Post-Concussion Tools to Assist with Assessment, Treatment, and Return to Duty

DTIC Science & Technology

2014-12-01

cognitively engaged in a challenging mental task. 15. SUBJECT TERMS Dizziness, balance dysfunction, vestibular, sway, instability, falls, physiotherapy ...test battery for monitoring treatment during the physiotherapy and 3) development of an enhanced program of rehabilitation. 2. KEYWORDS...Dizziness, balance dysfunction, vestibular, sway, instability, falls, physiotherapy , tactile cueing, vibrotactile, tactors, mild traumatic brain injury, mTBI

Cognitive complaints and predictors of perceived cognitive dysfunction in adults with major depressive disorder: Findings from the Cognitive Dysfunction in Asians with Depression (CogDAD) study.

PubMed

Srisurapanont, Manit; Mok, Yee Ming; Yang, Yen Kuang; Chan, Herng-Nieng; Della, Constantine D; Zainal, Nor Zuraida; Jambunathan, Stephen; Amir, Nurmiati; Kalita, Pranab

2018-05-01

Several studies have described the presence of perceived cognitive dysfunction amongst Asian patients with major depressive disorder (MDD). To date, no study has been conducted investigating the predictors of perceived cognitive dysfunction amongst Asian MDD patients. This was a post-hoc analysis of the Cognitive Dysfunction in Asian patients with Depression (CogDAD) study. Descriptive statistics were used to describe the most common cognitive complaints by patients. Univariate and multivariate analyses were performed to determine variables associated with perceived cognitive dysfunction (Perceived Deficit Questionnaire-Depression, PDQ-D). The CogDAD study population is comprised of MDD patients with mild-to-moderate depression (Patient Health Questionnaire 9-item [PHQ-9]: 11.3 ± 6.9) who reported perceived cognitive dysfunction (PDQ-D = 22.6 ± 16.2). The most common cognitive complaints were: mind drifting (42.3%), trouble making decision (39.6%) and trouble concentrating (38.0%). Predictors of perceived cognitive dysfunction were: being Southeast Asians (vs. Taiwanese) (p < 0.001), current episode longer than 8 weeks (vs. 1-8 weeks) (p < 0.05), the presence of disability (vs. no disability) (p < 0.05), younger age (p < 0.01), and higher PHQ-9 total scores (p < 0.001). The causal relationship between predictive variables and PDQ-D could not be tested due to the cross-sectional nature of the study. Furthermore, a neuropsychological test was not included in the CogDAD study and use of concomitant medications, including anti-depressants, could have impacted patient's perceived cognitive ability. The present study results suggest a potential role for subjective cognitive assessment in patients with MDD who are young, with long durations of depression or severe depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Investigating Metacognition, Cognition, and Behavioral Deficits of College Students with Acute Traumatic Brain Injuries

ERIC Educational Resources Information Center

Martinez, Sarah; Davalos, Deana

2016-01-01

Objective: Executive dysfunction in college students who have had an acute traumatic brain injury (TBI) was investigated. The cognitive, behavioral, and metacognitive effects on college students who endorsed experiencing a brain injury were specifically explored. Participants: Participants were 121 college students who endorsed a mild TBI, and 121…

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.

Post-operative cognitive dysfunction after knee arthroplasty: a diagnostic dilemma

PubMed Central

Yap, Kiryu K.; Joyner, Peter

2014-01-01

Post-operative cognitive dysfunction (POCD) is common in the elderly, and significantly impacts their recovery. We present an unusual diagnostic challenge where a 65-year-old male presented 4-week post-total knee arthroplasty with acute cognitive dysfunction lasting 19 days. Curiously, there were no findings uncovering a specific cause, but during investigation underlying predisposing factors such as depression, mild memory deficits and generalized brain volume loss were identified. The impression after psychogeriatric review was that of an organic brain syndrome with overlay of depression, with a complex presentation as POCD. After escalation of behavioural disturbance, he was commenced on anti-psychotic/depressant, with immediate response. We emphasize the importance of pre-operative evaluation of cognitive function and risk factors in all geriatric patients undergoing elective surgery, and the need for further characterization of POCD, as well as experimental research elucidating the underlying mechanisms to better identify and treat this important post-surgical phenomenon. PMID:25988029

Cerebrospinal fluid neurogranin: relation to cognition and neurodegeneration in Alzheimer's disease.

PubMed

Portelius, Erik; Zetterberg, Henrik; Skillbäck, Tobias; Törnqvist, Ulrika; Andreasson, Ulf; Trojanowski, John Q; Weiner, Michael W; Shaw, Leslie M; Mattsson, Niklas; Blennow, Kaj

2015-11-01

Synaptic dysfunction is linked to cognitive symptoms in Alzheimer's disease. Thus, measurement of synapse proteins in cerebrospinal fluid may be useful biomarkers to monitor synaptic degeneration. Cerebrospinal fluid levels of the postsynaptic protein neurogranin are increased in Alzheimer's disease, including in the predementia stage of the disease. Here, we tested the performance of cerebrospinal fluid neurogranin to predict cognitive decline and brain injury in the Alzheimer's Disease Neuroimaging Initiative study. An in-house immunoassay was used to analyse neurogranin in cerebrospinal fluid samples from a cohort of patients who at recruitment were diagnosed as having Alzheimer's disease with dementia (n = 95) or mild cognitive impairment (n = 173), as well as in cognitively normal subjects (n = 110). Patients with mild cognitive impairment were grouped into those that remained cognitively stable for at least 2 years (stable mild cognitive impairment) and those who progressed to Alzheimer's disease dementia during follow-up (progressive mild cognitive impairment). Correlations were tested between baseline cerebrospinal fluid neurogranin levels and baseline and longitudinal cognitive impairment, brain atrophy and glucose metabolism within each diagnostic group. Cerebrospinal fluid neurogranin was increased in patients with Alzheimer's disease dementia (P < 0.001), progressive mild cognitive impairment (P < 0.001) and stable mild cognitive impairment (P < 0.05) compared with controls, and in Alzheimer's disease dementia (P < 0.01) and progressive mild cognitive impairment (P < 0.05) compared with stable mild cognitive impairment. In the mild cognitive impairment group, high baseline cerebrospinal fluid neurogranin levels predicted cognitive decline as reflected by decreased Mini-Mental State Examination (P < 0.001) and increased Alzheimer's Disease Assessment Scale-cognitive subscale (P < 0.001) scores at clinical follow-up. In addition, high baseline cerebrospinal fluid neurogranin levels in the mild cognitive impairment group correlated with longitudinal reductions in cortical glucose metabolism (P < 0.001) and hippocampal volume (P < 0.001) at clinical follow-up. Furthermore, within the progressive mild cognitive impairment group, elevated cerebrospinal fluid neurogranin levels were associated with accelerated deterioration in Alzheimer's Disease Assessment Scale-cognitive subscale (β = 0.0017, P = 0.01). These data demonstrate that cerebrospinal fluid neurogranin is increased already at the early clinical stage of Alzheimer's disease and predicts cognitive deterioration and disease-associated changes in metabolic and structural biomarkers over time. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Mangifera indica Fruit Extract Improves Memory Impairment, Cholinergic Dysfunction, and Oxidative Stress Damage in Animal Model of Mild Cognitive Impairment

PubMed Central

Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-Mee, Wipawee; Ingkaninan, Kornkanok; Wittaya-Areekul, Sakchai

2014-01-01

To date, the effective preventive paradigm against mild cognitive impairment (MCI) is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv). At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism. PMID:24672632

Mangifera indica fruit extract improves memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment.

PubMed

Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-Mee, Wipawee; Ingkaninan, Kornkanok; Wittaya-Areekul, Sakchai

2014-01-01

To date, the effective preventive paradigm against mild cognitive impairment (MCI) is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180-200 g, were orally given the extract at doses of 12.5, 50, and 200 mg · kg(-1) BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv). At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg · kg(-1) BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism.

Cognitive Dysfunction in Asian Patients with Depression (CogDAD): A Cross-Sectional Study

PubMed Central

Manit, Srisurapanont; Yee Ming, Mok; Yen Kuang, Yang; Herng-Nieng, Chan; Constantine D, Della; Zuraida, Zainal, Nor; Stephen, Jambunathan; Nurmiati, Amir; Pranabi, Kalita

2017-01-01

Background: Cognitive dysfunction is a predominant symptom of Major Depressive Disorder (MDD), contributing to functional impairment. Objective: The primary objective of this study was to assess and describe perceived cognitive dysfunction amongst Asian patients diagnosed with MDD. The secondary objective was to explore the associations between depression severity, perceived cognitive dysfunction and functional disability. Methods: This was a multi-country, multi-centre, cross-sectional study. Adults with a current episode of MDD were recruited from 9 university/general hospital clinics in Asia. During a single study visit, psychiatrists assessed depression severity (Clinical Global Impression-Severity, CGI-S); patients completed questionnaires assessing depression severity (Patient Health Questionnaire-9 items, PHQ-9), perceived cognitive dysfunction (Perceived Deficit Questionnaire-Depression, PDQ-D) and functional disability (Sheehan Disability Scale, SDS). Results: Patients (n=664), predominantly women (66.3%), were aged 46.5±12.5 years, lived in urban areas (81.3%) and were employed (84.6%). 51.5% of patients were having their first depressive episode; 86.7% were receiving treatment; 82.2% had a current episode duration >8 weeks. Patients had mild-to-moderate depression (CGI-S=3.3±1.0; PHQ-9=11.3±6.9). Patients reported perceived cognitive dysfunction (PDQ-D=22.6±16.2) and functional disability (SDS=11.3±7.9). PHQ-9, PDQ-D and SDS were moderately-to-highly correlated (PHQ-9 and SDS: r=0.72; PHQ-9 and PDQ-D: r=0.69; PDQ-D and SDS, r=0.63). ANCOVA showed that after controlling for patient-reported depression severity (PHQ-9), perceived cognitive dysfunction (PDQ-D) was significantly associated with functional disability (SDS) (p<0.001). Conclusions: Asian patients with MDD reported perceived cognitive dysfunction. There is a need for physicians to evaluate cognitive dysfunction in the clinical setting in order to reach treatment goals, including functional recovery beyond remission of mood symptoms. PMID:29238395

Psychiatric and cognitive manifestations of hypothyroidism

PubMed Central

Samuels, Mary H

2014-01-01

Purpose of review Overt hypothyroidism has major effects on neuropsychiatric function, but patients with mild hypothyroidism may attribute unrelated neuropsychiatric symptoms to their thyroid condition. This review will summarize data on neuropsychiatric effects of hypothyroidism, and provide guidelines regarding the relationship between hypothyroidism and neuropsychiatric issues, and treatment indications. Recent findings Clinical investigations and functional imaging studies confirm that overt hypothyroidism is associated with affective and cognitive decrements, largely reversible with treatment. In contrast, subclinical hypothyroidism is not associated with major neuropsychiatric deficits, although studies utilizing sensitive measures show small deficits in memory and executive function. Neuropsychiatric complaints are more common when patients are aware of their thyroid disease, regardless of their thyroid function at the time of testing. Summary Neuropsychiatric dysfunction is common in overt hypothyroidism, and will improve (although perhaps not completely resolve) with therapy. On the other hand, deficits related to thyroid dysfunction are usually mild in subclinical hypothyroidism, and realistic expectations need to be set regarding symptom reversibility with treatment. Patients with mild hypothyroidism and significant distress related to neuropsychiatric symptoms most likely have independent diagnoses that should be evaluated separately. PMID:25122491

Local cerebral glucose metabolism in patients with long-term behavioral and cognitive deficits following mild traumatic brain injury.

PubMed

Gross, H; Kling, A; Henry, G; Herndon, C; Lavretsky, H

1996-01-01

A retrospective study of 20 patients with mild traumatic brain injury (MTBI) examined brain regions of interest by comparing [18F]-2-deoxyglucose PET, neuropsychological test results, and continuing behavioral dysfunction. Abnormal local cerebral metabolic rates (rLCMs) were most prominent in midtemporal, anterior cingulate, precuneus, anterior temporal, frontal white, and corpus callosum brain regions. Abnormal rLCMs were significantly correlated statistically with 1) overall clinical complaints, most specifically with inconsistent attention/concentration and 2) overall neuropsychological test results. The authors conclude that 1) even mild TBI may result in continuing brain behavioral deficits; 2) PET can help elucidate dysfunctional brain circuitry in neurobehavioral disorders; and 3) specific brain areas may correlate with deficits in daily neurobehavioral functioning and neuropsychological test findings.

Vascular impairment as a pathological mechanism underlying long-lasting cognitive dysfunction after pediatric traumatic brain injury.

PubMed

Ichkova, Aleksandra; Rodriguez-Grande, Beatriz; Bar, Claire; Villega, Frederic; Konsman, Jan Pieter; Badaut, Jerome

2017-12-01

Traumatic brain injury (TBI) is the leading cause of death and disability in children. Indeed, the acute mechanical injury often evolves to a chronic brain disorder with long-term cognitive, emotional and social dysfunction even in the case of mild TBI. Contrary to the commonly held idea that children show better recovery from injuries than adults, pediatric TBI patients actually have worse outcome than adults for the same injury severity. Acute trauma to the young brain likely interferes with the fine-tuned developmental processes and may give rise to long-lasting consequences on brain's function. This review will focus on cerebrovascular dysfunction as an important early event that may lead to long-term phenotypic changes in the brain after pediatric TBI. These, in turn may be associated with accelerated brain aging and cognitive dysfunction. Finally, since no effective treatments are currently available, understanding the unique pathophysiological mechanisms of pediatric TBI is crucial for the development of new therapeutic options. Copyright © 2017 Elsevier Ltd. All rights reserved.

Network Disruption and Cerebrospinal Fluid Amyloid-Beta and Phospho-Tau Levels in Mild Cognitive Impairment.

PubMed

Canuet, Leonides; Pusil, Sandra; López, María Eugenia; Bajo, Ricardo; Pineda-Pardo, José Ángel; Cuesta, Pablo; Gálvez, Gerardo; Gaztelu, José María; Lourido, Daniel; García-Ribas, Guillermo; Maestú, Fernando

2015-07-15

Synaptic dysfunction is a core deficit in Alzheimer's disease, preceding hallmark pathological abnormalities. Resting-state magnetoencephalography (MEG) was used to assess whether functional connectivity patterns, as an index of synaptic dysfunction, are associated with CSF biomarkers [i.e., phospho-tau (p-tau) and amyloid beta (Aβ42) levels]. We studied 12 human subjects diagnosed with mild cognitive impairment due to Alzheimer's disease, comparing those with normal and abnormal CSF levels of the biomarkers. We also evaluated the association between aberrant functional connections and structural connectivity abnormalities, measured with diffusion tensor imaging, as well as the convergent impact of cognitive deficits and CSF variables on network disorganization. One-third of the patients converted to Alzheimer's disease during a follow-up period of 2.5 years. Patients with abnomal CSF p-tau and Aβ42 levels exhibited both reduced and increased functional connectivity affecting limbic structures such as the anterior/posterior cingulate cortex, orbitofrontal cortex, and medial temporal areas in different frequency bands. A reduction in posterior cingulate functional connectivity mediated by p-tau was associated with impaired axonal integrity of the hippocampal cingulum. We noted that several connectivity abnormalities were predicted by CSF biomarkers and cognitive scores. These preliminary results indicate that CSF markers of amyloid deposition and neuronal injury in early Alzheimer's disease associate with a dual pattern of cortical network disruption, affecting key regions of the default mode network and the temporal cortex. MEG is useful to detect early synaptic dysfunction associated with Alzheimer's disease brain pathology in terms of functional network organization. In this preliminary study, we used magnetoencephalography and an integrative approach to explore the impact of CSF biomarkers, neuropsychological scores, and white matter structural abnormalities on neural function in mild cognitive impairment. Disruption in functional connectivity between several pairs of cortical regions associated with abnormal levels of biomarkers, cognitive deficits, or with impaired axonal integrity of hippocampal tracts. Amyloid deposition and tau protein-related neuronal injury in early Alzheimer's disease are associated with synaptic dysfunction and a dual pattern of cortical network disorganization (i.e., desynchronization and hypersynchronization) that affects key regions of the default mode network and temporal areas. Copyright © 2015 the authors 0270-6474/15/3510326-06$15.00/0.

Cognitive correlates of α4β2 nicotinic acetylcholine receptors in mild Alzheimer's dementia.

PubMed

Sabri, Osama; Meyer, Philipp M; Gräf, Susanne; Hesse, Swen; Wilke, Stephan; Becker, Georg-Alexander; Rullmann, Michael; Patt, Marianne; Luthardt, Julia; Wagenknecht, Gudrun; Hoepping, Alexander; Smits, Rene; Franke, Annegret; Sattler, Bernhard; Tiepolt, Solveig; Fischer, Steffen; Deuther-Conrad, Winnie; Hegerl, Ulrich; Barthel, Henryk; Schönknecht, Peter; Brust, Peter

2018-06-01

In early Alzheimer's dementia, there is a need for PET biomarkers of disease progression with close associations to cognitive dysfunction that may aid to predict further cognitive decline and neurodegeneration. Amyloid biomarkers are not suitable for that purpose. The α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs) are widely abundant in the human brain. As neuromodulators they play an important role in cognitive functions such as attention, learning and memory. Post-mortem studies reported lower expression of α4β2-nAChRs in more advanced Alzheimer's dementia. However, there is ongoing controversy whether α4β2-nAChRs are reduced in early Alzheimer's dementia. Therefore, using the recently developed α4β2-nAChR-specific radioligand (-)-18F-flubatine and PET, we aimed to quantify the α4β2-nAChR availability and its relationship to specific cognitive dysfunction in mild Alzheimer's dementia. Fourteen non-smoking patients with mild Alzheimer's dementia, drug-naïve for cholinesterase therapy, were compared with 15 non-smoking healthy controls matched for age, sex and education by applying (-)-18F-flubatine PET together with a neuropsychological test battery. The one-tissue compartment model and Logan plot method with arterial input function were used for kinetic analysis to obtain the total distribution volume (VT) as the primary, and the specific binding part of the distribution volume (VS) as the secondary quantitative outcome measure of α4β2-nAChR availability. VS was determined by using a pseudo-reference region. Correlations between VT within relevant brain regions and Z-scores of five cognitive functions (episodic memory, executive function/working memory, attention, language, visuospatial function) were calculated. VT (and VS) were applied for between-group comparisons. Volume of interest and statistical parametric mapping analyses were carried out. Analyses revealed that in patients with mild Alzheimer's dementia compared to healthy controls, there was significantly lower VT, especially within the hippocampus, fronto-temporal cortices, and basal forebrain, which was similar to comparisons of VS. VT decline in Alzheimer's dementia was associated with distinct domains of impaired cognitive functioning, especially episodic memory and executive function/working memory. Using (-)-18F-flubatine PET in patients with mild Alzheimer's dementia, we show for the first time a cholinergic α4β2-nAChR deficiency mainly present within the basal forebrain-cortical and septohippocampal cholinergic projections and a relationship between lower α4β2-nAChR availability and impairment of distinct cognitive domains, notably episodic memory and executive function/working memory. This shows the potential of (-)-18F-flubatine as PET biomarker of cholinergic α4β2-nAChR dysfunction and specific cognitive decline. Thus, if validated by longitudinal PET studies, (-)-18F-flubatine might become a PET biomarker of progression of neurodegeneration in Alzheimer's dementia.

Risk and Determinants of Dementia in Patients with Mild Cognitive Impairment and Brain Subcortical Vascular Changes: A Study of Clinical, Neuroimaging, and Biological Markers—The VMCI-Tuscany Study: Rationale, Design, and Methodology

PubMed Central

Poggesi, Anna; Salvadori, Emilia; Pantoni, Leonardo; Pracucci, Giovanni; Cesari, Francesca; Chiti, Alberto; Ciolli, Laura; Cosottini, Mirco; Del Bene, Alessandra; De Stefano, Nicola; Diciotti, Stefano; Dotti, Maria Teresa; Ginestroni, Andrea; Giusti, Betti; Gori, Anna Maria; Nannucci, Serena; Orlandi, Giovanni; Pescini, Francesca; Valenti, Raffaella; Abbate, Rosanna; Federico, Antonio; Mascalchi, Mario; Murri, Luigi; Inzitari, Domenico

2012-01-01

Dementia is one of the most disabling conditions. Alzheimer's disease and vascular dementia (VaD) are the most frequent causes. Subcortical VaD is consequent to deep-brain small vessel disease (SVD) and is the most frequent form of VaD. Its pathological hallmarks are ischemic white matter changes and lacunar infarcts. Degenerative and vascular changes often coexist, but mechanisms of interaction are incompletely understood. The term mild cognitive impairment defines a transitional state between normal ageing and dementia. Pre-dementia stages of VaD are also acknowledged (vascular mild cognitive impairment, VMCI). Progression relates mostly to the subcortical VaD type, but determinants of such transition are unknown. Variability of phenotypic expression is not fully explained by severity grade of lesions, as depicted by conventional MRI that is not sensitive to microstructural and metabolic alterations. Advanced neuroimaging techniques seem able to achieve this. Beside hypoperfusion, blood-brain-barrier dysfunction has been also demonstrated in subcortical VaD. The aim of the Vascular Mild Cognitive Impairment Tuscany Study is to expand knowledge about determinants of transition from mild cognitive impairment to dementia in patients with cerebral SVD. This paper summarizes the main aims and methodological aspects of this multicenter, ongoing, observational study enrolling patients affected by VMCI with SVD. PMID:22550606

Olfactory identification in amnestic and non-amnestic mild cognitive impairment and its neuropsychological correlates.

