducted. Part 1 assessed weighted, mean effect sizes of cognitive function in FED patients relative to healthy controls. Moderator analyses of clinical and demographical variables effects were conducted. Part 2 assessed weighted, mean effect sizes of change in cognitive function at remission compared with acute FED performance in longitudinal studies. Thirty-one studies including 994 FED patients were retained in Part 1. Relative to healthy controls, small to large impairments were observed across most cognitive domains. Remission was associated with a normalization of function in processing speed, learning and memory, autobiographical memory, shifting, and IQ. Lower FED age was associated with higher IQ, but more impairment in word-list delayed memory. Four studies including 92 FED patients were retained in Part 2. Following remission, FED patients showed small improvements in processing speed and shifting but persistent impairment in inhibition and verbal fluency. Significant cognitive deficits are already identifiable during a FED, with some functions showing persistent impairment upon remission. Clinicians must consider cognitive impairment alongside mood symptoms to ensure functional recovery from the FED. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Immunological characterization and transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): case study.

PubMed

Jyonouchi, Harumi; Geng, Lee; Streck, Deanna L; Toruner, Gokce A

2012-01-07

There exists a small subset of children with autism spectrum disorders (ASD) characterized by fluctuating behavioral symptoms and cognitive skills following immune insults. Some of these children also exhibit specific polysaccharide antibody deficiency (SPAD), resulting in frequent infection caused by encapsulated organisms, and they often require supplemental intravenous immunoglobulin (IVIG) (ASD/SPAD). This study assessed whether these ASD/SPAD children have distinct immunological findings in comparison with ASD/non-SPAD or non-ASD/SPAD children. We describe 8 ASD/SPAD children with worsening behavioral symptoms/cognitive skills that are triggered by immune insults. These ASD/SPAD children exhibited delayed type food allergy (5/8), treatment-resistant seizure disorders (4/8), and chronic gastrointestinal (GI) symptoms (5/8) at high frequencies. Control subjects included ASD children without SPAD (N = 39), normal controls (N = 37), and non-ASD children with SPAD (N = 12). We assessed their innate and adaptive immune responses, by measuring the production of pro-inflammatory and counter-regulatory cytokines by peripheral blood mononuclear cells (PBMCs) in responses to agonists of toll like receptors (TLR), stimuli of innate immunity, and T cell stimulants. Transcription profiling of PB monocytes was also assessed. ASD/SPAD PBMCs produced less proinflammatory cytokines with agonists of TLR7/8 (IL-6, IL-23), TLR2/6 (IL-6), TLR4 (IL-12p40), and without stimuli (IL-1ß, IL-6, and TNF-α) than normal controls. In addition, cytokine production of ASD/SPAD PBMCs in response to T cell mitogens (IFN-γ, IL-17, and IL-12p40) and candida antigen (Ag) (IL-10, IL-12p40) were less than normal controls. ASD/non-SPAD PBMDs revealed similar results as normal controls, while non-ASD/SPAD PBMCs revealed lower production of IL-6, IL-10 and IL-23 with a TLR4 agonist. Only common features observed between ASD/SPAD and non-ASD/SPAD children is lower IL-10 production in the absence of stimuli. Transcription profiling of PB monocytes revealed over a 2-fold up (830 and 1250) and down (653 and 1235) regulation of genes in ASD/SPAD children, as compared to normal (N = 26) and ASD/non-SPAD (N = 29) controls, respectively. Enriched gene expression of TGFBR (p < 0.005), Notch (p < 0.01), and EGFR1 (p < 0.02) pathways was found in the ASD/SPAD monocytes as compared to ASD/non-SPAD controls. The Immunological findings in the ASD/SPAD children who exhibit fluctuating behavioral symptoms and cognitive skills cannot be solely attributed to SPAD. Instead, these findings may be more specific for ASD/SPAD children with the above-described clinical characteristics, indicating a possible role of these immune abnormalities in their neuropsychiatric symptoms.

Memory Alteration Test to Detect Amnestic Mild Cognitive Impairment and Early Alzheimer's Dementia in Population with Low Educational Level.

PubMed

Custodio, Nilton; Lira, David; Herrera-Perez, Eder; Montesinos, Rosa; Castro-Suarez, Sheila; Cuenca-Alfaro, José; Valeriano-Lorenzo, Lucía

2017-01-01

Background/Aims : Short tests to early detection of the cognitive impairment are necessary in primary care setting, particularly in populations with low educational level. The aim of this study was to assess the performance of Memory Alteration Test (M@T) to discriminate controls, patients with amnestic Mild Cognitive Impairment (aMCI) and patients with early Alzheimer's Dementia (AD) in a sample of individuals with low level of education. Methods : Cross-sectional study to assess the performance of the M@T (study test), compared to the neuropsychological evaluation (gold standard test) scores in 247 elderly subjects with low education level from Lima-Peru. The cognitive evaluation included three sequential stages: (1) screening (to detect cases with cognitive impairment); (2) nosological diagnosis (to determinate specific disease); and (3) classification (to differentiate disease subtypes). The subjects with negative results for all stages were considered as cognitively normal (controls). The test performance was assessed by means of area under the receiver operating characteristic (ROC) curve. We calculated validity measures (sensitivity, specificity and correctly classified percentage), the internal consistency (Cronbach's alpha coefficient), and concurrent validity (Pearson's ratio coefficient between the M@T and Clinical Dementia Rating (CDR) scores). Results : The Cronbach's alpha coefficient was 0.79 and Pearson's ratio coefficient was 0.79 ( p < 0.01). The AUC of M@T to discriminate between early AD and aMCI was 99.60% (sensitivity = 100.00%, specificity = 97.53% and correctly classified = 98.41%) and to discriminate between aMCI and controls was 99.56% (sensitivity = 99.17%, specificity = 91.11%, and correctly classified = 96.99%). Conclusions : The M@T is a short test with a good performance to discriminate controls, aMCI and early AD in individuals with low level of education from urban settings.

Physical activity and cognitive trajectories in cognitively normal adults: the adult children study.

PubMed

Pizzie, Rachel; Hindman, Halley; Roe, Catherine M; Head, Denise; Grant, Elizabeth; Morris, John C; Hassenstab, Jason J

2014-01-01

Increased physical activity may protect against cognitive decline, the primary symptom of Alzheimer disease. In this study, we examined the relationship between physical activity and trajectories of cognitive functioning over serial assessments. Cognitively normal (Clinical Dementia Rating 0) middle-aged and older adults (N=173; mean age, 60.7 ± 7.8 y) completed a self-report measure of physical activity and a battery of standard neuropsychological tests assessing processing speed, attention, executive functioning, and verbal memory. At baseline, individuals with higher physical activity levels performed better on tests of episodic memory and visuospatial functioning. Over subsequent follow-up visits, higher physical activity was associated with small performance gains on executive functioning and working memory tasks in participants with one or more copies of the apolipoprotein ε4 allele (APOE4). In APOE4 noncarriers, slopes of cognitive performance over time were not related to baseline physical activity. Our results suggest that cognitively normal older adults who report higher levels of physical activity may have slightly better cognitive performance, but the potential cognitive benefits of higher levels of physical activity over time may be most evident in individuals at genetic risk for Alzheimer disease.

Distinct and shared cognitive functions mediate event- and time-based prospective memory impairment in normal ageing

PubMed Central

Gonneaud, Julie; Kalpouzos, Grégoria; Bon, Laetitia; Viader, Fausto; Eustache, Francis; Desgranges, Béatrice

2011-01-01

Prospective memory (PM) is the ability to remember to perform an action at a specific point in the future. Regarded as multidimensional, PM involves several cognitive functions that are known to be impaired in normal aging. In the present study, we set out to investigate the cognitive correlates of PM impairment in normal aging. Manipulating cognitive load, we assessed event- and time-based PM, as well as several cognitive functions, including executive functions, working memory and retrospective episodic memory, in healthy subjects covering the entire adulthood. We found that normal aging was characterized by PM decline in all conditions and that event-based PM was more sensitive to the effects of aging than time-based PM. Whatever the conditions, PM was linked to inhibition and processing speed. However, while event-based PM was mainly mediated by binding and retrospective memory processes, time-based PM was mainly related to inhibition. The only distinction between high- and low-load PM cognitive correlates lays in an additional, but marginal, correlation between updating and the high-load PM condition. The association of distinct cognitive functions, as well as shared mechanisms with event- and time-based PM confirms that each type of PM relies on a different set of processes. PMID:21678154

Content specificity of attentional bias to threat in post-traumatic stress disorder.

PubMed

Zinchenko, A; Al-Amin, M M; Alam, M M; Mahmud, W; Kabir, N; Reza, H M; Burne, T H J

2017-08-01

Attentional bias to affective information and reduced cognitive control may maintain the symptoms of post-traumatic stress disorder (PTSD) and impair cognitive functioning. However, the role of content specificity of affective stimuli (e.g., trauma-related, emotional trauma-unrelated) in the observed attentional bias and cognitive control is less clear, as this has not been tested simultaneously before. Therefore, we examined the content specificity of attentional bias to threat in PTSD. PTSD participants (survivors of a multistory factory collapse, n=30) and matched controls (n=30) performed an Eriksen Flanker task. They identified the direction of a centrally presented target arrow, which was flanked by several task-irrelevant distractor arrows pointed to the same (congruent) or opposite direction (incongruent). Additionally, participants were presented with a picture of a face (neutral, emotional) or building (neutral=normal, emotional=collapsed multistory factory) as a task-irrelevant background image. We found that PTSD participants produced overall larger conflict effects and longer reaction times (RT) to emotional than to neutral stimuli relative to their healthy counterparts. Moreover, PTSD, but not healthy participants showed a stimulus specific dissociation in processing emotional stimuli. Emotional faces elicited longer RTs compared to neutral faces, while emotional buildings elicited faster responses, compared to neutral buildings. PTSD patients show a content-sensitive attentional bias to emotional information and impaired cognitive control. Copyright © 2017 Elsevier Ltd. All rights reserved.

Differences in knowledge of dementia among older adults with normal cognition, mild cognitive impairment, and dementia: A representative nationwide sample of Korean elders.

PubMed

Lee, Jun-Young; Park, Soowon; Kim, Ki Woong; Kwon, Ji Eyon; Park, Joon Hyuk; Kim, Moon Doo; Kim, Bong-Jo; Kim, Jeong Lan; Moon, Seok Woo; Bae, Jae Nam; Ryu, Seung-Ho; Yoon, Jong Chul; Lee, Nam-Jin; Lee, Dong Young; Lee, Dong Woo; Lee, Seok Bum; Lee, Jung Jae; Lee, Chang-Uk; Jhoo, Jin Hyeong; Cho, Maeng Je

2016-01-01

Lack of knowledge about a disease could impede early diagnosis and may lead to delays in seeking appropriate medical care. The aim of this study was to explore knowledge of dementia (KOD) and to find the determinants of KOD among three groups: older adults with normal cognition, mild cognitive impairment (MCI), and dementia. A representative nationwide sample of 6141 Korean elders aged 65 years or older participated in face-to-face interviews and answered 14 questions pertaining to general information, etiology, symptoms, and treatment of dementia. Stepwise multiple regressions and path analyses probed the relationships between various sociodemographic variables and KOD. The percentage of correct responses was only 62%. The item 'A person who remembers things that happened in the past does not have dementia' was answered correctly (false) by only 24.8-27% of the respondents in all groups. Older adults with normal cognition had higher KOD scores than those with MCI or dementia. In the normal-cognition group, KOD scores were higher among highly educated, younger, and literate women with no depression and a family history of dementia. In contrast with the determinants in the normal-cognition group, only the ability to read and write predicted KOD scores in the dementia group. Efforts to enhance KOD in elder adults are needed. Public education regarding the differences between dementia and healthy aging may increase KOD among normal elders and those with MCI. Among elders with dementia, educational materials that do not require literacy may be more helpful in increasing KOD with the aim of preventing treatment delay. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Synchrony of corticostriatal-midbrain activation enables normal inhibitory control and conflict processing in recovering alcoholic men.

PubMed

Schulte, Tilman; Müller-Oehring, Eva M; Sullivan, Edith V; Pfefferbaum, Adolf

2012-02-01

Alcohol dependence is associated with inhibitory control deficits, possibly related to abnormalities in frontoparietal cortical and midbrain function and connectivity. We examined functional connectivity and microstructural fiber integrity between frontoparietal and midbrain structures using a Stroop Match-to-Sample task with functional magnetic resonance imaging and diffusion tensor imaging in 18 alcoholic and 17 control subjects. Manipulation of color cues and response repetition sequences modulated cognitive demands during Stroop conflict. Despite similar lateral frontoparietal activity and functional connectivity in alcoholic and control subjects when processing conflict, control subjects deactivated the posterior cingulate cortex (PCC), whereas alcoholic subjects did not. Posterior cingulum fiber integrity predicted the degree of PCC deactivation in control but not alcoholic subjects. Also, PCC activity was modulated by executive control demands: activated during response switching and deactivated during response repetition. Alcoholics showed the opposite pattern: activation during repetition and deactivation during switching. Here, in alcoholic subjects, greater deviations from the normal PCC activity correlated with higher amounts of lifetime alcohol consumption. A functional dissociation of brain network connectivity between the groups further showed that control subjects exhibited greater corticocortical connectivity among middle cingulate, posterior cingulate, and medial prefrontal cortices than alcoholic subjects. In contrast, alcoholic subjects exhibited greater midbrain-orbitofrontal cortical network connectivity than control subjects. Degree of microstructural fiber integrity predicted robustness of functional connectivity. Thus, even subtle compromise of microstructural connectivity in alcoholism can influence modulation of functional connectivity and underlie alcohol-related cognitive impairment. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Mood state dependency of dysfunctional attitudes in bipolar affective disorder.

PubMed

Babakhani, Anet; Startup, Mike

2012-01-01

Studies of cognitive styles among euthymic people with bipolar affective disorder (BAD) without use of mood induction techniques to access those cognitive styles give misleading impressions of normality of those cognitions. The aim of this study was to assess dysfunctional attitudes of participants with BAD, and control participants with no previous psychiatric histories, after mood inductions. Sad and happy moods were induced within 49 BAD and 37 controls. Dysfunctional attitudes were measured following mood inductions using the Dysfunctional Attitude Scale-short form (DAS-24), which has three subscales of achievement, interpersonal, and goal attainment. It was hypothesised that within BAD the sad mood induction would help in accessing dysfunctional attitudes in all three domains relative to the happy mood induction. This was supported. It was also hypothesised that the mood inductions would not affect dysfunctional attitudes within controls. This was supported. When diagnosis was entered as a between group variable, achievement dysfunctional attitudes were significantly higher in BAD compared to controls after a happy induction. Both sad and happy moods provoked higher levels of dysfunctional attitudes within BAD. Euphoria may be related to elevated achievement dysfunctional attitudes, raising risk for mania.

Extracommunicative functions of language: verbal interference causes selective categorization impairments.

PubMed

Lupyan, Gary

2009-08-01

In addition to its communicative functions, language has been argued to have a variety of extracommunicative functions, as assessed by its causal involvement in putatively nonlinguistic tasks. In the present work, I argue that language may be critically involved in the ability of human adults to categorize objects on a specific dimension (e.g., color) while abstracting over other dimensions (e.g., size). This ability is frequently impaired in aphasic patients. The present work demonstrates that normal participants placed under conditions of verbal interference show a pattern of deficits strikingly similar to that of aphasic patients: impaired taxonomic categorization along perceptual dimensions, and preserved thematic categorization. A control experiment using a visuospatial-interference task failed to find this selective pattern of deficits. The present work has implications for understanding the online role of language in normal cognition and supports the claim that language is causally involved in nonverbal cognition.

Brain abnormalities in cognition, anxiety, and depression regulatory regions in adolescents with single ventricle heart disease.

PubMed

Pike, Nancy A; Roy, Bhaswati; Gupta, Ritika; Singh, Sadhana; Woo, Mary A; Halnon, Nancy J; Lewis, Alan B; Kumar, Rajesh

2018-06-01

Single ventricle heart disease (SVHD) adolescents show cognitive impairments and anxiety and depressive symptoms, indicating the possibility of brain injury in regions that control these functions. However, brain tissue integrity in cognition, anxiety, and depression regulatory sites in SVHD remains unclear. We examined brain tissue changes in SVHD compared to controls using T2-relaxometry procedures, which measure free water content and show tissue injury. Proton-density and T2-weighted images, using a 3.0-Tesla MRI, as well as anxiety (Beck anxiety inventory [BAI]), depressive symptoms (patient health questionnaire-9 [PHQ-9]), and cognition (wide range assessment of memory and learning 2 [WRAML2] and Montreal cognitive assessment [MoCA]) data were collected from 20 SVHD (age: 15.8 ± 1.1 years, male/female: 11/9) and 36 controls (age: 16.0 ± 1.1 years, male/female: 19/17). Whole-brain T2-relaxation maps were calculated, normalized to a common space, smoothed, and compared between groups and sexes (analysis of covariance; covariates: age, sex; p < 0.001). SVHD subjects showed significantly increased BAI and PHQ-9 and reduced MoCA and WRAML2 scores over controls. Several brain regions in SVHD showed increased T2-relaxation values (chronic injury), including the cingulate, and insula, hippocampus/para-hippocampal gyrus, thalamus, hypothalamus, amygdala, frontal white matter, corpus callosum, brainstem, and cerebellar areas. Decreased T2-relaxation values (acute injury) emerged in a few regions, including the prefrontal and cerebellar cortices in SVHD over controls. In addition, male SVHD showed more brain changes over female SVHD. Adolescents with SVHD showed significant brain injury with variable male-female differences in areas that control cognition, anxiety, and depression, which may contribute to functional deficits found in the condition. © 2018 Wiley Periodicals, Inc.

A cognitive neuropsychological approach to the study of delusions in late-onset schizophrenia.

PubMed

Phillips, M L; Howard, R; David, A S

1997-09-01

Hypotheses to explain delusion formation include distorted perceptual processing of meaningful stimuli (e.g. faces), abnormal reasoning, or a combination of both. The study investigated these hypotheses using standardized neuropsychological tests. A three-patient case-study, compared with a small group (n = 8) of age-matched normal control subjects. Hospital in- and outpatients. Age-matched normal controls were from local residential homes. Three subjects with late-onset schizophrenia, two currently deluded and one in remission. Both deluded subjects had persecutory beliefs. One had a delusion of misidentification. All subjects were administered standardized neuropsychological tests of facial processing and tests of verbal reasoning. The test scores of the three patients were compared with published normal values and the age-matched control data. The tests demonstrated impaired matching of unfamiliar faces in deluded subjects, particularly in the subject with delusional misidentification. Increasing the emotional content of logical reasoning problems had a significant effect on the deluded subjects' reasoning but not that of the normal controls. The findings suggest impaired visual processing plus abnormal reasoning in deluded subjects. However, these impairments are relatively subtle given the severity of psychiatric disorder in the patients studied.

Study on cognitive impairment in diabetic rats by different behavioral experiments

NASA Astrophysics Data System (ADS)

Yu-bin, Ji; Zeng-yi, Li; Guo-song, Xin; Chi, Wei; Hong-jian, Zhu

2017-12-01

Object recognition test and Y maze test are widely used in learning and memory behavior evaluation techniques and methods. It was found that in the new object recognition experiment, the diabetic rats did more slowly than the normal rats in the discrimination of the old and new objects, and the learning and memory of the rats in the diabetic rats were injured. And the ratio of retention time and the number of errors in the Y maze test was much higher than that in the blank control group. These two methods can reflect the cognitive impairment in diabetic rats.

Highly religious participants recruit areas of social cognition in personal prayer.

PubMed

Schjoedt, Uffe; Stødkilde-Jørgensen, Hans; Geertz, Armin W; Roepstorff, Andreas

2009-06-01

We used functional magnetic resonance imaging (fMRI) to investigate how performing formalized and improvised forms of praying changed the evoked BOLD response in a group of Danish Christians. Distinct from formalized praying and secular controls, improvised praying activated a strong response in the temporopolar region, the medial prefrontal cortex, the temporo-parietal junction and precuneus. This finding supports our hypothesis that religious subjects, who consider their God to be 'real' and capable of reciprocating requests, recruit areas of social cognition when they pray. We argue that praying to God is an intersubjective experience comparable to 'normal' interpersonal interaction.

Chronic choline supplementation improves cognitive and motor performance via modulating oxidative and neurochemical status in rats.

PubMed

Tabassum, Saiqa; Haider, Saida; Ahmad, Saara; Madiha, Syeda; Parveen, Tahira

2017-08-01

Choline, an essential nutrient, accounts for multiple functions in the body and brain. While its beneficial effects on healthy adults are not clear, choline supplementation is important during pregnancy for brain development, in elderly patients for support of cognitive performance and in patients with neurological disorders to reduce memory deficits. Thus, the aim of this study is to investigate whether choline administration in healthy adult rats beneficially impacts cognitive and locomotor performance, and associated oxidative and neurochemical outcomes. Two groups, control and choline, received tap water and choline bitartrate, respectively at the dose equivalent to adequate intake for five weeks. Food intake and body weight were monitored daily. Behavioral analysis comprising assessment of cognitive performance (by novel object recognition, passive avoidance and Morris Water Maze test) and locomotor performance (by Open field, Kondziela's inverted screen and beam walking test) were performed. Following testing, rats were decapitated and brain samples were collected for estimation of acetylcholine, redox profile and monoamine measurements. The results showed that chronic choline administration significantly improves cognitive and locomotor performance accompanied by a reduction in oxidative stress, enhanced cholinergic neurotransmission and monoamine levels in the brain of healthy adult rats. Hence, chronic choline intake was found to improve behavioral, oxidative and neurochemical outcomes in the normal population, so it can be suggested that choline tablets can be used as a safe and effective supplement for improving the neurological health of normal individuals and that they might also be beneficial in preventing cognitive and motor disorders later in life. Copyright © 2017 Elsevier Inc. All rights reserved.

Cognitive Outcomes for Extremely Preterm/Extremely Low Birth Weight Children in Kindergarten

PubMed Central

Orchinik, Leah J.; Taylor, H. Gerry; Espy, Kimberly Andrews; Minich, Nori; Klein, Nancy; Sheffield, Tiffany; Hack, Maureen

2012-01-01

Our objectives were to examine cognitive outcomes for extremely preterm/extremely low birth weight (EPT/ELBW, gestational age <28 weeks and/or birth weight <1000 g) children in kindergarten and the associations of these outcomes with neonatal factors, early childhood neurodevelopmental impairment, and socioeconomic status (SES). The sample comprised a hospital-based 2001-2003 birth cohort of 148 EPT/ELBW children (mean birth weight 818 g; mean gestational age 26 weeks) and a comparison group of 111 term-born normal birth weight (NBW) classmate controls. Controlling for background factors, the EPT/ELBW group had pervasive deficits relative to the NBW group on a comprehensive test battery, with rates of cognitive deficits that were 3 to 6 times higher in the EPT/ELBW group. Deficits on a measure of response inhibition were found in 48% versus 10%, OR (95% CI) = 7.32 (3.32, 16.16), p <.001. Deficits on measures of executive function and motor and perceptual-motor abilities were found even when controlling for acquired verbal knowledge. Neonatal risk factors, early neurodevelopmental impairment, and lower SES were associated with higher rates of deficits within the EPT/ELBW group. The findings document both global and selective cognitive deficits in EPT/ELBW children at school entry and justify efforts at early identification and intervention. PMID:21923973

Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future "Non-Cognitive" Outcomes of Alzheimer's Disease.