PubMed

Vyhnalek, Martin; Magerova, Hana; Andel, Ross; Nikolai, Tomas; Kadlecova, Alexandra; Laczo, Jan; Hort, Jakub

2015-02-15

Olfactory identification impairment in amnestic mild cognitive impairment (aMCI) patients is well documented and considered to be caused by underlying Alzheimer's disease (AD) pathology, contrasting with less clear evidence in non-amnestic MCI (naMCI). The aim was to (a) compare the degree of olfactory identification dysfunction in aMCI, naMCI, controls and mild AD dementia and (b) assess the relation between olfactory identification and cognitive performance in aMCI compared to naMCI. 75 patients with aMCI and 32 with naMCI, 26 patients with mild AD and 27 controls underwent the multiple choice olfactory identification Motol Hospital Smell Test with 18 different odors together with a comprehensive neuropsychological examination. Controlling for age and gender, patients with aMCI and naMCI did not differ significantly in olfactory identification and both performed significantly worse than controls (p<0.001), albeit also better than patients with mild AD (p<.001). In the aMCI group, higher scores on MMSE, verbal and non-verbal memory and visuospatial tests were significantly related to better olfactory identification ability. Conversely, no cognitive measure was significantly related to olfactory performance in naMCI. Olfactory identification is similarly impaired in aMCI and naMCI. Olfactory impairment is proportional to cognitive impairment in aMCI but not in naMCI. Copyright © 2015. Published by Elsevier B.V.

Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer's Disease.

PubMed

Daulatzai, Mak Adam

2016-10-01

Sporadic Alzheimer's disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary "first-tier pathologies." Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson's disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented-it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD.

Old wine in new bottles: validating the clinical utility of SPECT in predicting cognitive performance in mild traumatic brain injury.

PubMed

Romero, Kristoffer; Lobaugh, Nancy J; Black, Sandra E; Ehrlich, Lisa; Feinstein, Anthony

2015-01-30

The neural underpinnings of cognitive dysfunction in mild traumatic brain injury (TBI) are not fully understood. Consequently, patient prognosis using existing clinical imaging is somewhat imprecise. Single photon emission computed tomography (SPECT) is a frequently employed investigation in this population, notwithstanding uncertainty over the clinical utility of the data obtained. In this study, subjects with mild TBI underwent (99m)Tc-ECD SPECT scanning, and were administered a brief battery of cognitive tests and self-report symptom scales of concussion and emotional distress. Testing took place 2 weeks (n=84) and 1 year (n=49) post-injury. Multivariate analysis (i.e., partial least squares analysis) revealed that frontal perfusion in right superior frontal and middle frontal gyri predicted poorer performance on the Stroop test, an index of executive function, both at initial and follow-up testing. Conversely, SPECT scans categorized as normal or abnormal by radiologists did not differentiate cognitively impaired from intact subjects. These results demonstrate the clinical utility of SPECT in mild TBI, but only when data are subjected to blood flow quantification analysis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Usefulness of the Montreal Cognitive Assessment (MoCA) in Huntington's disease.

PubMed

Gluhm, Shea; Goldstein, Jody; Brown, Daniel; Van Liew, Charles; Gilbert, Paul E; Corey-Bloom, Jody

2013-10-01

The Montreal Cognitive Assessment (MoCA) is a brief screening instrument for dementia that is sensitive to executive dysfunction. This study examined its usefulness for assessing cognitive performance in mild, moderate, and severe Huntington's disease (HD), compared with the use of the Mini-Mental State Examination (MMSE). We compared MoCA and MMSE total scores and the number of correct answers in 5 cognitive-specific domains in 104 manifest HD patients and 100 matched controls. For the total HD sample, and for the moderate and severe patients, significant differences between both MoCA and MMSE total scores and almost all cognitive-specific domains emerged. Even mild HD subjects showed significant differences with regard to total score and several cognitive domains on both instruments. We conclude that the MoCA, although not necessarily superior to the MMSE, is a useful instrument for assessing cognitive performance over a broad level of functioning in HD. © 2013 Movement Disorder Society.

Cognitive performance, symptoms and counter-regulation during hypoglycaemia in patients with type 1 diabetes and high or low renin-angiotensin system activity.

PubMed

Høi-Hansen, Thomas; Pedersen-Bjergaard, Ulrik; Andersen, Rikke Due; Kristensen, Peter Lommer; Thomsen, Carsten; Kjaer, Troels; Høgenhaven, Hans; Smed, Annelise; Holst, Jens Juul; Dela, Flemming; Boomsma, Frans; Thorsteinsson, Birger

2009-12-01

High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patients with low RAS activity. Nine patients with type 1 diabetes and high and nine with low RAS activity were subjected to hypoglycaemia and euglycaemia in a cross-over study using an intravenous insulin infusion protocol. Cognitive function, electroencephalography, auditory evoked potentials and hypoglycaemic symptoms were recorded. At a hypoglycaemic nadir of 2.2 (SD 0.3) mmol/L the high RAS group displayed significant deterioration in cognitive performance during hypoglycaemia in the three most complex reaction time tasks. In the low RAS group, hypoglycaemia led to cognitive dysfunction in only one reaction time task. The high RAS group reported lower symptom scores during hypoglycaemia than the low RAS group, suggesting poorer hypoglycaemia awareness. High RAS activity is associated with increased cognitive dysfunction and blunted symptoms during mild hypoglycaemia compared to low RAS activity. This may explain why high RAS activity is a risk factor for severe hypoglycaemia in type 1 diabetes.

Selective decline of neurotrophin and neurotrophin receptor genes within CA1 pyramidal neurons and hippocampus proper: Correlation with cognitive performance and neuropathology in mild cognitive impairment and Alzheimer's disease.

PubMed

Ginsberg, Stephen D; Malek-Ahmadi, Michael H; Alldred, Melissa J; Che, Shaoli; Elarova, Irina; Chen, Yinghua; Jeanneteau, Freddy; Kranz, Thorsten M; Chao, Moses V; Counts, Scott E; Mufson, Elliott J

2017-09-09

Hippocampal CA1 pyramidal neurons, a major component of the medial temporal lobe memory circuit, are selectively vulnerable during the progression of Alzheimer's disease (AD). The cellular mechanism(s) underlying degeneration of these neurons and the relationship to cognitive performance remains largely undefined. Here, we profiled neurotrophin and neurotrophin receptor gene expression within microdissected CA1 neurons along with regional hippocampal dissections from subjects who died with a clinical diagnosis of no cognitive impairment (NCI), mild cognitive impairment (MCI), or AD using laser capture microdissection (LCM), custom-designed microarray analysis, and qPCR of CA1 subregional dissections. Gene expression levels were correlated with cognitive test scores and AD neuropathology criteria. We found a significant downregulation of several neurotrophin genes (e.g., Gdnf, Ngfb, and Ntf4) in CA1 pyramidal neurons in MCI compared to NCI and AD subjects. In addition, the neurotrophin receptor transcripts TrkB and TrkC were decreased in MCI and AD compared to NCI. Regional hippocampal dissections also revealed select neurotrophic gene dysfunction providing evidence for vulnerability within the hippocampus proper during the progression of dementia. Downregulation of several neurotrophins of the NGF family and cognate neurotrophin receptor (TrkA, TrkB, and TrkC) genes correlated with antemortem cognitive measures including the Mini-Mental State Exam (MMSE), a composite global cognitive score (GCS), and Episodic, Semantic, and Working Memory, Perceptual Speed, and Visuospatial domains. Significant correlations were found between select neurotrophic expression downregulation and neuritic plaques (NPs) and neurofibrillary tangles (NFTs), but not diffuse plaques (DPs). These data suggest that dysfunction of neurotrophin signaling complexes have profound negative sequelae within vulnerable hippocampal cell types, which play a role in mnemonic and executive dysfunction during the progression of AD. © 2017 Wiley Periodicals, Inc.

Diffusion-Tensor Imaging Findings and Cognitive Function Following Hospitalized Mixed-Mechanism Mild Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

PubMed

Oehr, Lucy; Anderson, Jacqueline

2017-11-01

To undertake a systematic review and meta-analysis of the relationship between microstructural damage and cognitive function after hospitalized mixed-mechanism (HMM) mild traumatic brain injury (mTBI). PsycInfo, EMBASE, and MEDLINE were used to find relevant empirical articles published between January 2002 and January 2016. Studies that examined the specific relationship between diffusion tensor imaging (DTI) and cognitive test performance were included. The final sample comprised previously medically and psychiatrically healthy adults with HMM mTBI. Specific data were extracted including mTBI definitional criteria, descriptive statistics, outcome measures, and specific results of associations between DTI metrics and cognitive test performance. Of the 248 original articles retrieved and reviewed, 8 studies met all inclusion criteria and were included in the meta-analysis. The meta-analysis revealed statistically significant associations between reduced white matter integrity and poor performance on measures of attention (fractional anisotropy [FA]: d=.413, P<.001; mean diffusivity [MD]: d=-.407, P=.001), memory (FA: d=.347, P<.001; MD: d=-.568, P<.001), and executive function (FA: d=.246, P<.05), which persisted beyond 1 month postinjury. The findings from the meta-analysis provide clear support for an association between in vivo markers of underlying neuropathology and cognitive function after mTBI. Furthermore, these results demonstrate clearly for the first time that in vivo markers of structural neuropathology are associated with cognitive dysfunction within the domains of attention, memory, and executive function. These findings provide an avenue for future research to examine the causal relationship between mTBI-related neuropathology and cognitive dysfunction. Furthermore, they have important implications for clinical management of patients with mTBI because they provide a more comprehensive understanding of factors that are associated with cognitive dysfunction after mTBI. Copyright © 2017 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer's disease.

PubMed

Öhrfelt, Annika; Brinkmalm, Ann; Dumurgier, Julien; Brinkmalm, Gunnar; Hansson, Oskar; Zetterberg, Henrik; Bouaziz-Amar, Elodie; Hugon, Jacques; Paquet, Claire; Blennow, Kaj

2016-10-03

Synaptic degeneration is a central pathogenic event in Alzheimer's disease that occurs early during the course of disease and correlates with cognitive symptoms. The pre-synaptic vesicle protein synaptotagmin-1 appears to be essential for the maintenance of an intact synaptic transmission and cognitive function. Synaptotagmin-1 in cerebrospinal fluid is a candidate Alzheimer biomarker for synaptic dysfunction that also may correlate with cognitive decline. In this study, a novel mass spectrometry-based assay for measurement of cerebrospinal fluid synaptotagmin-1 was developed, and was evaluated in two independent sample sets of patients and controls. Sample set I included cerebrospinal fluid samples from patients with dementia due to Alzheimer's disease (N = 17, age 52-86 years), patients with mild cognitive impairment due to Alzheimer's disease (N = 5, age 62-88 years), and controls (N = 17, age 41-82 years). Sample set II included cerebrospinal fluid samples from patients with dementia due to Alzheimer's disease (N = 24, age 52-84 years), patients with mild cognitive impairment due to Alzheimer's disease (N = 18, age 58-83 years), and controls (N = 36, age 43-80 years). The reproducibility of the novel method showed coefficients of variation of the measured synaptotagmin-1 peptide 215-223 (VPYSELGGK) and peptide 238-245 (HDIIGEFK) of 14 % or below. In both investigated sample sets, the CSF levels of synaptotagmin-1 were significantly increased in patients with dementia due to Alzheimer's disease (P ≤ 0.0001) and in patients with mild cognitive impairment due to Alzheimer's disease (P < 0.001). In addition, in sample set I the synaptotagmin-1 level was significantly higher in patients with mild cognitive impairment due to Alzheimer's disease compared with patients with dementia due to Alzheimer's disease (P ≤ 0.05). Cerebrospinal fluid synaptotagmin-1 is a promising biomarker to monitor synaptic dysfunction and degeneration in Alzheimer's disease that may be useful for clinical diagnosis, to monitor effect on synaptic integrity by novel drug candidates, and to explore pathophysiology directly in patients with Alzheimer's disease.

Cognitive reactivity versus dysfunctional cognitions and the prediction of relapse in recurrent major depressive disorder.

PubMed

Figueroa, Caroline A; Ruhé, Henricus G; Koeter, Maarten W; Spinhoven, Philip; Van der Does, Willem; Bockting, Claudi L; Schene, Aart H

2015-10-01

Major depressive disorder (MDD) is a burdensome disease that has a high risk of relapse/recurrence. Cognitive reactivity appears to be a risk factor for relapse. It remains unclear, however, whether dysfunctional cognitions alone or the reactivity of such cognitions to mild states of sadness (ie, cognitive reactivity) is the crucial factor that increases relapse risk. We aimed to assess the long-term predictive value of cognitive reactivity versus dysfunctional cognitions and other risk factors for depressive relapse. In a prospective cohort of outpatients (N = 116; studied between 2000-2005) who had experienced ≥ 2 previous major depressive episodes (MDEs) and were in remission (DSM-IV) at the start of follow-up, we measured cognitive reactivity, with the Leiden Index of Depression Sensitivity (LEIDS), and dysfunctional cognitions, with the Dysfunctional Attitudes Scale, simultaneously. Course of illness (with the primary outcome of MDE assessed by the Structured Clinical Interview for DSM-IV Axis I Disorders Patient Edition) and time to relapse were monitored prospectively for 3.5 years. Cognitive reactivity scores were associated with time to relapse over the 3.5-year follow-up and also when corrected for the number of previous MDEs and concurrent depressive symptoms (hazard ratio for 1 standard deviation [(HR(SD)); 20 points of the LEIDS, measuring cognitive reactivity] = 1.47; 95% CI, 1.04-2.09; P = .031). Rumination appeared to be a particularly strong predictor of relapse (HR(SD) = 1.60; 95% CI, 1.13-2.26; P = .007). Dysfunctional cognitions did not predict relapse over 3.5 years (HR(SD) = 1.00; 95% CI, 0.74-1.37; P = .93). Every 20-point increase on the cognitive reactivity scale resulted in a 10% to 15% increase in risk of relapse (corrected for previous MDEs and concurrent depressive symptoms). Cognitive reactivity--and particularly rumination--is a long-term predictor of relapse. Future research should address whether psychological interventions can improve cognitive reactivity scores and thereby prevent depressive relapses. ISRCTN Identifier: 68246470. © Copyright 2015 Physicians Postgraduate Press, Inc.

Parvalbumin and neuropeptide Y expressing hippocampal GABA-ergic inhibitory interneuron numbers decline in a model of Gulf War illness.

PubMed

Megahed, Tarick; Hattiangady, Bharathi; Shuai, Bing; Shetty, Ashok K

2014-01-01

Cognitive dysfunction is amongst the most conspicuous symptoms in Gulf War illness (GWI). Combined exposure to the nerve gas antidote pyridostigmine bromide (PB), pesticides and stress during the Persian Gulf War-1 (PGW-1) are presumed to be among the major causes of GWI. Indeed, our recent studies in rat models have shown that exposure to GWI-related (GWIR) chemicals and mild stress for 4 weeks engenders cognitive impairments accompanied with several detrimental changes in the hippocampus. In this study, we tested whether reduced numbers of hippocampal gamma-amino butyric acid (GABA)-ergic interneurons are among the pathological changes induced by GWIR-chemicals and stress. Animals were exposed to low doses of GWIR-chemicals and mild stress for 4 weeks. Three months after this exposure, subpopulations of GABA-ergic interneurons expressing the calcium binding protein parvalbumin (PV), the neuropeptide Y (NPY) and somatostatin (SS) in the hippocampus were stereologically quantified. Animals exposed to GWIR-chemicals and stress for 4 weeks displayed reduced numbers of PV-expressing GABA-ergic interneurons in the dentate gyrus and NPY-expressing interneurons in the CA1 and CA3 subfields. However, no changes in SS+ interneuron population were observed in the hippocampus. Furthermore, GABA-ergic interneuron deficiency in these animals was associated with greatly diminished hippocampus neurogenesis. Because PV+ and NPY+ interneurons play roles in maintaining normal cognitive function and neurogenesis, and controlling the activity of excitatory neurons in the hippocampus, reduced numbers of these interneurons may be one of the major causes of cognitive dysfunction and reduced neurogenesis observed in GWI. Hence, strategies that improve inhibitory neurotransmission in the hippocampus may prove beneficial for reversing cognitive dysfunction in GWI.

Mixed membership trajectory models of cognitive impairment in the multicenter AIDS cohort study.

PubMed

Molsberry, Samantha A; Lecci, Fabrizio; Kingsley, Lawrence; Junker, Brian; Reynolds, Sandra; Goodkin, Karl; Levine, Andrew J; Martin, Eileen; Miller, Eric N; Munro, Cynthia A; Ragin, Ann; Sacktor, Ned; Becker, James T

2015-03-27

The longitudinal trajectories that individuals may take from a state of normal cognition to HIV-associated dementia are unknown. We applied a novel statistical methodology to identify trajectories to cognitive impairment, and factors that affected the 'closeness' of an individual to one of the canonical trajectories. The Multicenter AIDS Cohort Study (MACS) is a four-site longitudinal study of the natural and treated history of HIV disease among gay and bisexual men. Using data from 3892 men (both HIV-infected and HIV-uninfected) enrolled in the neuropsychology substudy of the MACS, a Mixed Membership Trajectory Model (MMTM) was applied to capture the pathways from normal cognitive function to mild impairment to severe impairment. MMTMs allow the data to identify canonical pathways and to model the effects of risk factors on an individual's 'closeness' to these trajectories. First, we identified three distinct trajectories to cognitive impairment: 'normal aging' (low probability of mild impairment until age 60); 'premature aging' (mild impairment starting at age 45-50); and 'unhealthy' (mild impairment in 20s and 30s) profiles. Second, clinically defined AIDS, and not simply HIV disease, was associated with closeness to the premature aging trajectory, and, third, hepatitis-C infection, depression, race, recruitment cohort and confounding conditions all affected individual's closeness to these trajectories. These results provide new insight into the natural history of cognitive dysfunction in HIV disease and provide evidence for a potential difference in the pathophysiology of the development of cognitive impairment based on trajectories to impairment.

A Pilot Study: The Beneficial Effects of Combined Statin-exercise Therapy on Cognitive Function in Patients with Coronary Artery Disease and Mild Cognitive Decline.

PubMed

Toyama, Kensuke; Sugiyama, Seigo; Oka, Hideki; Hamada, Mari; Iwasaki, Yuri; Horio, Eiji; Rokutanda, Taku; Nakamura, Shinichi; Spin, Joshua M; Tsao, Philip S; Ogawa, Hisao

2017-01-01

Objective Hypercholesterolemia, a risk factor in cognitive impairment, can be treated with statins. However, cognitive decline associated with "statins" (HMG-CoA reductase inhibitors) is a clinical concern. This pilot study investigated the effects of combining statins and regular exercise on cognitive function in coronary artery disease (CAD) patients with prior mild cognitive decline. Methods We recruited 43 consecutive CAD patients with mild cognitive decline. These patients were treated with a statin and weekly in-hospital aerobic exercise for 5 months. We measured serum lipids, exercise capacity, and cognitive function using the mini mental state examination (MMSE). Results Low-density lipoprotein cholesterol levels were significantly decreased, and maximum exercise capacity (workload) was significantly increased in patients with CAD and mild cognitive decline after treatment compared with before. Combined statin-exercise therapy significantly increased the median (range) MMSE score from 24 (22-25) to 25 (23-27) across the cohort (p<0.01). Changes in body mass index (BMI) were significantly and negatively correlated with changes in the MMSE. After treatment, MMSE scores in the subgroup of patients that showed a decrease in BMI were significantly improved, but not in the BMI-increased subgroup. Furthermore, the patients already on a statin at the beginning of the trial displayed a more significant improvement in MMSE score than statin-naïve patients, implying that exercise might be the beneficial aspect of this intervention as regards cognition. In a multivariate logistic regression analysis adjusted for age >65 years, sex, and presence of diabetes mellitus, a decrease in BMI during statin-exercise therapy was significantly correlated with an increase in the MMSE score (odds ratio: 4.57, 95% confidence interval: 1.05-20.0; p<0.05). Conclusion Statin-exercise therapy may help improve cognitive dysfunction in patients with CAD and pre-existing mild cognitive decline.