PubMed

Ingber, Adam P; Hassenstab, Jason; Fagan, Anne M; Benzinger, Tammie L S; Grant, Elizabeth A; Holtzman, David M; Morris, John C; Roe, Catherine M

2016-01-01

The influence of reserve variables and Alzheimer's disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on "non-cognitive" outcomes, including functional abilities and mood. We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD.

Past Taurine Intake Has a Positive Effect on Present Cognitive Function in the Elderly.

PubMed

Bae, Mi Ae; Gao, Ranran; Kim, Sung Hoon; Chang, Kyung Ja

2017-01-01

This study investigated the associations between dietary history of past taurine intake and cognitive function in the elderly. Subjects of this study were 40 elderly persons with dementia (men 14, women 26) and 37 normal elderly persons (men 5, women 32). Data were collected using questionnaires by investigator-based interview to the elderly and family caregivers. We examined their general characteristics, anthropometric data, cognitive function, and taurine index. Cognitive function was measured using MMSE-DS and higher score means better cognitive function. As dietary history of past taurine intake, taurine index was evaluated by scoring the intake frequency of 41 kinds of taurine-containing foods. Part correlation analysis (sex, age, and school educational period correction) was used to analyze associations between taurine index and cognitive function. The analysis of all data was carried out by the SPSS 20.0 program for windows. The age, height, weight, and BMI of elderly with dementia showed no statistical significance compared to normal elderly. The elderly with dementia had significantly higher school education period (7.4 years) than the normal elderly (4.8 years) (p < 0.01). Nevertheless, the average total score of cognitive function (MMSE-DS) of the elderly with dementia (18.1 points) was significantly lower than score of the normal elderly (21.7 points) (p < 0.05). The average taurine index of the elderly with dementia (104.7 points) was significantly lower than average taurine index of the normal elderly (123.7 points) (p < 0.01). There were positive correlations between total taurine index and total score of cognitive function in all the elderly subjects (p < 0.05). In particular, as taurine index was higher, there were significantly higher scores of cognitive function such as 'time orientation' and 'judgement and abstract thinking' (p < 0.01). In conclusion, these results suggest that past taurine intake may have a positive effect on present cognitive function in the elderly.

Influence of slight to moderate risk for birth hypoxia on acquisition of cognitive and language function in the preterm infant: a cross-sectional comparison with preterm-birth controls.

PubMed

Hopkins-Golightly, Tracy; Raz, Sarah; Sander, Craig J

2003-01-01

The cognitive and language performance of a group of 26 preterm-birth preschool and early school-age children with slight to moderate risk for perinatal hypoxia was compared with the performance of a preterm-birth comparison group of 26 children. Despite the relatively small discrepancy in degree of risk, the cognitive performance of the 2 groups diverged significantly. When data for children with known perinatal arterial pH were combined, a curvilinear (quadratic) regression model provided the best fit. Increasing acidosis was linearly related to decreases in cognitive skills, with the bend in the curve occurring well within the normal range of pH values. Hence, in the preterm infant, even minor risk for birth hypoxia may result in discernible deviation from the expected developmental trajectory.

Whole Brain Magnetic Resonance Spectroscopic Determinants of Functional Outcomes in Pediatric Moderate/Severe Traumatic Brain Injury.

PubMed

Babikian, Talin; Alger, Jeffry R; Ellis-Blied, Monica U; Giza, Christopher C; Dennis, Emily; Olsen, Alexander; Mink, Richard; Babbitt, Christopher; Johnson, Jeff; Thompson, Paul M; Asarnow, Robert F

2018-05-18

Diffuse axonal injury contributes to the long-term functional morbidity observed after pediatric moderate/severe traumatic brain injury (msTBI). Whole-brain proton magnetic resonance echo-planar spectroscopic imaging was used to measure the neurometabolite levels in the brain to delineate the course of disruption/repair during the first year post-msTBI. The association between metabolite biomarkers and functional measures (cognitive functioning and corpus callosum [CC] function assessed by interhemispheric transfer time [IHTT] using an event related potential paradigm) was also explored. Pediatric patients with msTBI underwent assessments at two times (post-acutely at a mean of three months post-injury, n = 31, and chronically at a mean of 16 months post-injury, n = 24). Healthy controls also underwent two evaluations, approximately 12 months apart. Post-acutely, in patients with msTBI, there were elevations in choline (Cho; marker for inflammation and/or altered membrane metabolism) in all four brain lobes and the CC and decreases in N-acetylaspartate (NAA; marker for neuronal and axonal integrity) in the CC compared with controls, all of which normalized by the chronic time point. Subgroups of TBI showed variable patterns chronically. Patients with slow IHTT had lower lobar Cho chronically than those with normal IHTT; they also did not show normalization in CC NAA whereas those with normal IHTT showed significantly higher levels of CC NAA relative to controls. In the normal IHTT group only, chronic CC Cho and NAA together explained 70% of the variance in long-term cognitive functioning. MR based whole brain metabolic evaluations show different patterns of neurochemistry after msTBI in two subgroups with different outcomes. There is a dynamic relationship between prolonged inflammatory responses to brain damage, reparative processes/remyelination, and subsequent neurobehavioral outcomes. Multimodal studies allow us to test hypotheses about degenerative and reparative processes in patient groups that have divergent functional outcome, with the ultimate goal of developing targeted therapeutic agents.

Association of subjective memory complaints with subsequent cognitive decline in community-dwelling elderly individuals with baseline cognitive impairment.

PubMed

Schofield, P W; Marder, K; Dooneief, G; Jacobs, D M; Sano, M; Stern, Y

1997-05-01

The validity of subjective memory complaints has been questioned by clinical studies that have shown little relationship between memory complaints and objective memory performance. These studies often have been cross-sectional in design, have excluded individuals with cognitive impairment, or have lacked a comparison group. The authors conducted a study that attempted to avoid these limitations. Memory complaints of 364 nondemented, community-dwelling elderly individuals were recorded as present or absent at the baseline evaluation. After 1 year, 169 subjects were reevaluated. Standardized neurologic and neuropsychological evaluations were used at each assessment to classify subjects as normal or cognitively impaired. At baseline, 31% of the normal subjects and 47% of those with cognitive impairment had memory complaints. Subjects with memory complaints had higher Hamilton depression scale scores than subjects without memory complaints but equivalent scores on a measure of total recall. At follow-up, multivariate analyses showed that subjects with baseline memory complaints had significantly greater decline in memory and cognition than subjects without memory complaints. Secondary analyses showed this effect to be confined to subjects with baseline cognitive impairment. Memory complaints may lack validity in subjects with normal cognition, but in nondemented individuals with cognitive impairment, memory complaints may predict subsequent cognitive decline.

Sexuality and gender role in autism spectrum disorder: a case control study.

PubMed

Bejerot, Susanne; Eriksson, Jonna M

2014-01-01

The 'extreme male brain theory of autism' describes an extreme male pattern of cognitive traits defined as strong systemising abilities paired with empathising weaknesses in autism spectrum disorder. However, beyond these cognitive traits, clinical observations have suggested an ambiguous gender-typed pattern regarding several sexually dimorphic traits. The aim of the present study was to investigate if patterns of non-cognitive sexually dimorphic traits differed between the autism spectrum disorder and control groups. Fifty adults with autism spectrum disorder and intelligence within the normal range, and 53 neurotypical controls responded to questions on gender role, self-perceived gender typicality and gender identity, as well as sexuality. Measures used were a Swedish modification of the Bem Sex Role Inventory and questions on sexuality and gender designed for the purpose of this study. Our results showed that one common gender role emerged in the autism spectrum disorder group. Masculinity (e.g. assertiveness, leadership and competitiveness) was weaker in the autism spectrum disorder group than in the controls, across men and women. Self-perceived gender typicality did not differ between the groups but tomboyism and bisexuality were overrepresented amongst women with autism spectrum disorder. Lower libido was reported amongst both male and female participants with autism spectrum disorder compared with controls. We conclude that the extreme male patterns of cognitive functions in the autistic brain do not seem to extend to gender role and sexuality. A gender-atypical pattern for these types of characteristics is suggested in autism spectrum disorder.

Sexuality and Gender Role in Autism Spectrum Disorder: A Case Control Study

PubMed Central

Bejerot, Susanne; Eriksson, Jonna M.

2014-01-01

The ‘extreme male brain theory of autism’ describes an extreme male pattern of cognitive traits defined as strong systemising abilities paired with empathising weaknesses in autism spectrum disorder. However, beyond these cognitive traits, clinical observations have suggested an ambiguous gender-typed pattern regarding several sexually dimorphic traits. The aim of the present study was to investigate if patterns of non-cognitive sexually dimorphic traits differed between the autism spectrum disorder and control groups. Fifty adults with autism spectrum disorder and intelligence within the normal range, and 53 neurotypical controls responded to questions on gender role, self-perceived gender typicality and gender identity, as well as sexuality. Measures used were a Swedish modification of the Bem Sex Role Inventory and questions on sexuality and gender designed for the purpose of this study. Our results showed that one common gender role emerged in the autism spectrum disorder group. Masculinity (e.g. assertiveness, leadership and competitiveness) was weaker in the autism spectrum disorder group than in the controls, across men and women. Self-perceived gender typicality did not differ between the groups but tomboyism and bisexuality were overrepresented amongst women with autism spectrum disorder. Lower libido was reported amongst both male and female participants with autism spectrum disorder compared with controls. We conclude that the extreme male patterns of cognitive functions in the autistic brain do not seem to extend to gender role and sexuality. A gender-atypical pattern for these types of characteristics is suggested in autism spectrum disorder. PMID:24498228

A cross-sectional and longitudinal study evaluating brain volumes, RNFL, and cognitive functions in MS patients and healthy controls.

PubMed

Frau, Jessica; Fenu, Giuseppe; Signori, Alessio; Coghe, Giancarlo; Lorefice, Lorena; Barracciu, Maria Antonietta; Sechi, Vincenzo; Cabras, Federico; Badas, Mauro; Marrosu, Maria Giovanna; Cocco, Eleonora

2018-05-11

The principal biomarker of neurodegeneration in multiple sclerosis (MS) is believed to be brain volume, which is associated with cognitive functions and retinal nerve fibre layer (RNFL). A cross-sectional and longitudinal assessment of the relationship between RNFL, cognitive functions and brain volume. At baseline, relapsing patients and healthy controls underwent 1.5 T MRI to estimate the normalized volume of brain (NBV), grey (NGV), white (NWV) and peripheral grey (pNGV) matter. Cognitive functions were evaluated by BICAMS, RNFL by Spectral-Domain OCT. Patients were re-evaluated after 12 months. Cognitive functions, brain volume, and RNFL differed between the group of 66 patients and that of 16 healthy controls. In the MS group, at baseline, an association was found between: p-NGV and symbol-digit (SDMT) (p = 0.022); temporal-RNFL and NBV (p = 0.007), NWV (p = 0.012), NGV (p = 0.048), and p-NGV (p = 0.021); papillo-macular bundle-RNFL and NBV (p = 0.013), NWV (p = 0.02), NGV (p = 0.049), and p-NGV (p = 0.032). Over the observational period, we found a reduction of brain volume (p < 0.001), average-RNFL (p = 0.001), temporal-RNFL (p = 0.006), and papillo-macular bundle-RNFL (p = 0.009). No association was found between OCT, MRI, and cognitive changes. Brain volume, cognitive functions, and RNFL are continuous measures of different neurodegenerative aspects. BICAMS and OCT have low costs and can be easily used in clinical practice to monitor neurodegeneration.

Comparative study of impact of hemodialysis and renal transplantation on cognitive functions in ESRD patients.

PubMed

Anwar, Waleed; Ezzat, Haitham; Mohab, Amr

2015-01-01

Cognitive impairment is defined as a newly appeared deficit in at least two areas of cognitive functions, including disturbances in memory, executive functioning, attention or speed of information processing, perceptual motor abilities, or language. Cognitive impairment is highly prevalent in ESRD patients when compared with the general population. It has also been associated with a decreased quality of life. Cognitive functions in patients with ESRD showed improvement with dialysis and renal transplantation. These findings illustrate the potential importance of evaluating and comparing the effects of hemodialysis and transplantation regarding cognitive performance and thus quality of life in ESRD patients and normal subjects. This study was carried out in 100 patients (50 ESRD patients on regular hemodialysis for at least 6 months and 50 post-transplant patients who had maintained successful kidney graft for at least 3 months). All patients underwent laboratory and psychometric scoring tests, including trail making test part A, trail making test part B, digit span, and mini-mental state examination. Thirty healthy adults matched by age and sex served as a control group. The results showed significant differences in cognitive function tests results between transplant and hemodialysis patients (P<0.01), suggesting that transplant patients were superior in their cognitive performance, with the correction of anemia being the most important factor for improving cognitive performance in both groups. There were no significant differences between transplant patients and control subjects in psychometric measures (P>0.05). Renal transplantation as a modality of treatment, in ESRD patients, is superior to hemodialysis in terms of cognitive performance improvement. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Mapping the neuropsychological profile of temporal lobe epilepsy using cognitive network topology and graph theory.

PubMed

Kellermann, Tanja S; Bonilha, Leonardo; Eskandari, Ramin; Garcia-Ramos, Camille; Lin, Jack J; Hermann, Bruce P

2016-10-01

Normal cognitive function is defined by harmonious interaction among multiple neuropsychological domains. Epilepsy has a disruptive effect on cognition, but how diverse cognitive abilities differentially interact with one another compared with healthy controls (HC) is unclear. This study used graph theory to analyze the community structure of cognitive networks in adults with temporal lobe epilepsy (TLE) compared with that in HC. Neuropsychological assessment was performed in 100 patients with TLE and 82 HC. For each group, an adjacency matrix was constructed representing pair-wise correlation coefficients between raw scores obtained in each possible test combination. For each cognitive network, each node corresponded to a cognitive test; each link corresponded to the correlation coefficient between tests. Global network structure, community structure, and node-wise graph theory properties were qualitatively assessed. The community structure in patients with TLE was composed of fewer, larger, more mixed modules, characterizing three main modules representing close relationships between the following: 1) aspects of executive function (EF), verbal and visual memory, 2) speed and fluency, and 3) speed, EF, perception, language, intelligence, and nonverbal memory. Conversely, controls exhibited a relative division between cognitive functions, segregating into more numerous, smaller modules consisting of the following: 1) verbal memory, 2) language, perception, and intelligence, 3) speed and fluency, and 4) visual memory and EF. Overall node-wise clustering coefficient and efficiency were increased in TLE. Adults with TLE demonstrate a less clear and poorly structured segregation between multiple cognitive domains. This panorama suggests a higher degree of interdependency across multiple cognitive domains in TLE, possibly indicating compensatory mechanisms to overcome functional impairments. Copyright © 2016 Elsevier Inc. All rights reserved.

Ethnicity/culture modulates the relationships of the haptoglobin (Hp) 1-1 phenotype with cognitive function in older individuals with type 2 diabetes.

PubMed

Guerrero-Berroa, Elizabeth; Ravona-Springer, Ramit; Heymann, Anthony; Schmeidler, James; Hoffman, Hadas; Preiss, Rachel; Koifmann, Keren; Greenbaum, Lior; Levy, Andrew; Silverman, Jeremy M; Leroith, Derek; Sano, Mary; Schnaider-Beeri, Michal

2016-05-01

The haptoglobin (Hp) genotype has been associated with cognitive function in type 2 diabetes. Because ethnicity/culture has been associated with both cognitive function and Hp genotype frequencies, we examined whether it modulates the association of Hp with cognitive function. This cross-sectional study evaluated 787 cognitively normal older individuals (>65 years of age) with type 2 diabetes participating in the Israel Diabetes and Cognitive Decline study. Interactions in two-way analyses of covariance compared Group (Non-Ashkenazi versus Ashkenazi Jews) on the associations of Hp phenotype (Hp 1-1 versus non- Hp 1-1) with five cognitive outcome measures. The primary control variables were age, gender, and education. Compared with Ashkenazi Jews, non-Ashkenazi Jews with the Hp 1-1 phenotype had significantly poorer cognitive function than non-Hp 1-1 in the domains of Attention/Working Memory (p = 0.035) and Executive Function (p = 0.023), but not in Language/Semantic Categorization (p = 0.432), Episodic Memory (p = 0.268), or Overall Cognition (p = 0.082). After controlling for additional covariates (type 2 diabetes-related characteristics, cardiovascular risk factors, Mini-mental State Examination, and extent of depressive symptoms), Attention/Working Memory (p = 0.038) and Executive Function (p = 0.013) remained significant. Older individuals from specific ethnic/cultural backgrounds with the Hp 1-1 phenotype may benefit more from treatment targeted at decreasing or halting the detrimental effects of Hp 1-1 on the brain. Future studies should examine differential associations of Hp 1-1 and cognitive impairment, especially for groups with high prevalence of both, such as African-Americans and Hispanics. Copyright © 2015 John Wiley & Sons, Ltd.

The impact of junk foods on the adolescent brain.

PubMed

Reichelt, Amy C; Rank, Michelle M

2017-12-01

Adolescence is a significant period of physical, social, and emotional development, and is characterized by prominent neurobiological changes in the brain. The maturational processes that occur in brain regions responsible for cognitive control and reward seeking may underpin excessive consumption of palatable high fat and high sugar "junk" foods during adolescence. Recent studies have highlighted the negative impact of these foods on brain function, resulting in cognitive impairments and altered reward processing. The increased neuroplasticity during adolescence may render the brain vulnerable to the negative effects of these foods on cognition and behavior. In this review, we describe the mechanisms by which junk food diets influence neurodevelopment during adolescence. Diet can lead to alterations in dopamine-mediated reward signaling, and inhibitory neurotransmission controlled by γ-aminobutyric acid (GABA), two major neurotransmitter systems that are under construction across adolescence. We propose that poor dietary choices may derail the normal adolescent maturation process and influence neurodevelopmental trajectories, which can predispose individuals to dysregulated eating and impulsive behaviors. © 2017 Wiley Periodicals, Inc.

Magnetic Resonance Elastography Demonstrates Increased Brain Stiffness in Normal Pressure Hydrocephalus

PubMed Central

N, Fattahi; A, Arani; A, Perry; F, Meyer; A, Manduca; K, Glaser; ML, Senjem; RL, Ehman; J, Huston

2015-01-01

Introduction Normal pressure hydrocephalus (NPH) is a reversible neurologic disorder characterized by a triad of cognitive impairment, gait abnormality and urinary incontinence that is commonly treated with ventriculoperitoneal shunt placement. However, there are multiple overlapping symptoms which often make it difficult to differentiate NPH from other types of dementia and improved diagnostic techniques would help patient management. MR elastography (MRE) is a novel diagnostic tool that could potentially identify patients with NPH. The purpose of this study was to assess brain stiffness changes in NPH patients compared with age- and sex-matched cognitively normal individuals. Methods MRE was performed on 10 NPH patients and 21 age- and sex-matched volunteers with no known neurologic disorders. Image acquisition was conducted on a 3T MRI scanner. Shear waves with 60Hz vibration frequency were transmitted into the brain by a pillow-like passive driver. A novel postprocessing technique resistant to noise and edge artifacts was implemented to determine regional brain stiffness. The Wilcoxon rank sum test and linear regression were used for statistical analysis. Results A significant increase in stiffness was observed in the cerebrum (p = 0.001), occipital lobe (p = 0.0002), parietal lobe (p= 0.001), and the temporal lobe (p = 0.02) in the NPH group compared with normal controls. However, no significant difference was noted in other regions of the brain including the frontal lobe (p = 0.07), deep gray and white matter (p = 0.43), or the cerebellum (p = 0.20). Conclusion This study demonstrates increased brain stiffness in NPH patients compared to age- and sex-matched normal controls which motivates future studies investigating the use of MRE for NPH diagnosis and efficacy of shunt therapy. PMID:26542235

Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease

PubMed Central

Reiman, Eric M.; Chen, Kewei; Liu, Xiaofen; Bandy, Daniel; Yu, Meixiang; Lee, Wendy; Ayutyanont, Napatkamon; Keppler, Jennifer; Reeder, Stephanie A.; Langbaum, Jessica B. S.; Alexander, Gene E.; Klunk, William E.; Mathis, Chester A.; Price, Julie C.; Aizenstein, Howard J.; DeKosky, Steven T.; Caselli, Richard J.

2009-01-01

Fibrillar amyloid-beta (Aβ) is found in the brains of many cognitively normal older people. Whether or not this reflects a predisposition to Alzheimer's disease (AD) is unknown. We used Pittsburgh Compound B (PiB) PET to characterize the relationship between fibrillar Aβ burden and this predisposition in cognitively normal older people at 3 mean levels of genetic risk for AD. Dynamic PiB PET scans, the Logan method, statistical parametric mapping, and automatically labeled regions of interest (ROIs) were used to characterize and compare cerebral-to-cerebellar PIB distribution volume ratios, reflecting fibrillar Aβ burden, in 28 cognitively normal persons (mean age, 64 years) with a reported family history of AD and 2 copies, 1 copy, and no copies of the apolipoprotein E (APOE) ε4 allele. The 8 ε4 homozygotes, 8 heterozygotes, and 12 noncarriers did not differ significantly in terms of age, sex, or cognitive scores. Fibrillar Aβ was significantly associated with APOE ε4 carrier status and ε4 gene dose in AD-affected mean cortical, frontal, temporal, posterior cingulate-precuneus, parietal, and basal ganglia ROIs, and was highest in an additional homozygote who had recently developed mild cognitive impairment. These findings suggest that fibrillar Aβ burden in cognitively normal older people is associated with APOE ε4 gene dose, the major genetic risk factor for AD. Additional studies are needed to track fibrillar Aβ accumulation in persons with different kinds and levels of AD risk; to determine the extent to which fibrillar Aβ, alone or in combination with other biomarkers and risk factors, predicts rates of cognitive decline and conversion to clinical AD; and to establish the role of fibrillar Aβ imaging in primary prevention trials. PMID:19346482

Normal Performance in Non-Visual Social Cognition Tasks in Women with Turner Syndrome.

PubMed

Anaki, David; Zadikov-Mor, Tal; Gepstein, Vardit; Hochberg, Ze'ev

2018-01-01

Turner syndrome (TS) is a chromosomal disorder in women resulting from a partial or complete absence of the X chromosome. In addition to physical and hormonal dysfunctions, along with a unique neurocognitive profile, women with TS are reported to suffer from social functioning difficulties. Yet, it is unclear whether these difficulties stem from impairments in social cognition per se or from other deficits that characterize TS but are not specific to social cognition. Previous research that has probed social functioning in TS is equivocal regarding the source of these psychosocial problems since they have mainly used tasks that were dependent on visual-spatial skills, which are known to be compromised in TS. In the present study, we tested 26 women with TS and 26 matched participants on three social cognition tasks that did not require any visual-spatial capacities but rather relied on auditory-verbal skills. The results revealed that in all three tasks the TS participants did not differ from their control counterparts. The same TS cohort was found, in an earlier study, to be impaired, relative to controls, in other social cognition tasks that were dependent on visual-spatial skills. Taken together these findings suggest that the social problems, documented in TS, may be related to non-specific spatial-visual factors that affect their social cognition skills.

Analysis of the relationship between cognitive skills and unilateral sensory hearing loss.

PubMed

Calderón-Leyva, I; Díaz-Leines, S; Arch-Tirado, E; Lino-González, A L

2018-06-01

To analyse cognitive skills in patients with severe unilateral hearing loss versus those in subjects with normal hearing. 40 adults participated: 20 patients (10 women and 10 men) with severe unilateral hearing loss and 20 healthy subjects matched to the study group. Cognitive abilities were measured with the Spanish version of the Woodcock Johnson Battery-Revised; central auditory processing was assessed with monaural psychoacoustic tests. Box plots were drawn and t tests were performed for samples with a significance of P≤.05. A comparison of performances on the filtered word testing and time-compressed disyllabic word tests between patients and controls revealed a statistically significant difference (P≤.05) with greater variability among responses by hearing impaired subjects. This same group also showed a better cognitive performance on the numbers reversed, visual auditory learning, analysis synthesis, concept formation, and incomplete words tests. Patients with hearing loss performed more poorly than controls on the filtered word and time-compressed disyllabic word tests, but more competently on memory, reasoning, and auditory processing tasks. Complementary tests, such as those assessing central auditory processes and cognitive ability tests, are important and helpful for designing habilitation/rehabilitation and therapeutic strategies intended to optimise and stimulate cognitive skills in subjects with unilateral hearing impairment. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Distinct brain metabolic patterns separately associated with cognition, motor function, and aging in Parkinson's disease dementia.

PubMed

Ko, Ji Hyun; Katako, Audrey; Aljuaid, Maram; Goertzen, Andrew L; Borys, Andrew; Hobson, Douglas E; Kim, Seok Min; Lee, Chong Sik

2017-12-01

We explored whether patients with Parkinson's disease dementia (PDD) show a distinct spatial metabolic pattern that characterizes cognitive deficits in addition to motor dysfunction. Eighteen patients with PDD underwent 3 separate positron emission tomography sessions with [ 18 F]fluorodeoxyglucose (for glucose metabolism), fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane (for dopamine transporter density) and Pittsburgh compound-B (for beta-amyloid load). We confirmed in PDD versus normal controls, overall hypometabolism in the posterior and prefrontal brain regions accompanied with hypermetabolism in subcortical structures and the cerebellar vermis. A multivariate network analysis then revealed 3 metabolic patterns that are separately associated with cognitive performance (p = 0.042), age (p = 0.042), and motor symptom severity (p = 0.039). The age-related pattern's association with aging was replicated in healthy controls (p = 0.047) and patients with Alzheimer's disease (p = 0.002). The cognition-related pattern's association with cognitive performance was observed, with a trend-level of correlation, in patients with dementia with Lewy bodies (p = 0.084) but not in patients with Alzheimer's disease (p = 0.974). We found no association with fluorinated N-3-fluoropropyl-2-beta-carboxymethoxy-3-beta-(4-iodophenyl) nortropane and Pittsburgh compound-B positron emission tomography with patients' cognitive performance. Copyright © 2017 Elsevier Inc. All rights reserved.

The Sounds of Silence: Language, Cognition, and Anxiety in Selective Mutism

ERIC Educational Resources Information Center

Manassis, Katharina; Tannock, Rosemary; Garland, E. Jane; Minde, Klaus; McInnes, Alison; Clark, Sandra

2007-01-01

Objectives: To determine whether oral language, working memory, and social anxiety differentiate children with selective mutism (SM), children with anxiety disorders (ANX), and normal controls (NCs) and explore predictors of mutism severity. Method: Children ages 6 to 10 years with SM (n = 44) were compared with children with ANX (n = 28) and NCs…

Electrophysiological (Event-Related Potentials) Indices of Cognitive Processing in Autistic Learners.

ERIC Educational Resources Information Center

Shibley, Ralph, Jr.; And Others

Event-related Potentials (ERPs) were recorded to both auditory and visual stimuli from the scalps of nine autistic males and nine normal controls (all Ss between 12 and 22 years of age) to examine the differences in information processing strategies. Ss were tested on three different tasks: an auditory missing stimulus paradigm, a visual color…

Short-Term Effects of Playing Computer Games on Attention

ERIC Educational Resources Information Center

Tahiroglu, Aysegul Yolga; Celik, Gonca Gul; Avci, Ayse; Seydaoglu, Gulsah; Uzel, Mehtap; Altunbas, Handan

2010-01-01

Objective: The main aim of the present study is to investigate the short-term cognitive effects of computer games in children with different psychiatric disorders and normal controls. Method: One hundred one children are recruited for the study (aged between 9 and 12 years). All participants played a motor-racing game on the computer for 1 hour.…

Exploring the Williams Syndrome Face-Processing Debate: The Importance of Building Developmental Trajectories

ERIC Educational Resources Information Center

Karmiloff-Smith, Annette; Thomas, Michael; Annaz, Dagmara; Humphreys, Kate; Ewing, Sandra; Brace, Nicola; Van Duuren, Mike; Pike, Graham; Grice, Sarah; Campbell, Ruth

2004-01-01

Background: Face processing in Williams syndrome (WS) has been a topic of heated debate over the past decade. Initial claims about a normally developing ("intact") face-processing module were challenged by data suggesting that individuals with WS used a different balance of cognitive processes from controls, even when their behavioural scores fell…

Departure from Normality in Multivariate Normative Comparison: The Cramer Alternative for Hotelling's "T[squared]"

ERIC Educational Resources Information Center

Grasman, Raoul P. P. P.; Huizenga, Hilde M.; Geurts, Hilde M.

2010-01-01

Crawford and Howell (1998) have pointed out that the common practice of z-score inference on cognitive disability is inappropriate if a patient's performance on a task is compared with relatively few typical control individuals. Appropriate univariate and multivariate statistical tests have been proposed for these studies, but these are only valid…

Limbic and Basal Ganglia Neuroanatomical Correlates of Gait and Executive Function: Older Adults With Mild Cognitive Impairment and Intact Cognition.

PubMed

McGough, Ellen L; Kelly, Valerie E; Weaver, Kurt E; Logsdon, Rebecca G; McCurry, Susan M; Pike, Kenneth C; Grabowski, Thomas J; Teri, Linda

2018-04-01

This study aimed to examine differences in spatiotemporal gait parameters between older adults with amnestic mild cognitive impairment and normal cognition and to examine limbic and basal ganglia neural correlates of gait and executive function in older adults without dementia. This was a cross-sectional study of 46 community-dwelling older adults, ages 70-95 yrs, with amnestic mild cognitive impairment (n = 23) and normal cognition (n = 23). Structural magnetic resonance imaging was used to attain volumetric measures of limbic and basal ganglia structures. Quantitative motion analysis was used to measure spatiotemporal parameters of gait. The Trail Making Test was used to assess executive function. During fast-paced walking, older adults with amnestic mild cognitive impairment demonstrated significantly slower gait speed and shorter stride length compared with older adults with normal cognition. Stride length was positively correlated with hippocampal, anterior cingulate, and nucleus accumbens volumes (P < 0.05). Executive function was positively correlated with hippocampal, anterior cingulate, and posterior cingulate volumes (P < 0.05). Compared with older adults with normal cognition, those with amnestic mild cognitive impairment demonstrated slower gait speed and shorter stride length, during fast-paced walking, and lower executive function. Hippocampal and anterior cingulate volumes demonstrated moderate positive correlation with both gait and executive function, after adjusting for age. Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) discuss gait performance and cognitive function in older adults with amnestic mild cognitive impairment versus normal cognition, (2) discuss neurocorrelates of gait and executive function in older adults without dementia, and (3) recognize the importance of assessing gait speed and cognitive function in the clinical management of older adults at risk for dementia. Advanced ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 0.5 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Effects of Water Provision and Hydration on Cognitive Function among Primary-School Pupils in Zambia: A Randomized Trial

PubMed Central

Trinies, Victoria; Chard, Anna N.; Mateo, Tommy; Freeman, Matthew C.

2016-01-01

There is a well-established link between hydration and improved cognitive performance among adults, with evidence of similar findings among children. No trials have investigated the impact of water provision on cognitive performance among schoolchildren in hot and arid low-resource settings. We conducted a randomized-controlled trial in five schools with limited water access in Chipata district in Eastern province, Zambia, to assess the efficacy of water provision on cognition. Pupils in grades 3–6 were randomly assigned to either receive a bottle of drinking water that they could refill throughout the day (water group, n = 149) or only have access to drinking water that was normally available at the school (control group, n = 143). Hydration was assessed in the morning before provision of water and in the afternoon through urine specific gravity (Usg) measured with a portable refractometer. In the afternoon we administered six cognitive tests to assess short-term memory, concentration, visual attention, and visual motor skills. Morning prevalence of dehydration, defined as Usg≥1.020, was 42%. Afternoon dehydration increased to 67% among the control arm and dropped to 10% among the intervention arm. We did not find that provision of water or hydration impacted cognitive test scores, although there were suggestive relationships between both water provision and hydration and increased scores on tests measuring visual attention. We identified key improvements to the study design that are warranted to further investigate this relationship. Trial Registration: ClinicalTrials.gov NCT01924546 PMID:26950696

A randomized controlled trial to test the effect of multispecies probiotics on cognitive reactivity to sad mood.

PubMed

Steenbergen, Laura; Sellaro, Roberta; van Hemert, Saskia; Bosch, Jos A; Colzato, Lorenza S

2015-08-01

Recent insights into the role of the human microbiota in cognitive and affective functioning have led to the hypothesis that probiotic supplementation may act as an adjuvant strategy to ameliorate or prevent depression. Heightened cognitive reactivity to normal, transient changes in sad mood is an established marker of vulnerability to depression and is considered an important target for interventions. The present study aimed to test if a multispecies probiotic containing Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, and Lactococcus lactis (W19 and W58) may reduce cognitive reactivity in non-depressed individuals. In a triple-blind, placebo-controlled, randomized, pre- and post-intervention assessment design, 20 healthy participants without current mood disorder received a 4-week probiotic food-supplement intervention with the multispecies probiotics, while 20 control participants received an inert placebo for the same period. In the pre- and post-intervention assessment, cognitive reactivity to sad mood was assessed using the revised Leiden index of depression sensitivity scale. Compared to participants who received the placebo intervention, participants who received the 4-week multispecies probiotics intervention showed a significantly reduced overall cognitive reactivity to sad mood, which was largely accounted for by reduced rumination and aggressive thoughts. These results provide the first evidence that the intake of probiotics may help reduce negative thoughts associated with sad mood. Probiotics supplementation warrants further research as a potential preventive strategy for depression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Can cognitive enhancers reduce the risk of falls in older people with Mild Cognitive Impairment? A protocol for a randomised controlled double blind trial

PubMed Central

2009-01-01

Background Older adults with cognitive problems have a higher risk of falls, at least twice that of cognitively normal older adults. The consequences of falls in this population are very serious: fallers with cognitive problems suffer more injuries due to falls and are approximately five times more likely to be admitted to institutional care. Although the mechanisms of increased fall risk in cognitively impaired people are not completely understood, it is known that impaired cognitive abilities can reduce attentional resource allocation while walking. Since cognitive enhancers, such as cholinesterase inhibitors, improve attention and executive function, we hypothesise that cognitive enhancers may reduce fall risk in elderly people in the early stages of cognitive decline by improving their gait and balance performance due to an enhancement in attention and executive function. Method/Design Double blinded randomized controlled trial with 6 months follow-up in 140 older individuals with Mild Cognitive Impairment (MCI). Participants will be randomized to the intervention group, receiving donepezil, and to the control group, receiving placebo. A block randomization by four and stratification based on fall history will be performed. Primary outcomes are improvements in gait velocity and reduction in gait variability. Secondary outcomes are changes in the balance confidence, balance sway, attention, executive function, and number of falls. Discussion By characterizing and understanding the effects of cognitive enhancers on fall risk in older adults with cognitive impairments, we will be able to pave the way for a new approach to fall prevention in this population. This RCT study will provide, for the first time, information regarding the effect of a medication designed to augment cognitive functioning have on the risk of falls in older adults with Mild Cognitive Impairment. We expect a significant reduction in the risk of falls in this vulnerable population as a function of the reduced gait variability achieved by treatment with cognitive enhancers. This study may contribute to a new approach to prevent and treat fall risk in seniors in early stages of dementia. Trial Registration The protocol for this study is registered with the Clinical Trials Registry, identifier number: NCT00934531 http://www.clinicaltrials.gov PMID:19674471

Analysis of brief language tests in the detection of cognitive decline and dementia

PubMed Central

Radanovic, Marcia; Carthery-Goulart, Maria Teresa; Charchat-Fichman, Helenice; Herrera Jr., Emílio; Lima, Edson Erasmo Pereira; Smid, Jerusa; Porto, Cláudia Sellitto; Nitrini, Ricardo

2007-01-01

Lexical access difficulties are frequent in normal aging and initial stages of dementia.Verbal fluency tests are valuable to detect cognitive decline, evidencing lexico-semantic and executive dysfunction. Objectives To establish which language tests can contribute in detecting dementia and to verify schooling influence on subject performance. Method 74 subjects: 33 controls, 17 Clinical Dementia Rating (CDR) 0.5 and 24 (Brief Cognitive Battery - BCB e Boston Naming Test - BNT) 1 were compared in tests of semantic verbal fluency (animal and fruit), picture naming (BCB and BNT) and the language items of Mini Mental State Examination (MMSE). Results There were significant differences between the control group and both CDR 0.5 and CDR 1 in all tests. Cut-off scores were: 11 and 10 for animal fluency, 8 for fruit fluency (in both), 8 and 9 for BCB naming. The CDR 0.5 group performed better than the CDR 1 group only in animal fluency. Stepwise multiple regression revealed fruit fluency, animal fluency and BCB naming as the best discriminators between patients and controls (specificity: 93.8%; sensitivity: 91.3%). In controls, comparison between illiterates and literates evidenced schooling influence in all tests, except for fruit fluency and BCB naming. In patients with dementia, only fruit fluency was uninfluenced by schooling. Conclusion The combination of verbal fluency tests in two semantic categories along with a simple picture naming test is highly sensitive in detecting cognitive decline. Comparison between literate and illiterate subjects shows a lesser degree of influence of schooling on the selected tests, thus improving discrimination between low performance and incipient cognitive decline. PMID:29213366

MEG Network Differences between Low- and High-Grade Glioma Related to Epilepsy and Cognition

PubMed Central

van Dellen, Edwin; Douw, Linda; Hillebrand, Arjan; Ris-Hilgersom, Irene H. M.; Schoonheim, Menno M.; Baayen, Johannes C.; De Witt Hamer, Philip C.; Velis, Demetrios N.; Klein, Martin; Heimans, Jan J.; Stam, Cornelis J.; Reijneveld, Jaap C.

2012-01-01

Objective To reveal possible differences in whole brain topology of epileptic glioma patients, being low-grade glioma (LGG) and high-grade glioma (HGG) patients. We studied functional networks in these patients and compared them to those in epilepsy patients with non-glial lesions (NGL) and healthy controls. Finally, we related network characteristics to seizure frequency and cognitive performance within patient groups. Methods We constructed functional networks from pre-surgical resting-state magnetoencephalography (MEG) recordings of 13 LGG patients, 12 HGG patients, 10 NGL patients, and 36 healthy controls. Normalized clustering coefficient and average shortest path length as well as modular structure and network synchronizability were computed for each group. Cognitive performance was assessed in a subset of 11 LGG and 10 HGG patients. Results LGG patients showed decreased network synchronizability and decreased global integration compared to healthy controls in the theta frequency range (4–8 Hz), similar to NGL patients. HGG patients’ networks did not significantly differ from those in controls. Network characteristics correlated with clinical presentation regarding seizure frequency in LGG patients, and with poorer cognitive performance in both LGG and HGG glioma patients. Conclusion Lesion histology partly determines differences in functional networks in glioma patients suffering from epilepsy. We suggest that differences between LGG and HGG patients’ networks are explained by differences in plasticity, guided by the particular lesional growth pattern. Interestingly, decreased synchronizability and decreased global integration in the theta band seem to make LGG and NGL patients more prone to the occurrence of seizures and cognitive decline. PMID:23166829

Bacopa monnieri (Brahmi) Enhanced Cognitive Function and Prevented Cognitive Impairment by Increasing VGLUT2 Immunodensity in Prefrontal Cortex of Sub-Chronic Phencyclidine Rat Model of Schizophrenia.

PubMed

Piyabhan, Pritsana; Wetchateng, Thanitsara

2015-04-01

Glutamatergic hypofunction is affected in schizophrenia. The decrement ofpresynaptic glutamatergic marker remarkably vesicular glutamate transporter type 1 (VGLUT1) indicates the deficit ofglutamatergic and cognitive function in schizophrenic brain. However there have been afew studies in VGLUT2. Brahmi, a traditional herbal medicine, might be a new frontier of cognitive deficit treatment and prevention in schizophrenia by changing cerebral VGLUT2 density. To study cognitive enhancement- and neuroprotective-effects of Brahmi on novel object recognition task and cerebral VGLUT2 immunodensity in sub-chronic phencyclidine (PCP) rat model of schizophrenia. Cognitive enhancement effect study; rats were assigned to three groups; Group-1: Control, Group-2: PCP administration and Group-3: PCP + Brahmi. Neuroprotective effect study; rats were assigned to three groups; Group-1: Control, Group-2: PCP administration and Group-3: Brahmi + PCP Discrimination ratio (DR) representing cognitive ability was obtained from novel object recognition task. VGLUT2 immunodensity was measured in prefrontal cortex, striatum, cornu ammonis fields 1 (CA1) and 2/3 (CA2/3) of hippocampus using immunohistochemistry. DR was significantly reduced in PCP group compared with control. This occurred alongside VGLUT2 reduction in prefrontal cortex, but not in striatum, CA1 or CA2/3. Both PCP + Brahmi and Brahmi + PCP groups showed an increased DR score up to normal, which occurred alongside a significantly increased VGLUT2 immunodensity in the prefrontal cortex, compared with PCP group. The decrement of VGLUT2 density in prefrontal cortex resulted in cognitive deficit in rats receiving PCP. Interestingly, receiving Brahmi after PCP administration can restore this cognitive deficit by increasing VGLUT2 density in prefrontal cortex. This investigation is defined as Brahmi's cognitive enhancement effect. Additionally, receiving Brahmi before PCP administration can also prevent cognitive impairment by elevating VGLUT2 density in prefrontal cortex. This observation indicates neuroprotective effect of Brahmi. Therefore, Brahmi could be a new frontier of restoration and prevention of cognitive deficit in schizophrenia.

Improved power for characterizing longitudinal amyloid-β PET changes and evaluating amyloid-modifying treatments with a cerebral white matter reference region.

PubMed

Chen, Kewei; Roontiva, Auttawut; Thiyyagura, Pradeep; Lee, Wendy; Liu, Xiaofen; Ayutyanont, Napatkamon; Protas, Hillary; Luo, Ji Luo; Bauer, Robert; Reschke, Cole; Bandy, Daniel; Koeppe, Robert A; Fleisher, Adam S; Caselli, Richard J; Landau, Susan; Jagust, William J; Weiner, Michael W; Reiman, Eric M

2015-04-01

In this article, we describe an image analysis strategy with improved power for tracking longitudinal amyloid-β (Aβ) PET changes and evaluating Aβ-modifying treatments. Our aims were to compare the power of template-based cerebellar, pontine, and cerebral white matter reference regions to track 24-mo florbetapir standardized uptake value (SUV) ratio (SUVR) changes; to relate those changes to 24-mo clinical declines; and to evaluate Aβ-modifying treatments in Aβ-positive (Aβ+) and Aβ-negative (Aβ-) patients with probable Alzheimer dementia (pAD), in patients with mild cognitive impairment (MCI), in cognitively normal controls (NCs), and in cognitively normal apolipoprotein E4 (APOE4) carriers and noncarriers. We used baseline and follow-up (∼24 mo) florbetapir PET scans from 332 Aβ+ and Aβ- subjects participating in the multicenter Alzheimer's Disease Neuroimaging Initiative. Each of the proposed analyses included 31 pAD patients, 187 MCI patients, and 114 NCs. Cerebral-to-white matter, cerebellar, and pontine SUVRs were characterized in terms of their longitudinal variability; their power to track longitudinal fibrillar Aβ increases in Aβ+ and Aβ- subgroups and cognitively normal APOE4 carriers and noncarriers; the sample sizes needed to detect attenuated accumulation of or clearance of fibrillar Aβ accumulation in randomized clinical trials; and their ability to relate 24-mo fibrillar Aβ increases to clinical declines. As predicted, cerebral-to-white matter SUVR changes were significantly less variable and had significantly greater power to detect 24-mo fibrillar Aβ increases and evaluate Aβ-modifying treatment effects in Aβ+ pAD, MCI, and NC subjects and cognitively normal APOE4 carriers. They were also distinguished by the ability to detect significant associations between 24-mo Aβ increases and clinical declines. A cerebral white matter reference region may improve the power to track longitudinal fibrillar Aβ increases, to characterize their relationship to longitudinal clinical declines, and to evaluate Aβ-modifying treatments in randomized clinical trials. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Adaptation, expertise, and giftedness: towards an understanding of cortical, subcortical, and cerebellar network contributions.

PubMed

Koziol, Leonard F; Budding, Deborah Ely; Chidekel, Dana

2010-12-01

Current cortico-centric models of cognition lack a cohesive neuroanatomic framework that sufficiently considers overlapping levels of function, from "pathological" through "normal" to "gifted" or exceptional ability. While most cognitive theories presume an evolutionary context, few actively consider the process of adaptation, including concepts of neurodevelopment. Further, the frequent co-occurrence of "gifted" and "pathological" function is difficult to explain from a cortico-centric point of view. This comprehensive review paper proposes a framework that includes the brain's vertical organization and considers "giftedness" from an evolutionary and neurodevelopmental vantage point. We begin by discussing the current cortico-centric model of cognition and its relationship to intelligence. We then review an integrated, dual-tiered model of cognition that better explains the process of adaptation by simultaneously allowing for both stimulus-based processing and higher-order cognitive control. We consider the role of the basal ganglia within this model, particularly in relation to reward circuitry and instrumental learning. We review the important role of white matter tracts in relation to speed of adaptation and development of behavioral mastery. We examine the cerebellum's critical role in behavioral refinement and in cognitive and behavioral automation, particularly in relation to expertise and giftedness. We conclude this integrated model of brain function by considering the savant syndrome, which we believe is best understood within the context of a dual-tiered model of cognition that allows for automaticity in adaptation as well as higher-order executive control.

Initial cognitive decline is associated with cortical thinning in early Parkinson disease

PubMed Central

Svenningsson, Per; Weintraub, Daniel; Brønnick, Kolbjørn; Lebedev, Alexander; Westman, Eric; Aarsland, Dag

2014-01-01

Objectives: Our aim was to assess cortical thickness in a large multicenter cohort of drug-naive patients with early Parkinson disease (PD), with and without mild cognitive impairment (MCI), and explore the cognitive correlates of regional cortical thinning. Methods: One hundred twenty-three newly diagnosed patients with PD and 56 healthy controls with 3-tesla structural MRI scans and complete neuropsychological assessment from the Parkinson's Progression Markers Initiative were included. Modified Movement Disorders Society Task Force level II criteria were applied to diagnose MCI in PD. FreeSurfer image processing and analysis software was used to measure cortical thickness across groups and the association with cognitive domains and tests. Results: In patients with MCI, atrophy was found in temporal, parietal, frontal, and occipital areas compared with controls. Specific regional thinning in the right inferior temporal cortex was also found in cognitively normal patients. Memory, executive, and visuospatial performance was associated with temporoparietal and superior frontal thinning, suggesting a relationship between cognitive impairment and both anterior and posterior cortical atrophy in the whole patient sample. Conclusions: These findings confirm that MCI is associated with widespread cortical atrophy. In addition, they suggest that regional cortical thinning is already present at the time of diagnosis in patients with early, untreated PD who do not meet the criteria for MCI. Together, the results indicate that cortical thinning can serve as a marker for initial cognitive decline in early PD. PMID:24808018

An investigation of mental imagery in bipolar disorder: Exploring "the mind's eye".