Preliminary report of the Hepatic Encephalopathy Assessment Driving Simulator (HEADS) score.

PubMed

Baskin-Bey, Edwina S; Stewart, Charmaine A; Mitchell, Mary M; Bida, John P; Rosenthal, Theodore J; Nyberg, Scott L

2008-01-01

Audiovisual simulations of real-life driving (ie, driving simulators) have been used to assess neurologic dysfunction in a variety of medical applications. However, the use of simulated driving to assess neurologic impairment in the setting of liver disease (ie, hepatic encephalopathy) is limited. The aim of this analysis was to develop a scoring system based on simulated driving performance to assess mild cognitive impairment in cirrhotic patients with hepatic encephalopathy. This preliminary analysis was conducted as part of the Hepatic Encephalopathy Assessment Driving Simulator (HEADS) pilot study. Cirrhotic volunteers initially underwent a battery of neuropsychological tests to identify those cirrhotic patients with mild cognitive impairment. Performance during an audiovisually simulated course of on-road driving was then compared between mildly impaired cirrhotic patients and healthy volunteers. A scoring system was developed to quantify the likelihood of cognitive impairment on the basis of data from the simulated on-road driving. Mildly impaired cirrhotic patients performed below the level of healthy volunteers on the driving simulator. Univariate logistic regression and correlation models indicated that several driving simulator variables were significant predictors of cognitive impairment. Five variables (run time, total map performance, number of collisions, visual divided attention response, and average lane position) were incorporated into a quantitative model, the HEADS scoring system. The HEADS score (0-9 points) showed a strong correlation with cognitive impairment as measured by area under the receiver-operator curve (.89). The HEADS system appears to be a promising new tool for the assessment of mild hepatic encephalopathy.

Specific Features of Executive Dysfunction in Alzheimer-Type Mild Dementia Based on Computerized Cambridge Neuropsychological Test Automated Battery (CANTAB) Test Results.

PubMed

Kuzmickienė, Jurgita; Kaubrys, Gintaras

2016-10-08

BACKGROUND The primary manifestation of Alzheimer's disease (AD) is decline in memory. Dysexecutive symptoms have tremendous impact on functional activities and quality of life. Data regarding frontal-executive dysfunction in mild AD are controversial. The aim of this study was to assess the presence and specific features of executive dysfunction in mild AD based on Cambridge Neuropsychological Test Automated Battery (CANTAB) results. MATERIAL AND METHODS Fifty newly diagnosed, treatment-naïve, mild, late-onset AD patients (MMSE ≥20, AD group) and 25 control subjects (CG group) were recruited in this prospective, cross-sectional study. The CANTAB tests CRT, SOC, PAL, SWM were used for in-depth cognitive assessment. Comparisons were performed using the t test or Mann-Whitney U test, as appropriate. Correlations were evaluated by Pearson r or Spearman R. Statistical significance was set at p<0.05. RESULTS AD and CG groups did not differ according to age, education, gender, or depression. Few differences were found between groups in the SOC test for performance measures: Mean moves (minimum 3 moves): AD (Rank Sum=2227), CG (Rank Sum=623), p<0.001. However, all SOC test time measures differed significantly between groups: SOC Mean subsequent thinking time (4 moves): AD (Rank Sum=2406), CG (Rank Sum=444), p<0.001. Correlations were weak between executive function (SOC) and episodic/working memory (PAL, SWM) (R=0.01-0.38) or attention/psychomotor speed (CRT) (R=0.02-0.37). CONCLUSIONS Frontal-executive functions are impaired in mild AD patients. Executive dysfunction is highly prominent in time measures, but minimal in performance measures. Executive disorders do not correlate with a decline in episodic and working memory or psychomotor speed in mild AD.

Brain aging in the canine: a diet enriched in antioxidants reduces cognitive dysfunction.

PubMed

Cotman, Carl W; Head, Elizabeth; Muggenburg, Bruce A; Zicker, S; Milgram, Norton W

2002-01-01

Animal models that simulate various aspects of human brain aging are an essential step in the development of interventions to manage cognitive dysfunction in the elderly. Over the past several years we have been studying cognition and neuropathology in the aged-canine (dog). Like humans, canines naturally accumulate deposits of beta-amyloid (Abeta) in the brain with age. Further, canines and humans share the same Abeta sequence and also first show deposits of the longer Abeta1-42 species followed by the deposition of Abeta1-40. Aged canines like humans also show increased oxidative damage. As a function of age, canines show impaired learning and memory on tasks similar to those used in aged primates and humans. The extent of Abeta deposition correlates with the severity of cognitive dysfunction in canines. To test the hypothesis that a cascade of mechanisms centered on oxidative damage and Abeta results in cognitive dysfunction we have evaluated the cognitive effects of an antioxidant diet in aged canines. The diet resulted in a significant improvement in the ability of aged but not young animals to acquire progressively more difficult learning tasks (e.g. oddity discrimination learning). The canine represent a higher animal model to study the earliest declines in the cognitive continuum that includes age associated memory impairments (AAMI) and mild cognitive impairment (MCI) observed in human aging. Thus, studies in the canine model suggest that oxidative damage impairs cognitive function and that antioxidant treatment can result in significant improvements, supporting the need for further human studies. Copyright 2002 Elsevier Science Inc.

Site differences in mild cognitive dysfunction (MCD) among patients with systemic lupus erythematosus (SLE).

PubMed

Kozora, E; Erkan, D; West, S G; Filley, C M; Zhang, L; Ramon, G; Duggan, E; Lockshin, M D

2013-01-01

Mild cognitive dysfunction (MCD) is common in patients with systemic lupus erythematosus (MCD-SLE) but few studies have investigated potential site differences. SLE patients from Denver, CO, and New York, NY, were enrolled in two different cognition studies employing similar screening methods. Using the resulting neuropsychological scores, cognitive impairment was calculated using a cognitive impairment index (CII). The rate of MCD-SLE was 24% at the Denver, CO, site and 60% at the New York, NY, site. The mean CII was 2.6 ± 2.3 versus 4.4 ± 2.7, respectively (p = 0.005). The NY participants had a significantly longer disease duration (p = 0.13) and higher American College of Rheumatology SLE criteria scores (p > 0.001). NY participants had a higher frequency of impairment in semantic verbal fluency (p = 0.005), visuomotor speed (p = 0.013), and motor sequencing (p = 0.001). A correlation was found between cognitive impairment and SLE disease duration (p = 0.03). The rate of MCD-SLE was greater in SLE patients from New York, NY, compared to patients in the Denver, CO, area. The greater duration of disease and higher prevalence of medical complications in the NY group might contribute to this difference. Findings suggest that MCD-SLE may differ by site, but future studies that better evaluate site or selection bias are recommended.

ALS and Frontotemporal Dysfunction: A Review

PubMed Central

Achi, Eugene Y.; Rudnicki, Stacy A.

2012-01-01

Though once believed to be a disease that was limited to the motor system, it is now apparent that amyotrophic lateral sclerosis (ALS) may be associated with cognitive changes in some patients. Changes are consistent with frontotemporal dysfunction, and may range from mild abnormalities only recognized with formal neuropsychological testing, to profound frontotemporal dementia (FTD). Executive function, behavior, and language are the most likely areas to be involved. Screening helpful in detecting abnormalities includes verbal or categorical fluency, behavioral inventories filled out by the caregiver, and evaluation for the presence of depression and pseudobulbar affect. Patients with cognitive dysfunction have shortened survival and may be less compliant with recommendations regarding use of feeding tubes and noninvasive ventilation. Evolving knowledge of genetic and pathological links between ALS and FTD has allowed us to better understand the overlapping spectrum of ALS and FTD. PMID:22919484

Oculomotor Reflexes as a Test of Visual Dysfunctions in Cognitively Impaired Observers

DTIC Science & Technology

2013-09-01

right. Gaze horizontal position is plotted along the y-axis. The red bar indicates a visual nystagmus event detected by the filter. (d) A mild curse word...experimental conditions were chosen to simulate testing cognitively impaired observers. Reflex Stimulus Functions Visual Nystagmus luminance grating low-level...developed a new stimulus for visual nystagmus to 8 test visual motion processing in the presence of incoherent motion noise. The drifting equiluminant

Frontal white matter hyperintensity predicts lower urinary tract dysfunction in older adults with amnestic mild cognitive impairment and Alzheimer's disease.

PubMed

Ogama, Noriko; Yoshida, Masaki; Nakai, Toshiharu; Niida, Shumpei; Toba, Kenji; Sakurai, Takashi

2016-02-01

Lower urinary tract symptoms often limit activities of daily life and impair quality of life in the elderly. The purpose of the present study was to determine whether regional white matter hyperintensity (WMH) can predict lower urinary tract symptoms in elderly with amnestic mild cognitive impairment or Alzheimer's disease. The participants were 461 patients aged 65-85 years diagnosed with amnestic mild cognitive impairment or Alzheimer's disease. Patients and their caregivers were asked about symptoms of lower urinary tract symptoms (urinary difficulty, frequency and incontinence). Cognition, behavior and psychological symptoms of dementia and medication were evaluated. WMH and brain atrophy were analyzed using an automatic segmentation program. Regional WMH was evaluated in the frontal, parietal, temporal and occipital lobes. Patients with urinary incontinence showed significantly greater volume of WMH. WMH increased with age, especially in the frontal lobe. WMH in the frontal lobe was closely associated with urinary incontinence after adjustment for brain atrophy and classical confounding factors. Frontal WMH was a predictive factor for urinary incontinence in older adults with amnestic mild cognitive impairment or Alzheimer's disease. Urinary incontinence in demented older adults is not an incidental event, and careful insight into regional WMH on brain magnetic resonance imaging might greatly help in diagnosing individuals with a higher risk of urinary incontinence. © 2015 Japan Geriatrics Society.

Association between White Matter Lesions and Non-Motor Symptoms in Parkinson Disease.

PubMed

Lee, Jeong-Yoon; Kim, Ji Sun; Jang, Wooyoung; Park, Jinse; Oh, Eungseok; Youn, Jinyoung; Park, Suyeon; Cho, Jin Whan

2018-06-05

There are only few studies exploring the relationship between white matter lesions (WMLs) and non-motor symptoms in Parkinson disease (PD). This study aimed to investigate the association between WMLs and the severity of non-motor symptoms in PD. The severity of motor dysfunction, cognitive impairment, and non-motor symptoms was assessed by various scales in 105 PD patients. We used a visual semiquantitative rating scale and divided the subjects into four groups: no, mild, moderate, and severe WMLs. We compared the means of all scores between the four groups and analyzed the association between the severity of WMLs and the specific domain of non-motor symptoms. The non-motor symptoms as assessed by the Non-Motor Symptoms Scale, Parkinson's Disease Questionnaire (PDQ-39), Parkinson's Disease Sleep Scale, Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Neuropsychiatric Inventory (NPI), and Parkinson Fatigue Scale (PFS) were significantly worse in the patients with moderate and severe WMLs than in those without WMLs. Compared with the no WML group, the scores for motor dysfunction were significantly higher in the mild, moderate, and severe WML groups. The scores for cognitive dysfunction were significantly higher in the patients with severe WMLs than in those without WMLs. The severity of WMLs showed linear associations with PFS, BDI, BAI, NPI, and PDQ-39 scores. The severity of WMLs also correlated linearly with scores for motor and cognitive dysfunction. Among the non-motor symptoms, fatigue, depression, anxiety, and quality of life were significantly affected by WMLs in PD. Confirmation of the possible role of WMLs in non-motor symptoms associated with PD in a prospective manner may be crucial not only for understanding non-motor symptoms but also for the development of treatment strategies. © 2018 S. Karger AG, Basel.

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.

Dreaming and cognition in patients with frontotemporal dysfunction.

PubMed

Paiva, Teresa; Bugalho, Paulo; Bentes, Carla

2011-12-01

Individuals with Parkinson's disease (PD) and temporal lobe epilepsy (TLE) have hallucinations and mild cognitive dysfunction. The objective of this work was to study dreams in PD and TLE patients using a common functional model of dream production involving the limbic and paralimbic structures. Dreams were characterised in early-stage PD (19 males) and TLE patients (52) with dream diaries classified by the Hall van de Castle system and were compared with matched controls. In PD, there were significant differences between patients' dreams and those of controls: animals, physical aggression, and a befriender were more common in patients, and aggressor and bodily misfortunes were less common. The dreams of patients with frontal dysfunction showed more aggressive features. TLE patients had lower recall than PD patients and a higher proportion of dreams involving family and familiar settings, lower proportions involving success, and a higher incidence of frontal dysfunction. The dreams of PD and TLE patients share important features. Copyright © 2011. Published by Elsevier Inc.

Heart Rate Variability Indexes in Dementia: A Systematic Review with a Quantitative Analysis.

PubMed

da Silva, Vanessa Pereira; Ramalho Oliveira, Bruno Ribeiro; Tavares Mello, Roger Gomes; Moraes, Helena; Deslandes, Andrea Camaz; Laks, Jerson

2018-01-01

Decreased heart rate variability (HRV) indexes indicate low vagal activity and may be associated with development of dementia. The neurodegenerative process is associated with the cardiovascular autonomic control. The aim of this systematic review was to investigate the effect size (ES) magnitude of the HRV indexes in the evaluation of autonomic dysfunction in older persons with dementia. PubMed (Medline), Web of Science, Scopus, Scielo, Lilacs, and APA Psycnet were consulted. Complete original articles published in English or Portuguese, investigating the association between autonomic dysfunction and dementia, using the HRV indexes were included. The search identified 97 potentially relevant articles. After screening the full text, eight articles were included in the qualitative analysis and six were included in the quantitative analysis. Almost all indexes showed a negative ES for all types of dementia and mild cognitive impairment. The most common frequency band of the power spectrum density function was the high frequency, which was reported by six studies. The meta-analysis of high frequency power in Alzheimer's disease group showed high heterogeneity and inconsistent results. The negative effect size suggests an autonomic dysfunction in all types of dementia as well as mild cognitive impairment. However, further analysis is necessary to support these results. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Subtypes of mild cognitive impairment in patients with Parkinson's disease: evidence from the LANDSCAPE study.

PubMed

Kalbe, Elke; Rehberg, Sarah Petra; Heber, Ines; Kronenbuerger, Martin; Schulz, Jörg B; Storch, Alexander; Linse, Katharina; Schneider, Christine; Gräber, Susanne; Liepelt-Scarfone, Inga; Berg, Daniela; Dams, Judith; Balzer-Geldsetzer, Monika; Hilker, Rüdiger; Oberschmidt, Carola; Witt, Karsten; Schmidt, Nele; Mollenhauer, Brit; Trenkwalder, Claudia; Spottke, Annika; Roeske, Sandra; Wittchen, Hans-Ulrich; Riedel, Oliver; Dodel, Richard

2016-10-01

Inconsistent results exist regarding the cognitive profile in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI. Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed. 269 patients with PD-MCI (age 67.8±7.4, Unified Parkinson's Disease Rating Scale (UPDRS-III) scores 23.2±11.6) were included. PD-MCI subtypes were 39.4% non-amnestic single domain, 30.5% amnestic multiple domain, 23.4% non-amnestic multiple domain and 6.7% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes. This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia. 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/

Cardiovascular disease and cognitive dysfunction in systemic lupus erythematosus.

PubMed

Murray, Sara G; Yazdany, Jinoos; Kaiser, Rachel; Criswell, Lindsey A; Trupin, Laura; Yelin, Edward H; Katz, Patricia P; Julian, Laura J

2012-09-01

Cognitive dysfunction and cardiovascular disease are common and debilitating manifestations of systemic lupus erythematosus (SLE). In this study, we evaluated the relationship between cardiovascular events, traditional cardiovascular risk factors, and SLE-specific risk factors as predictors of cognitive dysfunction in a large cohort of participants with SLE. Subjects included 694 participants from the Lupus Outcomes Study (LOS), a longitudinal study of SLE outcomes based on an annual telephone survey querying demographic and clinical variables. The Hopkins Verbal Learning Test-Revised and the Controlled Oral Word Association Test were administered to assess cognitive function. Multiple logistic regression was used to identify cardiovascular events (myocardial infarction, stroke), traditional cardiovascular risk factors (hypertension, hyperlipidemia, diabetes mellitus, obesity, smoking), and SLE-specific risk factors (antiphospholipid antibodies [aPL], disease activity, disease duration) associated with cognitive impairment in year 7 of the LOS. The prevalence of cognitive impairment as measured by verbal memory and verbal fluency metrics was 15%. In adjusted multiple logistic regression analyses, aPL (odds ratio [OR] 2.10, 95% confidence interval [95% CI] 1.3-3.41), hypertension (OR 2.06, 95% CI 1.19-3.56), and a history of stroke (OR 2.27, 95% CI 1.16-4.43) were significantly associated with cognitive dysfunction. In additional analyses evaluating the association between these predictors and severity of cognitive impairment, stroke was significantly more prevalent in participants with severe impairment when compared to those with mild or moderate impairment (P = 0.036). These results suggest that the presence of aPL, hypertension, and stroke are key variables associated with cognitive impairment, which may aid in identification of patients at greatest risk. Copyright © 2012 by the American College of Rheumatology.

Balance and mobility dysfunction and falls risk in older people with mild to moderate Alzheimer disease.

PubMed

Suttanon, Plaiwan; Hill, Keith D; Said, Catherine M; Logiudice, Dina; Lautenschlager, Nicola T; Dodd, Karen J

2012-01-01

This study aimed to identify the magnitude and type of balance and mobility impairments in people with Alzheimer disease by comparing their performance with that of older people without cognitive impairment. Twenty-five community-dwelling people with mild to moderate Alzheimer disease and a comparison group of 25 cognitively intact age- and sex-matched people completed a comprehensive balance and mobility assessment. This included computerized posturography measures of static and dynamic balance under various conditions, clinical balance, and mobility measures, and measures of falls and falls risk. The level of falls risk was higher in people with Alzheimer disease. Standing balance in people with Alzheimer disease was significantly impaired across a range of static and dynamic balance conditions. Activity level, gait, and mobility measures were also impaired, particularly turning and dual tasks. The findings of the study highlight the value of including balance screening as a routine component of early dementia assessment. This would allow for the early detection of balance dysfunction and the introduction of balance retraining before impairments progress to more advanced levels.

Comparison of odor identification among amnestic and non-amnestic mild cognitive impairment, subjective cognitive decline, and early Alzheimer's dementia.

PubMed

Park, Sung-Jin; Lee, Jee-Eun; Lee, Kwang-Soo; Kim, Joong-Seok

2018-03-01

Olfactory impairment might be an important clinical marker and predictor of Alzheimer's disease (AD). In the present study, we aimed to compare the degree of olfactory identification impairment in each mild cognitive impairment (MCI) subtype, subjective memory impairment, and early AD dementia and assessed the relationship between olfactory identification and cognitive performance. We consecutively included 50 patients with amnestic MCI, 28 patients with non-amnestic MCI, 20 patients with mild AD, and 17 patients with subjective memory impairment (SMI). All patients underwent clinical and neuropsychological assessments. A multiple choice olfactory identification cross-cultural smell identification test was also utilized. Controlling for age and gender, olfactory impairment was significantly more severe in patients with AD and amnestic MCI compared with the results from the non-amnestic MCI and SMI groups. Higher scores on MMSE, verbal and non-verbal memory, and frontal executive function tests were significantly related to olfactory identification ability. In conclusion, olfactory identification is impaired in amnestic MCI and AD. These findings are consistent with previous studies. In amnestic MCI patients, this dysfunction is considered to be caused by underlying AD pathology.

Entorhinal Cortex Volume Is Associated With Dual-Task Gait Cost Among Older Adults With MCI: Results From the Gait and Brain Study.

PubMed

Sakurai, Ryota; Bartha, Robert; Montero-Odasso, Manuel

2018-05-15

Low dual-task gait performance (the slowing of gait speed while performing a demanding cognitive task) is associated with low cognitive performance and an increased risk of progression to dementia in older adults with mild cognitive impairment. However, the reason for this remains unclear. This study aimed to examine the relationship between dual-task cost and regional brain volume, focusing on the hippocampus, parahippocampal gyrus, entorhinal cortex, and motor and lateral frontal cortices in older adults with mild cognitive impairment. Forty older adults with mild cognitive impairment from the "Gait and Brain Study" were included in this study. Gait velocity was measured during single-task (ie, walking alone) and dual-task (ie, counting backwards, subtracting serial sevens, and naming animals, in addition to walking) conditions, using an electronic walkway. Regional brain volumes were derived by automated segmentation, using 3T magnetic resonance imaging. Partial rank correlation analyses demonstrated that a smaller volume of the left entorhinal cortex was associated with higher dual-task costs in counting backwards and subtracting serial sevens conditions. Subsequent logistic regression analyses demonstrated that a smaller volume of the left entorhinal cortex was independently associated with higher dual-task cost (slowing down >20% when performing cognitive task) in these two conditions. There were no other significant associations. Our results show that lower dual-task gait performance is associated with volume reduction in the entorhinal cortex. Cognitive and motor dysfunction in older adults with mild cognitive impairment may reflect a shared pathogenic mechanism, and dual-task-related gait changes might be a surrogate motor marker for Alzheimer's disease pathology.

Early cognitive impairment along with decreased stress-induced BDNF in male and female patients with newly diagnosed multiple sclerosis.

PubMed

Prokopova, Barbora; Hlavacova, Natasa; Vlcek, Miroslav; Penesova, Adela; Grunnerova, Lucia; Garafova, Alexandra; Turcani, Peter; Kollar, Branislav; Jezova, Daniela

2017-01-15

The aim of this study was to evaluate neuroendocrine activation during stress in patients with recently diagnosed multiple sclerosis before starting the immunomodulatory therapy (EDSS score≤2.0). We verified the hypothesis that certain cognitive and affective dysfunction is present already at this early stage of the disease. The sample consisted of 38 subjects, which involved patients who were recently diagnosed multiple sclerosis and age- and sex-matched healthy volunteers. Stroop test served as mental stress model enabling measurement of cognitive performance. Present results showed increased state anxiety, depression scores and poorer performance in the Stroop test in the group of patients compared to healthy subjects. The cognitive dysfunction was particularly evident in male patients with simultaneously decreased concentrations of the brain-derived neurotrophic factor (BDNF) in plasma. The patients at this stage of the disease have not yet developed the hyperactivity of the hypothalamic-pituitary-adrenocortical axis. They showed normal levels of plasma copeptin and reduced aldosterone response to mental stress test in women only. Concentrations of plasma copeptin were higher in men compared to women. Very early stages of multiple sclerosis are accompanied by disturbances in psychological well-being, mild cognitive dysfunction and decreased plasma concentrations of BDNF, particularly in male patients. Copyright © 2016. Published by Elsevier B.V.

Psychometrics of the AAN Caregiver Driving Safety Questionnaire and contributors to caregiver concern about driving safety in older adults.

PubMed

Carvalho, Janessa O; Springate, Beth; Bernier, Rachel A; Davis, Jennifer

2018-03-01

ABSTRACTBackground:The American Academy of Neurology (AAN) updated their practice parameters in the evaluation of driving risk in dementia and developed a Caregiver Driving Safety Questionnaire, detailed in their original manuscript (Iverson Gronseth, Reger, Classen, Dubinsky, & Rizzo, 2010). They described four factors associated with decreased driving ability in dementia patients: history of crashes or citations, informant-reported concerns, reduced mileage, and aggressive driving. An informant-reported AAN Caregiver Driving Safety Questionnaire was designed with these elements, and the current study was the first to explore the factor structure of this questionnaire. Additionally, we examined associations between these factors and cognitive and behavioral measures in patients with mild cognitive impairment or early Alzheimer's disease and their informants. Exploratory factor analysis revealed a four-component structure, consistent with the theory behind the AAN scale composition. These four factor scores also were significantly associated with performance on cognitive screening instruments and informant reported behavioral dysfunction. Regressions revealed that behavioral dysfunction predicted caregiver concerns about driving safety beyond objective patient cognitive dysfunction. In this first known quantitative exploration of the scale, our results support continued use of this scale in office driving safety assessments. Additionally, patient behavioral changes predicted caregiver concerns about driving safety over and above cognitive status, which suggests that caregivers may benefit from psychoeducation about cognitive factors that may negatively impact driving safety.

Cognitive Behavioral Performance of Untreated Depressed Patients with Mild Depressive Symptoms

PubMed Central

Li, Mi; Zhong, Ning; Lu, Shengfu; Wang, Gang; Feng, Lei; Hu, Bin

2016-01-01

This study evaluated the working memory performance of 18 patients experiencing their first onset of mild depression without treatment and 18 healthy matched controls. The results demonstrated that working memory impairment in patients with mild depression occurred when memorizing the position of a picture but not when memorizing the pictures themselves. There was no significant difference between the two groups in the emotional impact on the working memory, indicating that the attenuation of spatial working memory was not affected by negative emotion; however, cognitive control selectively affected spatial working memory. In addition, the accuracy of spatial working memory in the depressed patients was not significantly reduced, but the reaction time was significantly extended compared with the healthy controls. This finding indicated that there was no damage to memory encoding and function maintenance in the patients but rather only impaired memory retrieval, suggesting that the extent of damage to the working memory system and cognitive control abilities was associated with the corresponding depressive symptoms. The development of mild to severe depressive symptoms may be accompanied by spatial working memory damage from the impaired memory retrieval function extending to memory encoding and memory retention impairments. In addition, the impaired cognitive control began with an inadequate capacity to automatically process internal negative emotions and further extended to impairment of the ability to regulate and suppress external emotions. The results of the mood-congruent study showed that the memory of patients with mild symptoms of depression was associated with a mood-congruent memory effect, demonstrating that mood-congruent memory was a typical feature of depression, regardless of the severity of depression. This study provided important information for understanding the development of cognitive dysfunction. PMID:26730597

Impact of Rivastigmine on Cognitive Dysfunction and Falling in Parkinson's Disease Patients.

PubMed

Li, Zhenguang; Yu, Zhancai; Zhang, Jinbiao; Wang, Jing; Sun, Chao; Wang, Pengfei; Zhang, Jiangshan

2015-01-01

The purpose of this study was to observe the incidence of falls in Parkinson's disease (PD) patients with different cognitive levels and to investigate the effect of the cholinesterase inhibitor Rivastigmine on cognitive dysfunction and falling in PD patients. Data from 176 PD patients participating in the collaborative PD study between June 2010 and June 2014 were collected; the Chinese edition of the Montreal Cognitive Assessment (MoCA) score was used to evaluate the cognitive function of patients, and falls were recorded. PD patients with cognitive dysfunction were randomly administered either a placebo or Rivastigmine. The cognitive function changes and difference in fall incidence were compared between the 2 groups. The average number of falls per person in PD patients without cognitive impairment dysfunction was significantly lower than that in patients in the PD mild cognitive impairment (PD-MCI) group and that in the PD dementia (PDD) group (p < 0.01, p < 0.001, respectively), and the incidence of falls was significantly lower than that in patients in the PD-MCI and PDD groups (p < 0.01, p < 0.01, respectively). Compared to the PD-MCI group, the incidence of falls of patients in the PDD group (OR 2.45, 95% CI 0.97-6.20, p < 0.01) and the number of falls per person were significantly increased (p < 0.01). After taking the placebo or Rivastigmine for 12 months, the MoCA scores of patients in the Rivastigmine treatment group were significantly higher than those of the control group (p = 0.002). The number of falls per person and the incidence of falls of patients in Rivastigmine treatment group were significantly lower than those in the placebo group (p < 0.01). This study suggests that the degree of cognitive impairment is closely associated with the incidence of falls, and the cholinesterase inhibitor Rivastigmine can delay the deterioration of cognitive function and lower the incidence of falls in PD patients. © 2015 S. Karger AG, Basel.

Contribution of the Cholinergic System to Verbal Memory Performance in Mild Cognitive Impairment.

PubMed

Peter, Jessica; Lahr, Jacob; Minkova, Lora; Lauer, Eliza; Grothe, Michel J; Teipel, Stefan; Köstering, Lena; Kaller, Christoph P; Heimbach, Bernhard; Hüll, Michael; Normann, Claus; Nissen, Christoph; Reis, Janine; Klöppel, Stefan

2016-06-18

Acetylcholine is critically involved in modulating learning and memory function, which both decline in neurodegeneration. It remains unclear to what extent structural and functional changes in the cholinergic system contribute to episodic memory dysfunction in mild cognitive impairment (MCI), in addition to hippocampal degeneration. A better understanding is critical, given that the cholinergic system is the main target of current symptomatic treatment in mild to moderate Alzheimer's disease. We simultaneously assessed the structural and functional integrity of the cholinergic system in 20 patients with MCI and 20 matched healthy controls and examined their effect on verbal episodic memory via multivariate regression analyses. Mediating effects of either cholinergic function or hippocampal volume on the relationship between cholinergic structure and episodic memory were computed. In MCI, a less intact structure and function of the cholinergic system was found. A smaller cholinergic structure was significantly correlated with a functionally more active cholinergic system in patients, but not in controls. This association was not modulated by age or disease severity, arguing against compensational processes. Further analyses indicated that neither functional nor structural changes in the cholinergic system influence verbal episodic memory at the MCI stage. In fact, those associations were fully mediated by hippocampal volume. Although the cholinergic system is structurally and functionally altered in MCI, episodic memory dysfunction results primarily from hippocampal neurodegeneration, which may explain the inefficiency of cholinergic treatment at this disease stage.

Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension: Relative Contribution of Fibrosis and Myofibril Stiffness.

PubMed

Rain, Silvia; Andersen, Stine; Najafi, Aref; Gammelgaard Schultz, Jacob; da Silva Gonçalves Bós, Denielli; Handoko, M Louis; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton; Andersen, Asger; van der Velden, Jolanda; Ottenheijm, Coen A C; de Man, Frances S

2016-07-01

The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction. By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membrane-permeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction. RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosis-mediated stiffness contribute to increased RV myocardial stiffness. © 2016 The Authors.

Right Ventricular Myocardial Stiffness in Experimental Pulmonary Arterial Hypertension

PubMed Central

Rain, Silvia; Andersen, Stine; Najafi, Aref; Gammelgaard Schultz, Jacob; da Silva Gonçalves Bós, Denielli; Handoko, M. Louis; Bogaard, Harm-Jan; Vonk-Noordegraaf, Anton; Andersen, Asger; van der Velden, Jolanda; Ottenheijm, Coen A.C.

2016-01-01

Background— The purpose of this study was to determine the relative contribution of fibrosis-mediated and myofibril-mediated stiffness in rats with mild and severe right ventricular (RV) dysfunction. Methods and Results— By performing pulmonary artery banding of different diameters for 7 weeks, mild RV dysfunction (Ø=0.6 mm) and severe RV dysfunction (Ø=0.5 mm) were induced in rats. The relative contribution of fibrosis- and myofibril-mediated RV stiffness was determined in RV trabecular strips. Total myocardial stiffness was increased in trabeculae from both mild and severe RV dysfunction in comparison to controls. In severe RV dysfunction, increased RV myocardial stiffness was explained by both increased fibrosis-mediated stiffness and increased myofibril-mediated stiffness, whereas in mild RV dysfunction, only myofibril-mediated stiffness was increased in comparison to control. Histological analyses revealed that RV fibrosis gradually increased with severity of RV dysfunction, whereas the ratio of collagen I/III expression was only elevated in severe RV dysfunction. Stiffness measurements in single membrane-permeabilized RV cardiomyocytes demonstrated a gradual increase in RV myofibril stiffness, which was partially restored by protein kinase A in both mild and severe RV dysfunction. Increased expression of compliant titin isoforms was observed only in mild RV dysfunction, whereas titin phosphorylation was reduced in both mild and severe RV dysfunction. Conclusions— RV myocardial stiffness is increased in rats with mild and severe RV dysfunction. In mild RV dysfunction, stiffness is mainly determined by increased myofibril stiffness. In severe RV dysfunction, both myofibril- and fibrosis-mediated stiffness contribute to increased RV myocardial stiffness. PMID:27370069

Postconcussion Syndrome: A Review.

PubMed

Barlow, Karen M

2016-01-01

Postconcussion syndrome is a symptom complex with a wide range of somatic, cognitive, sleep, and affective features, and is the most common consequence of traumatic brain injury. Between 14% and 29% of children with mild traumatic brain injury will continue to have postconcussion symptoms at 3 months, but the pathophysiological mechanisms driving this is poorly understood. The relative contribution of injury factors to postconcussion syndrome decreases over time and, instead, premorbid factors become important predictors of symptom persistence by 3 to 6 months postinjury. The differential diagnoses include headache disorder, cervical injury, anxiety, depression, somatization, vestibular dysfunction, and visual dysfunction. The long-term outcome for most children is good, although there is significant morbidity in the short term. Management strategies target problematic symptoms such as headaches, sleep and mood disturbances, and cognitive complaints. © The Author(s) 2014.

Rationale and clinical data supporting nutritional intervention in Alzheimer's disease.

PubMed

Engelborghs, S; Gilles, C; Ivanoiu, A; Vandewoude, M

2014-01-01

Adequate nutrition plays an important role in the maintenance of cognitive function, particularly during aging. Malnutrition is amongst the risk factors for developing mild cognitive impairment (MCI) and Alzheimer's disease (AD). Epidemiological studies have associated deficiencies in some nutrients with a higher risk of cognitive dysfunction and/or AD. Cognitive decline in AD is correlated with synaptic loss and many of the components required to maintain optimal synaptic function are derived from dietary sources. As synapses are part of the neuronal membrane and are continuously being remodelled, the availability of sufficient levels of nutritional precursors (mainly uridine monophosphate, choline and omega-3 fatty acids) to make the phospholipids required to build neuronal membranes may have beneficial effects on synaptic degeneration in AD. In addition, B-vitamins, phospholipids and other micronutrients act as cofactors to enhance the supply of precursors required to make neuronal membranes and synapses. Despite this, no randomized controlled trial has hitherto provided evidence that any single nutrient has a beneficial effect on cognition or lowers the risk for AD. However, a multi-target approach using combinations of (micro)nutrients might have beneficial effects on cognitive function in neurodegenerative brain disorders like AD leading to synaptic degeneration. Here we review the clinical evidence for supplementation, based on a multi-target approach with a focus on key nutrients with a proposed role in synaptic dysfunction. Based on preclinical evidence, a nutrient mixture, Souvenaid(®) (Nutricia N.V., Zoetermeer, The Netherlands) was developed. Clinical trials with Souvenaid(®) have shown improved memory performance in patients with mild AD. Further clinical trials to evaluate the effects of nutritional intervention in MCI and early dementia due to AD are on-going.

Color discrimination deficits in Parkinson's disease are related to cognitive impairment and white-matter alterations.

PubMed

Bertrand, Josie-Anne; Bedetti, Christophe; Postuma, Ronald B; Monchi, Oury; Génier Marchand, Daphné; Jubault, Thomas; Gagnon, Jean-François

2012-12-01

Color discrimination deficit is a common nonmotor manifestation of Parkinson's disease (PD). However, the pathophysiology of this dysfunction remains poorly understood. Although retinal structure changes found in PD have been suggested to cause color discrimination deficits, the impact of cognitive impairment and cortical alterations remains to be determined. We investigated the contribution of cognitive impairment to color discrimination deficits in PD and correlated them with cortical anomalies. Sixty-six PD patients without dementia and 20 healthy controls performed the Farnsworth-Munsell 100 hue test and underwent a comprehensive neuropsychological assessment for mild cognitive impairment diagnosis. In a subgroup of 26 PD patients, we also used high-definition neuroanatomical magnetic resonance imaging for cortical thickness and diffusion tensor analysis. PD patients with mild cognitive impairment performed poorly on the Farnsworth-Munsell 100 hue test compared with PD patients without mild cognitive impairment and controls. In PD patients, performance on the Farnsworth-Munsell 100 hue test was correlated with measures of visuospatial abilities and executive functions. Neuroimaging analysis revealed higher mean and radial diffusivity values in right posterior white-matter structures that correlated with poor performance on the Farnsworth-Munsell 100 hue test. No cortical thickness correlation reached significance. This study showed that cognitive impairment makes a major contribution to the color discrimination deficits reported in PD. Thus, performance on the Farnsworth-Munsell 100 hue test may reflect cognitive impairment more than color discrimination deficits in PD. Poor performance on the Farnsworth-Munsell 100 hue test was also associated with white-matter alterations in right posterior brain regions. Copyright © 2012 Movement Disorder Society.

Extracorporeal life support for critical enterovirus 71 rhombencephalomyelitis: long-term neurologic follow-up.

PubMed

Lee, Hsiu-Fen; Chi, Ching-Shiang; Jan, Sheng-Ling; Fu, Yun-Ching; Huang, Fang-Liang; Chen, Po-Yen; Wang, Chung-Chi; Wei, Hao-Ji

2012-04-01

Enterovirus 71 rhombencephalomyelitis with cardiopulmonary dysfunction has become an endemic problem in Taiwan since an epidemic outbreak in 1998. Such cases frequently involve significant morbidity and mortality. From October 2000-June 2008, we collected 10 consecutive patients diagnosed with enterovirus 71 rhombencephalomyelitis complicated by left heart failure, with or without pulmonary edema, and surviving more than 3 months after receiving extracorporeal life support. Follow-up neurologic outcomes were analyzed prospectively. The median duration of neurologic follow-up was 7 years and 2 months. Significant morbidities included bulbar dysfunction, respiratory failure, and flaccid quadriparesis. Eight patients exhibited bulbar dysfunction, and feeding tubes could be removed from four patients (median, 15.5 months). Respiratory failure was observed in seven patients. Three patients were gradually withdrawn from their tracheostomy tube (median period, 30 months). Intelligence tests revealed four patients with normal cognitive function, one with borderline cognitive function, and one with mild mental retardation. Four were bedridden survivors. Extracorporeal life support for critical enterovirus 71 rhombencephalomyelitis demonstrated decreased neurologic sequelae during long-term follow-up, allowing for decannulation of feeding and tracheostomy tubes, and resulting in improved cognitive function. Copyright © 2012 Elsevier Inc. All rights reserved.

Malva Sylvestris Attenuates Cognitive Deficits in a Repetitive Mild Traumatic Brain Injury Rat Model by Reducing Neuronal Degeneration and Astrocytosis in the Hippocampus

PubMed Central

Qin, Hailin; Qin, Jie; Hu, Junmin; Huang, He; Ma, Lianting

2017-01-01

Background The aim of our study was to evaluate the effect of Malva sylvestris (MS) on cognitive dysfunction in a repetitive mild traumatic brain injury (MTBI). Material/Methods MTBI was induced in all the study animals by hitting a metallic pendulum near the parietal-occipital area of the skull three times a day for ten days. Animals were treated with MS (250 mg/kg and 500 mg/kg) intragastrically per day for seven consecutive days. Cognitive function was estimated by the Morris water maze (MWM) method. Histopathology studies were performed on the hippocampal region by Nissl staining and anti GFAP staining. Concentrations of reactive oxygen species (ROS), and oxidative parameters including superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPO), and inflammatory cytokines in the brain tissues were measured. Result Treatment with MS significantly improved cognitive function compared to the negative control. Histopathology studies suggested that treatment with MS significantly decreased (p<0.01) the count of neurodegenerative cells and induction of astrocytosis in the MTBI treated group compared to the negative control group. However, the concentrations of ROS and LPO, and the activities of SOD and CAT were significantly decreased in the MS treated groups of MTBI rats compared to the negative control group. Inflammatory cytokines, such as IL-1β, IL6, and TNF-α were significantly decreased (p<0.01) in the brain tissues of the MTBI treated group compared to the control group of rats. Conclusions This study concluded that treatment with MS significantly improved cognitive dysfunction by reducing neurodegeneration and astrocytosis in brain tissues via decreasing oxidative stress and inflammation in neuronal cells. PMID:29276216

Dysfunctional Incidental Olfaction in Mild Cognitive Impairment (MCI): An Electroencephalography (EEG) Study

PubMed Central

Walla, Peter; Duregger, Cornelia; Deecke, Lüder; Dal-Bianco, Peter

2011-01-01

Our study provides evidence that Mild Cognitive Impairment (MCI) is associated with olfactory dysfunction on both conscious and non-conscious levels. MCI patients and age-matched controls underwent a face processing task during which sympathy decisions had to be made via button presses. Incidentally, some of the faces were associated with a simultaneously presented odour. Although attention was paid to faces, brain activities were analysed with respect to odour versus no-odour conditions. Behavioural differences were found related to overall face recognition performance, but these were not statistically significant. However, odour-related neurophysiology differed between both groups. Normal controls demonstrated brain activity differences between odour and no-odour conditions that resemble difference activity patterns in healthy young participants as described in a previous magnetoencephalography (MEG) study [1]. They showed odour-related activity patterns between about 160 ms and 320 ms after stimulus onset and between about 640 ms and 720 ms. On the other hand, the patient group did not show any such difference activities. Based on previous research we interpret the early odour-related brain activity pattern in controls as being associated with subliminal olfaction and the later activity pattern with conscious olfaction. None of these were found in MCI patients, although it has to be emphasised that our sample size was rather small. We confirm previous findings about olfactory related dysfunction in patients with MCI and conclude from our findings that even subliminal odour-related information processing is impaired. PMID:24962612

Electrophysiological correlates of word recognition memory process in patients with ischemic left ventricular dysfunction.