PubMed

Di Simplicio, Martina; Renner, Fritz; Blackwell, Simon E; Mitchell, Heather; Stratford, Hannah J; Watson, Peter; Myers, Nick; Nobre, Anna C; Lau-Zhu, Alex; Holmes, Emily A

2016-12-01

Mental imagery abnormalities occur across psychopathologies and are hypothesized to drive emotional difficulties in bipolar disorder (BD). A comprehensive assessment of mental imagery in BD is lacking. We aimed to test whether (i) mental imagery abnormalities (abnormalities in cognitive stages and subjective domains) occur in BD relative to non-clinical controls; and (ii) to determine the specificity of any abnormalities in BD relative to depression and anxiety disorders. Participants included 54 subjects in the BD group (depressed/euthymic; n=27 in each subgroup), subjects with unipolar depression (n=26), subjects with anxiety disorders (n=25), and non-clinical controls (n=27) matched for age, gender, ethnicity, education, and premorbid IQ. Experimental tasks assessed cognitive (non-emotional) measures of mental imagery (cognitive stages). Questionnaires, experimental tasks, and a phenomenological interview assessed subjective domains including spontaneous imagery use, interpretation bias, and emotional mental imagery. (i) Compared to non-clinical controls, the BD combined group reported a greater impact of intrusive prospective imagery in daily life, more vivid and "real" negative images (prospective imagery task), and higher self-involvement (picture-word task). The BD combined group showed no clear abnormalities in cognitive stages of mental imagery. (ii) When depressed individuals with BD were compared to the depressed or anxious clinical control groups, no significant differences remained-across all groups, imagery differences were associated with affective lability and anxiety. Compared to non-clinical controls, BD is characterized by abnormalities in aspects of emotional mental imagery within the context of otherwise normal cognitive aspects. When matched for depression and anxiety, these abnormalities are not specific to BD-rather, imagery may reflect a transdiagnostic marker of emotional psychopathology. © 2016 Medical Research Council. Bipolar Disorders Published by John Wiley & Sons Ltd.

Preterm birth leads to hyper-reactive cognitive control processing and poor white matter organization in adulthood.

PubMed

Olsen, Alexander; Dennis, Emily L; Evensen, Kari Anne I; Husby Hollund, Ingrid Marie; Løhaugen, Gro C C; Thompson, Paul M; Brubakk, Ann-Mari; Eikenes, Live; Håberg, Asta K

2018-02-15

Individuals born preterm with very low birth weight (VLBW; birth weight ≤ 1500 g) are at high risk for perinatal brain injuries and deviant brain development, leading to increased chances of later cognitive, emotional, and behavioral problems. Here we investigated the neuronal underpinnings of both reactive and proactive cognitive control processes in adults with VLBW. We included 32 adults born preterm with VLBW (before 37th week of gestation) and 32 term-born controls (birth weight ≥10th percentile for gestational age) between 22 and 24 years of age that have been followed prospectively since birth. Participants performed a well-validated Not-X continuous performance test (CPT) adapted for use in a mixed block- and event-related fMRI protocol. BOLD fMRI and DTI data was acquired on a 3T scanner. Performance on the Not-X CPT was highly similar between groups. However, the VLBW group demonstrated hyper-reactive cognitive control processing and disrupted white matter organization. The hyper-reactive brain activation signature in VLBW adults was associated with lower gestational age, lower fluid intelligence score, and anxiety problems. Automated Multi-Atlas Tract Extraction (AutoMATE) analyses revealed that this disruption of normal brain function was accompanied by poorer white matter organization in the anterior thalamic radiation and the cingulum, as reflected in both reduced fractional anisotropy and increased mean diffusivity. These findings show that the preterm behavioral phenotype is associated with predominantly reactive-, rather than proactive cognitive control processing, as well as white matter abnormalities, that may underlie common difficulties that many preterm born individuals experience in everyday life. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The Effects of BDNF Val66Met Gene Polymorphism on Serum BDNF and Cognitive Function in Methamphetamine-Dependent Patients and Normal Controls: A Case-Control Study.

PubMed

Su, Hang; Tao, Jingyan; Zhang, Jie; Xie, Ying; Wang, Yue; Zhang, Yu; Han, Bin; Lu, Yuling; Sun, Haiwei; Wei, Youdan; Zou, Shengzhen; Wu, Wenxiu; Zhang, Jiajia; Xu, Ke; Zhang, Xiangyang; He, Jincai

2015-10-01

Studies suggest that a functional polymorphism of the brain-derived neurotrophic factor gene (BDNF Val66Met) may contribute to methamphetamine dependence. We hypothesized that this polymorphism had a role in cognitive deficits in methamphetamine-dependent patients and in the relationship of serum BDNF with cognitive impairments. We conducted a case-control study by assessing 194 methamphetamine-dependent patients and 378 healthy volunteers without history of drug use on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the presence of the BDNF Val66Met polymorphism and serum BDNF levels. We showed no significant differences in genotype and allele distributions between the methamphetamine-dependent patients and controls. Some aspects of cognitive function significantly differed in the 2 groups. The serum BDNF levels in methamphetamine-dependent patients were significantly higher than those of the healthy controls. In the patients, partial correlation analysis showed a significant positive correlation between serum BDNF and the delayed memory index score. The RBANS scores showed statistically significant BDNF level × genotype interaction. Further regression analyses showed a significant positive association between BDNF levels and the RBANS total score, immediate memory or attention index among Val homozygote patients, whereas a significant negative association of BDNF levels with the RBANS total score, visuospatial/constructional, or language index was found among Met/Val heterozygous patients. We demonstrated significant impairment on some aspects of cognitive function and increased BDNF levels in methamphetamine-dependent patients as well as genotypic differences in the relationships between BDNF levels and RBANS scores on the BDNF Val66Met polymorphism only in these patients.

Targeting Alertness to Improve Cognition in Older Adults: A Preliminary Report of Benefits in Executive Function and Skill Acquisition

PubMed Central

Van Vleet, Thomas M.; DeGutis, Joseph M.; Merzenich, Michael M.; Simpson, Gregory V.; Zomet, Ativ; Dabit, Sawsan

2016-01-01

Efficient self-regulation of alertness declines with age exacerbating normal declines in performance across multiple cognitive domains, including learning and skill acquisition. Previous cognitive intervention studies have shown that it is possible to enhance alertness in patients with acquired brain injury and marked attention impairments, and that this benefit generalizes to improvements in more global cognitive functions. In the current preliminary studies, we sought to test whether this approach, that targets both tonic (over a period of minutes) and phasic (moment-to-moment) alertness, can improve key executive functioning declines in older adults, and enhance the rate of skill acquisition. The results of both experiments 1 and 2 demonstrate that, compared to active control training, alertness training significantly enhanced performance in several validated executive function measures. In experiment 2, alertness training significantly improved skill acquisition compared to active control training in a well-characterized speed of processing task, with the largest benefits shown in the most challenging speed of processing blocks. The results of the current study suggest that targeting intrinsic alertness in cognitive training provides a novel approach to improve executive functions in older adults and may be a useful adjunct treatment to enhance benefits gained in other clinically validated treatments. PMID:27372902

Electroacupuncture for older adults with mild cognitive impairment: study protocol for a randomized controlled trial.

PubMed

Leung, Albert Wing Nang; Lam, Linda Chiu Wa; Kwan, Andrew Ka Lun; Tsang, Celia Lai Lin; Zhang, Hong Wei; Guo, Yuan Qi; Xu, Chuan Shan

2015-05-27

Mild cognitive impairment is an intermediary state between normal aging and clinical Alzheimer's disease. Early intervention of mild cognitive impairment may be an important strategy in the management of Alzheimer's disease. The proposal aims to evaluate if electroacupuncture would optimize cognitive function in subjects with mild cognitive impairment and understand the role of electroacupuncture in the treatment of Alzheimer's disease. A randomised patient- and assessor-blind sham-controlled trial is designed to assess whether electroacupuncture intervention decreases the rate of cognitive decline amongst older adults with mild cognitive impairment. One hundred and fifty subjects aged 65 years of age or over with a diagnosis of mild cognitive impairment are recruited from the community and elderly centre in Hong Kong. All subjects are randomly allocated into two groups (75 subjects each group): the electroacupuncture group and sham control. Participants in the electroacupuncture group receive electroacupuncture stimulation by sterile, disposable acupuncture needles inserted to the acupoints with a depth of 1 to 3 cm. The acupuncture needles are subjected to 2 Hz electroacupuncture with an intensity of 5 to 10 mA. Each participant receives electroacupuncture for 8 weeks (once a day, 3 days a week) and the treatment lasts for 30 minutes each time. For sham electroacupuncture, needles are inserted to a depth of 1 to 2 mm, and connected to the electroacupuncture device without any current passing through. Outcome measures (including primary and secondary outcome measures) are collected at baseline, at the end day of intervention, and months 4 and 6 after intervention. The primary outcome is measured by the Alzheimer Disease Assessment Scale-Cognitive subscale. Secondary outcomes are measured by the mini-mental state examination, category fluency text and the Short Form 12. The study will provide evidence for evaluating and understanding the role of electroacupuncture in the treatment of Alzheimer's disease. This trial is registered with chictr.org (registration number: ChiCTR-TRC-12002414 . Registration date: 11 August 2012.

Patients with primary biliary cholangitis and fatigue present with depressive symptoms and selected cognitive deficits, but with normal attention performance and brain structure.

PubMed

Zenouzi, Roman; von der Gablentz, Janina; Heldmann, Marcus; Göttlich, Martin; Weiler-Normann, Christina; Sebode, Marcial; Ehlken, Hanno; Hartl, Johannes; Fellbrich, Anja; Siemonsen, Susanne; Schramm, Christoph; Münte, Thomas F; Lohse, Ansgar W

2018-01-01

In primary biliary cholangitis (PBC) fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI) study and correlated changes of white and grey brain matter with the cognitive and attention performance. 20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI) scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM) and DTI analyses. Results were correlated to the cognitive and attention performance. Compared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance. Despite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain changes underlie fatigue in PBC.

Cognitive function in elderly marathon runners: cross-sectional data from the marathon trial (APSOEM).

PubMed

Winker, Robert; Lukas, Ina; Perkmann, Thomas; Haslacher, Helmut; Ponocny, Elisabeth; Lehrner, Johann; Tscholakoff, Dimiter; Dal-Bianco, Peter

2010-12-01

Cognitive impairment of the elderly contributes to morbidity, loss of quality of life, and impairment of work ability in aging western societies. Thus strategies to maintain cognitive function at an advanced age imply a great challenge to Occupational Medicine. To study whether intensive endurance exercise training is associated with better cognitive performance and increases brain-derived neurotrophic factor (BDNF) and insulin-like growth factor (IGF). Active elderly marathon runners or bicyclists older than 60 years were recruited and matched with an inactive control group according to age, sex, and education years. After exclusion of various diseases according to the study protocol 56 athletes and 58 controls could be selected for follow-up studies. The influence of endurance training on cognitive function was assessed by the use of the Vienna Neuropsychological Test Battery and the CERAD test battery. Other relevant outcomes were the levels of BDNF, IGF-1, Apo e4 carrier state, and self-ratings. The elderly marathon group performed better only in one specific cognitive task (the Five Point Test, p = 0.04) and almost significantly better in one additional test (the NAI Stroop Test, p = 0.08). Neither BDNF nor IGF-1 was related to the duration of daily exercise and no differences in the basal levels of these humoral growth factors in the exercise and the control cohort were found. Interestingly, we also found significantly decreased BDNF levels in subjects with Alzheimer's disease in the family in spite of the maintained normal cognitive performance (p = 0.01). These results suggest that extensive endurance exercise training might be beneficial for maintaining cognitive function in elderly persons. Our data demonstrate that beneficial endurance training effects are not linked to the upregulation of the examined neurotrophins. Since we found reduced BDNF-levels in subjects with a positive family history of Alzheimer's disease, we speculate that BDNF-reduction might precede cognitive impairment.

How do health and biological age influence chronological age and sex differences in cognitive aging: moderating, mediating, or both?

PubMed

Wahlin, Ake; MacDonald, Stuart W S; deFrias, Cindy M; Nilsson, Lars-Göran; Dixon, Roger A

2006-06-01

Much research on cognitive competence in normal older adults has documented age and sex differences. The authors used new cross-sectional data from the Victoria Longitudinal Study (VLS) (n=386; age 61 to 95 years) to examine how health and biological age influence age and sex differences in cognitive aging. The authors found evidence for both moderating and mediating influences. Age differences were moderated by health status, such that the negative effects of age were most pronounced among participants of relatively better health. Sex differences were moderated by health and were more pronounced among participants reporting comparatively poorer health. Although health mediated a notable amount of age-related cognitive variation, BioAge mediated considerably more variance, even after statistical control for differences in health. A complex pattern emerged for the mediation of sex differences: Although BioAge accounted for sex-related variation in cognitive performance, health operated to suppress these differences. Overall, both health and BioAge predicted cognitive variation independently of chronological age. Copyright (c) 2006 APA, all rights reserved.

Age-related Effects on Word Recognition: Reliance on Cognitive Control Systems with Structural Declines in Speech-responsive Cortex

PubMed Central

Walczak, Adam; Ahlstrom, Jayne; Denslow, Stewart; Horwitz, Amy; Dubno, Judy R.

2008-01-01

Speech recognition can be difficult and effortful for older adults, even for those with normal hearing. Declining frontal lobe cognitive control has been hypothesized to cause age-related speech recognition problems. This study examined age-related changes in frontal lobe function for 15 clinically normal hearing adults (21–75 years) when they performed a word recognition task that was made challenging by decreasing word intelligibility. Although there were no age-related changes in word recognition, there were age-related changes in the degree of activity within left middle frontal gyrus (MFG) and anterior cingulate (ACC) regions during word recognition. Older adults engaged left MFG and ACC regions when words were most intelligible compared to younger adults who engaged these regions when words were least intelligible. Declining gray matter volume within temporal lobe regions responsive to word intelligibility significantly predicted left MFG activity, even after controlling for total gray matter volume, suggesting that declining structural integrity of brain regions responsive to speech leads to the recruitment of frontal regions when words are easily understood. Electronic supplementary material The online version of this article (doi:10.1007/s10162-008-0113-3) contains supplementary material, which is available to authorized users. PMID:18274825

Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer's disease.

PubMed

Kirova, Anna-Mariya; Bays, Rebecca B; Lagalwar, Sarita

2015-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by deficits in episodic memory, working memory (WM), and executive function. Examples of executive dysfunction in AD include poor selective and divided attention, failed inhibition of interfering stimuli, and poor manipulation skills. Although episodic deficits during disease progression have been widely studied and are the benchmark of a probable AD diagnosis, more recent research has investigated WM and executive function decline during mild cognitive impairment (MCI), also referred to as the preclinical stage of AD. MCI is a critical period during which cognitive restructuring and neuroplasticity such as compensation still occur; therefore, cognitive therapies could have a beneficial effect on decreasing the likelihood of AD progression during MCI. Monitoring performance on working memory and executive function tasks to track cognitive function may signal progression from normal cognition to MCI to AD. The present review tracks WM decline through normal aging, MCI, and AD to highlight the behavioral and neurological differences that distinguish these three stages in an effort to guide future research on MCI diagnosis, cognitive therapy, and AD prevention.

An Evaluation of Deficits in Semantic Cuing, Proactive and Retroactive Interference as Early Features of Alzheimer’s disease

PubMed Central

Crocco, Elizabeth; Curiel, Rosie E.; Acevedo, Amarilis; Czaja, Sara J.; Loewenstein, David A.

2015-01-01

OBJECTIVE To determine the degree to which susceptibility to different types of semantic interference may reflect the earliest manifestations of early Alzheimer disease (AD) beyond the effects of global memory impairment. METHODS Normal elderly (NE) subjects (n= 47), subjects with amnestic mild cognitive impairment (aMCI: n=34) and 40 subjects with probable AD were evaluated using a unique cued recall paradigm that allowed for an evaluation of both proactive and retroactive interference effects while controlling for global memory impairment (LASSI-L procedure). RESULTS Controlling for overall memory impairment, aMCI subjects had much greater proactive and retroactive interference effects than NE subjects. LASSI-L indices of learning using cued recall evidenced high levels of sensitivity and specificity with an overall correct classification rate of 90%. These provided better discrimination than traditional neuropsychological measures of memory function. CONCLUSION The LASSI-L paradigm is unique and unlike other assessments of memory in that items presented for cued recall are explicitly presented, and semantic interference and cuing effects can be assessed while controlling for initial level of memory impairment. This represents a powerful procedure allowing the participant to serve as his or her own control. The high levels of discrimination between subjects with aMCI and normal cognition that exceeded traditional neuropsychological measures makes the LASSI-L worthy of further research in the detection of early AD. PMID:23768680

Effect of Different Starvation Levels on Cognitive Ability in Mice

NASA Astrophysics Data System (ADS)

Li, Xiaobing; Zhi, Guoguo; Yu, Yi; Cai, Lingyu; Li, Peng; Zhang, Danhua; Bao, Shuting; Hu, Wenlong; Shen, Haiyan; Song, Fujuan

2018-01-01

Objective: To study the effect of different starvation levels on cognitive ability in mice. Method: Mice were randomly divided into four groups: normal group, dieting group A, dieting group B, dieting group C. The mice of normal group were given normal feeding amount, the rest of groups were given 3/4 of normal feeding amount, 2/4 of normal feeding amount and 1/4 of normal feeding amount. After feeding mice four days, the weight was observed and T-maze experiment, Morris water maze test, open field test and Serum Catalase activity were detected. Result: Compared with the normal group, the correct rate of the intervention group in the T-maze experiment was decreased and dieting group A> dieting group B> dieting group C. In the Morris water maze test, Compared with the normal group, the correct rate of the intervention group was increased. Among these three intervention groups, dieting group A had the highest correct rate and the difference of dieting group B and dieting group C were similar. In the open field test, Compared with the normal group, the exploration rate of the surrounding environment in the intervention group was increased. In the Serum Catalase test, Compared with the normal group, the activities of serum peroxidase in the intervention groups were decreased and dieting group A> dieting group B> dieting group C. Conclusion: A certain level of starvation could affect the cognitive ability of mice. In a certain range, the level of starvation is inversely proportional to cognitive ability in mice.

Longitudinal Change of Biomarkers in Cognitive Decline

PubMed Central

Lo, Raymond Y.; Hubbard, Alan E.; Shaw, Leslie M.; Trojanowski, John Q.; Petersen, Ronald C.; Aisen, Paul S.; Weiner, Michael W.; Jagust, William J.

2017-01-01

Objective To delineate the trajectories of Aβ42 level in cerebrospinal fluid (CSF), fludeoxyglucose F18 (FDG) uptake using positron emission tomography, and hippocampal volume using magnetic resonance imaging and their relative associations with cognitive change at different stages in aging and Alzheimer disease (AD). Design Cohort study. Setting The 59 study sites for the Alzheimer’s Disease Neuroimaging Initiative. Participants A total of 819 participants 55 to 90 years of age with normal cognition, mild cognitive impairment, and AD who were followed up during the period from 2005 to 2007. Main Outcome Measures Rates of change in level of Aβ42 in CSF, FDG uptake, hippocampal volume, and the Alzheimer Disease’s Assessment Scale–cognitive subscale score during up to 36 months of follow-up by diagnostic group as well as prediction of cognitive change by each biomarker. Results Reductions in the level of Aβ42 in CSF were numerically greater in participants with normal cognition than in participants with mild cognitive impairment or AD; whereas both glucose metabolic decline and hippocampal atrophy were significantly slower in participants with normal cognition than in participants with mild cognitive impairment or AD. Positive APOE4 status accelerated hippocampal atrophic changes in participants with mild cognitive impairment or AD, but did not modify rates of change in level of Aβ42 in CSF or FDG uptake. The Alzheimer Disease’s Assessment Scale–cognitive subscale scores were related only to the baseline level of Aβ42 in CSF and the baseline FDG uptake in participants with normal cognition, which were about equally associated with change in FDG uptake and hippocampal volume in participants with mild cognitive impairment and best modeled by change in FDG uptake in participants with AD. Conclusion Trajectories of Aβ42 level in CSF, FDG uptake, and hippocampal volume vary across different cognitive stages. The longitudinal patterns support a hypothetical sequence of AD pathology in which amyloid deposition is an early event before hypometabolism or hippocampal atrophy, suggesting that biomarker prediction for cognitive change is stage dependent. PMID:21670386

Fluid intelligence and brain functional organization in aging yoga and meditation practitioners

PubMed Central

Gard, Tim; Taquet, Maxime; Dixit, Rohan; Hölzel, Britta K.; de Montjoye, Yves-Alexandre; Brach, Narayan; Salat, David H.; Dickerson, Bradford C.; Gray, Jeremy R.; Lazar, Sara W.

2014-01-01

Numerous studies have documented the normal age-related decline of neural structure, function, and cognitive performance. Preliminary evidence suggests that meditation may reduce decline in specific cognitive domains and in brain structure. Here we extended this research by investigating the relation between age and fluid intelligence and resting state brain functional network architecture using graph theory, in middle-aged yoga and meditation practitioners, and matched controls. Fluid intelligence declined slower in yoga practitioners and meditators combined than in controls. Resting state functional networks of yoga practitioners and meditators combined were more integrated and more resilient to damage than those of controls. Furthermore, mindfulness was positively correlated with fluid intelligence, resilience, and global network efficiency. These findings reveal the possibility to increase resilience and to slow the decline of fluid intelligence and brain functional architecture and suggest that mindfulness plays a mechanistic role in this preservation. PMID:24795629

Impact of glycemic status on longitudinal cognitive performance in men with and without HIV Infection.

PubMed

Yang, Jingyan; Jacobson, Lisa P; Becker, James T; Levine, Andrew; Martin, Eileen M; Munro, Cynthia A; Palella, Frank J; Lake, Jordan E; Sacktor, Ned C; Brown, Todd T

2018-05-08

To determine the relationship between glycemic status and cognitive performance in men living with (MLWH) and without HIV infection. A prospective HIV/AIDS cohort study in four U.S. cities between 1999 and 2016. Glycemic status was categorized as normal glucose (NG), impaired fasting glucose (IFG), controlled diabetes mellitus (DM) and uncontrolled DM at each semi-annual visit. Cognitive performance was evaluated using nine neuropsychological tests which measure attention, constructional ability, verbal learning, executive functioning, memory, and psychomotor speed. Linear mixed models were used to assess the association between glycemic status and cognition. Overall, 900 MLWH and 1149 men without HIV were included. MLWH had significantly more person-visits with IFG (52.1% vs 47.9%) and controlled DM (58.2% vs 41.8%) than men without HIV (p < 0.05). Compared to men with NG, men with DM had significantly poorer performance on psychomotor speed, executive function and verbal learning (all p < 0.05). There was no difference in cognition by HIV serostatus. The largest effect was observed in individuals with uncontrolled DM throughout the study period, equivalent to 16.5 and 13.4 years of aging on psychomotor speed and executive function, respectively, the effect of which remained significant after adjusting for HIV-related risk factors. Lower CD4+ nadir was also associated with worse cognitive performance. Abnormalities in glucose metabolism were more common among MLWH than men without HIV and were related to impaired cognitive performance. Metabolic status, along with advanced age and previous immunosuppression, may be important predictors of cognition in the modern antiretroviral therapy era.

Progression to dementia in memory clinic patients without dementia: a latent profile analysis.