PubMed

Giovannelli, Fabio; Simoni, David; Gavazzi, Gioele; Giganti, Fiorenza; Olivotto, Iacopo; Cincotta, Massimo; Pratesi, Alessandra; Baldasseroni, Samuele; Viggiano, Maria Pia

2016-09-01

The relationship between left ventricular ejection fraction (LVEF) and cognitive performance in patients with coronary artery disease without overt heart failure is still under debate. In this study we combine behavioral measures and event-related potentials (ERPs) to verify whether electrophysiological correlates of recognition memory (old/new effect) are modulated differently as a function of LVEF. Twenty-three male patients (12 without [LVEF>55%] and 11 with [LVEF<40%] left ventricular dysfunction), and a Mini Mental State Examination score >25 were enrolled. ERPs were recorded while participants performed an old/new visual word recognition task. A late positive ERP component between 350 and 550ms was differentially modulated in the two groups: a clear old/new effect (enhanced mean amplitude for old respect to new items) was observed in patients without LVEF dysfunction; whereas patients with overt LVEF dysfunction did not show such effect. In contrast, no significant differences emerged for behavioral performance and neuropsychological evaluations. These data suggest that ERPs may reveal functional brain abnormalities that are not observed at behavioral level. Detecting sub-clinical measures of cognitive decline may contribute to set appropriate treatments and to monitor asymptomatic or mildly symptomatic patients with LVEF dysfunction. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Regional neuronal network failure and cognition in late-onset sporadic Alzheimer disease.

PubMed

Carter, S F; Embleton, K V; Anton-Rodriguez, J M; Burns, A; Ralph, M A L; Herholz, K

2014-06-01

The severe cognitive deficits in Alzheimer disease are associated with structural lesions in gray and white matter in addition to changes in synaptic function. The current investigation studied the breakdown of the structure and function in regional networks involving the Papez circuit and extended neocortical association areas. Cortical volumetric and diffusion tensor imaging (3T MR imaging), positron-emission tomography with (18)F fluorodeoxyglucose on a high-resolution research tomograph, and comprehensive neuropsychological assessments were performed in patients with late-onset sporadic Alzheimer disease, those with mild cognitive impairment, and elderly healthy controls. Atrophy of the medial temporal lobes was the strongest and most consistent abnormality in patients with mild cognitive impairment and Alzheimer disease. Atrophy in the temporal, frontal, and parietal regions was most strongly related to episodic memory deficits, while deficits in semantic cognition were also strongly related to reductions of glucose metabolism in the posterior cingulate cortex and temporoparietal regions. Changes in fractional anisotropy within white matter tracts, particularly in the left cingulum bundle, uncinate fasciculus, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus, were significantly associated with the cognitive deficits in multiple regression analyses. Posterior cingulate and orbitofrontal metabolic deficits appeared to be related to microstructural changes in projecting white matter tracts. Many lesioned network components within the Papez circuit and extended neocortical association areas were significantly associated with cognitive dysfunction in both mild cognitive impairment and late-onset sporadic Alzheimer disease. Hippocampal atrophy was the most prominent lesion, with associated impairment of the uncinate and cingulum white matter microstructures and hippocampal and posterior cingulate metabolic impairment. © 2014 by American Journal of Neuroradiology.

Urine Metabonomics Reveals Early Biomarkers in Diabetic Cognitive Dysfunction.

PubMed

Song, Lili; Zhuang, Pengwei; Lin, Mengya; Kang, Mingqin; Liu, Hongyue; Zhang, Yuping; Yang, Zhen; Chen, Yunlong; Zhang, Yanjun

2017-09-01

Recently, increasing attention has been paid to diabetic encephalopathy, which is a frequent diabetic complication and affects nearly 30% of diabetics. Because cognitive dysfunction from diabetic encephalopathy might develop into irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. An ultra-high performance liquid-chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from diabetic mice that were associated with mild cognitive impairment (MCI) and nonassociated with MCI in the stage of diabetes (prior to the onset of DCD). We then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found that seven metabolites could be accepted as early biomarkers of DCD, and the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study first revealed reliable biomarkers for early diagnosis of DCD. It provides new insight and strategy for the early diagnosis and treatment of DCD.

Italian version of the Parkinson Neuropsychometric Dementia Assessment (PANDA): a useful instrument to detect cognitive impairments in Parkinson's Disease.

PubMed

Pignatti, Riccardo; Bertella, Laura; Scarpina, Federica; Mauro, Alessandro; Portolani, Elisa; Calabrese, Pasquale

2014-01-01

Parkinson's disease (PD) is frequently characterized by cognitive and affective dysfunctions. The "Parkinson Neuropsychometric Dementia Assessment" (PANDA) is a screening tool designed for the early detection of mild cognitive impairment as well as dementia in PD. The PANDA is already validated in German and in French. The aim of the present work was to provide normative data for the Italian-speaking population, Swiss regions included; moreover, the effectiveness of the PANDA compared to the Mini Mental State Examination (MMSE) was tested. One-hundred and eleven PD patients with and without cognitive impairment and one-hundred and three matched healthy subjects participated at this study; all patients underwent an extensive neuropsychological evaluation. A PANDA total score of 13 appeared to be the most fitting cut-off with a sensitivity of 96.6% and a specificity of 82.2%; with the MMSE, the same value of sensitivity but with a specificity of 72,4% was reached only by adopting a cut-off of 28. Moreover, a PANDA range of 13-17 appeared to be suggestive for possible cognitive disturbance. The present work provides evidence for the effectiveness of the PANDA in evaluating cognitive deficits also in PD Italian-speaking patients, even when their pathological degree is still initial or very mild.

Writing errors as a result of frontal dysfunction in Japanese patients with amyotrophic lateral sclerosis.

PubMed

Tsuji-Akimoto, Sachiko; Hamada, Shinsuke; Yabe, Ichiro; Tamura, Itaru; Otsuki, Mika; Kobashi, Syoji; Sasaki, Hidenao

2010-12-01

Loss of communication is a critical problem for advanced amyotrophic lateral sclerosis (ALS) patients. This loss of communication is mainly caused by severe dysarthria and disability of the dominant hand. However, reports show that about 50% of ALS patients have mild cognitive dysfunction, and there are a considerable number of case reports on Japanese ALS patients with agraphia. To clarify writing disabilities in non-demented ALS patients, eighteen non-demented ALS patients and 16 controls without neurological disorders were examined for frontal cognitive function and writing ability. To assess writing errors statistically, we scored them on their composition ability with the original writing error index (WEI). The ALS and control groups did not differ significantly with regard to age, years of education, or general cognitive level. Two patients could not write a letter because of disability of the dominant hand. The WEI and results of picture arrangement tests indicated significant impairment in the ALS patients. Auditory comprehension (Western Aphasia Battery; WAB IIC) and kanji dictation also showed mild impairment. Patients' writing errors consisted of both syntactic and letter-writing mistakes. Omission, substitution, displacement, and inappropriate placement of the phonic marks of kana were observed; these features have often been reported in Japanese patients with agraphia resulted from a frontal lobe lesion. The most frequent type of error was an omission of kana, the next most common was a missing subject. Writing errors might be a specific deficit for some non-demented ALS patients.

Learning temporal statistics for sensory predictions in mild cognitive impairment.

PubMed

Di Bernardi Luft, Caroline; Baker, Rosalind; Bentham, Peter; Kourtzi, Zoe

2015-08-01

Training is known to improve performance in a variety of perceptual and cognitive skills. However, there is accumulating evidence that mere exposure (i.e. without supervised training) to regularities (i.e. patterns that co-occur in the environment) facilitates our ability to learn contingencies that allow us to interpret the current scene and make predictions about future events. Recent neuroimaging studies have implicated fronto-striatal and medial temporal lobe brain regions in the learning of spatial and temporal statistics. Here, we ask whether patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) that are characterized by hippocampal dysfunction are able to learn temporal regularities and predict upcoming events. We tested the ability of MCI-AD patients and age-matched controls to predict the orientation of a test stimulus following exposure to sequences of leftwards or rightwards orientated gratings. Our results demonstrate that exposure to temporal sequences without feedback facilitates the ability to predict an upcoming stimulus in both MCI-AD patients and controls. However, our fMRI results demonstrate that MCI-AD patients recruit an alternate circuit to hippocampus to succeed in learning of predictive structures. In particular, we observed stronger learning-dependent activations for structured sequences in frontal, subcortical and cerebellar regions for patients compared to age-matched controls. Thus, our findings suggest a cortico-striatal-cerebellar network that may mediate the ability for predictive learning despite hippocampal dysfunction in MCI-AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Developing physician consensus on the reporting of patients with mild cognitive impairment and mild dementia to transportation authorities in a region with mandatory reporting legislation.

PubMed

Rapoport, Mark J; Naglie, Gary; Herrmann, Nathan; Zucchero Sarracini, Carla; Mulsant, Benoit H; Frank, Christopher; Kiss, Alex; Seitz, Dallas; Vrkljan, Brenda; Masellis, Mario; Tang-Wai, David; Pimlott, Nicholas; Molnar, Frank

2014-12-01

To establish consensus among dementia experts about which patients with mild cognitive impairment (MCI) or mild dementia should be reported to transportation authorities. We conducted a literature review of predictors of driving safety in patients with dementia and combined these into 26 case scenarios. Using a modified Delphi technique, case scenarios were reviewed by 38 dementia experts (geriatric psychiatrists, geriatricians, cognitive neurologists and family physicians with expertise in elder care) who indicated whether or not they would report the patient in each scenario to regional transportation authorities and recommend a specialized on-road driving test. Scenarios were presented up to five times to achieve consensus, defined as 85% agreement, and discrepancies were discussed anonymously online. By the end of the fifth iteration, there was cumulative consensus on 18 scenarios (69%). The strongest predictors of decision to report were the combination of caregiver concern about the patient's driving and abnormal Clock Drawing Test, which accounted for 62% of the variance in decision to report at the same time as or without a road test (p <0.01). Based on these data, an algorithm was developed to guide physician decision-making about reporting patients with MCI or mild dementia to transportation authorities. This study supports existing international guidelines that recommend specialized on-road testing when driving safety is uncertain for patients with MCI and emphasizes the importance of assessing executive dysfunction and caregiver concern about driving. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Riser Blood Pressure Pattern Is Associated With Mild Cognitive Impairment in Heart Failure Patients.

PubMed

Komori, Takahiro; Eguchi, Kazuo; Saito, Toshinobu; Nishimura, Yoshioki; Hoshide, Satoshi; Kario, Kazuomi

2016-02-01

The riser pattern, an abnormal blood pressure (BP) rhythm in which sleep BP exceeds awake BP, is a predictor of future stroke events. Although the riser pattern is caused by autonomic dysfunction, its significance in heart failure (HF) patients is not established. HF patients often suffered from cognitive impairment (CI), but the relationship between riser pattern and CI is not clearly understood. We tested the hypothesis that the riser pattern is associated with mild CI, a form of brain damage that could develop to dementia. We performed Mini-Mental State Examination (MMSE), ambulatory BP monitoring (ABPM), echocardiography, and blood tests in 444 HF patients just before leaving hospitals. Mild CI, a measure of cognitive function, was defined as the score <26. The mean age of the patients was 68±13 years; 61.5% were male; 22.5% were riser pattern. The MMSE score was significantly lower in the Riser group than in the Non-dipper and Dipper group (23±4 vs. 25±5, 26±4, respectively, P < 0.01). In multivariable logistic regression analysis, a riser pattern was significantly associated with mild CI (odds ratio 2.38, 95% confidence intervals 1.29-4.42, P < 0.01) after adjusting for significant covariates. The riser pattern was associated with mild CI in HF patients. An abnormal circadian BP rhythm in HF patients is clinically significant as a potential indicator of subclinical brain damage. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Early diagnosis of Alzheimer's disease and Parkinson's disease associated with dementia using cerebral perfusion SPECT.

PubMed

Song, In-Uk; Chung, Yong-An; Chung, Sung-Woo; Jeong, Jaeseung

2014-01-01

Since patterns of cognitive dysfunction in mild Parkinson's disease associated with dementia (PDD) are similar to those in mild Alzheimer's disease (AD), it is difficult to accurately differentiate between these two types of dementia in their early phases using neuropsychological tests. The purpose of the current study was to investigate differences in cerebral perfusion patterns of patients with AD and PDD at the earliest stages using single photon emission computed tomography (SPECT). We consecutively recruited 31 patients with mild PDD, 32 patients with mild probable AD and 33 age-matched healthy subjects. All subjects underwent (99m)Tc-hexamethylpropyleneamine oxime perfusion SPECT and completed general neuropsychological tests. We found that both mild PDD and AD patients showed distinct hypoperfusion in frontal, parietal and temporal regions, compared with healthy subjects. More importantly, hypoperfusion in occipital and cerebellar regions was observed only in mild PDD. The observation of a significant decrease in cerebral perfusion in occipital and cerebellar regions in patients with mild PDD is likely useful to differentiate between PDD and AD at the earliest stages. © 2013 S. Karger AG, Basel.

Neurocognitive Dysfunction in Systemic Lupus Erythematosus: Association with Antiphospholipid Antibodies, Disease Activity and Chronic Damage

PubMed Central

Conti, Fabrizio; Alessandri, Cristiano; Perricone, Carlo; Scrivo, Rossana; Rezai, Soheila; Ceccarelli, Fulvia; Spinelli, Francesca Romana; Ortona, Elena; Marianetti, Massimo; Mina, Concetta; Valesini, Guido

2012-01-01

Introduction Systemic lupus erythematosus (SLE) is characterized by frequent neuropsychiatric involvement, which includes cognitive impairment (CI). We aimed at assessing CI in a cohort of Italian SLE patients by using a wide range of neurocognitive tests specifically designed to evaluate the fronto-subcortical dysfunction. Furthermore, we aimed at testing whether CI in SLE is associated with serum autoantibodies, disease activity and chronic damage. Methods Fifty-eight consecutive patients were enrolled. Study protocol included data collection, evaluation of serum levels of ANA, anti-dsDNA, anti-cardiolipin, anti-β2-glycoprotein I, anti-P ribosomal, anti-endothelial cell, and anti-Nedd5 antibodies. SLEDAI-2000 and SLICC were used to assess disease activity and chronic damage. Patients were administered a test battery specifically designed to detect fronto-subcortical dysfunction across five domains: memory, attention, abstract reasoning, executive function and visuospatial function. For each patient, the raw scores from each test were compared with published norms, then transformed into Z scores (deviation from normal mean), and finally summed in the Global Cognitive Dysfunction score (GCDs). Results Nineteen percent of patients had mild GCDs impairment (GCDs 2–3), 7% moderate (GCDs 4–5) and 5% severe (GCDs≥6). The visuospatial domain was the most compromised (MDZs = −0.89±1.23). Anti-cardiolipin IgM levels were associated with visuospatial domain impairment (r = 0.331, P = 0.005). SLEDAI correlated with GCDs, and attentional and executive domains; SLICC correlated with GCDs, and with visuospatial and attentional domains impairment. Conclusions Anti-phospholipids, disease activity, and chronic damage are associated with cognitive dysfunction in SLE. The use of a wide spectrum of tests allowed for a better selection of the relevant factors involved in SLE cognitive dysfunction, and standardized neuropsychological testing methods should be used for routine assessment of SLE patients. PMID:22461897

FGF21 Attenuates High-Fat Diet-Induced Cognitive Impairment via Metabolic Regulation and Anti-inflammation of Obese Mice.

PubMed

Wang, Qingzhi; Yuan, Jing; Yu, Zhanyang; Lin, Li; Jiang, Yinghua; Cao, Zeyuan; Zhuang, Pengwei; Whalen, Michael J; Song, Bo; Wang, Xiao-Jie; Li, Xiaokun; Lo, Eng H; Xu, Yuming; Wang, Xiaoying

2018-06-01

Accumulating studies suggest that overnutrition-associated obesity may lead to development of type 2 diabetes mellitus and metabolic syndromes (MetS). MetS and its components are important risk factors of mild cognitive impairment, age-related cognitive decline, vascular dementia, and Alzheimer's disease. It has been recently proposed that development of a disease-course modification strategy toward early and effective risk factor management would be clinically significant in reducing the risk of metabolic disorder-initiated cognitive decline. In the present study, we propose that fibroblast growth factor 21 (FGF21) is a novel candidate for the disease-course modification approach. Using a high-fat diet (HFD) consumption-induced obese mouse model, we tested our hypothesis that recombinant human FGF21 (rFGF21) administration is effective for improving obesity-induced cognitive dysfunction and anxiety-like behavior, by its multiple metabolic modulation and anti-pro-inflammation actions. Our experimental findings support our hypothesis that rFGF21 is protective to HFD-induced cognitive impairment, at least in part by metabolic regulation in glucose tolerance impairment, insulin resistance, and hyperlipidemia; potent systemic pro-inflammation inhibition; and improvement of hippocampal dysfunction, particularly by inhibiting pro-neuroinflammation and neurogenesis deficit. This study suggests that FGF21 might be a novel molecular target of the disease-course-modifying strategy for early intervention of MstS-associated cognitive decline.

Executive Dysfunctions Predict Self-Restricted Driving Habits in Elderly People with or without Alzheimer's Dementia.

PubMed

Kurzthaler, Ilsemarie; Kemmler, Georg; Defrancesco, Michaela; Moser, Bernadette; Fleischhacker, Wolfgang W; Weiss, Elisabeth M

2017-09-01

Introduction The purpose of this study was to elucidate the impact of specific cognitive functions on self-restricted driving habits in healthy elderly drivers and patients suffering from mild cognitive impairment (MCI) and Alzheimer's dementia (AD). Method Our study population included 35 cognitively healthy controls, 10 MCI patients, and 16 patients with AD. All participants completed a neuropsychological examination and a self-reported questionnaire assessing driving habits and patterns. Results In challenging driving conditions, patients with MCI or AD showed significantly more driving self-restriction than healthy subjects (effect size d=1.06, p=0.007). Ordinal regression analysis across the entire group revealed that deficits in executive functions and reaction had a higher impact on driving restriction (p=0.002) than deficits in memory functions (p=0.570). Additionally, our data showed that 40% of patients with mild to moderate AD still drive in challenging conditions. Discussion Our results illustrate that elderly individuals use self-imposed driving restrictions as compensatory strategies. These restrictions increase with cognitive decline mainly in the field of executive functions, but they do not change once patients convert from MCI to AD. © Georg Thieme Verlag KG Stuttgart · New York.

Toward systems neuroscience in mild cognitive impairment and Alzheimer's disease: a meta-analysis of 75 fMRI studies.

PubMed

Li, Hui-Jie; Hou, Xiao-Hui; Liu, Han-Hui; Yue, Chun-Lin; He, Yong; Zuo, Xi-Nian

2015-03-01

Most of the previous task functional magnetic resonance imaging (fMRI) studies found abnormalities in distributed brain regions in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and few studies investigated the brain network dysfunction from the system level. In this meta-analysis, we aimed to examine brain network dysfunction in MCI and AD. We systematically searched task-based fMRI studies in MCI and AD published between January 1990 and January 2014. Activation likelihood estimation meta-analyses were conducted to compare the significant group differences in brain activation, the significant voxels were overlaid onto seven referenced neuronal cortical networks derived from the resting-state fMRI data of 1,000 healthy participants. Thirty-nine task-based fMRI studies (697 MCI patients and 628 healthy controls) were included in MCI-related meta-analysis while 36 task-based fMRI studies (421 AD patients and 512 healthy controls) were included in AD-related meta-analysis. The meta-analytic results revealed that MCI and AD showed abnormal regional brain activation as well as large-scale brain networks. MCI patients showed hypoactivation in default, frontoparietal, and visual networks relative to healthy controls, whereas AD-related hypoactivation mainly located in visual, default, and ventral attention networks relative to healthy controls. Both MCI-related and AD-related hyperactivation fell in frontoparietal, ventral attention, default, and somatomotor networks relative to healthy controls. MCI and AD presented different pathological while shared similar compensatory large-scale networks in fulfilling the cognitive tasks. These system-level findings are helpful to link the fundamental declines of cognitive tasks to brain networks in MCI and AD. © 2014 Wiley Periodicals, Inc.