PubMed

Köhler, Sebastian; Hamel, Renske; Sistermans, Nicole; Koene, Ted; Pijnenburg, Yolande A L; van der Flier, Wiesje M; Scheltens, Philip; Visser, Pieter-Jelle; Aalten, Pauline; Verhey, Frans R J; Ramakers, Inez

2013-10-08

To identify the existence of discrete cognitive subtypes among memory clinic patients without dementia and test their prognostic values. In a retrospective cohort study of 635 patients without dementia visiting the Alzheimer centers in Maastricht or Amsterdam, latent profile analysis identified cognitive subtypes based on immediate and delayed memory recall, delayed recognition, information-processing speed, attention, verbal fluency, and executive functions. Time to dementia was tested in weighted Cox proportional hazard models adjusted for confounders. Five latent classes represented participants with high-normal cognition (15%), low-normal cognition (37%), primary memory impairment in recall (MI) (36%), memory impairment in recall and recognition (MI+) (5%), and primary nonmemory impairment (NMI) (6%). Compared with low-normal cognition, participants with NMI had the highest risk of dementia (hazard ratio [HR] = 5.94, 95% confidence interval [CI] = 3.46-10.18) followed by MI (HR = 3.05, 95% CI = 2.09-4.46) and MI+ (HR = 3.26, 95% CI = 1.72-6.17), while participants with high-normal cognition had the lowest risk (HR = 0.24, 95% CI = 0.07-0.80). Subtypes further showed differential relationships with dementia types, with MI and MI+ most often converting to Alzheimer-type dementia and NMI to other forms of dementia. Cognitive subtypes can be empirically identified in otherwise heterogeneous samples of memory clinic patients and largely confirm current strategies to distinguish between amnestic and nonamnestic impairment. Studying more homogeneous cognitive subtypes may improve understanding of disease mechanisms and outcomes.

Depersonalization Disorder: Disconnection of Cognitive Evaluation from Autonomic Responses to Emotional Stimuli

PubMed Central

Michal, Matthias; Koechel, Ansgar; Canterino, Marco; Adler, Julia; Reiner, Iris; Vossel, Gerhard; Beutel, Manfred E.; Gamer, Matthias

2013-01-01

Background Patients with depersonalization disorder (DPD) typically complain about emotional detachment. Previous studies found reduced autonomic responsiveness to emotional stimuli for DPD patients as compared to patients with anxiety disorders. We aimed to investigate autonomic responsiveness to emotional auditory stimuli of DPD patients as compared to patient controls. Furthermore, we examined the modulatory effect of mindful breathing on these responses as well as on depersonalization intensity. Methods 22 DPD patients and 15 patient controls balanced for severity of depression and anxiety, age, sex and education, were compared regarding 1) electrodermal and heart rate data during a resting period, and 2) autonomic responses and cognitive appraisal of standardized acoustic affective stimuli in two conditions (normal listening and mindful breathing). Results DPD patients rated the emotional sounds as significantly more neutral as compared to patient controls and standardized norm ratings. At the same time, however, they responded more strongly to acoustic emotional stimuli and their electrodermal response pattern was more modulated by valence and arousal as compared to patient controls. Mindful breathing reduced severity of depersonalization in DPD patients and increased the arousal modulation of electrodermal responses in the whole sample. Finally, DPD patients showed an increased electrodermal lability in the rest period as compared to patient controls. Conclusions These findings demonstrated that the cognitive evaluation of emotional sounds in DPD patients is disconnected from their autonomic responses to those emotional stimuli. The increased electrodermal lability in DPD may reflect increased introversion and cognitive control of emotional impulses. The findings have important psychotherapeutic implications. PMID:24058547

Motor-symptom laterality affects acquisition in Parkinson's disease: A cognitive and functional magnetic resonance imaging study.

PubMed

Huang, Pei; Tan, Yu-Yan; Liu, Dong-Qiang; Herzallah, Mohammad M; Lapidow, Elizabeth; Wang, Ying; Zang, Yu-Feng; Gluck, Mark A; Chen, Sheng-Di

2017-07-01

Asymmetric onset of motor symptoms in PD can affect cognitive function. We examined whether motor-symptom laterality could affect feedback-based associative learning and explored its underlying neural mechanism by functional magnetic resonance imaging in PD patients. We recruited 63 early-stage medication-naïve PD patients (29 left-onset medication-naïve patients, 34 right-onset medication-naïve patients) and 38 matched normal controls. Subjects completed an acquired equivalence task (including acquisition, retention, and generalization) and resting-state functional magnetic resonance imaging scans. Learning accuracy and response time in each phase of the task were recorded for behavioral measures. Regional homogeneity was used to analyze resting-state functional magnetic resonance imaging data, with regional homogeneity lateralization to evaluate hemispheric functional asymmetry in the striatum. Left-onset patients made significantly more errors in acquisition (feedback-based associative learning) than right-onset patients and normal controls, whereas right-onset patients performed as well as normal controls. There was no significant difference among these three groups in the accuracy of either retention or generalization phase. The three groups did not show significant differences in response time. In the left-onset group, there was an inverse relationship between acquisition errors and regional homogeneity in the right dorsal rostral putamen. There were no significant regional homogeneity changes in either the left or the right dorsal rostral putamen in right-onset patients when compared to controls. Motor-symptom laterality could affect feedback-based associative learning in PD, with left-onset medication-naïve patients being selectively impaired. Dysfunction in the right dorsal rostral putamen may underlie the observed deficit in associative learning in patients with left-sided onset.© 2016 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

[Electroencephalogram power development of cognitive function at age 7 to 12 years: a comparative study between attention deficit hyperactivity disorder and healthy children].

PubMed

Cheng, Q R; Shen, H J; Tu, W J; Zhang, Q F; Dong, X

2016-12-02

Objective: To compare brain electrical cognitive tasks and brain development between study about 7 to 12 years old attention deficit hyperactivity disorder (ADHD) and normal children. Method: Prospectic case-control study was used. A total of 110 children with ADHD (63 boys and 47 girls) and 116 normal children (66 boys and 50 girls), were enrolled in this study. The electroencephalogram (EEG) was recorded when attention tasks were conducted, the EEG power was extracted from the original data and comparatively analyzed the absolute power (θ, α, β spectrum) and relative power (θ/total, α/total, θ/α, θ/β). Result: (1) Absolute power: ADHD children θ absolute power was higher than that of normal children in Pz lead ((52±28) vs . (40±30)μV 2 , t =3.906, P <0.05), with statistical significance. (2) Relative power: θ/total, θ/α, θ/β in ADHD are higher than normal children(0.23±0.07 vs . 0.20±0.05, 1.35±0.76 vs . 1.00±0.56, 4.75±2.49 vs . 3.56±2.08, t =2.900 and 3.954 and 3.901, P =0.004 and 0.000 and 0.000), α/total in ADHD is lower (0.21±0.09 vs. 0.24±0.10, t =-2.517, P =0.013). (3) The comparative study of the development of EEG power θ/β between ADHD and normal children showed age-related correlation in both groups ( r =-0.378 and -0.398, P =0.000 for both). Conclusion: ADHD children's EEG power on slow spectrum was higher than that of the normal children, it was more significant in the parietal region than in frontal region. With the increase of age, the θ relative power in ADHD and normal children gradually declined, in the normal children it linearly related, but in ADHD there was no significant regularity. θ/β can be used as a sensitive index to assess ADHD children's cognitive function.

Theory-of-mind use in remitted schizophrenia patients: The role of inhibition and perspective-switching.

PubMed

Wang, Yong-Guang; Shi, Jian-fei; Roberts, David L; Jiang, Xiao-ying; Shen, Zhi-hua; Wang, Yi-quan; Wang, Kai

2015-09-30

In social interaction, Theory of Mind (ToM) enables us to construct representations of others' mental states, and to use those representations flexibly to explain or predict others' behavior. Although previous literature has documented that schizophrenia is associated with poor ToM ability, little is known about the cognitive mechanisms underlying their difficulty in ToM use. This study developed a new methodology to test whether the difficulty in false-belief-use might be related to deficits in perspective-switching or impaired inhibitory control among 23 remitted schizophrenia patients and 18 normal controls. Patients showed a significantly greater error rate in a perspective-switching condition than a perspective-repeating position in a false-belief-use task, whereas normal controls did not show a difference between the two conditions. In addition, a larger main effect of inhibition was found in remitted schizophrenia patients than normal controls in both a false-belief-use task and control task. Thus, remitted schizophrenia patients' impairment in ToM use might be accounted for, at least partially, by deficits in perspective-switching and impaired inhibitory control. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Analysis of the posterior cingulate cortex with [18F]FDG-PET and Naa/mI in mild cognitive impairment and Alzheimer's disease: Correlations and differences between the two methods.

PubMed

Coutinho, Artur M N; Porto, Fábio H G; Zampieri, Poliana F; Otaduy, Maria C; Perroco, Tíbor R; Oliveira, Maira O; Nunes, Rafael F; Pinheiro, Toulouse Leusin; Bottino, Cassio M C; Leite, Claudia C; Buchpiguel, Carlos A

2015-01-01

Reduction of regional brain glucose metabolism (rBGM) measured by [18F]FDG-PET in the posterior cingulate cortex (PCC) has been associated with a higher conversion rate from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Magnetic Resonance Spectroscopy (MRS) is a potential biomarker that has disclosed Naa/mI reductions within the PCC in both MCI and AD. Studies investigating the relationships between the two modalities are scarce. To evaluate differences and possible correlations between the findings of rBGM and NAA/mI in the PCC of individuals with AD, MCI and of cognitively normal volunteers. Patients diagnosed with AD (N=32) or MCI (N=27) and cognitively normal older adults (CG, N=28), were submitted to [18F]FDG-PET and MRS to analyze the PCC. The two methods were compared and possible correlations between the modalities were investigated. The AD group exhibited rBGM reduction in the PCC when compared to the CG but not in the MCI group. MRS revealed lower NAA/mI values in the AD group compared to the CG but not in the MCI group. A positive correlation between rBGM and NAA/mI in the PCC was found. NAA/mI reduction in the PCC differentiated AD patients from control subjects with an area under the ROC curve of 0.70, while [18F]FDG-PET yielded a value of 0.93. rBGM and Naa/mI in the PCC were positively correlated in patients with MCI and AD. [18F]FDG-PET had greater accuracy than MRS for discriminating AD patients from controls.

Analysis of the posterior cingulate cortex with [18F]FDG-PET and Naa/mI in mild cognitive impairment and Alzheimer's disease: Correlations and differences between the two methods

PubMed Central

Coutinho, Artur M.N.; Porto, Fábio H.G.; Zampieri, Poliana F.; Otaduy, Maria C.; Perroco, Tíbor R.; Oliveira, Maira O.; Nunes, Rafael F.; Pinheiro, Toulouse Leusin; Bottino, Cassio M.C.; Leite, Claudia C.; Buchpiguel, Carlos A.

2015-01-01

Reduction of regional brain glucose metabolism (rBGM) measured by [18F]FDG-PET in the posterior cingulate cortex (PCC) has been associated with a higher conversion rate from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Magnetic Resonance Spectroscopy (MRS) is a potential biomarker that has disclosed Naa/mI reductions within the PCC in both MCI and AD. Studies investigating the relationships between the two modalities are scarce. Objective To evaluate differences and possible correlations between the findings of rBGM and NAA/mI in the PCC of individuals with AD, MCI and of cognitively normal volunteers. Methods Patients diagnosed with AD (N=32) or MCI (N=27) and cognitively normal older adults (CG, N=28), were submitted to [18F]FDG-PET and MRS to analyze the PCC. The two methods were compared and possible correlations between the modalities were investigated. Results The AD group exhibited rBGM reduction in the PCC when compared to the CG but not in the MCI group. MRS revealed lower NAA/mI values in the AD group compared to the CG but not in the MCI group. A positive correlation between rBGM and NAA/mI in the PCC was found. NAA/mI reduction in the PCC differentiated AD patients from control subjects with an area under the ROC curve of 0.70, while [18F]FDG-PET yielded a value of 0.93. Conclusion rBGM and Naa/mI in the PCC were positively correlated in patients with MCI and AD. [18F]FDG-PET had greater accuracy than MRS for discriminating AD patients from controls. PMID:29213988

Maternal Personality, Parenting Cognitions and Parenting Practices

PubMed Central

Bornstein, Marc H.; Hahn, Chun-Shin; Haynes, O. Maurice

2011-01-01

A community sample of 262 European American mothers of firstborn 20-month-olds completed a personality inventory and measures of parenting cognitions (knowledge, self-perceptions, and reports about behavior) and was observed in interaction with their children from which measures of parenting practices (language, sensitivity, affection, and play) were independently coded. Factor analyses of the personality inventory replicated extraction of the Five-Factor model of personality (Openness, Neuroticism, Extraversion, Agreeableness, and Conscientiousness). Controlling for sociodemographic characteristics, the five personality factors qua variables and in patterns qua clusters related differently to diverse parenting cognitions and practices, supporting the multidimensional, modular, and specific nature of parenting. Maternal personality in the normal range, a theoretically important but empirically neglected factor in everyday parenting, has meaning in studies of parenting, child development, and family process. PMID:21443335

Pathological Correlates of Cognitive Impairment in The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age.

PubMed

Robinson, Andrew C; Davidson, Yvonne S; Horan, Michael A; Pendleton, Neil; Mann, David M A

2018-01-01

The neuropathological changes responsible for cognitive impairment and dementia remain incompletely understood. Longitudinal studies with a brain donation end point allow the opportunity to examine relationships between cognitive status and neuropathology. We report on the first 97 participants coming to autopsy with sufficient clinical information from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age. This study began in 1983 and recruited 6,542 healthy individuals between 1983 and 1994, 312 of whom consented to brain donation. Alzheimer-type pathology was common throughout the cohort and generally correlated well with cognitive status. However, there was some overlap between cognitive status and measures of Alzheimer pathology with 26% of cognitively intact participants reaching either CERAD B or C, 11% reaching Thal phase 4 or 5, and 29% reaching Braak stage III- VI. Cerebral amyloid angiopathy(CAA), α-synuclein, and TDP-43 pathology was less common, but when present correlated well with cognitive status. Possession of APOEɛ4 allele(s) was associated with more severe Alzheimer-type and CAA pathology and earlier death, whereas possession of APOEɛ2 allele(s) had no effect on pathology but was more common in cognitively intact individuals. The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age cohort is pathologically representative when compared with similar studies. Cognitive impairment in life correlates strongly with all pathologies examined and the APOE status of an individual can affect pathology severity and longevity.

Influence of Competition Day on Cognitive Control and HRV in Young Male Gymnasts.

PubMed

Sartor, Francesco; Capuzzoni, Silvia; Rospo, Gianluca; La Torre, Antonio; Vailati, Fulvio; Vailati, Emanuele

2017-07-01

Sartor, F, Capuzzoni, S, Rospo, G, La Torre, A, Vailati, F, and Vailati, E. Influence of competition day on cognitive control and HRV in young male gymnasts. J Strength Cond Res 31(7): 1982-1993, 2017-In gymnastics, high levels of executive attention and physical and coordinative capacities are required. However, training planning does not usually account for dynamic alterations in cognitive capacity. This study investigated whether cognitive capacity was altered by the approach of a competition. Ten elite male gymnasts (16 ± 2 years, 57.3 ± 16.1 kg, 1.64 ± 1.27 m) were monitored for sleep, life demands, rating of perceived exertion (RPE), and pain, starting 5 days before the competition and up to 5 days after it. Stroop task performance and concomitant heart rate variability (HRV) were monitored 5 days and 1 day before the competition and then 1 and 5 days after. Sleep and life demands were not affected by the competition. Localized pain ranged from mild to moderate levels throughout the observation period. It weakly correlated with RPE (r = 0.241, p = 0.010) and moderately with number of errors (NoEs) (r = 0.639, p = 0.047). The RPE was higher for the competition day (p = 0.002). Median reaction times during the Stroop task were higher in the period preceding the competition (p < 0.001) for similar NoEs. The HRV during the congruent stimuli task showed higher root mean square differences of successive beats, portion of normal to normal intervals exceeding 50 milliseconds, and high frequency after the competition (p ≤ 0.05). Poincare plot SD2 showed a positive correlation with Stroop task NoEs (r = 0.590, p < 0.001). In conclusion, the period preceding an important competition affected cognitive performance and HRV in young male gymnasts. A practical implication of this study is that training loads could be adjusted according to mental stress before a competition.

The G72/G30 gene complex and cognitive abnormalities in schizophrenia.

PubMed

Goldberg, Terry E; Straub, Richard E; Callicott, Joseph H; Hariri, Ahmad; Mattay, Venkata S; Bigelow, Llewellyn; Coppola, Richard; Egan, Michael F; Weinberger, Daniel R

2006-09-01

A recently discovered gene complex, G72/G30 (hereafter G72, but now termed DAOA), was found to be associated with schizophrenia and with bipolar disorder, possibly because of an indirect effect on NMDA neurotransmission. In principle, if G72 increases risk for psychosis by this mechanism, it might impact with greater penetrance those cortically based cognitive and neurophysiological functions associated with NMDA signaling. We performed two independent family-based association studies (one sample contained more than 200 families and the other more than 65) of multiple SNPs in the G72 region and of multiple SNPs in the gene for D-amino acid oxidase (DAAO), which may be modulated by G72. We examined the relationship between select cognitive measures in attention, working memory, and episodic memory and a restricted set of G72 SNPs in over 600 normal controls, schizophrenic patients, and their nonpsychotic siblings using mixed model ANOVAs. We also determined genotype effects on neurophysiology measures in normal controls using the fMRI BOLD response obtained during activation procedures involving either episodic memory or working memory. There were no significant single G72 SNP associations and clinical diagnosis in either sample, though one approached significance (p=0.06). Diagnosis by genotype interaction effects for G72 SNP 10 were significant for cognitive variables assessing working memory and attention (p=0.05), and at the trend level for episodic memory, such that in the schizophrenia group an exaggerated allele load effect in the predicted directions was observed. In the fMRI paradigms, a strong effect of G72 SNP 10 genotype was observed on BOLD activation in the hippocampus during the episodic memory paradigm. Tests of association with DAAO were consistently nonsignificant. We present evidence that SNP variations in the G72 gene region increase risk of cognitive impairment in schizophrenia. SNP variations were not strongly associated with clinical diagnosis in family-based analyses.

Feeling Older and the Development of Cognitive Impairment and Dementia.

PubMed

Stephan, Yannick; Sutin, Angelina R; Luchetti, Martina; Terracciano, Antonio

2017-10-01

Subjective age is a biopsychosocial marker of aging associated with a range of outcomes in old age. In the domain of cognition, feeling older than one's chronological age is related to lower cognitive performance and steeper cognitive decline among older adults. The present study examines whether an older subjective age is associated with the risk of incident cognitive impairment and dementia. Participants were 5,748 individuals aged 65 years and older drawn from the Health and Retirement Study. Measures of subjective age, cognition, and covariates were obtained at baseline, and follow-up cognition was assessed over a 2- to 4-year period. Only participants without cognitive impairment were included at baseline. At follow-up, participants were classified into one of the three categories: normal functioning, cognitive impairment without dementia (CIND), and dementia. An older subjective age at baseline was associated with higher likelihood of CIND (odds ratio [OR] = 1.18; 1.09-1.28) and dementia (OR = 1.29; 1.02-1.63) at follow-up, controlling for chronological age, other demographic factors, and baseline cognition. Physical inactivity and depressive symptoms partly accounted for these associations. An older subjective age is a marker of individuals' risk of subsequent cognitive impairment and dementia. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Information flow dynamics in the brain

NASA Astrophysics Data System (ADS)

Rabinovich, Mikhail I.; Afraimovich, Valentin S.; Bick, Christian; Varona, Pablo

2012-03-01

Timing and dynamics of information in the brain is a hot field in modern neuroscience. The analysis of the temporal evolution of brain information is crucially important for the understanding of higher cognitive mechanisms in normal and pathological states. From the perspective of information dynamics, in this review we discuss working memory capacity, language dynamics, goal-dependent behavior programming and other functions of brain activity. In contrast with the classical description of information theory, which is mostly algebraic, brain flow information dynamics deals with problems such as the stability/instability of information flows, their quality, the timing of sequential processing, the top-down cognitive control of perceptual information, and information creation. In this framework, different types of information flow instabilities correspond to different cognitive disorders. On the other hand, the robustness of cognitive activity is related to the control of the information flow stability. We discuss these problems using both experimental and theoretical approaches, and we argue that brain activity is better understood considering information flows in the phase space of the corresponding dynamical model. In particular, we show how theory helps to understand intriguing experimental results in this matter, and how recent knowledge inspires new theoretical formalisms that can be tested with modern experimental techniques.

The Swedish Hayling task, and its relation to working memory, verbal ability, and speech-recognition-in-noise.

PubMed

Stenbäck, Victoria; Hällgren, Mathias; Lyxell, Björn; Larsby, Birgitta

2015-06-01

Cognitive functions and speech-recognition-in-noise were evaluated with a cognitive test battery, assessing response inhibition using the Hayling task, working memory capacity (WMC) and verbal information processing, and an auditory test of speech recognition. The cognitive tests were performed in silence whereas the speech recognition task was presented in noise. Thirty young normally-hearing individuals participated in the study. The aim of the study was to investigate one executive function, response inhibition, and whether it is related to individual working memory capacity (WMC), and how speech-recognition-in-noise relates to WMC and inhibitory control. The results showed a significant difference between initiation and response inhibition, suggesting that the Hayling task taps cognitive activity responsible for executive control. Our findings also suggest that high verbal ability was associated with better performance in the Hayling task. We also present findings suggesting that individuals who perform well on tasks involving response inhibition, and WMC, also perform well on a speech-in-noise task. Our findings indicate that capacity to resist semantic interference can be used to predict performance on speech-in-noise tasks. © 2015 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

Oxidative Glial Cell Damage Associated with White Matter Lesions in the Aging Human Brain

PubMed Central

Al-Mashhadi, Sufana; Simpson, Julie E.; Heath, Paul R.; Dickman, Mark; Forster, Gillian; Matthews, Fiona E.; Brayne, Carol; Ince, Paul G.; Wharton, Stephen B.

2016-01-01

White matter lesions (WML) are common in brain aging and are associated with dementia. We aimed to investigate whether oxidative DNA damage and occur in WML and in apparently normal white matter in cases with lesions. Tissue from WML and control white matter from brains with lesions (controls lesional) and without lesions (controls non-lesional) were obtained, using post-mortem magnetic resonance imaging-guided sampling, from the Medical Research Council Cognitive Function and Ageing Study. Oxidative damage was assessed by immunohistochemistry to 8-hydroxy-2′-deoxoguanosine (8-OHdG) and Western blotting for malondialdehyde. DNA response was assessed by phosphorylated histone H2AX (γH2AX), p53, senescence markers and by quantitative Reverse transcription polymerase chain reaction (RT-PCR) panel for candidate DNA damage-associated genes. 8-OHdG was expressed in glia and endothelium, with increased expression in both WML and controls lesional compared with controls non-lesional (P < 0.001). γH2Ax showed a similar, although attenuated difference among groups (P = 0.03). Expression of senescence-associated β-galactosidase and p16 suggested induction of senescence mechanisms in glia. Oxidative DNA damage and a DNA damage response are features of WML pathogenesis and suggest candidate mechanisms for glial dysfunction. Their expression in apparently normal white matter in cases with WML suggests that white matter dysfunction is not restricted to lesions. The role of this field-effect lesion pathogenesis and cognitive impairment are areas to be defined. PMID:25311358

Effect of Baduanjin exercise on cognitive function in older adults with mild cognitive impairment: study protocol for a randomised controlled trial.