Measuring illness insight in patients with alcohol-related cognitive dysfunction using the Q8 questionnaire: a validation study

PubMed Central

Walvoort, Serge JW; van der Heijden, Paul T; Kessels, Roy PC; Egger, Jos IM

2016-01-01

Aim Impaired illness insight may hamper treatment outcome in patients with alcohol-related cognitive deficits. In this study, a short questionnaire for the assessment of illness insight (eg, the Q8) was investigated in patients with Korsakoff’s syndrome (KS) and in alcohol use disorder (AUD) patients with mild neurocognitive deficits. Methods First, reliability coefficients were computed and internal structure was investigated. Then, comparisons were made between patients with KS and patients with AUD. Furthermore, correlations with the Dysexecutive Questionnaire (DEX) were investigated. Finally, Q8 total scores were correlated with neuropsychological tests for processing speed, memory, and executive function. Results Internal consistency of the Q8 was acceptable (ie, Cronbach’s α =0.73). The Q8 items represent one factor, and scores differ significantly between AUD and KS patients. The Q8 total score, related to the DEX discrepancy score and scores on neuropsychological tests as was hypothesized, indicates that a higher degree of illness insight is associated with a higher level of cognitive functioning. Conclusion The Q8 is a short, valid, and easy-to-administer questionnaire to reliably assess illness insight in patients with moderate-to-severe alcohol-related cognitive dysfunction. PMID:27445476

White matter lesions and the cholinergic deficit in aging and mild cognitive impairment.

PubMed

Richter, Nils; Michel, Anne; Onur, Oezguer A; Kracht, Lutz; Dietlein, Markus; Tittgemeyer, Marc; Neumaier, Bernd; Fink, Gereon R; Kukolja, Juraj

2017-05-01

In Alzheimer's disease (AD), white matter lesions (WMLs) are associated with an increased risk of progression from mild cognitive impairment (MCI) to dementia, while memory deficits have, at least in part, been linked to a cholinergic deficit. We investigated the relationship between WML load assessed with the Scheltens scale, cerebral acetylcholinesterase (AChE) activity measured with [ 11 C]N-methyl-4-piperidyl acetate PET, and neuropsychological performance in 17 patients with MCI due to AD and 18 cognitively normal older participants. Only periventricular, not nonperiventricular, WML load negatively correlated with AChE activity in both groups. Memory performance depended on periventricular and total WML load across groups. Crucially, AChE activity predicted memory function better than WML load, gray matter atrophy, or age. The effects of WML load on memory were fully mediated by AChE activity. Data suggest that the contribution of WML to the dysfunction of the cholinergic system in MCI due to AD depends on WML distribution. Pharmacologic studies are warranted to explore whether this influences the response to cholinergic treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal

PubMed Central

Ries, Michele L.; Jabbar, Britta M.; Schmitz, Taylor W.; Trivedi, Mehul A.; Gleason, Carey E.; Carlsson, Cynthia M.; Rowley, Howard A.; Asthana, Sanjay; Johnson, Sterling C.

2009-01-01

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer’s disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants’ activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly-significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD. PMID:17445294

The Role of Executive Control and Readiness to Change in Problematic Drinkers with Mild to Borderline Intellectual Disability.

PubMed

van Duijvenbode, Neomi; Didden, Robert; Korzilius, Hubert P L M; Engels, Rutger C M E

2017-09-01

Problematic alcohol use is associated with neuropsychological consequences, including cognitive biases. The goal of the study was to explore the moderating role of executive control and readiness to change on the relationship between alcohol use and cognitive biases in light and problematic drinkers with and without mild to borderline intellectual disability (MBID). Participants (N = 112) performed the visual dot probe task to measure the strength of the cognitive biases. Executive control was measured using two computerised tasks for working memory capacity (Corsi block-tapping task) and inhibitory control (Go/No-go task). Readiness to change was measured using the Readiness to Change Questionnaire. No cognitive biases or executive dysfunctions were found in problematic drinkers. Working memory capacity and inhibitory control were impaired among individuals with MBID, irrespective of severity of alcohol use-related problems. Executive control and readiness to change did not moderate the relationship between alcohol use and cognitive biases. The results fail to support the dual-process models of addiction, but results need to be treated with caution given the problematic psychometric qualities of the visual dot probe task. Implementing a neurocognitive assessment and protocols in the treatment of substance use disorders seems premature. © 2016 John Wiley & Sons Ltd.

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.

Treating attention in mild aphasia: evaluation of attention process training-II.

PubMed

Murray, Laura L; Keeton, R Jessica; Karcher, Laura

2006-01-01

This study examined whether attention processing training-II [Sohlberg, M. M., Johnson, L., Paule, L., Raskin, S. A., & Mateer, C. A. (2001). Attention Process Training-II: A program to address attentional deficits for persons with mild cognitive dysfunction (2nd ed.). Wake Forest, NC: Lash & Associates.; APT-II], when applied in the context of a multiple baseline ABA design, would improve the attention abilities of RW, a patient with mild conduction aphasia and concomitant attention and working memory deficits. We also explored whether APT-II training would enhance RW's auditory comprehension, other cognitive abilities such as memory, and his and his spouse's perceptions of his daily attention and communication difficulties. With treatment, RW improved on trained attention tasks and made modest gains on standardized tests and probes that evaluated cognitive skills related to treatment activities. Nominal change in auditory comprehension and untrained attention and memory functions was observed, and neither RW nor his spouse reported noticeable improvements in his daily attention or communication abilities. These and previous findings indicate that structured attention retraining may enhance specific attention skills, but that positive changes in broader attention and untrained functions are less likely. As a result of reading this article, the participant will be able to: (1) summarize the previous literature regarding attention impairments and treatment approaches for patients with aphasia. (2) describe how Attention Processing Training-II affected the attention, auditory comprehension, and other cognitive abilities of the patient in this study.

Cognitive processes and attitudes in bipolar disorder: a study into personality, dysfunctional attitudes and attention bias in patients with bipolar disorder and their relatives.

PubMed

Jabben, Nienke; Arts, Baer; Jongen, Ellen M M; Smulders, Fren T Y; van Os, Jim; Krabbendam, Lydia

2012-12-20

Research in cognitive processes and attitudes in bipolar disorder is scarce and has provided mixed findings, possibly due to differences in current mood state. It is unclear whether alterations in cognitive processes and attitudes are only related to the depressive mood states of bipolar patients or also represent a vulnerability marker for the development of future (depressive) episodes. This was investigated in the current study. Both implicit (attentional bias for emotional words) and explicit (dysfunctional attitudes and personality characteristics) measures of cognitive processes and attitudes were assessed in 77 bipolar patients with varying levels of depressive symptoms (depressed=17, euthymic n=60), their healthy first-degree relatives (n=39) and a healthy control group (n=61). Analyses of variance were used to investigate differences between groups. Mildly depressed patients with bipolar disorder demonstrated an attentional bias away from positive emotional words and showed increased dysfunctional attitudes and higher levels of neuroticism. Euthymic patients were largely comparable to healthy controls and only differed from controls in higher levels of neuroticism. Relatives were similar to controls on all measures, although they significantly differed from bipolar patients in displaying less neuroticism and more extraversion. No firm conclusions regarding causality can be drawn from the associations that were found between cognitive processes and attitudes and the evolution of mood symptoms in bipolar disorder. Alterations in cognitive processes and attitudes in bipolar patients appear to be mostly related to the expression of mood symptomatology rather than to the vulnerability for bipolar disorder. Copyright © 2012 Elsevier B.V. All rights reserved.

Cognitive Function Among Obstructive Sleep Apnea Patients in North East Malaysia.

PubMed

Yusop, Che Yusfarina Che; Mohamad, Irfan; Mohammad, Wan Mohd Zahiruddin Wan; Abdullah, Baharudin

2017-01-01

Obstructive sleep apnea patients may develop deficits in the cognitive domains of attention, concentration, executive function, verbal and visuospatial memory, constructional abilities, and psychomotor functioning. As cognitive performance will improve with the treatment, early screening for cognitive dysfunction should be done to prevent further deterioration. We aim to evaluate the cognitive function of obstructive sleep apnea patients by using the 'Mini Mental State Examination'. This was a cross sectional study to evaluate the cognitive function of moderate and severe obstructive sleep apnea patients with age ranged from 18 to 60 old who attended our sleep clinic. These patients were confirmed to have moderate and severe obstructive sleep apnea by Type 1 polysomnography (attended full overnight study). The age, gender and ethnicity were noted and other relevant data such as weight, height, body mass index and apnea and hypopnoea index were recorded accordingly. The cognitive function was evaluated using validated Malay version of Mini Mental State Examination which measured 5 areas of cognitive functions comprising orientation, registration, attention and calculation, word recall and language abilities, and visuospatial. A total of 38 patients participated in this study. All 19 patients of moderate group and 14 patients of severe group had normal cognitive function while only 5 patients in severe group had mild cognitive function impairment. There was a statistically significant difference between the moderate group and severe group on cognitive performance (p value = 0.042). Severe obstructive sleep apnea patients may have impaired cognitive function. Mini Mental State Examination is useful in the screening of cognitive function of obstructive sleep apnea patients but in normal score, more sophisticated test batteries are required as it is unable to identify in 'very minimal' or 'extremely severe' cognitive dysfunction. Copyright © 2017 National Medical Association. Published by Elsevier Inc. All rights reserved.

Insulin dysfunction and Tau pathology.

PubMed

El Khoury, Noura B; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

2014-01-01

The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia.

Insulin dysfunction and Tau pathology

PubMed Central

El Khoury, Noura B.; Gratuze, Maud; Papon, Marie-Amélie; Bretteville, Alexis; Planel, Emmanuel

2013-01-01

The neuropathological hallmarks of Alzheimer's disease (AD) include senile plaques of β-amyloid (Aβ) peptides (a cleavage product of the Amyloid Precursor Protein, or APP) and neurofibrillary tangles (NFT) of hyperphosphorylated Tau protein assembled in paired helical filaments (PHF). NFT pathology is important since it correlates with the degree of cognitive impairment in AD. Only a small proportion of AD is due to genetic variants, whereas the large majority of cases (~99%) is late onset and sporadic in origin. The cause of sporadic AD is likely to be multifactorial, with external factors interacting with biological or genetic susceptibilities to accelerate the manifestation of the disease. Insulin dysfunction, manifested by diabetes mellitus (DM) might be such factor, as there is extensive data from epidemiological studies suggesting that DM is associated with an increased relative risk for AD. Type 1 diabetes (T1DM) and type 2 diabetes (T2DM) are known to affect multiple cognitive functions in patients. In this context, understanding the effects of diabetes on Tau pathogenesis is important since Tau pathology show a strong relationship to dementia in AD, and to memory loss in normal aging and mild cognitive impairment. Here, we reviewed preclinical studies that link insulin dysfunction to Tau protein pathogenesis, one of the major pathological hallmarks of AD. We found more than 30 studies reporting Tau phosphorylation in a mouse or rat model of insulin dysfunction. We also payed attention to potential sources of artifacts, such as hypothermia and anesthesia, that were demonstrated to results in Tau hyperphosphorylation and could major confounding experimental factors. We found that very few studies reported the temperature of the animals, and only a handful did not use anesthesia. Overall, most published studies showed that insulin dysfunction can promote Tau hyperphosphorylation and pathology, both directly and indirectly, through hypothermia. PMID:24574966

Undetected cognitive impairment and decision-making capacity in patients receiving hospice care.

PubMed

Burton, Cynthia Z; Twamley, Elizabeth W; Lee, Lana C; Palmer, Barton W; Jeste, Dilip V; Dunn, Laura B; Irwin, Scott A

2012-04-01

: Cognitive dysfunction is common in patients with advanced, life-threatening illness and can be attributed to a variety of factors (e.g., advanced age, opiate medication). Such dysfunction likely affects decisional capacity, which is a crucial consideration as the end-of-life approaches and patients face multiple choices regarding treatment, family, and estate planning. This study examined the prevalence of cognitive impairment and its impact on decision-making abilities among hospice patients with neither a chart diagnosis of a cognitive disorder nor clinically apparent cognitive impairment (e.g., delirium, unresponsiveness). : A total of 110 participants receiving hospice services completed a 1-hour neuropsychological battery, a measure of decisional capacity, and accompanying interviews. : In general, participants were mildly impaired on measures of verbal learning, verbal memory, and verbal fluency; 54% of the sample was classified as having significant, previously undetected cognitive impairment. These individuals performed significantly worse than the other participants on all neuropsychological and decisional capacity measures, with effect sizes ranging from medium to very large (0.43-2.70). A number of verbal abilities as well as global cognitive functioning significantly predicted decision-making capacity. : Despite an absence of documented or clinically obvious impairment, more than half of the sample had significant cognitive impairments. Assessment of cognition in hospice patients is warranted, including assessment of verbal abilities that may interfere with understanding or reasoning related to treatment decisions. Identification of patients at risk for impaired cognition and decision making may lead to effective interventions to improve decision making and honor the wishes of patients and families.

School and the Concussed Youth – Recommendations for Concussion Education and Management

PubMed Central

Sady, Maegan D.; Vaughan, Christopher G.; Gioia, Gerard A.

2011-01-01

Synopsis School learning and performance is arguably the critical centerpiece of child and adolescent development, and there can be significant temporary upset in cognitive processing after a mild traumatic brain injury, also called a concussion. This injury results in a cascade of neurochemical abnormalities, and in the wake of this dysfunction, both physical activity and cognitive activity become sources of additional neurometabolic demand on the brain and may cause symptoms to re-emerge or worsen. This paper provides a foundation for post-injury management of cognitive activity, particularly in the school setting, including design and implementation of school-wide concussion education and management programs. Definitions of cognitive over-exertion and cognitive rest are provided, with guidelines for managing cognitive load in individuals based on their symptom profile and neurocognitive performance. On a broader scale, guidance for the development of comprehensive concussion education and management programs in schools is provided. Proactive management could facilitate recovery by ensuring less cognitive exertion and stress during the recovery period. PMID:22050944

Brain and Plasma Molecular Characterization of the Pathogenic TBI-AD Interrelationship in Mouse Models

DTIC Science & Technology

2015-10-01

collegiate football players: the NCAA Concussion Study. JAMA 290, 2549-2555. Hinkebein, J.H., Martin, T.A., Callahan, C.D., and Johnstone, B. (2003). Concept...al., 2014). We have also developed a novel mouse model of mild TBI (mTBI)/ concussion in which we have demonstrated cognitive dysfunction at 6, 12...2010). Boxing-acute complications and late sequelae: from concussion to dementia. Dtsch Arztebl Int 107, 835-839. Gaetz, M., and Weinberg, H

Cerebrovascular regulation, exercise, and mild traumatic brain injury

PubMed Central

Meehan, William P.; Iverson, Grant L.; Taylor, J. Andrew

2014-01-01

A substantial number of people who sustain a mild traumatic brain injury report persistent symptoms. Most common among these symptoms are headache, dizziness, and cognitive difficulties. One possible contributor to sustained symptoms may be compromised cerebrovascular regulation. In addition to injury-related cerebrovascular dysfunction, it is possible that prolonged rest after mild traumatic brain injury leads to deconditioning that may induce physiologic changes in cerebral blood flow control that contributes to persistent symptoms in some people. There is some evidence that exercise training may reduce symptoms perhaps because it engages an array of cerebrovascular regulatory mechanisms. Unfortunately, there is very little work on the degree of impairment in cerebrovascular control that may exist in patients with mild traumatic brain injury, and there are no published studies on the subacute phase of recovery from this injury. This review aims to integrate the current knowledge of cerebrovascular mechanisms that might underlie persistent symptoms and seeks to synthesize these data in the context of exploring aerobic exercise as a feasible intervention to treat the underlying pathophysiology. PMID:25274845

Emotion recognition in mild cognitive impairment: relationship to psychosocial disability and caregiver burden.

PubMed

McCade, Donna; Savage, Greg; Guastella, Adam; Hickie, Ian B; Lewis, Simon J G; Naismith, Sharon L

2013-09-01

Impaired emotion recognition in dementia is associated with increased patient agitation, behavior management difficulties, and caregiver burden. Emerging evidence supports the presence of very early emotion recognition difficulties in mild cognitive impairment (MCI); however, the relationship between these impairments and psychosocial measures is not yet explored. Emotion recognition abilities of 27 patients with nonamnestic MCI (naMCI), 29 patients with amnestic MCI (aMCI), and 22 control participants were assessed. Self-report measures assessed patient functional disability, while informants rated the degree of burden they experienced. Difficulties in recognizing anger was evident in the amnestic subtype. Although both the patient groups reported greater social functioning disability, compared with the controls, a relationship between social dysfunction and anger recognition was evident only for patients with naMCI. A significant association was found between burden and anger recognition in patients with aMCI. Impaired emotion recognition abilities impact MCI subtypes differentially. Interventions targeted at patients with MCI, and caregivers are warranted.

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.

Consequences of Traumatic Brain Injury in Professional American Football Players: A Systematic Review of the Literature.

PubMed

Vos, Bodil C; Nieuwenhuijsen, Karen; Sluiter, Judith K

2018-03-01

The purpose of this study was to systematically review the literature for the consequences Traumatic brain injury (TBI) has on cognitive, psychological, physical, and sports-related functioning in professional American Football players. We performed a systematic search in 2 databases, PubMed and SPORTDiscus, to obtain literature from January 1990 to January 2015. To be eligible for inclusion, a study had to examine the relationship between TBI and the consequences for several aspects of functioning in professional American football players older than 18 years. Methodological quality was assessed using a 5-item checklist which assessed selection bias, information bias, and correct reporting of the population and exposure characteristics. The search yielded 21 studies that met our inclusion criteria. An evidence synthesis was performed on the extracted data and resulted in 5 levels of evidence. The evidence synthesis revealed that there is strong evidence that concussions are associated with late-life depression and short-term physical dysfunctions. Evidence for the relationship between concussion and impaired sports-related function, prolonged reaction time, memory impairment, and visual-motor speed was inconclusive. Moderate evidence was found for the association between TBI and mild cognitive impairment (MCI), and limited evidence was found for the association between TBI and executive dysfunction. There is strong evidence that a history of concussion in American football players is associated with depression later in life and short-term physical dysfunctions. Also cognitive dysfunctions such as MCI are seen in older players with a history of TBI. These results provide input for actions to prevent TBI and their consequences in (retired) American football players.

[A case of neuro-neutrophilic disease presenting with 5 months' with cognitive decline, meningoencephalitis, and marked systemic inflammatory findings, and diagnosed with brain biopsy].

PubMed

Ohe, Yasuko; Nakazato, Yoshihiko; Ishizawa, Keisuke; Deguchi, Ichiro; Tamura, Naotoshi; Araki, Nobuo

2011-01-01

A 63-year-old man was admitted to our hospital with cognitive decline. On admission, he had a fever and mild cognitive dysfunction, suggesting chronic meningoencephalitis. Apart from a mild increase in serum C-reactive protein level and marked neutrophilia, laboratory findings were unremarkable. Brain magnetic resonance (MR) imaging showed multiple small T2-hyperintense lesions in the white matter. Systemic evaluations for infectious organisms, autoantibodies, and malignancy were all negative. For 5 months we conducted therapeutic trials of various antibacterial, antifungal, and antituberculous drugs, but these were completely ineffective, and both meningoencephalitis and inflammatory signs persisted. Repeated brain MRI during the clinical course showed growth of the white matter lesions and progressive cerebral atrophy. C11-methionine positron emission tomography demonstrated a bright focus in the right frontal lobe, and this was biopsied. Key neuropathological findings were neutrophilic infiltration in the subarachnoid space and the frontal lobe without necrotic angiitis. These findings confirmed the diagnosis of neuro-neutrophilic disease, although skin tissue findings characteristic of Sweet disease and a B51, B54, or Cw1 HLA-profile were absent. After intravenous bolus administration of steroid and prolonged oral steroid therapy, fever and inflammatory signs diminished and cognitive symptoms improved.

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.

Physical Exercise And Cognitive Engagement Outcomes for Mild Neurocognitive Disorder

ClinicalTrials.gov

2018-03-21

Mild Cognitive Impairment; Memory Disorders; Mild Dementia; Impaired Cognition; Mild Cognitive Disorder; Amnestic Disorder; Dementia and Amnestic Conditions; Poor Short-term Memory; Memory Impairment; Mild Neurocognitive Disorder

[Stress and coping with stress by mothers of children with mild cerebral dysfunctions].

PubMed

Virtanen, T; Moilanen, I

1991-09-01

Adapting the paradigm developed by Richard Lazarus, parenting stress and coping were studied among mothers of children (n = 42) with Minimal Brain Dysfunction (MBD) and mothers with non-disabled children (n = 42), aged 6 to 9. The children of control mothers were matched by age, sex, social status, and maternal marital status with the MBD children. The mothers of MBD children were found to experience more parenting difficulties, more negatively toned cognitive appraisals of their stakes in parenting and less positive adaptational outcomes than their controls. The mothers of MBD children appraised their mastery lower than their controls. However, family well-being, or self-esteem did not differ between the mothers of MBD children and their controls.

Deficits of spatial and task-related attentional selection in mild cognitive impairment and Alzheimer's disease.