PubMed

Zheng, Guohua; Huang, Maomao; Li, Shuzhen; Li, Moyi; Xia, Rui; Zhou, Wenji; Tao, Jing; Chen, Lidian

2016-04-11

Mild cognitive impairment (MCI) is an intermediate stage between the cognitive changes of normal aging and dementia characterised by a reduction in memory and/or other cognitive processes. An increasing number of studies have indicated that regular physical activity/exercise may have beneficial association with cognitive function of older adults with or without cognitive impairment. As a traditional Chinese Qigong exercise, Baduanjin may be even more beneficial in promoting cognitive ability in older adults with MCI, but the evidence is still insufficient. The main purpose of this study is to investigate the effect of Baduanjin exercise on neuropsychological outcomes of community-dwelling older adults with MCI, and to explore its mechanism of action from neuroimaging based on functional MRI (fMRI) and cerebrovascular function. The design of this study is a randomised, controlled trial with three parallel groups in a 1:1:1 allocation ratio with allocation concealment and assessor blinding. A total of 135 participants will be enrolled and randomised to the 24-week Baduanjin exercise intervention, 24-week brisk walking intervention and 24-week usual physical activity control group. Global cognitive function and the specific domains of cognition (memory, processing speed, executive function, attention and verbal learning and memory) will be assessed at baseline and 9, 17, 25 and 37 weeks after randomisation, while the structure and function of brain regions related to cognitive function and haemodynamic variables of the brain will be measured by fMRI and transcranial Doppler, respectively, at baseline and 25 and 37 weeks after randomisation. Ethics approval was given by the Medical Ethics Committee of the Second People's Hospital of Fujian Province (approval number 2014-KL045-02). The findings will be disseminated through peer-reviewed publications and at scientific conferences. ChiCTR-ICR-15005795; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Grey matter damage and overall cognitive impairment in primary progressive multiple sclerosis.

PubMed

Tur, C; Penny, S; Khaleeli, Z; Altmann, D R; Cipolotti, L; Ron, M; Thompson, A J; Ciccarelli, O

2011-11-01

To identify associations between cognitive impairment and imaging measures in a cross-sectional study of patients with primary progressive multiple sclerosis (PPMS). Neuropsychological tests were administered to 27 patients with PPMS and 31 controls. Patients underwent brain conventional magnetic resonance imaging (MRI) sequences, volumetric scans and magnetization transfer (MT) imaging; MT ratio (MTR) parameters, grey matter (GM) and normal-appearing white matter (NAWM) volumes, and WM T2 lesion load (T2LL) were obtained. In patients, multiple linear regression models identified the imaging measure associated with the abnormal cognitive tests independently from the other imaging variables. Partial correlation coefficients (PCC) were reported. Patients performed worse on tests of attention/speed of visual information processing, delayed verbal memory, and executive function, and had a worse overall cognitive performance index, when compared with controls. In patients, a lower GM peak location MTR was associated with worse overall cognitive performance (p < 0.001, PCC = 0.77). GM mean and peak height MTR showed the strongest association with the estimated verbal intelligence quotient (IQ) decline (p < 0.001, PCC = -0.62), and executive function (p < 0.001, PCC = 0.79). NAWM volume was associated with attention/speed of visual information processing (p < 0.001, PCC = 0.74), while T2LL was associated with delayed verbal memory (p = 0.007, PCC = -0.55). The finding of strong associations between GM MTR, NAWM volume and T2LL and specific cognitive impairments suggests that models that predict cognitive impairment in PPMS should include comprehensive MRI assessments of both GM and WM. However, GM MTR appears to be the main correlate of overall cognitive dysfunction, underlining the role of abnormal GM integrity in determining cognitive impairment in PPMS.

Cold pressor-induced pain does not impair WAIS-IV processing speed index or working memory index performance.

PubMed

Etherton, Joseph

2014-01-01

Chronic pain frequently involves cognitive complaints such as concentration and memory deficits, but studies of the effects of pain on cognition have not consistently demonstrated deficits and have not typically utilized standard neuropsychological instruments. Effects of cold pressor-induced pain on Wechsler Adult Intelligence Scale-Fourth Edition Processing Speed Index (PSI) and Working Memory Index (WMI) performance was examined in nonclinical volunteers (n = 40). All took one PSI subtest and one WMI subtest normally, and then took different PSI and WMI subtests during cold pressor-induced pain or painless warm-water immersion. Scaled scores for normal administration versus pain or painless water immersion did not differ and there was no interaction between group (control vs. pain) and manner of administration, despite moderately severe mean pain ratings (M = 6.8 on a 0-10 pain-rating scale). Results indicate that induced pain in nonclinical volunteers does not impair PSI or WMI performance, and they suggest that chronic pain per se should not be expected to substantially affect these cognitive functions. However, patients with chronic pain may differ from nonclinical volunteers in their experience of pain, potentially limiting generalizability.

Dementia and Out-of-Pocket Spending on Health Care Services

PubMed Central

Delavande, Adeline; Hurd, Michael D.; Martorell, Francisco; Langa, Kenneth M.

2014-01-01

Background High levels of out-of-pocket (OOP) spending for health care may lead patients to forego needed services and medications, as well as hamper their ability to pay for other essential goods. Dementia, because it leads to disability and the loss of independence may put patients and their families at risk for high OOP spending, especially for long-term care services. Methods We used data from the Aging, Demographics, and Memory Study, a nationally representative sub-sample (n=743) of the Health and Retirement Study, to determine whether individuals with dementia had higher self-reported OOP spending compared to those with cognitive impairment without dementia (CIND) and those with normal cognitive function. We also examined the relationship between dementia and utilization of dental care and prescription medications, two types of health care that are frequently paid for out-of-pocket. Multivariate and logistic regression models were used to adjust for the influence of potential confounders. Results After controlling for demographics and comorbidities, those with dementia had more than three times the yearly OOP spending compared to those with normal cognition ($8,216 for those with dementia vs. $2,570 for those with normal cognition, p<.01) Higher OOP spending for those with dementia was mainly driven by greater expenditures on nursing home care (p<.01). Dementia was not associated with the likelihood of visiting the dentist (p=0.76) or foregoing prescription medications due to cost (p=.34). Conclusions Dementia is associated with high levels of OOP spending, but not with the use of dental care or foregoing prescription medications, suggesting that excess OOP spending among those with dementia does not “crowd out” spending on these other health care services. PMID:23154049

Reducing case ascertainment costs in U.S. population studies of Alzheimer's disease, dementia, and cognitive impairment-Part 2.

PubMed

Evans, Denis A; Grodstein, Francine; Loewenstein, David; Kaye, Jeffrey; Weintraub, Sandra

2011-01-01

Dementia of the Alzheimer's type (DAT) is a major public health threat in developed countries where longevity has been extended to the eighth decade of life. Estimates of prevalence and incidence of DAT vary with what is measured, be it change from a baseline cognitive state or a clinical diagnostic endpoint, such as Alzheimer's disease. Judgment of what is psychometrically "normal" at the age of 80 years implicitly condones a decline from what is normal at the age of 30. However, because cognitive aging is very heterogeneous, it is reasonable to ask "Is 'normal for age' good enough to screen for DAT or its earlier precursors of cognitive impairment?" Cost containment and accessibility of ascertainment methods are enhanced by well-validated and reliable methods such as screening for cognitive impairment by telephone interviews. However, focused assessment of episodic memory, the key symptom associated with DAT, might be more effective at distinguishing normal from abnormal cognitive aging trajectories. Alternatively, the futuristic "Smart Home," outfitted with unobtrusive sensors and data storage devices, permits the moment-to-moment recording of activities so that changes that constitute risk for DAT can be identified before the emergence of symptoms. Copyright © 2011. Published by Elsevier Inc.

Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer’s Disease

PubMed Central

Cunnane, Stephen C.; Courchesne-Loyer, Alexandre; Vandenberghe, Camille; St-Pierre, Valérie; Fortier, Mélanie; Hennebelle, Marie; Croteau, Etienne; Bocti, Christian; Fulop, Tamas; Castellano, Christian-Alexandre

2016-01-01

We propose that brain energy deficit is an important pre-symptomatic feature of Alzheimer’s disease (AD) that requires closer attention in the development of AD therapeutics. Our rationale is fourfold: (i) Glucose uptake is lower in the frontal cortex of people >65 years-old despite cognitive scores that are normal for age. (ii) The regional deficit in brain glucose uptake is present in adults <40 years-old who have genetic or lifestyle risk factors for AD but in whom cognitive decline has not yet started. Examples include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of AD. (iii) Regional brain glucose uptake is impaired in AD and mild cognitive impairment (MCI), but brain uptake of ketones (beta-hydroxybutyrate and acetoacetate), remains the same in AD and MCI as in cognitively healthy age-matched controls. These observations point to a brain fuel deficit which appears to be specific to glucose, precedes cognitive decline associated with AD, and becomes more severe as MCI progresses toward AD. Since glucose is the brain’s main fuel, we suggest that gradual brain glucose exhaustion is contributing significantly to the onset or progression of AD. (iv) Interventions that raise ketone availability to the brain improve cognitive outcomes in both MCI and AD as well as in acute experimental hypoglycemia. Ketones are the brain’s main alternative fuel to glucose and brain ketone uptake is still normal in MCI and in early AD, which would help explain why ketogenic interventions improve some cognitive outcomes in MCI and AD. We suggest that the brain energy deficit needs to be overcome in order to successfully develop more effective therapeutics for AD. At present, oral ketogenic supplements are the most promising means of achieving this goal. PMID:27458340

Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder.

PubMed

Bilder, Robert M; Loo, Sandra K; McGough, James J; Whelan, Fiona; Hellemann, Gerhard; Sugar, Catherine; Del'Homme, Melissa; Sturm, Alexandra; Cowen, Jennifer; Hanada, Grant; McCracken, James T

2016-08-01

Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD. Children with ADHD (n = 182; aged 7-14 years) completed an 8-week, double blind, randomized, controlled trial with 3 arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A nonclinical comparison group (n = 93) had baseline testing, and a subset was retested 8 weeks later (n = 38). Analyses examined treatment effects in 4 cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables. The ADHD group showed impaired working memory relative to the nonclinical comparison group (effect size = -0.53 SD unit). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group. Combined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear to be necessary to achieve normalization of cognitive function in ADHD. Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Epidemiology of apathy in older adults: the Cache County Study.

PubMed

Onyike, Chiadi U; Sheppard, Jeannie-Marie E; Tschanz, JoAnn T; Norton, Maria C; Green, Robert C; Steinberg, Martin; Welsh-Bohmer, Kathleen A; Breitner, John C; Lyketsos, Constantine G

2007-05-01

The objectives of this study are to describe the distribution of apathy in community-based older adults and to investigate its relationships with cognition and day-to-day functioning. Data from the Cache County Study on Memory, Health and Aging were used to estimate the frequency of apathy in groups of elders defined by demographic, cognitive, and functional status and to examine the associations of apathy with impairments of cognition and day-to-day functioning. Apathy was measured with the Neuropsychiatric Inventory. Clinical apathy (Neuropsychiatric Inventory score > or = 4) was found in 1.4% of individuals classified as cognitively normal, 3.1% of those with a mild cognitive syndrome, and 17.3% of those with dementia. Apathy status was associated with cognitive and functional impairments and higher levels of stress experienced by caregivers. Among participants with normal cognition, apathy was associated with worse performance on the Mini-Mental State Examination, the Boston Naming and Animal Fluency tests, and the Trail Making Test-Part B. The association of apathy with cognitive impairment was independent of its association with Neuropsychiatric Inventory depression. In a cohort of community-based older adults, the frequency and severity of apathy is positively correlated with the severity of cognitive impairment. In addition, apathy is associated with cognitive and functional impairments in elders adjudged to have normal cognition. The results suggest that apathy is an early sign of cognitive decline and that delineating phenotypes in which apathy and a mild cognitive syndrome co-occur may facilitate earlier identification of individuals at risk for dementia.

Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease

PubMed Central

Fernández, Maria Victoria; Kim, Jong Hun; Budde, John P.; Black, Kathleen; Medvedeva, Alexandra; Saef, Ben; Del-Aguila, Jorge; Ibañez, Laura; Dube, Umber; Harari, Oscar; Norton, Joanne; Chasse, Rachel; Morris, John C.; Goate, Alison

2017-01-01

Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations. PMID:29091718

Association Between Serum Triglycerides and Cerebral Amyloidosis in Cognitively Normal Elderly.

PubMed

Choi, Hyo Jung; Byun, Min Soo; Yi, Dahyun; Choe, Young Min; Sohn, Bo Kyung; Baek, Hye Won; Lee, Jun Ho; Kim, Hyun Jung; Han, Ji Young; Yoon, Eun Jin; Kim, Yu Kyeong; Woo, Jong Inn; Lee, Dong Young

2016-08-01

Although many preclinical studies have suggested the possible linkage between dyslipidemia and cerebral amyloid deposition, the association between serum lipid measures and cerebral amyloid-beta (Aβ) deposition in human brain is still poorly known. We aimed to investigate the association in cognitively normal (CN) elderly individuals. Cross-sectional study. University hospital dementia clinic. 59 CN elderly. The study measures included comprehensive clinical and neuropsychological assessment based on the CERAD protocol, magnetic resonance imaging and (11)C-labelled Pittsburgh Compound B positron emission tomography scans, and quantification for serum lipid biomarkers. Multiple linear regression analyses showed that a higher serum triglycerides level was associated with heavier global cerebral Aβ deposition even after controlling age, sex, and apolipoprotein E ε4 genotype. Serum apolipoprotein B also showed significant positive association with global cerebral Aβ deposition, but the significance disappeared after controlling serum triglycerides level. No association was found between other lipid measures and global cerebral Aβ deposition. The findings suggest that serum triglycerides are closely associated with cerebral amyloidosis, although population-based prospective studies are needed to provide further evidence of the causative effect of triglycerides on cerebral amyloidosis. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease.

PubMed

Fernández, Maria Victoria; Kim, Jong Hun; Budde, John P; Black, Kathleen; Medvedeva, Alexandra; Saef, Ben; Deming, Yuetiva; Del-Aguila, Jorge; Ibañez, Laura; Dube, Umber; Harari, Oscar; Norton, Joanne; Chasse, Rachel; Morris, John C; Goate, Alison; Cruchaga, Carlos

2017-11-01

Alzheimer disease (AD), Frontotemporal lobar degeneration (FTD), Amyotrophic lateral sclerosis (ALS) and Parkinson disease (PD) have a certain degree of clinical, pathological and molecular overlap. Previous studies indicate that causative mutations in AD and FTD/ALS genes can be found in clinical familial AD. We examined the presence of causative and low frequency coding variants in the AD, FTD, ALS and PD Mendelian genes, in over 450 families with clinical history of AD and over 11,710 sporadic cases and cognitive normal participants from North America. Known pathogenic mutations were found in 1.05% of the sporadic cases, in 0.69% of the cognitively normal participants and in 4.22% of the families. A trend towards enrichment, albeit non-significant, was observed for most AD, FTD and PD genes. Only PSEN1 and PINK1 showed consistent association with AD cases when we used ExAC as the control population. These results suggest that current study designs may contain heterogeneity and contamination of the control population, and that current statistical methods for the discovery of novel genes with real pathogenic variants in complex late onset diseases may be inadequate or underpowered to identify genes carrying pathogenic mutations.

Fish oil promotes survival and protects against cognitive decline in severely undernourished mice by normalizing satiety signals

PubMed Central

Avraham, Yosefa; Saidian, Mayer; Burston, James J.; Mevorach, Raphael; Vorobiev, Lia; Magen, Iddo; Kunkes, Eithan; Borges, Beatriz; Lichtman, Aron H.; Berry, Elliot M.

2010-01-01

Severe malnutrition resulting from anorexia nervosa or involuntary starvation leads to low weight, cognitive deficits, and increased mortality rates. In the present study, we examined whether fish oil supplementation, compared with canola oil, would ameliorate the morbidity and mortality associated with these conditions by normalizing endocannabinoid and monoaminergeric systems as well as other systems involved in satiety and cognitive function within the hypothalamus and hippocampus. Female Sabra mice restricted to 40% of their daily food intake exhibited decreased body weight, were sickly in appearance, displayed cognitive deficits, and had increased mortality rates. Strikingly, fish oil supplementation that contains high omega-3 fatty acids levels decreased mortality and morbidity, and normalized the expression of genes and neurotransmitters in the hippocampus and hypothalamus. Fish oil supplementation, but not canola oil, increased survival rates, improved general appearance, and prevented cognitive decline, despite the facts that both diets contained an equivalent number of calories and that there were no differences in weight between mice maintained on the two diets in 100% but decrease in the 40%. In the hypothalamus, the beneficial effects of fish oil supplementation were related to normalization of the endocannabinoid 2-arachidonylglycerol (2-AG), serotonin (5-HT) (p<0.056), dopamine (DA), neuropeptide Y (NPY), and Ca2+/calmodulin (CaM)-dependent protein kinase (Camkk2). In the hippocampus, fish oil supplementation normalized 5-HT, Camkk2, silent mating type information regulation 1 (SIRT-1), and brain-derived neurotrophic factor (BDNF). In conclusion, dietary supplements of fish oil, as source of omega-3 fatty acids, may alleviate cognitive impairments associated with severe diet restriction and prolong survival independently of weight gain by normalizing neurochemical systems. PMID:21109417

Role of Educational Status in Explaining the Association between Body Mass Index and Cognitive Function

PubMed Central

Ho, Yi-Te; Kao, Tung-Wei; Peng, Tao-Chun; Liaw, Fang-Yih; Yang, Hui-Fang; Sun, Yu-Shan; Chang, Yaw-Wen; Chen, Wei-Liang

2016-01-01

Abstract Preserving physical and cognitive function becomes an important issue as people age. A growing number of studies have found that the correlation between body mass index (BMI) and cognitive function changes in different age groups. It is obvious that higher educational status is linked to higher cognitive function in terms of numerous risk factors that influence cognitive function. This study aimed to investigate the interplay between obesity and cognitive function categorized by different educational status. This study included 5021 participants aged 20 to 59 years who completed 3 neurocognitive function tests, including a simple reaction time test (SRTT), a symbol digit substitution test (SDST), and a serial digit learning test (SDLT) as reported in the National Health and Nutrition Examination Survey (NHANES) III database. The associations between neurocognitive function and BMI were analyzed using multivariate linear regression while controlling for confounders. After adjusting for pertinent covariates in mode 3, the β coefficients in the female participants with more than 12 years of education (interpreted as change of 3 neurocognitive function tests for each increment in BMI) comparing obesity groups to those with normal BMI were 16.2 (P < 0.001 for SRTT), 0.14 (P < 0.05 for SDST), and 0.9 (P < 0.05 for SDLT). Male participants with more than 12 years of education and female participants with fewer than 12 years of education demonstrated increased impairment as their BMI increased. However, this association was not significant after adjustments. Obese individuals had worse neurocognitive function than those of normal weight or overweight, especially in women with a high educational level. PMID:26844489

Role of Educational Status in Explaining the Association between Body Mass Index and Cognitive Function.

PubMed

Ho, Yi-Te; Kao, Tung-Wei; Peng, Tao-Chun; Liaw, Fang-Yih; Yang, Hui-Fang; Sun, Yu-Shan; Chang, Yaw-Wen; Chen, Wei-Liang

2016-02-01

Preserving physical and cognitive function becomes an important issue as people age. A growing number of studies have found that the correlation between body mass index (BMI) and cognitive function changes in different age groups. It is obvious that higher educational status is linked to higher cognitive function in terms of numerous risk factors that influence cognitive function. This study aimed to investigate the interplay between obesity and cognitive function categorized by different educational status.This study included 5021 participants aged 20 to 59 years who completed 3 neurocognitive function tests, including a simple reaction time test (SRTT), a symbol digit substitution test (SDST), and a serial digit learning test (SDLT) as reported in the National Health and Nutrition Examination Survey (NHANES) III database. The associations between neurocognitive function and BMI were analyzed using multivariate linear regression while controlling for confounders.After adjusting for pertinent covariates in mode 3, the β coefficients in the female participants with more than 12 years of education (interpreted as change of 3 neurocognitive function tests for each increment in BMI) comparing obesity groups to those with normal BMI were 16.2 (P < 0.001 for SRTT), 0.14 (P < 0.05 for SDST), and 0.9 (P < 0.05 for SDLT). Male participants with more than 12 years of education and female participants with fewer than 12 years of education demonstrated increased impairment as their BMI increased. However, this association was not significant after adjustments.Obese individuals had worse neurocognitive function than those of normal weight or overweight, especially in women with a high educational level.

Neural correlates of genetically abnormal social cognition in Williams syndrome.

PubMed

Meyer-Lindenberg, Andreas; Hariri, Ahmad R; Munoz, Karen E; Mervis, Carolyn B; Mattay, Venkata S; Morris, Colleen A; Berman, Karen Faith

2005-08-01

Williams-Beuren syndrome (WBS), caused by a microdeletion of approximately 21 genes on chromosome 7q11.23, is characterized by unique hypersociability combined with increased non-social anxiety. Using functional neuroimaging, we found reduced amygdala activation in individuals with WBS for threatening faces but increased activation for threatening scenes, relative to matched normal controls. Activation and interactions of prefrontal regions linked to amygdala, especially orbitofrontal cortex, were abnormal, suggesting a genetically controlled neural circuitry for regulating human social behavior.

Carry-over fluency induced by extreme prolongations: A new behavioral paradigm.

PubMed

Briley, P M; Barnes, M P; Kalinowski, J S

2016-04-01

Extreme prolongations, which can be generated via extreme delayed auditory feedback (DAF) (e.g., 250-500 ms) or mediated cognitively with timing applications (e.g., analog stopwatch) at 2 s per syllable, have long been behavioral techniques used to inhibit stuttering. Some therapies have used this rate solely to establish initial fluency, while others use extremely slowed speech to establish fluency and add other strategic techniques such as easy onsets and diaphragmatic breathing. Extreme prolongations generate effective, efficient, and immediate forward flowing fluent speech, removing the signature behaviors of discrete stuttering (i.e., syllable repetitions and audible and inaudible postural fixations). Prolonged use of extreme prolongations establishes carry-over fluency, which is spontaneous, effortless speech absent of most, if not all, overt and covert manifestations of stuttering. The creation of this immediate fluency and the immense potential of extreme prolongations to generate long periods of carry-over fluency have been overlooked by researchers and clinicians alike. Clinicians depart from these longer prolongation durations as they attempt to achieve the same fluent results at a near normal rate of speech. Clinicians assume they are re-teaching fluency and slow rates will give rise to more normal rates with less control, but without carry-over fluency, controls and cognitive mediation are always needed for the inherently unstable speech systems of persons who stutter to experience fluent speech. The assumption being that the speech system is untenable without some level of cognitive and motoric monitoring that is always necessary. The goal is omnipresent "near normal rate sounding fluency" with continuous mediation via cognitive and motoric processes. This pursuit of "normal sounding fluency" continues despite ever-present relapse. Relapse has become so common that acceptance of stuttering is the new therapy modality because relapse has come to be understood as somewhat inevitable. Researchers and clinicians fail to recognize that immediate amelioration of stuttering and its attendant carry-over fluency are signs of a different pathway to fluency. In this path, clinicians focus on extreme prolongations and the extent of their carry-over. While fluency is automatically generated under these extreme prolongations, the realization is that communication at this rate in routine speaking tasks is not feasible. The perceived solution is a systematic reduction in the duration of these prolongations, which attempts to approximate "normal speech." Typically, the reintroduction of speech at a normalized rate precipitates a laborious style that is undesirable to the person who stutters (PWS) and is discontinued, once departed from the comforts of the clinical setting. The inevitable typically occurs; the well-intentioned therapist instructs the PWS to focus on the techniques while speaking at a rate that is nearest normal speech, but the overlooked extreme prolongations are unlikely to ever be revisited. The foundation of this hypothesis is that the departure from fluency generators (e.g. extreme prolongations) is the cause of regression to the stuttering set point. In turn, we postulate that the continued use of extreme prolongations, as a solitary practice method, will establish and nurture different neural pathways that will create a modality of fluent speech, able to be experienced without cognitive or motoric mediation. This would therefore result in fewer occurrences of stuttering due to a phenomenon called carry-over fluency. Thus, we hypothesize that the use of extreme prolongations fosters neural pathways for fluent speech, which will result in carry-over fluency that does not require mediation by the speaker. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Study on the Validity of a Computer-Based Game to Assess Cognitive Processes, Reward Mechanisms, and Time Perception in Children Aged 4-8 Years

PubMed Central

Hurks, Petra PM; Aldenkamp, Albert P; van der Spek, Erik D; Rauterberg, GWM; Vles, Johan SH; Hendriksen, Jos GM

2016-01-01

Background A computer-based game, named Timo’s Adventure, was developed to assess specific cognitive functions (eg, attention, planning, and working memory), time perception, and reward mechanisms in young school-aged children. The game consists of 6 mini-games embedded in a story line and includes fantasy elements to enhance motivation. Objective The aim of this study was to investigate the validity of Timo’s Adventure in normally developing children and in children with attention-deficit/hyperactivity disorder (ADHD). Methods A total of 96 normally developing children aged 4-8 years and 40 children with ADHD were assessed using the game. Clinical validity was investigated by examining the effects of age on performances within the normally developing children, as well as performance differences between the healthy controls and the ADHD group. Results Our analyses in the normally developing children showed developmental effects; that is, older children made fewer inhibition mistakes (r=−.33, P=.001), had faster (and therefore better) reaction times (r=−.49, P<.001), and were able to produce time intervals more accurately than younger children (ρ=.35, P<.001). Discriminant analysis showed that Timo’s Adventure was accurate in most classifications whether a child belonged to the ADHD group or the normally developing group: 78% (76/97) of the children were correctly classified as having ADHD or as being in the normally developing group. The classification results showed that 72% (41/57) children in the control group were correctly classified, and 88% (35/40) of the children in the ADHD group were correctly classified as having ADHD. Sensitivity (0.89) and specificity (0.69) of Timo’s Adventure were satisfying. Conclusions Computer-based games seem to be a valid tool to assess specific strengths and weaknesses in young children with ADHD. PMID:27658428

Kinematic and Pressure Features of Handwriting and Drawing: Preliminary Results Between Patients with Mild Cognitive Impairment, Alzheimer Disease and Healthy Controls

PubMed Central

Garre-Olmo, Josep; Faúndez-Zanuy, Marcos; López-de-Ipiña, Karmele; Calvó-Perxas, Laia; Turró-Garriga, Oriol

2017-01-01

Background: Alzheimer’s disease (AD) is the most common neurodegenerative dementia of old age, and the leading chronic disease contributor to disability and dependence among older people worldwide. Clinically, AD is characterized by a progressive cognitive decline that interferes with the abil-ity to perform the activities of daily living. Handwriting and drawing are complex human activities that entail an intricate blend of cognitive, kinesthetic, and perceptual-motor features. Objective: To compare the kinematic characteristics of handwriting and drawing between patients with AD, patients with mild cognitive impairment (MCI) and healthy controls. Methods: We used a cross-sectional and observational design to assess the kinematic and pressure fea-tures of handwriting and drawing using a computerized system. Participants were asked to copy one sen-tence, write a dictated sentence and an own sentence, copy two and-three dimensions drawings, and to execute the clock drawing test. By means of discriminant analyses, we explored the value of several kin-ematic features in order to classify participants depending on their degree of cognitive functioning. Results: The sample consisted of 52 participants (23 AD, 12 MCI, and 17 healthy controls) with a mean age of 69.7 years (SD=8.11). The degree of correct classification was largely dependent on the nature of the groups to be classified and the specific task, and ranged between 63.5% and 100%. Diagnostic accu-racy based on kinematic measures showed higher specificity values for distinguishing between normal and impaired cognition (MCI and AD), and higher sensitivity was obtained when distinguishing between impaired cognition levels (MCI vs. AD). Conclusion: The kinematic features of writing and drawing procedures, rather than the final product, may be a useful and objective complement to the clinical assessment of patients with cognitive impairment. PMID:28290244

Kinematic and Pressure Features of Handwriting and Drawing: Preliminary Results Between Patients with Mild Cognitive Impairment, Alzheimer Disease and Healthy Controls.

PubMed

Garre-Olmo, Josep; Faúndez-Zanuy, Marcos; López-de-Ipiña, Karmele; Calvó-Perxas, Laia; Turró-Garriga, Oriol

2017-01-01

Alzheimer's disease (AD) is the most common neurodegenerative dementia of old age, and the leading chronic disease contributor to disability and dependence among older people worldwide. Clinically, AD is characterized by a progressive cognitive decline that interferes with the ability to perform the activities of daily living. Handwriting and drawing are complex human activities that entail an intricate blend of cognitive, kinesthetic, and perceptual-motor features. To compare the kinematic characteristics of handwriting and drawing between patients with AD, patients with mild cognitive impairment (MCI) and healthy controls. We used a cross-sectional and observational design to assess the kinematic and pressure features of handwriting and drawing using a computerized system. Participants were asked to copy one sentence, write a dictated sentence and an own sentence, copy two and-three dimensions drawings, and to execute the clock drawing test. By means of discriminant analyses, we explored the value of several kinematic features in order to classify participants depending on their degree of cognitive functioning. The sample consisted of 52 participants (23 AD, 12 MCI, and 17 healthy controls) with a mean age of 69.7 years (SD=8.11). The degree of correct classification was largely dependent on the nature of the groups to be classified and the specific task, and ranged between 63.5% and 100%. Diagnostic accuracy based on kinematic measures showed higher specificity values for distinguishing between normal and impaired cognition (MCI and AD), and higher sensitivity was obtained when distinguishing between impaired cognition levels (MCI vs. AD). The kinematic features of writing and drawing procedures, rather than the final product, may be a useful and objective complement to the clinical assessment of patients with cognitive impairment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study.

PubMed

Sharma, Ram A; Varga, Andrew W; Bubu, Omonigho M; Pirraglia, Elizabeth; Kam, Korey; Parekh, Ankit; Wohlleber, Margaret; Miller, Margo D; Andrade, Andreia; Lewis, Clifton; Tweardy, Samuel; Buj, Maja; Yau, Po L; Sadda, Reem; Mosconi, Lisa; Li, Yi; Butler, Tracy; Glodzik, Lidia; Fieremans, Els; Babb, James S; Blennow, Kaj; Zetterberg, Henrik; Lu, Shou E; Badia, Sandra G; Romero, Sergio; Rosenzweig, Ivana; Gosselin, Nadia; Jean-Louis, Girardin; Rapoport, David M; de Leon, Mony J; Ayappa, Indu; Osorio, Ricardo S

2018-04-01

Recent evidence suggests that obstructive sleep apnea (OSA) may be a risk factor for developing mild cognitive impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood. To test the hypothesis that there is an association between severity of OSA and longitudinal increase in amyloid burden in cognitively normal elderly. Data were derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 and 90, were nondepressed, and had a consensus clinical diagnosis of cognitively normal. Cerebrospinal fluid amyloid β was measured using ELISA. Subjects received Pittsburgh compound B positron emission tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device. We found that severity of OSA indices (AHIall [F 1,88  = 4.26; P < 0.05] and AHI4% [F 1,87  = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β 42 using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in AD PiB -mask (Alzheimer's disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask) most likely because of the small sample size, although there was a trend for AHIall (F 1,28  = 2.96, P = 0.09; and F 1,28  = 2.32, not significant, respectively). In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2-year follow-up. Sleep fragmentation and/or intermittent hypoxia from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly.

Task-evoked fMRI changes in attention networks are associated with preclinical Alzheimer's disease biomarkers.

PubMed

Gordon, Brian A; Zacks, Jeffrey M; Blazey, Tyler; Benzinger, Tammie L S; Morris, John C; Fagan, Anne M; Holtzman, David M; Balota, David A

2015-05-01

There is a growing emphasis on examining preclinical levels of Alzheimer's disease (AD)-related pathology in the absence of cognitive impairment. Previous work examining biomarkers has focused almost exclusively on memory, although there is mounting evidence that attention also declines early in disease progression. In the current experiment, 2 attentional control tasks were used to examine alterations in task-evoked functional magnetic resonance imaging data related to biomarkers of AD pathology. Seventy-one cognitively normal individuals (females = 44, mean age = 63.5 years) performed 2 attention-demanding cognitive tasks in a design that modeled both trial- and task-level functional magnetic resonance imaging changes. Biomarkers included amyloid β42, tau, and phosphorylated tau measured from cerebrospinal fluid and positron emission tomography measures of amyloid deposition. Both tasks elicited widespread patterns of activation and deactivation associated with large task-level manipulations of attention. Importantly, results from both tasks indicated that higher levels of tau and phosphorylated tau pathologies were associated with block-level overactivations of attentional control areas. This suggests early alteration in attentional control with rising levels of AD pathology. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive reserve and long-term change in cognition in aging and preclinical Alzheimer's disease.

PubMed

Soldan, Anja; Pettigrew, Corinne; Cai, Qing; Wang, Jiangxia; Wang, Mei-Cheng; Moghekar, Abhay; Miller, Michael I; Albert, Marilyn

2017-12-01

We examined if baseline levels of cognitive reserve (CR) and of Alzheimer's disease (AD) biomarkers modify the rate of change in cognition among individuals with normal cognition at baseline (n = 303, mean baseline age = 57 years, mean follow-up = 12 years); 66 participants subsequently developed mild cognitive impairment (MCI) or dementia due to AD. CR was indexed by years of education, reading, and vocabulary measures. AD biomarkers were measured with a composite score composed of measures of amyloid, phosphorylated tau, and neurodegeneration. Higher CR scores were associated with better cognitive performance but did not modify the rate of change in cognition among those who remained cognitively normal, nor among those who progressed to MCI before symptom onset, independent of baseline biomarker levels. However, higher CR scores were associated with faster cognitive decline after symptom onset of MCI. These results suggest that the mechanism by which CR mediates the relationship between pathology and cognitive function is by delaying the onset of symptoms rather than reducing the rate of cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional connectivity changes detected with magnetoencephalography after mild traumatic brain injury

PubMed Central

Dimitriadis, Stavros I.; Zouridakis, George; Rezaie, Roozbeh; Babajani-Feremi, Abbas; Papanicolaou, Andrew C.

2015-01-01

Mild traumatic brain injury (mTBI) may affect normal cognition and behavior by disrupting the functional connectivity networks that mediate efficient communication among brain regions. In this study, we analyzed brain connectivity profiles from resting state Magnetoencephalographic (MEG) recordings obtained from 31 mTBI patients and 55 normal controls. We used phase-locking value estimates to compute functional connectivity graphs to quantify frequency-specific couplings between sensors at various frequency bands. Overall, normal controls showed a dense network of strong local connections and a limited number of long-range connections that accounted for approximately 20% of all connections, whereas mTBI patients showed networks characterized by weak local connections and strong long-range connections that accounted for more than 60% of all connections. Comparison of the two distinct general patterns at different frequencies using a tensor representation for the connectivity graphs and tensor subspace analysis for optimal feature extraction showed that mTBI patients could be separated from normal controls with 100% classification accuracy in the alpha band. These encouraging findings support the hypothesis that MEG-based functional connectivity patterns may be used as biomarkers that can provide more accurate diagnoses, help guide treatment, and monitor effectiveness of intervention in mTBI. PMID:26640764

Effect of simvastatin on CSF Alzheimer disease biomarkers in cognitively normal adults.

PubMed

Li, Ge; Mayer, Cynthia L; Morelli, Daniel; Millard, Steven P; Raskind, Wendy H; Petrie, Eric C; Cherrier, Monique; Fagan, Anne M; Raskind, Murray A; Peskind, Elaine R

2017-09-19

To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure. Participants were 45-64 years old and statin-naive with normal cognition and normal or mildly elevated cholesterol. Forty-six participants completed the 1-year study per protocol (25 in the simvastatin and 21 in the placebo group). Simvastatin was titrated to 40 mg/d. CSF Aβ 42 , total tau, and p-tau 181 were measured at baseline and after 12 months of treatment using the INNO-BIA AlzBio3 assay. We used analysis of covariance to assess differences in biomarker change from baseline between treatment groups, adjusting for age, sex, and APOE ε4 status. Changes from baseline did not differ significantly between treatment groups for any CSF biomarker, with p values of 0.53, 0.36, and 0.25 for CSF Aβ 42 , total tau, and p-tau 181 , respectively. There was no significant modifying effect of sex, APOE ε4, or baseline high-density lipoprotein or triglycerides on treatment group for any of the biomarkers (all p > 0.18). However, a significant interaction between treatment group and baseline low-density lipoprotein (LDL) was observed for p-tau 181 ( p = 0.003), where greater decreases from baseline in CSF p-tau 181 concentrations were associated with higher baseline LDL level for the simvastatin group. Simvastatin-related reductions in CSF p-tau 181 concentrations may be modulated by LDL cholesterol. The potential disease-modifying effects of simvastatin on CSF phospho-tau should be further investigated in persons with hypercholesterolemia. © 2017 American Academy of Neurology.

An acute, double-blind, placebo-controlled crossover study of 320 mg and 640 mg doses of a special extract of Bacopa monnieri (CDRI 08) on sustained cognitive performance.

PubMed

Downey, Luke A; Kean, James; Nemeh, Fiona; Lau, Angela; Poll, Alex; Gregory, Rebecca; Murray, Margaret; Rourke, Johanna; Patak, Brigit; Pase, Matthew P; Zangara, Andrea; Lomas, Justine; Scholey, Andrew; Stough, Con

2013-09-01

Standardized extracts of the traditional Ayurvedic medicine Bacopa monnieri (BM) (Brahmi) have been recently shown to have cognitive enhancing effects in chronic administration studies. Pre-clinical work has also identified a number of acute anxiolytic, nootropic, and cardiovascular effects of BM. There has, however, been little research on the acute effects of BM on cognitive function. The current study aimed to assess the acute effects of a specific extract of BM (KeenMind®-CDRI 08) in a double-blind, placebo-controlled study in normal healthy participants who completed a cognitively demanding series of tests. Twenty-four healthy volunteers completed six repetitions of the Cognitive Demand Battery (CDB) after consuming a placebo, 320 mg BM or 640 mg of BM in a cross-over design and provided cardiovascular and mood assessments before and after treatment. Change from baseline scores indicated that the 320 mg dose of BM improved performance at the first, second, and fourth repetition post-dosing on the CDB, and the treatments had no effect upon cardiovascular activity or in attenuating task-induced ratings of stress and fatigue. It was concluded that assessment of an earlier pharmacological window and use of less memory-specific cognitive tests together with more temporally sensitive measures of brain activity may improve our understanding of the acute neurocognitive properties of BM. Copyright © 2012 John Wiley & Sons, Ltd.

Connecting a cognitive architecture to robotic perception

NASA Astrophysics Data System (ADS)

Kurup, Unmesh; Lebiere, Christian; Stentz, Anthony; Hebert, Martial

2012-06-01

We present an integrated architecture in which perception and cognition interact and provide information to each other leading to improved performance in real-world situations. Our system integrates the Felzenswalb et. al. object-detection algorithm with the ACT-R cognitive architecture. The targeted task is to predict and classify pedestrian behavior in a checkpoint scenario, most specifically to discriminate between normal versus checkpoint-avoiding behavior. The Felzenswalb algorithm is a learning-based algorithm for detecting and localizing objects in images. ACT-R is a cognitive architecture that has been successfully used to model human cognition with a high degree of fidelity on tasks ranging from basic decision-making to the control of complex systems such as driving or air traffic control. The Felzenswalb algorithm detects pedestrians in the image and provides ACT-R a set of features based primarily on their locations. ACT-R uses its pattern-matching capabilities, specifically its partial-matching and blending mechanisms, to track objects across multiple images and classify their behavior based on the sequence of observed features. ACT-R also provides feedback to the Felzenswalb algorithm in the form of expected object locations that allow the algorithm to eliminate false-positives and improve its overall performance. This capability is an instance of the benefits pursued in developing a richer interaction between bottom-up perceptual processes and top-down goal-directed cognition. We trained the system on individual behaviors (only one person in the scene) and evaluated its performance across single and multiple behavior sets.

Insulin-like Growth Factor 1 (IGF-1) as a marker of cognitive decline in normal ageing: A review.

PubMed

Frater, Julanne; Lie, David; Bartlett, Perry; McGrath, John J

2018-03-01

Insulin-like Growth Factor 1 (IGF-1) and its signaling pathway play a primary role in normal growth and ageing, however serum IGF-1 is known to reduce with advancing age. Recent findings suggest IGF-1 is essential for neurogenesis in the adult brain, and this reduction of IGF-1 with ageing may contribute to age-related cognitive decline. Experimental studies have shown manipulation of the GH/GF-1 axis can slow rates of cognitive decline in animals, making IGF-1 a potential biomarker of cognition, and/or its signaling pathway a possible therapeutic target to prevent or slow age-related cognitive decline. A systematic literature review and qualitative narrative summary of current evidence for IGF-1 as a biomarker of cognitive decline in the ageing brain was undertaken. Results indicate IGF-1 concentrations do not confer additional diagnostic information for those with cognitive decline, and routine clinical measurement of IGF-1 is not currently justified. In cases of established cognitive impairment, it remains unclear whether increasing circulating or brain IGF-1 may reverse or slow down the rate of further decline. Advances in neuroimaging, genetics, neuroscience and the availability of large well characterized biobanks will facilitate research exploring the role of IGF-1 in both normal ageing and age-related cognitive decline. Copyright © 2017 Elsevier B.V. All rights reserved.

Mild cognitive impairment and everyday function: evidence of reduced speed in performing instrumental activities of daily living.

PubMed

Wadley, Virginia G; Okonkwo, Ozioma; Crowe, Michael; Ross-Meadows, Lesley A

2008-05-01

Mild cognitive impairment (MCI) may involve subtle functional losses that are not detected with typical self- or informant-report assessments of daily function. Information about the nature of functional difficulties in MCI can be used to augment common clinical assessment procedures, and aspects of function that are affected in MCI can serve as meaningful endpoints for intervention trials. Cross-sectional case and comparison group study. University medical center. Fifty participants with MCI and 59 cognitively normal participants. The authors compared the groups on dimensions of both speed and accuracy in performing instrumental activities of daily living (IADLs), using a standardized Timed IADL measure that evaluates five functional domains commonly encountered in everyday life (telephone use, locating nutrition information on food labels, financial abilities, grocery shopping, medication management). Across Timed IADL domains, MCI participants demonstrated accuracy comparable with cognitively normal participants but took significantly longer to complete the functional activities, controlling for depressive symptoms (p< 0.001). Slower performance was demonstrated in each discrete domain except financial abilities. These results suggest that slower speed of task performance is an important component and perhaps an early marker of functional change in MCI that would not be detected using traditional measurements of daily function. Future research should address the question of whether performance-based functional measures, as well as simple queries regarding whether functional activities take longer than usual to complete, may improve the prediction of future cognitive decline and disease progression among those individuals in whom MCI represents impending dementia.

Metal chaperones prevent zinc-mediated cognitive decline.

PubMed

Adlard, Paul A; Parncutt, Jacqui; Lal, Varsha; James, Simon; Hare, Dominic; Doble, Philip; Finkelstein, David I; Bush, Ashley I

2015-09-01

Zinc transporter-3 (ZnT3) protein is responsible for loading zinc into presynaptic vesicles and consequently controls the availability of zinc at the glutamatergic synapse. ZnT3 has been shown to decline with age and in Alzheimer's disease (AD) and is crucially involved in learning and memory. In this study, we utilised whole animal behavioural analyses in the ZnT3 KO mouse line, together with electrophysiological analysis of long-term potentiation in brain slices from ZnT3 KO mice, to show that metal chaperones (clioquinol, 30 mg/kg/day for 6weeks) can prevent the age-dependent cognitive phenotype that characterises these animals. This likely occurs as a result of a homeostatic restoration of synaptic protein expression, as clioquinol significantly restored levels of various pre- and postsynaptic proteins that are critical for normal cognition, including PSD-95; AMPAR and NMDAR2b. We hypothesised that this clioquinol-mediated restoration of synaptic health resulted from a selective increase in synaptic zinc content within the hippocampus. While we demonstrated a small regional increase in hippocampal zinc content using synchrotron x-ray fluorescence microscopy, further sub-region analyses are required to determine whether this effect is seen in other regions of the hippocampal formation that are more closely linked to the synaptic plasticity effects observed in this study. These data support our recent report on the use of a different metal chaperone (PBT2) to prevent normal age-related cognitive decline and demonstrate that metal chaperones are efficacious in preventing the zinc-mediated cognitive decline that characterises ageing and disease. Copyright © 2014 Elsevier Inc. All rights reserved.

Sphingolipid Metabolism Correlates with Cerebrospinal Fluid Beta Amyloid Levels in Alzheimer’s Disease

PubMed Central

Fonteh, Alfred N.; Ormseth, Cora; Chiang, Jiarong; Cipolla, Matthew; Arakaki, Xianghong; Harrington, Michael G.