PubMed

Redel, P; Bublak, P; Sorg, C; Kurz, A; Förstl, H; Müller, H J; Schneider, W X; Perneczky, R; Finke, K

2012-01-01

Visual selective attention was assessed with a partial-report task in patients with probable Alzheimer's disease (AD), amnestic mild cognitive impairment (MCI), and healthy elderly controls. Based on Bundesen's "theory of visual attention" (TVA), two parameters were derived: top-down control of attentional selection, representing task-related attentional weighting for prioritizing relevant visual objects, and spatial distribution of attentional weights across the left and the right hemifield. Compared with controls, MCI patients showed significantly reduced top-down controlled selection, which was further deteriorated in AD subjects. Moreover, attentional weighting was significantly unbalanced across hemifields in MCI and tended to be more lateralized in AD. Across MCI and AD patients, carriers of the apolipoprotein E ε4 allele (ApoE4) displayed a leftward spatial bias, which was the more pronounced the younger the ApoE4-positive patients and the earlier disease onset. These results indicate that impaired top-down control may be linked to early dysfunction of fronto-parietal networks. An early temporo-parietal interhemispheric asymmetry might cause a pathological spatial bias which is associated with ApoE4 genotype and may therefore function as early cognitive marker of upcoming AD. Copyright © 2012 Elsevier Inc. All rights reserved.

Bihemispheric cerebral FDG PET correlates of cognitive dysfunction as assessed by the CERAD in Alzheimer's disease.

PubMed

Schönknecht, Oskar Dieter Peter; Hunt, Aoife; Toro, Pablo; Guenther, Thomas; Henze, Marcus; Haberkorn, Uwe; Schröder, Johannes

2011-04-01

Alzheimer's disease (AD) is characterized by a variety of cognitive deficits which can be reliably assessed by the neuropsychological test battery of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), but the cerebral changes underlying the respective cognitive deficits are only partly understood. Measures of severity of dementia in AD as well as delayed episodic memory performance in mild cognitive impairment significantly correlated with bihemispheric cerebral glucose hypometabolism. We therefore hypothesized that the CERAD cognitive battery may represent cerebral dysfunction of both hemispheres in patients with AD. In 32 patients with AD, cerebral glucose metabolism was investigated using positron-emission-tomography with 18Fluorodeoxyglucose (FDG PET) and associated with the test scores of the CERAD cognitive battery by statistical parametric mapping. Episodic memory scores significantly correlated with temporopari etal glucose metabolism of both hemispheres while delayed episodic memory significantly was correlated with the right frontotemporal cortices. Verbal fluency and naming scores significantly correlated with glucose metabolism in left temporoparietal and right frontal cortices, whereas constructional praxis predominantly correlated significantly with the bilateral precuneus. In conclusion, the results of our study demonstrate that not only memory function but also functions of language and constructional praxis in AD are associated with glucose metabolism as revealed by FDG PET in subsets of uni- and bilateral brain areas. The findings of our study for the first time demonstrate that in AD neuropsychological deficits as assessed by the CERAD refer to different cerebral sites of both hemispheres.

Contributions to Executive Dysfunction in Operation Enduring Freedom/Operation Iraqi Freedom Veterans With Posttraumatic Stress Disorder and History of Mild Traumatic Brain Injury.

PubMed

Jurick, Sarah M; Crocker, Laura D; Sanderson-Cimino, Mark; Keller, Amber V; Trenova, Liljana S; Boyd, Briana L; Twamley, Elizabeth W; Rodgers, Carie S; Schiehser, Dawn M; Aupperle, Robin L; Jak, Amy J

Posttraumatic stress disorder (PTSD), history of mild traumatic brain injury (mTBI), and executive function (EF) difficulties are prevalent in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans. We evaluated the contributions of injury variables, lower-order cognitive component processes (processing speed/attention), and psychological symptoms to EF. OEF/OIF Veterans (N = 65) with PTSD and history of mTBI were administered neuropsychological tests of EF and self-report assessments of PTSD and depression. Those impaired on one or more EF measures had higher PTSD and depression symptoms and lower processing speed/attention performance than those with intact performance on all EF measures. Across participants, poorer attention/processing speed performance and higher psychological symptoms were associated with worse performance on specific aspects of EF (eg, inhibition and switching) even after accounting for injury variables. Although direct relationships between EF and injury variables were equivocal, there was an interaction between measures of injury burden and processing speed/attention such that those with greater injury burden exhibited significant and positive relationships between processing speed/attention and inhibition/switching, whereas those with lower injury burden did not. Psychological symptoms as well as lower-order component processes of EF (attention and processing speed) contribute significantly to executive dysfunction in OEF/OIF Veterans with PTSD and history of mTBI. However, there may be equivocal relationships between injury variables and EF that warrant further study. Results provide groundwork for more fully understanding cognitive symptoms in OEF/OIF Veterans with PTSD and history of mTBI that can inform psychological and cognitive interventions in this population.

Increased circulating stem cells and better cognitive performance in traumatic brain injury subjects following hyperbaric oxygen therapy.

PubMed

Shandley, Sabrina; Wolf, E George; Schubert-Kappan, Christine M; Baugh, Laura M; Richards, Michael F; Prye, Jennifer; Arizpe, Helen M; Kalns, John

2017-01-01

Traumatic brain injury (TBI) may cause persistent cognitive dysfunction. A pilot clinical study was performed to determine if hyperbaric oxygen (HBO₂) treatment improves cognitive performance. It was hypothesized that stem cells, mobilized by HBO₂ treatment, are recruited to repair damaged neuronal tissue. This hypothesis was tested by measuring the relative abundance of stem cells in peripheral blood and cognitive performance during this clinical trial. The subject population consisted of 28 subjects with persistent cognitive impairment caused by mild to moderate TBI suffered during military deployment to Iraq or Afghanistan. Fluorescence-activated cell sorting (FACS) analysis was performed for stem cell markers in peripheral blood and correlated with variables resulting from standard tests of cognitive performance and post-traumatic stress disorder: ImPACT, BrainCheckers and PCL-M test results. HBO₂ treatment correlated with stem cell mobilization as well as increased cognitive performance. Together these results support the hypothesis that stem cell mobilization may be required for cognitive improvement in this population. Copyright© Undersea and Hyperbaric Medical Society.

Burden of Sexual Dysfunction.

PubMed

Balon, Richard

2017-01-02

Similar to the burden of other diseases, the burden of sexual dysfunction has not been systematically studied. However, there is growing evidence of various burdens (e.g., economic, symptomatic, humanistic) among patients suffering from sexual dysfunctions. The burden of sexual dysfunction has been studied a bit more often in men, namely the burden of erectile dysfunction (ED), premature ejaculation (PE) and testosterone deficiency syndrome (TDS). Erectile dysfunction is frequently associated with chronic conditions such as cardiovascular disease, diabetes, and depression. These conditions could go undiagnosed, and ED could be a marker of those diseases. The only available report from the United Kingdom estimated the total economic burden of ED at £53 million annually in terms of direct costs and lost productivity. The burden of PE includes significant psychological distress: anxiety, depression, lack of sexual confidence, poor self-esteem, impaired quality of life, and interpersonal difficulties. Some suggest that increase in female sexual dysfunction is associated with partner's PE, in addition to significant interpersonal difficulties. The burden of TDS includes depression, sexual dysfunction, mild cognitive impairment, and osteoporosis. One UK estimate of the economic burden of female sexual dysfunctions demonstrated that the average cost per patient was higher than the per annum cost of ED. There are no data on burden of paraphilic disorders. The burden of sexual dysfunctions is underappreciated and not well studied, yet it is significant for both the patients and the society.

Mild Cognitive Impairment

MedlinePlus

... your local chapter Join our online community Mild Cognitive Impairment Mild cognitive impairment (MCI) causes a slight ... About Symptoms Diagnosis Causes & risks Treatments About Mild Cognitive Impairment Prevalence of MCI Approximately 15 to 20 ...

Association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment in type 2 diabetic patients.

PubMed

Huang, Rong; Han, Jing; Tian, Sai; Cai, Rongrong; Sun, Jie; Shen, Yanjue; Wang, Shaohua

2017-02-28

People with insulin resistance and type 2 diabetes mellitus (T2DM) are at increased risks of cognitive impairment. We aimed to investigate the association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment (MCI) in T2DM patients. In addition to elevated glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR), T2DM patients with MCI had decreased plasma ghrelin levels compared with their healthy-cognition subjects (all p < 0.05). Further logistic regression analysis showed that ghrelin level was one of independent factors for MCI in T2DM patients (p < 0.05). Moreover, partial correlation analysis demonstrated that ghrelin levels were positively associated with the scores of Montreal Cognitive Assessment (r = 0.196, p = 0.041) and Auditory Verbal Learning Test-delayed recall (r = 0.197, p = 0.040) after adjustment for HbA1c, FBG and HOMA-IR, wherein the latter represented episodic memory functions. No significant differences were found for the distributions of genotype and allele of ghrelin rs4684677 polymorphism between MCI and control group. A total of 218 T2DM patients, with 112 patients who satisfied the MCI diagnostic criteria and 106 who exhibited healthy cognition, were enrolled in this study. Demographic characteristics, clinical variables and cognitive performances were extensively assessed. Plasma ghrelin levels and ghrelin rs4684677 polymorphism were also determined. Our results suggest that decreased ghrelin levels are associated with MCI, especially with episodic memory dysfunction in T2DM populations.

Multiple sclerosis with predominant, severe cognitive impairment

PubMed Central

Staff, Nathan P.; Lucchinetti, Claudia F.; Keegan, B. Mark

2009-01-01

Objective To describe the characteristics of multiple sclerosis (MS) presenting with severe cognitive impairment as its primary disabling manifestation. Design Retrospective case series. Setting Tertiary referral center. Patients Patients were identified through the Mayo Clinic data retrieval system (1996–2008) with definite MS (McDonald criteria) and severe cognitive impairment as their primary neurological symptom without accompanying significant MS-related impairment or alternative diagnosis for cognitive dysfunction. Twenty-three patients meeting inclusion criteria were compared regarding demographics, clinical course and radiological features. Main Outcome Measures Demographic, clinical, and radiological characteristics of the disease. Results Twelve patients were men. The median age of the first clinical symptom suggestive of CNS demyelination was 33 years, and severe MS-related cognitive impairment developed at a median of 39 years. Cognitive impairment could be dichotomized as subacute fulminant (n=9) or chronic progressive (n=14) in presentation, which corresponded to subsequent relapsing or progressive MS courses. Study patients commonly exhibited psychiatric (65%), mild cerebellar (57%) and cortical symptoms and signs (e.g. seizure, aphasia, apraxia) (39%). Fourteen of 21 (67%), where documented, smoked cigarettes. Brain MRI demonstrated diffuse cerebral atrophy in 16 and gadolinium enhancing lesions in 11. Asymptomatic spinal cord MRI lesions were present in 12 of 16 patients (75%). Immunomodulatory therapies were generally ineffective in improving these patients. Conclusions We describe patients with MS whose clinical phenotype is characterized by severe cognitive dysfunction and prominent cortical and psychiatric signs presenting as a subacute fulminant or chronic progressive clinical course. Cigarette smokers may be over represented in this phenotype. PMID:19752304

Discriminative analysis of non-linear brain connectivity for leukoaraiosis with resting-state fMRI

NASA Astrophysics Data System (ADS)

Lai, Youzhi; Xu, Lele; Yao, Li; Wu, Xia

2015-03-01

Leukoaraiosis (LA) describes diffuse white matter abnormalities on CT or MR brain scans, often seen in the normal elderly and in association with vascular risk factors such as hypertension, or in the context of cognitive impairment. The mechanism of cognitive dysfunction is still unclear. The recent clinical studies have revealed that the severity of LA was not corresponding to the cognitive level, and functional connectivity analysis is an appropriate method to detect the relation between LA and cognitive decline. However, existing functional connectivity analyses of LA have been mostly limited to linear associations. In this investigation, a novel measure utilizing the extended maximal information coefficient (eMIC) was applied to construct non-linear functional connectivity in 44 LA subjects (9 dementia, 25 mild cognitive impairment (MCI) and 10 cognitively normal (CN)). The strength of non-linear functional connections for the first 1% of discriminative power increased in MCI compared with CN and dementia, which was opposed to its linear counterpart. Further functional network analysis revealed that the changes of the non-linear and linear connectivity have similar but not completely the same spatial distribution in human brain. In the multivariate pattern analysis with multiple classifiers, the non-linear functional connectivity mostly identified dementia, MCI and CN from LA with a relatively higher accuracy rate than the linear measure. Our findings revealed the non-linear functional connectivity provided useful discriminative power in classification of LA, and the spatial distributed changes between the non-linear and linear measure may indicate the underlying mechanism of cognitive dysfunction in LA.

Copolymer-1 enhances cognitive performance in young adult rats

PubMed Central

Meneses, Alfredo; Cruz-Martínez, Yolanda; Anaya-Jiménez, Rosa María; Liy-Salmerón, Gustavo; Carvajal, Horacio Guillermo; Ponce-López, Maria Teresa

2018-01-01

Cognitive impairment is a dysfunction observed as a sequel of various neurodegenerative diseases, as well as a concomitant element in the elderly stages of life. In clinical settings, this malfunction is identified as mild cognitive impairment. Previous studies have suggested that cognitive impairment could be the result of a reduction in the expression of brain-derived neurotrophic factor (BDNF) and/or immune dysfunction. Copolymer-1 (Cop-1) is an FDA-approved synthetic peptide capable of inducing the activation of Th2/3 cells, which are able to release BDNF, as well as to migrate and accumulate in the brain. In this study, we evaluated the effect of Cop-1 immunization on improvement of cognition in adult rats. For this purpose, we performed four experiments. We evaluated the effect of Cop-1 immunization on learning/memory using the Morris water maze for spatial memory and autoshaping for associative memory in 3- or 6-month-old rats. BDNF concentrations at the hippocampus were determined by ELISA. Cop-1 immunization induced a significant improvement of spatial memory and associative memory in 6-month-old rats. Likewise, Cop-1 improved spatial memory and associative memory when animals were immunized at 3 months and evaluated at 6 months old. Additionally, Cop-1 induced a significant increase in BDNF levels at the hippocampus. To our knowledge, the present investigation reports the first instance of Cop-1 treatment enhancing cognitive function in normal young adult rats, suggesting that Cop-1 may be a practical therapeutic strategy potentially useful for age- or disease-related cognitive impairment. PMID:29494605

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.

Episodic, but not semantic, autobiographical memory is reduced in amnestic mild cognitive impairment.

PubMed

Murphy, Kelly J; Troyer, Angela K; Levine, Brian; Moscovitch, Morris

2008-11-01

Amnestic mild cognitive impairment (aMCI) is characterized by decline in anterograde memory as measured by the ability to learn and remember new information. We investigated whether retrograde memory for autobiographical information was affected by aMCI. Eighteen control (age 66-84 years) and 17 aMCI (age 66-84 years) participants described a personal event from each of the five periods across the lifespan. These events were transcribed and scored according to procedures that separate episodic (specific happenings) from semantic (general knowledge) elements of autobiographical memory. Although both groups generated protocols of similar length, the composition of autobiographical recall differentiated the groups. The aMCI group protocols were characterized by reduced episodic and increased semantic information relative to the control group. Both groups showed a similar pattern of recall across time periods, with no evidence that the aMCI group had more difficulty recalling recent, rather than remote, life events. These results indicate that episodic and semantic autobiographical memories are differentially affected by the early brain changes associated with aMCI. Reduced autobiographical episodic memories in aMCI may be the result of medial temporal lobe dysfunction, consistent with multiple trace theory, or alternatively, could be related to dysfunction of a wider related network of neocortical structures. In contrast, the preservation of autobiographical semantic memories in aMCI suggests neural systems, such as lateral temporal cortex, that support these memories, may remain relatively intact.

Cognitive dysfunction among newly diagnosed older patients with hematological malignancy: frequency, clinical indicators and predictors.

PubMed

Aiki, Sayo; Okuyama, Toru; Sugano, Koji; Kubota, Yosuke; Imai, Fuminobu; Nishioka, Masahiro; Ito, Yoshinori; Iida, Shinsuke; Komatsu, Hirokazu; Ishida, Takashi; Kusumoto, Shigeru; Akechi, Tatsuo

2018-01-01

Medical staff often overlook or underestimate the presence or severity of cognitive dysfunction. The purpose of this study was to clarify the frequency, clinical indicators and predictors of cognitive dysfunction among newly diagnosed older patients with hematologic malignancy receiving first-line chemotherapy. Patients aged 65 years or over with a primary diagnosis of malignant lymphoma or multiple myeloma were consecutively recruited. Cognitive dysfunction was evaluated using the Mini-Mental State Examination (MMSE) twice: before starting chemotherapy (T1) and 1 month later (T2). Participants also underwent a comprehensive geriatric assessment at T1. Potential clinical indicators that were associated with cognitive dysfunction were explored via cross-sectional analysis at T1. Predictors of cognitive dysfunction at T2 were also investigated among patients without cognitive dysfunction at T1. A total of 145 participants participated in the study; cognitive dysfunction at T1 was present in 20%. Multivariate analysis demonstrated that lower educational attainment and poorer instrumental activities of daily living were significant clinical indicators of cognitive dysfunction. Among 99 patients who did not have cognitive dysfunction at T1 and underwent cognitive assessment at T2, 7% developed dysfunction. Subjective perception of difficulty remembering at T1 was the only factor which significantly predicted new-onset cognitive dysfunction at T2. The prevalence rate of cognitive dysfunction was non-negligible among older patients with hematologic malignancy before and immediately after initial chemotherapy. Attention to the clinical indicators and predictors found in this study may provide facilitate the identification of cognitive dysfunction in patients with cancer. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Dimensions of dependence and their influence on the outcome of cognitive behaviour therapy for health anxiety: randomized controlled trial.

PubMed

Tyrer, Peter; Wang, Duolao; Tyrer, Helen; Crawford, Mike; Cooper, Sylvia

2016-05-01

The personality trait of dependence is common in health-seeking behaviour. We therefore examined its impact in a large randomized controlled trial of psychological treatment for health anxiety. To test whether dependent personality traits were positive or negative in determining the outcome of an adapted form of cognitive behaviour therapy for health anxiety (CBT-HA) over the course of 5 years and whether dependent personality dysfunction could be viewed dimensionally in a similar way to the new ICD-11 diagnostic system for general personality disorder. Dependent personality dysfunction was assessed using a self-rated questionnaire, the Dependent Personality Questionnaire, at baseline in a randomized controlled trial of 444 patients from medical clinics with pathological health anxiety treated with a modified form of CBT-HA or standard treatment in the medical clinics, with assessment on five occasions over 5 years. Dependent personality dysfunction was assessed using four severity groups. Patients with mild and moderate dependent personality disorder treated with CBT-HA showed the greatest reduction in health anxiety compared with standard care, and those with no dependent dysfunction showed the least benefit. Patients with higher dependent traits received significantly more treatment sessions (8.6) than those with low trait levels (5.4) (p < 0.01). The results suggest that patients treated with cognitive behaviour therapy for health anxiety respond better if they have moderate dependent personality. The reasons for this may be related to better adherence to psychological treatment and greater negative effects of frequent reassurance and excessive consultation in those treated in standard care. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Global Efficiency of Structural Networks Mediates Cognitive Control in Mild Cognitive Impairment

PubMed Central

Berlot, Rok; Metzler-Baddeley, Claudia; Ikram, M. Arfan; Jones, Derek K.; O’Sullivan, Michael J.

2016-01-01

Background: Cognitive control has been linked to both the microstructure of individual tracts and the structure of whole-brain networks, but their relative contributions in health and disease remain unclear. Objective: To determine the contribution of both localized white matter tract damage and disruption of global network architecture to cognitive control, in older age and Mild Cognitive Impairment (MCI). Materials and Methods: Twenty-five patients with MCI and 20 age, sex, and intelligence-matched healthy volunteers were investigated with 3 Tesla structural magnetic resonance imaging (MRI). Cognitive control and episodic memory were evaluated with established tests. Structural network graphs were constructed from diffusion MRI-based whole-brain tractography. Their global measures were calculated using graph theory. Regression models utilized both global network metrics and microstructure of specific connections, known to be critical for each domain, to predict cognitive scores. Results: Global efficiency and the mean clustering coefficient of networks were reduced in MCI. Cognitive control was associated with global network topology. Episodic memory, in contrast, correlated with individual temporal tracts only. Relationships between cognitive control and network topology were attenuated by addition of single tract measures to regression models, consistent with a partial mediation effect. The mediation effect was stronger in MCI than healthy volunteers, explaining 23-36% of the effect of cingulum microstructure on cognitive control performance. Network clustering was a significant mediator in the relationship between tract microstructure and cognitive control in both groups. Conclusion: The status of critical connections and large-scale network topology are both important for maintenance of cognitive control in MCI. Mediation via large-scale networks is more important in patients with MCI than healthy volunteers. This effect is domain-specific, and true for cognitive control but not for episodic memory. Interventions to improve cognitive control will need to address both dysfunction of local circuitry and global network architecture to be maximally effective. PMID:28018208

The Effects of Intellectual, Physical, and Social Activity on Further Prognosis in Mild Cognitive Impairment.