2015-01-01

Sphingolipids are important in many brain functions but their role in Alzheimer’s disease (AD) is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF) contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a) total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b) levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c) three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β42 concentration in CSF from cognitively normal but not impaired participants. In dementia, altered sphingolipid metabolism, decreased acid sphingomyelinase activity and its lost association with CSF amyloid β42 concentration, underscores the potential of sphingolipids as disease biomarkers, and acid sphingomyelinase as a target for AD diagnosis and/or treatment. PMID:25938590

Involvement of PTPN5, the gene encoding the STriatal-Enriched protein tyrosine Phosphatase (STEP), in schizophrenia and cognition

PubMed Central

Pelov, Ilana; Teltsh, Omri; Greenbaum, Lior; Rigbi, Amihai; Kanyas-Sarner, Kyra; Lerer, Bernard; Lombroso, Paul; Kohn, Yoav

2013-01-01

Objective STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-specific member of the PTP family that has been implicated in learning and memory. In this study, we examined the association of the PTPN5 (protein-tyrosine-phosphatase non-receptor 5) gene, which encodes for STEP, with both schizophrenia and cognitive functioning in the Israeli Jewish population. Methods A 868 subjects schizophrenia (SZ) case-control study was performed (286 cases and 582 controls). Eleven STEP tagging SNPs were selected, and single markers and haplotypes association analyses were performed. A cognitive variability study included 437 healthy females who completed a computerized cognitive battery. We performed univariate associations between the SNPs and cognitive performance. The possible functional role of these variants was examined by studying their association with gene expression levels in the brain. Results In the SZ study, we found nominal association in the whole sample between rs4075664 and SZ. SZ males showed a more significant association for 3 SNPs (rs4075664, rs2278732, rs4757710). Haplotypes of the studied SNPs were associated with SZ both in the overall sample and within the male sub-sample. Expression analysis provided some support for the effects of the associated SNPs on PTPN5 expression level. The cognitive variability study showed positive associations between PTPN5 SNPs and different cognitive subtests. Principal component analysis demonstrated an “Attention Index” neurocognitive component that was associated with two SNP pairs (rs10832983*rs10766504 and rs7932938*rs4757718). Conclusion The results imply a model in which PTPN5 may play a role in normal cognitive functioning and contributes to aspects of the neuropathology of schizophrenia. PMID:22555153

A new cognitive evaluation battery for Down syndrome and its relevance for clinical trials

PubMed Central

de Sola, Susana; de la Torre, Rafael; Sánchez-Benavides, Gonzalo; Benejam, Bessy; Cuenca-Royo, Aida; del Hoyo, Laura; Rodríguez, Joan; Catuara-Solarz, Silvina; Sanchez-Gutierrez, Judit; Dueñas-Espin, Ivan; Hernandez, Gimena; Peña-Casanova, Jordi; Langohr, Klaus; Videla, Sebastia; Blehaut, Henry; Farre, Magi; Dierssen, Mara; Cuenca-Royo, Aida

2015-01-01

The recent prospect of pharmaceutical interventions for cognitive impairment of Down syndrome (DS) has boosted a number of clinical trials in this population. However, running the trials has raised some methodological challenges and questioned the prevailing methodology used to evaluate cognitive functioning of DS individuals. This is usually achieved by comparing DS individuals to matched healthy controls of the same mental age. We propose a new tool, the TESDAD Battery that uses comparison with age-matched typically developed adults. This is an advantageous method for probing the clinical efficacy of DS therapies, allowing the interpretation and prediction of functional outcomes in clinical trials. In our DS population the TESDAD battery permitted a quantitative assessment of cognitive defects, which indicated language dysfunction and deficits in executive function, as the most important contributors to other cognitive and adaptive behavior outcomes as predictors of functional change in DS. Concretely, auditory comprehension and functional academics showed the highest potential as end-point measures of therapeutic intervention for clinical trials: the former as a cognitive key target for therapeutic intervention, and the latter as a primary functional outcome measure of clinical efficacy. Our results also emphasize the need to explore the modulating effects of IQ, gender and age on cognitive enhancing treatments. Noticeably, women performed significantly better than men of the same age and IQ in most cognitive tests, with the most consistent differences occurring in memory and executive functioning and negative trends rarely emerged on quality of life linked to the effect of age after adjusting for IQ and gender. In sum, the TESDAD battery is a useful neurocognitive tool for probing the clinical efficacy of experimental therapies in interventional studies in the DS population suggesting that age-matched controls are advantageous for determining normalization of DS. PMID:26089807

Cerebrospinal Fluid Biomarkers and Reserve Variables as Predictors of Future “Non-Cognitive” Outcomes of Alzheimer’s Disease

PubMed Central

Ingber, Adam P.; Hassenstab, Jason; Fagan, Anne M.; Benzinger, Tammie L.S.; Grant, Elizabeth A.; Holtzman, David M.; Morris, John C.; Roe, Catherine M.

2016-01-01

Background The influence of reserve variables and Alzheimer’s disease (AD) biomarkers on cognitive test performance has been fairly well-characterized. However, less is known about the influence of these factors on “non-cognitive” outcomes, including functional abilities and mood. Objective We examined whether cognitive and brain reserve variables mediate how AD biomarker levels in cognitively normal persons predict future changes in function, mood, and neuropsychiatric behavior. Methods Non-cognitive outcomes were examined in 328 individuals 50 years and older enrolled in ongoing studies of aging and dementia at the Knight Alzheimer Disease Research Center (ADRC). All participants were cognitively normal at baseline (Clinical Dementia Rating [CDR] 0), completed cerebrospinal fluid (CSF) and structural neuroimaging studies within one year of baseline, and were followed for an average of 4.6 annual visits. Linear mixed effects models explored how cognitive reserve and brain reserve variables mediate the relationships between AD biomarker levels and changes in function, mood, and neuropsychiatric behavior in cognitively normal participants. Results Education levels did not have a significant effect on predicting non-cognitive decline. However, participants with smaller brain volumes exhibited the worst outcomes on measures of mood, functional abilities, and behavioral disturbance. This effect was most pronounced in individuals who also had abnormal CSF biomarkers. Conclusions The findings suggest that brain reserve plays a stronger, or earlier, role than cognitive reserve in protecting against non-cognitive impairment in AD. PMID:27104893

The value of Bayes' theorem for interpreting abnormal test scores in cognitively healthy and clinical samples.

PubMed

Gavett, Brandon E

2015-03-01

The base rates of abnormal test scores in cognitively normal samples have been a focus of recent research. The goal of the current study is to illustrate how Bayes' theorem uses these base rates--along with the same base rates in cognitively impaired samples and prevalence rates of cognitive impairment--to yield probability values that are more useful for making judgments about the absence or presence of cognitive impairment. Correlation matrices, means, and standard deviations were obtained from the Wechsler Memory Scale--4th Edition (WMS-IV) Technical and Interpretive Manual and used in Monte Carlo simulations to estimate the base rates of abnormal test scores in the standardization and special groups (mixed clinical) samples. Bayes' theorem was applied to these estimates to identify probabilities of normal cognition based on the number of abnormal test scores observed. Abnormal scores were common in the standardization sample (65.4% scoring below a scaled score of 7 on at least one subtest) and more common in the mixed clinical sample (85.6% scoring below a scaled score of 7 on at least one subtest). Probabilities varied according to the number of abnormal test scores, base rates of normal cognition, and cutoff scores. The results suggest that interpretation of base rates obtained from cognitively healthy samples must also account for data from cognitively impaired samples. Bayes' theorem can help neuropsychologists answer questions about the probability that an individual examinee is cognitively healthy based on the number of abnormal test scores observed.

Cognitively Elite, Cognitively Normal, and Cognitively Impaired Aging: Neurocognitive Status and Stability Moderate Memory Performance

PubMed Central

Dixon, Roger A.; de Frias, Cindy M.

2014-01-01

Objective Although recent theories of brain and cognitive aging distinguish among normal, exceptional, and impaired groups, further empirical evidence is required. We adapted and applied standard procedures for classifying groups of cognitively impaired (CI) and cognitively normal (CN) older adults to a third classification, cognitively healthy, exceptional, or elite (CE) aging. We then examined concurrent and two-wave longitudinal performance on composite variables of episodic, semantic, and working memory. Method We began with a two-wave source sample from the Victoria Longitudinal Study (VLS) (source n=570; baseline age=53–90 years). The goals were to: (a) apply standard and objective classification procedures to discriminate three cognitive status groups, (b) conduct baseline comparisons of memory performance, (c) develop two-wave status stability and change subgroups, and (d) compare of stability subgroup differences in memory performance and change. Results As expected, the CE group performed best on all three memory composites. Similarly, expected status stability effects were observed: (a) stable CE and CN groups performed memory tasks better than their unstable counterparts and (b) stable (and chronic) CI group performed worse than its unstable (variable) counterpart. These stability group differences were maintained over two waves. Conclusion New data validate the expectations that (a) objective clinical classification procedures for cognitive impairment can be adapted for detecting cognitively advantaged older adults and (b) performance in three memory systems is predictably related to the tripartite classification. PMID:24742143

Enhancement of cognitive and neural functions through complex reasoning training: evidence from normal and clinical populations

PubMed Central

Chapman, Sandra B.; Mudar, Raksha A.

2014-01-01

Public awareness of cognitive health is fairly recent compared to physical health. Growing evidence suggests that cognitive training offers promise in augmenting cognitive brain performance in normal and clinical populations. Targeting higher-order cognitive functions, such as reasoning in particular, may promote generalized cognitive changes necessary for supporting the complexities of daily life. This data-driven perspective highlights cognitive and brain changes measured in randomized clinical trials that trained gist reasoning strategies in populations ranging from teenagers to healthy older adults, individuals with brain injury to those at-risk for Alzheimer's disease. The evidence presented across studies support the potential for Gist reasoning training to strengthen cognitive performance in trained and untrained domains and to engage more efficient communication across widespread neural networks that support higher-order cognition. The meaningful benefits of Gist training provide compelling motivation to examine optimal dose for sustained benefits as well as to explore additive benefits of meditation, physical exercise, and/or improved sleep in future studies. PMID:24808834

The relationship of working memory, inhibition, and response variability in child psychopathology.

PubMed

Verté, Sylvie; Geurts, Hilde M; Roeyers, Herbert; Oosterlaan, Jaap; Sergeant, Joseph A

2006-02-15

The aim of this study was to investigate the relationship between working memory and inhibition in children with attention deficit hyperactivity disorder (ADHD), high-functioning autism (HFA), and Tourette syndrome (TS), compared to normally developing children. Furthermore, the contribution of variation in processing speed on working memory and inhibition was investigated in these childhood psychopathologies. Four groups of children are reported in this study: 65 children with ADHD, 66 children with HFA, 24 children with TS, and 82 normal control children. All children were in the age range of 6-13 years. The relationship between working memory and inhibition was similar in children with ADHD, HFA, TS, and normally developing children. The relationship between both domains did not alter significantly for any of the groups, when variation in processing speed was taken into account. More symptoms of hyperactivity/impulsivity are related to a poorer inhibitory process and greater response variability. More symptoms of autism are related to a poorer working memory process. The current study showed that working memory, inhibition, and response variability, are distinct, but related cognitive domains in children with developmental psychopathologies. Research with experimental manipulations is needed to tackle the exact relationship between these cognitive domains.

The Worried Well? Characteristics of Cognitively Normal Patients Presenting to a Rural and Remote Memory Clinic.

PubMed

Verity, Ryan; Kirk, Andrew; O'Connell, Megan E; Karunanayake, Chandima; Morgan, Debra G

2018-03-01

In an effort to better understand why cognitively normal patients were referred to a memory clinic, we sought to identify features of "worried well" patients to better identify those more likely to be cognitively normal. In total, 375 consecutive patients referred by primary care practitioners to a Rural and Remote Memory Clinic were categorized into two groups based on their neurologic diagnosis, "worried well" (cognitively normal, N=81) or "other" (patients with any neurologic diagnosis, N=294). Data collected included: age, sex, years of formal education, Mini-Mental Status Examination score from initial visit, Center for Epidemiologic Studies Depression Scale score, Self-Rating of Memory Scale, alcohol consumption, marital status, hours per week of work, past medical history, sleep concerns, and family history of memory concerns. The two groups were compared using t-tests and χ2 tests. The same comparison was done between the same set of "worried well" patients (cognitively normal, N=81) and the subgroup of patients with a diagnosis of Alzheimer's disease (N=146) from the "other" group. Significant differences included younger age, more formal education, more frequently having previous psychiatric diagnosis and more self-reported alcohol consumption in the "worried well" group. The "worried well" and "Alzheimer's disease" comparison had the same significant differences as the "worried well" and "other" comparison. We observed a pattern of differences unfold between the "worried well" patients and those with cognitive disease. No one variable was pathognomonic of a "worried well" patient. However, taking all the above into account when evaluating a patient may help clinically.

Metabolic Free Energy and Biological Codes: A 'Data Rate Theorem' Aging Model.

PubMed

Wallace, Rodrick

2015-06-01

A famous argument by Maturana and Varela (Autopoiesis and cognition. Reidel, Dordrecht, 1980) holds that the living state is cognitive at every scale and level of organization. Since it is possible to associate many cognitive processes with 'dual' information sources, pathologies can sometimes be addressed using statistical models based on the Shannon Coding, the Shannon-McMillan Source Coding, the Rate Distortion, and the Data Rate Theorems, which impose necessary conditions on information transmission and system control. Deterministic-but-for-error biological codes do not directly invoke cognition, but may be essential subcomponents within larger cognitive processes. A formal argument, however, places such codes within a similar framework, with metabolic free energy serving as a 'control signal' stabilizing biochemical code-and-translator dynamics in the presence of noise. Demand beyond available energy supply triggers punctuated destabilization of the coding channel, affecting essential biological functions. Aging, normal or prematurely driven by psychosocial or environmental stressors, must interfere with the routine operation of such mechanisms, initiating the chronic diseases associated with senescence. Amyloid fibril formation, intrinsically disordered protein logic gates, and cell surface glycan/lectin 'kelp bed' logic gates are reviewed from this perspective. The results generalize beyond coding machineries having easily recognizable symmetry modes, and strip a layer of mathematical complication from the study of phase transitions in nonequilibrium biological systems.

In Search of Sleep Biomarkers of Alzheimer’s Disease: K-Complexes Do Not Discriminate between Patients with Mild Cognitive Impairment and Healthy Controls

PubMed Central

Reda, Flaminia; Gorgoni, Maurizio; Lauri, Giulia; Truglia, Ilaria; Cordone, Susanna; Scarpelli, Serena; Mangiaruga, Anastasia; D’Atri, Aurora; Ferrara, Michele; Lacidogna, Giordano; Marra, Camillo; Rossini, Paolo Maria; De Gennaro, Luigi

2017-01-01

The K-complex (KC) is one of the hallmarks of Non-Rapid Eye Movement (NREM) sleep. Recent observations point to a drastic decrease of spontaneous KCs in Alzheimer’s disease (AD). However, no study has investigated when, in the development of AD, this phenomenon starts. The assessment of KC density in mild cognitive impairment (MCI), a clinical condition considered a possible transitional stage between normal cognitive function and probable AD, is still lacking. The aim of the present study was to compare KC density in AD/MCI patients and healthy controls (HCs), also assessing the relationship between KC density and cognitive decline. Twenty amnesic MCI patients underwent a polysomnographic recording of a nocturnal sleep. Their data were compared to those of previously recorded 20 HCs and 20 AD patients. KCs during stage 2 NREM sleep were visually identified and KC densities of the three groups were compared. AD patients showed a significant KC density decrease compared with MCI patients and HCs, while no differences were observed between MCI patients and HCs. KC density was positively correlated with Mini-Mental State Examination (MMSE) scores. Our results point to the existence of an alteration of KC density only in a full-blown phase of AD, which was not observable in the early stage of the pathology (MCI), but linked with cognitive deterioration. PMID:28468235

Group cognitive behavioural therapy and group recreational activity for adults with autism spectrum disorders: A preliminary randomized controlled trial

PubMed Central

Plenty, Stephanie; Bejerot, Susanne

2014-01-01

Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This preliminary randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive behavioural therapy and recreational activity. Both interventions comprised 36 weekly 3-h sessions led by two therapists in groups of 6–8 patients. A total of 68 psychiatric patients with autism spectrum disorders participated in the study. Outcome measures were Quality of Life Inventory, Sense of Coherence Scale, Rosenberg Self-Esteem Scale and an exploratory analysis on measures of psychiatric health. Participants in both treatment conditions reported an increased quality of life at post-treatment (d = 0.39, p < 0.001), with no difference between interventions. No amelioration of psychiatric symptoms was observed. The dropout rate was lower with cognitive behavioural therapy than with recreational activity, and participants in cognitive behavioural therapy rated themselves as more generally improved, as well as more improved regarding expression of needs and understanding of difficulties. Both interventions appear to be promising treatment options for adults with autism spectrum disorder. The interventions’ similar efficacy may be due to the common elements, structure and group setting. Cognitive behavioural therapy may be additionally beneficial in terms of increasing specific skills and minimizing dropout. PMID:24089423

Evidence of neurodegeneration in brains of older adults who do not yet fulfill MCI criteria

PubMed Central

Chao, L.L.; Mueller, S.G.; Buckley, S.T.; Peek, K.; Raptentsetseng, S.; Elman, J.; Yaffe, K.; Miller, B.L.; Kramer, J.H.; Madison, C.; Mungas, D.; Schuff, N.; Weiner, M.W.

2008-01-01

We sought to determine whether there are structural and metabolic changes in the brains of older adults with cognitive complaints yet who do not meet MCI criteria (i.e., preMCI). We compared the volumes of regional lobar gray matter (GM) and medial temporal lobe structures, including the hippocampus, entorhinal cortex (ERC), fusiform and parahippocampal gyri, and metabolite ratios from the posterior cingulate in individuals who had a Clinical Demetia Rating (CDR) of 0.5, but who did not meet MCI criteria (preMCI, N = 17), patients with mild cognitive impairment (MCI, N = 13), and cognitively normal controls (N = 18). Controls had more ERC, fusiform, and frontal gray matter volume than preMCI and MCI subjects and greater parahippocampal volume and more posterior cingulate N-acetylaspartate (NAA)/myoinosotil (mI) than MCI. There were no significant differences between MCI and preMCI subjects on any of these measures. These findings suggest there are neurodegenerative changes in the brains of older adults who have cognitive complaints severe enough to qualify for CDR = 0.5 yet show no deficits on formal neuropsychological testing. The results further support the hypothesis that detection of individuals with very mild forms of Alzheimer's disease (AD) may be facilitated by use of the CDR, which emphasizes changes in cognition over time within individuals rather than comparison with group norms. PMID:18550226

Group cognitive behavioural therapy and group recreational activity for adults with autism spectrum disorders: a preliminary randomized controlled trial.

PubMed

Hesselmark, Eva; Plenty, Stephanie; Bejerot, Susanne

2014-08-01

Although adults with autism spectrum disorder are an increasingly identified patient population, few treatment options are available. This preliminary randomized controlled open trial with a parallel design developed two group interventions for adults with autism spectrum disorders and intelligence within the normal range: cognitive behavioural therapy and recreational activity. Both interventions comprised 36 weekly 3-h sessions led by two therapists in groups of 6-8 patients. A total of 68 psychiatric patients with autism spectrum disorders participated in the study. Outcome measures were Quality of Life Inventory, Sense of Coherence Scale, Rosenberg Self-Esteem Scale and an exploratory analysis on measures of psychiatric health. Participants in both treatment conditions reported an increased quality of life at post-treatment (d = 0.39, p < 0.001), with no difference between interventions. No amelioration of psychiatric symptoms was observed. The dropout rate was lower with cognitive behavioural therapy than with recreational activity, and participants in cognitive behavioural therapy rated themselves as more generally improved, as well as more improved regarding expression of needs and understanding of difficulties. Both interventions appear to be promising treatment options for adults with autism spectrum disorder. The interventions' similar efficacy may be due to the common elements, structure and group setting. Cognitive behavioural therapy may be additionally beneficial in terms of increasing specific skills and minimizing dropout. © The Author(s) 2013.

Intelligence and cognitive function in children and adolescents with spinal muscular atrophy.

PubMed

von Gontard, A; Zerres, K; Backes, M; Laufersweiler-Plass, C; Wendland, C; Melchers, P; Lehmkuhl, G; Rudnik-Schöneborn, S

2002-02-01

Spinal muscular atrophy is a chronic disease characterised by loss of motor function. The aim of the study was to analyse cognitive functions in a large group of patients with spinal muscular atrophy. It was hypothesised that their intelligence is comparable to controls, but not above average as previously postulated. Ninety-six children and adolescents with spinal muscular atrophy I-III, aged 6.0-18.11 years, 45 non-affected siblings and 59 healthy, matched controls were examined with one- (CPM/SPM), as well as multi-dimensional intelligence tests (Kaufman-ABC; Wechsler tests). The mean IQ measured with the CPM/SPM tests was 109.6 for the spinal muscular atrophy group, 107.3 for the sibs and 104.1 for the healthy controls (no significant difference). In the older children and adolescents (SPM only) the mean IQ was significantly higher for the spinal muscular atrophy patients (109.6) than for the controls (95.4). The standard score in the 'mental processing composite' scale of the Kaufman-ABC was identical in the spinal muscular atrophy group and controls (103.8). The cognitive profile was relatively homogeneous. However, the older children and adolescents did have a significantly higher verbal IQ (113.8) than controls (104.6) in the Wechsler tests. There were no significant differences in any of the tests among different grades of severity (spinal muscular atrophy types I-III). It can be concluded that children and adolescents with spinal muscular atrophy have a general intelligence in the normal range. By adolescence, environmentally mediated aspects of intelligence are higher in patients with spinal muscular atrophy. It could be speculated that the development of cognitive skills and knowledge is a creative way to compensate the many restrictions due to their physical handicap.

Regularity of center-of-pressure trajectories depends on the amount of attention invested in postural control

PubMed Central

Donker, Stella F.; Roerdink, Melvyn; Greven, An J.

2007-01-01

The influence of attention on the dynamical structure of postural sway was examined in 30 healthy young adults by manipulating the focus of attention. In line with the proposed direct relation between the amount of attention invested in postural control and regularity of center-of-pressure (COP) time series, we hypothesized that: (1) increasing cognitive involvement in postural control (i.e., creating an internal focus by increasing task difficulty through visual deprivation) increases COP regularity, and (2) withdrawing attention from postural control (i.e., creating an external focus by performing a cognitive dual task) decreases COP regularity. We quantified COP dynamics in terms of sample entropy (regularity), standard deviation (variability), sway-path length of the normalized posturogram (curviness), largest Lyapunov exponent (local stability), correlation dimension (dimensionality) and scaling exponent (scaling behavior). Consistent with hypothesis 1, standing with eyes closed significantly increased COP regularity. Furthermore, variability increased and local stability decreased, implying ineffective postural control. Conversely, and in line with hypothesis 2, performing a cognitive dual task while standing with eyes closed led to greater irregularity and smaller variability, suggesting an increase in the “efficiency, or “automaticity” of postural control”. In conclusion, these findings not only indicate that regularity of COP trajectories is positively related to the amount of attention invested in postural control, but also substantiate that in certain situations an increased internal focus may in fact be detrimental to postural control. PMID:17401553

CHAMP: Cognitive behaviour therapy for health anxiety in medical patients, a randomised controlled trial

PubMed Central

2011-01-01

Background Abnormal health anxiety, also called hypochondriasis, has been successfully treated by cognitive behaviour therapy (CBT) in patients recruited from primary care, but only one pilot trial has been carried out among those attending secondary medical clinics where health anxiety is likely to be more common and have a greater impact on services. The CHAMP study extends this work to examine both the clinical and cost effectiveness of CBT in this population. Method/Design The study is a randomized controlled trial with two parallel arms and equal randomization of 466 eligible patients (assuming a 20% drop-out) to an active treatment group of 5-10 sessions of cognitive behaviour therapy and to a control group. The aim at baseline, after completion of all assessments but before randomization, was to give a standard simple explanation of the nature of health anxiety for all participants. Subsequently the control group was to receive whatever care might usually be available in the clinics, which is normally a combination of clinical assessment, appropriate tests and reassurance. Those allocated to the active treatment group were planned to receive between 5 and 10 sessions of an adapted form of cognitive behaviour therapy based on the Salkovskis/Warwick model, in which a set of treatment strategies are chosen aimed at helping patients understand the factors that drive and maintain health anxiety. The therapy was planned to be given by graduate research workers, nurses or other health professionals trained for this intervention whom would also have their competence assessed independently during the course of treatment. The primary outcome is reduction in health anxiety symptoms after one year and the main secondary outcome is the cost of care after two years. Discussion This represents the first trial of adapted cognitive behaviour therapy in health anxiety that is large enough to test not only the clinical benefits of treatment but also whether the cost of treatment is offset by savings from reduced use of other health services in comparison to the control group. Cognitive behaviour therapy for Health Anxiety in Medical Patients (CHAMP) Trial registration Current Controlled Trials ISRCTN14565822 PMID:21672205

Comprehending Psychological Defenses: Developmental Differences between Normal and Disturbed Children and Adolescents.

ERIC Educational Resources Information Center

Kinney, Andrew; Rybash, John

Investigated were similarities and differences in the ability of 26 normally developing and 26 conduct-disordered children and adolescents to comprehend psychologically defensive behavior and the cognitive processes underlying differences due to age. Matched by cognitive level, subjects viewed vignettes depicting another child behaving…