PubMed

Bidzan, Leszek; Bidzan, Mariola; Pąchalska, Maria

2016-07-19

BACKGROUND Our goal was to specify the relationship between the level of activity (intellectual, physical, and social) in persons diagnosed with mild cognitive impairment (MCI) and the further progression of cognitive dysfunction. MATERIAL AND METHODS We examined 193 patients diagnosed with MCI (according to the criteria of the Working Group on Mild Cognitive Impairment) and under treatment at our Mental Disorders Clinic. It was assumed that these persons would remain under systematic psychiatric observation until dementia was diagnosed. The present study results from a seven-year observation period. The mini-mental state examination (MMSE), the Activity Scale (with the intellectual, physical, and social subscales), and the Instrumental Activities of Daily Living (IADL) scale were used to evaluate the participants' status at baseline. The MMSE was re-administered after one year and again at the end of the observation (either upon diagnosis of dementia or after seven years). At each meeting with the participant, the clinical diagnosis was verified to determine if the patient had dementia or not. Of the 193 people initially qualified for the study, 75 were available for the final analysis. RESULTS It was found that there was no statistically significant difference in the baseline MMSE scores between the persons with stable MCI and the persons who had progressed to dementia. However, statistically significant differences in the level of activity at baseline on both the global IADL scale and the Activity Scale between those with stable MCI and those who had progressed to dementia were found. These differences were manifested in the IADL subscales for telephone use, shopping, transportation, and personal finances, and in the physical activity subscale. CONCLUSIONS An evaluation of intellectual, physical, and social activity can be useful in determining the prognosis for the future course of MCI.

Characterization of Mexican Americans with mild cognitive impairment and Alzheimer's disease.

PubMed

O'Bryant, Sid E; Johnson, Leigh; Balldin, Valerie; Edwards, Melissa; Barber, Robert; Williams, Benjamin; Devous, Michael; Cushings, Blair; Knebl, Janice; Hall, James

2013-01-01

The purpose of the study was to provide characterization of Mexican Americans who meet criteria for Alzheimer's disease (AD) and mild cognitive impairment (MCI). For the study, 1,069 participants ages 40 and above who self-identified as either non-Hispanic white (n = 633) or Mexican American (n = 436) were recruited using a community-based participatory research approach. Global cognition was assessed via the Mini-Mental State Examination (MMSE), dementia severity by the Clinical Dementia Rating Scale, and depression via the Geriatric Depression Scale 30-item version. Age, gender, education, ApoE ε4 allele frequency, and diabetic diagnoses were also analyzed. The findings showed that Mexican Americans (normal controls, MCI, and AD) were younger, less highly educated, performed more poorly on the MMSE, endorsed more symptoms of depression, were more likely to be diagnosed with diabetes, and possessed the ApoE ε4 allele less frequently. Age was the only significant risk factor for cognitive dysfunction (AD/MCI) among Mexican Americans (OR = 1.06, 95% CI = 1.03-1.09). Age (B = 0.07, std = 0.02, p < 0.001) and ApoE ε4 presence (B = 0.9, std = 0.4, p = 0.02) were significantly related to increased disease severity. Given the rapidly growing and aging Mexican American population, there is a substantial need for research into cognitive aging, MCI, and AD among this ethnic group. The current findings hold important implications for both clinic and research settings and point to additional research needs.

Effects of task-irrelevant emotional stimuli on working memory processes in mild cognitive impairment.

PubMed

Berger, Christoph; Erbe, Anna-Katharina; Ehlers, Inga; Marx, Ivo; Hauenstein, Karlheinz; Teipel, Stefan

2015-01-01

Research suggests generally impaired cognitive control functions in working memory (WM) processes in amnestic mild cognitive impairment (MCI) and incipient Alzheimer's disease (AD). Little is known how emotional salience of task-irrelevant stimuli may modulate cognitive control of WM performance and neurofunctional activation in MCI and AD individuals. We investigated the impact of emotional task-irrelevant visual stimuli on cortical activation during verbal WM. Twelve AD/MCI individuals and 12 age-matched healthy individuals performed a verbal WM (nback-) task with task-irrelevant emotionally neutral and emotionally negative background pictures during fMRI measurement. AD/MCI individuals showed decreased WM performance compared with controls; both AD/MCI and control groups reacted slower during presentation of negative pictures, regardless of WM difficulty. The AD/MCI group showed increased activation in the left hemispheric prefrontal network, higher amygdala and less cerebellar activation with increasing WM task difficulty compared to healthy controls. Correlation analysis between neurofunctional activation and WM performance revealed a negative correlation between task sensitivity and activation in the dorsal anterior cingulum for the healthy controls but not for the AD/MCI group. Our data suggest compensatory activation in prefrontal cortex and amygdala, but also dysfunctional inhibition of distracting information in the AD/MCI group during higher WM task difficulty. Additionally, attentional processes affecting the correlation between WM performance and neurofunctional activation seem to be different between incipient AD and healthy aging.

MDS Task Force on Mild Cognitive Impairment in Parkinson’s disease: Critical Review of PD-MCI

PubMed Central

Litvan, I; Aarsland, D; Adler, CH; Goldman, JG; Kulisevsky, J; Mollenhauer, B; Rodriguez-Oroz, MC; Tröster, AI; Weintraub, D

2011-01-01

Background There is controversy regarding the definition and characteristics of mild cognitive impairment in Parkinson’s disease. Objective The Movement Disorders Society commissioned a Task Force to critically evaluate the literature and determine the frequency and characteristics of Parkinson’s disease-mild cognitive impairment and its association with dementia. Methods Comprehensive PubMed literature review using systematic inclusion and exclusion criteria. Results A mean of 26.7% (range, 18.9–38.2%) of non-demented Parkinson’s disease patients have mild cognitive impairment. The frequency of Parkinson’s disease mild cognitive impairment increases with age, disease duration, and disease severity. Impairments occur in a range of cognitive domains, but single domain impairment is more common than multiple domain impairment, and within single domain impairment, non-amnestic is more common than amnestic impairment. A high proportion of patients with Parkinson’s disease-mild cognitive impairment progress to dementia in a relatively short period of time. Conclusions The primary conclusions of the Task Force are that: (1) Parkinson’s disease-mild cognitive impairment is common; (2) there is significant heterogeneity within Parkinson’s disease-mild cognitive impairment in the number and types of cognitive domain impairments; (3) Parkinson’s disease-mild cognitive impairment appears to place patients at risk of progressing to dementia; and (4) formal diagnostic criteria for Parkinson’s disease-mild cognitive impairment are needed. PMID:21661055

The Association between Daytime Napping and Cognitive Functioning in Chronic Fatigue Syndrome

PubMed Central

Gotts, Zoe M.; Ellis, Jason G.; Deary, Vincent; Barclay, Nicola; Newton, Julia L.

2015-01-01

Objectives The precise relationship between sleep and physical and mental functioning in chronic fatigue syndrome (CFS) has not been examined directly, nor has the impact of daytime napping. This study aimed to examine self-reported sleep in patients with CFS and explore whether sleep quality and daytime napping, specific patient characteristics (gender, illness length) and levels of anxiety and depression, predicted daytime fatigue severity, levels of daytime sleepiness and cognitive functioning, all key dimensions of the illness experience. Methods 118 adults meeting the 1994 CDC case criteria for CFS completed a standardised sleep diary over 14 days. Momentary functional assessments of fatigue, sleepiness, cognition and mood were completed by patients as part of usual care. Levels of daytime functioning and disability were quantified using symptom assessment tools, measuring fatigue (Chalder Fatigue Scale), sleepiness (Epworth Sleepiness Scale), cognitive functioning (Trail Making Test, Cognitive Failures Questionnaire), and mood (Hospital Anxiety and Depression Scale). Results Hierarchical Regressions demonstrated that a shorter time since diagnosis, higher depression and longer wake time after sleep onset predicted 23.4% of the variance in fatigue severity (p <.001). Being male, higher depression and more afternoon naps predicted 25.6% of the variance in objective cognitive dysfunction (p <.001). Higher anxiety and depression and morning napping predicted 32.2% of the variance in subjective cognitive dysfunction (p <.001). When patients were classified into groups of mild and moderate sleepiness, those with longer daytime naps, those who mainly napped in the afternoon, and those with higher levels of anxiety, were more likely to be in the moderately sleepy group. Conclusions Napping, particularly in the afternoon is associated with poorer cognitive functioning and more daytime sleepiness in CFS. These findings have clinical implications for symptom management strategies. PMID:25575044

The association between daytime napping and cognitive functioning in chronic fatigue syndrome.

PubMed

Gotts, Zoe M; Ellis, Jason G; Deary, Vincent; Barclay, Nicola; Newton, Julia L

2015-01-01

The precise relationship between sleep and physical and mental functioning in chronic fatigue syndrome (CFS) has not been examined directly, nor has the impact of daytime napping. This study aimed to examine self-reported sleep in patients with CFS and explore whether sleep quality and daytime napping, specific patient characteristics (gender, illness length) and levels of anxiety and depression, predicted daytime fatigue severity, levels of daytime sleepiness and cognitive functioning, all key dimensions of the illness experience. 118 adults meeting the 1994 CDC case criteria for CFS completed a standardised sleep diary over 14 days. Momentary functional assessments of fatigue, sleepiness, cognition and mood were completed by patients as part of usual care. Levels of daytime functioning and disability were quantified using symptom assessment tools, measuring fatigue (Chalder Fatigue Scale), sleepiness (Epworth Sleepiness Scale), cognitive functioning (Trail Making Test, Cognitive Failures Questionnaire), and mood (Hospital Anxiety and Depression Scale). Hierarchical Regressions demonstrated that a shorter time since diagnosis, higher depression and longer wake time after sleep onset predicted 23.4% of the variance in fatigue severity (p <.001). Being male, higher depression and more afternoon naps predicted 25.6% of the variance in objective cognitive dysfunction (p <.001). Higher anxiety and depression and morning napping predicted 32.2% of the variance in subjective cognitive dysfunction (p <.001). When patients were classified into groups of mild and moderate sleepiness, those with longer daytime naps, those who mainly napped in the afternoon, and those with higher levels of anxiety, were more likely to be in the moderately sleepy group. Napping, particularly in the afternoon is associated with poorer cognitive functioning and more daytime sleepiness in CFS. These findings have clinical implications for symptom management strategies.

Magnetic resonance spectroscopy in mild cognitive impairment: systematic review and meta-analysis.

PubMed

Tumati, Shankar; Martens, Sander; Aleman, André

2013-12-01

Research using proton magnetic resonance spectroscopy (MRS) can potentially elucidate metabolite changes representing early degeneration in Mild Cognitive Impairment (MCI), an early stage of dementia. We integrated the published literature using meta-analysis to identify patterns of metabolite changes in MCI. 29 MRS studies (with a total of 607 MCI patients and 862 healthy controls) were classified according to brain regions. Hedges' g was used as effect size in a random effects model. N-Acetyl Aspartate (NAA) measures were consistently reduced in posterior cingulate (PC), hippocampus, and the paratrigonal white matter (PWM). Creatine (Cr) concentration was reduced in the hippocampus and PWM. Choline (Cho) concentration was reduced in the hippocampus while Cho/Cr ratio was raised in the PC. Myo-inositol (mI) concentration was raised in the PC and mI/Cr ratio was raised in the hippocampus. NAA/mI ratio was reduced in the PC. NAA may be the most reliable marker of brain dysfunction in MCI though mI, Cho, and Cr may also contribute towards this. Copyright © 2013 Elsevier Ltd. All rights reserved.

Predictable chronic mild stress improves mood, hippocampal neurogenesis and memory.

PubMed

Parihar, V K; Hattiangady, B; Kuruba, R; Shuai, B; Shetty, A K

2011-02-01

Maintenance of neurogenesis in adult hippocampus is important for functions such as mood and memory. As exposure to unpredictable chronic stress (UCS) results in decreased hippocampal neurogenesis, enhanced depressive- and anxiety-like behaviors, and memory dysfunction, it is believed that declined hippocampal neurogenesis mainly underlies the behavioral and cognitive abnormalities after UCS. However, the effects of predictable chronic mild stress (PCMS) such as the routine stress experienced in day-to-day life on functions such as mood, memory and hippocampal neurogenesis are unknown. Using FST and EPM tests on a prototype of adult rats, we demonstrate that PCMS (comprising 5 min of daily restraint stress for 28 days) decreases depressive- and anxiety-like behaviors for prolonged periods. Moreover, we illustrate that decreased depression and anxiety scores after PCMS are associated with ~1.8-fold increase in the production and growth of new neurons in the hippocampus. Additionally, we found that PCMS leads to enhanced memory function in WMT as well as NORT. Collectively, these findings reveal that PCMS is beneficial to adult brain function, which is exemplified by increased hippocampal neurogenesis and improved mood and cognitive function.

Non-pharmacological cognitive intervention for aging and dementia: Current perspectives

PubMed Central

Alves, Jorge; Magalhães, Rosana; Machado, Álvaro; Gonçalves, Óscar F; Sampaio, Adriana; Petrosyan, Agavni

2013-01-01

In recent years, cognitive difficulties associated with normal aging and dementia have been receiving increased attention from both public and scientific communities. With an increase in overall lifespan, promoting healthy cognition has become a priority and a necessity for minimizing and preventing individual and societal burdens associated with cognitive dysfunctions in the elderly. The general awareness concerning the efficacy of preventive (e.g., lifestyles) and palliative treatment strategies of cognitive impairments, related to either healthy or unhealthy trajectories in cognitive aging, is continuously rising. There are several therapeutic strategies which can be broadly classified as either pharmacological or non-pharmacological/psychosocial. In face of the modest evidence for success of pharmacological treatments, especially for dementia related impairments, psychosocial interventions are progressively considered as a complementary treatment. Despite the relative spread of psychosocial interventions in clinical settings, research in this area is rather scarce with evidence for success of these therapies remaining controversial. In this work we provide an evidence based perspective on cognitive intervention(s) for healthy aging, pre-dementia (mild cognitive impairment), and dementia populations. Current evidence and future directions for improving cognitive functions in the elderly are discussed as well. PMID:24340275

Comorbid Mild Cognitive Impairment and Depressive Symptoms Predict Future Dementia in Community Older Adults: A 24-Month Follow-Up Longitudinal Study.

PubMed

Makizako, Hyuma; Shimada, Hiroyuki; Doi, Takehiko; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Makino, Keitaro; Suzuki, Takao

2016-10-18

Older adults with mild cognitive impairment (MCI) are non-demented, but demonstrate cognitive dysfunction, and have significantly higher risk of progressing to dementia. A better understanding of more sensitive risk factors, such as combination of cognitive and psychological status, for progression of MCI to dementia may be crucial for prevention of development of dementia. To examine MCI, depressive symptoms, and comorbid MCI and depressive symptoms as risk factors for development of dementia. A total of 3,663 community-dwelling older people were included in this prospective longitudinal study. MCI was determined by age- and education-adjusted objective cognitive impairment using computerized comprehensive cognitive measures including memory, attention/executive function, and processing speed. Depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS) and defined by a GDS score of 6 or more. During the 24-month follow-up period, 72 participants (2.0%) developed dementia. Baseline MCI was significantly associated with an increased risk of incident dementia (hazard ratio [HR], 3.2; 95% confidence interval [CI], 1.8-5.5) but depressive symptoms were not (2.0; 1.0-4.2) after adjusting for age, sex, education, prescribed medications, and walking speed. Participants with comorbid MCI and depressive symptoms at baseline had a higher risk of developing dementia (HR, 4.8; 2.3-10.5). Although MCI and depressive symptoms may be associated with increased risk for incident dementia independently, comorbid MCI and depressive symptoms have a significantly greater impact on dementia development among community-dwelling older adults.

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 ...

Repressive Coping Does Not Contribute to Anosognosia in First-Diagnosis Patients With Alzheimer Disease.

PubMed

Verhülsdonk, Sandra; Lange-Asschenfeldt, Christian; Höft, Barbara; Schwender, Holger; Supprian, Tillmann; Hellen, Florence; Kalbe, Elke

2017-01-01

Anosognosia is common in patients with Alzheimer disease (AD) even in early stages. Although neural correlates and the impact of cognitive dysfunctions have been described, possible psychodynamic processes such as a repressive coping style as described in other illnesses, have not been examined. Our study aimed to examine possible psychological influence factors on illness perception embracing a repressive coping style and cognitive functions in AD patients in the diagnostic process. Fifty-four subjects with mild AD diagnosed in our memory clinic were enrolled. Anosognosia was evaluated using a patient-caregiver discrepancy rating. All patients underwent comprehensive neuropsychological testing. In addition, characteristics of a repressive coping style were assessed. In total, 79.6% of our patients showed a lack of awareness at least to some degree. 33.3% of the patients were classified as repressors. Repressors and nonrepressors did not differ in cognition, or the unawareness score. Multivariate regression analysis showed that repressive coping style did not significantly contribute to anosognosia, but that verbal memory and naming ability had a strong influence. Although our data indicate that a high proportion of patients with mild AD show characteristics of repressive coping, this possible defense mechanism had no influence on the awareness of illness-related deficits measured by caregiver patient discrepancy.

Neurologic manifestations in welders with pallidal MRI T1 hyperintensity.

PubMed

Josephs, K A; Ahlskog, J E; Klos, K J; Kumar, N; Fealey, R D; Trenerry, M R; Cowl, C T

2005-06-28

Neurologic symptoms have been attributed to manganese fumes generated during welding. Increased T1 MRI signal in the basal ganglia is a biologic marker of manganese accumulation. Recent studies have associated welding and parkinsonism, but generally without MRI corroboration. To characterize the clinical and neuropsychological features of patients with MRI basal ganglia T1 hyperintensity, who were ultimately diagnosed with neurotoxicity from welding fumes. The medical records of welders referred to the Department of Neurology with neurologic problems and basal ganglia T1 hyperintensity were reviewed. All eight patients were male career welders with increased T1 basal ganglia signal on MRI of the brain. Several different clinical syndromes were recognized: a parkinsonian syndrome (three patients), a syndrome of multifocal myoclonus and limited cognitive impairment (two patients), a mixed syndrome with vestibular-auditory dysfunction (two patients), and minor subjective cognitive impairment, anxiety, and sleep apnea (one patient). Neuropsychometric testing suggested subcortical or frontal involvement. Inadequate ventilation or lack of personal respiratory protection during welding was a common theme. Welding without proper protection was associated with syndromes of parkinsonism, multifocal myoclonus, mild cognitive impairment, and vestibular-auditory dysfunction. The MRI T1 hyperintensity in the basal ganglia suggests that these may have been caused by manganese neurotoxicity.

Prevalence of and factors associated with sarcopenia in elderly patients with end-stage renal disease.

PubMed

Kim, Jwa-Kyung; Choi, Sun Ryoung; Choi, Myung Jin; Kim, Sung Gyun; Lee, Young Ki; Noh, Jung Woo; Kim, Hyung Jik; Song, Young Rim

2014-02-01

We investigated the prevalence of sarcopenia in elderly patients with end-stage renal disease (ESRD) and its relationship with various markers of nutrition, cognitive function, depressive symptoms, inflammation and β2-microglobulin. A cross-sectional study was conducted with 95 patients having ESRD aged over 50 years. Sarcopenia was defined as a decline in both muscle mass and strength. The mean age was 63.9 ± 10.0 years; 56.8% were men and 52.6% had diabetes. Sarcopenia was highly prevalent in elderly patients with ESRD (37.0% in men and 29.3% in women). Subjective Global Assessment (SGA), inflammatory markers and β2-microglobulin levels were significantly associated with sarcopenia, even after adjustment for age, gender, diabetes, and body mass index. Additionally, patients with depressive symptoms showed a higher risk of sarcopenia relative to those without depressive symptoms (odds ratio, OR = 6.87, 95% confidence interval, CI = 2.06-22.96) and sarcopenia was more likely to be present in patients with mild cognitive dysfunction (OR = 6.35, 95% CI = 1.62-34.96). Sarcopenia is highly prevalent in elderly patients with ESRD and is closely associated with SGA, inflammatory markers, β2-microglobulin, depression and cognitive dysfunction. Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Is the epicardial left ventricular lead implantation an alternative approach to percutaneous attempt in patients with Steinert disease? A case report

PubMed Central

PAPA, ANDREA ANTONIO; RAGO, ANNA; PETILLO, ROBERTA; D’AMBROSIO, PAOLA; SCUTIFERO, MARIANNA; FEO, MARISA DE; MAIELLO, CIRO; PALLADINO, ALBERTO

2017-01-01

Steinert’s disease or Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder characterized by myotonia, muscle and facial weakness, cataracts, cognitive, endocrine and gastrointestinal involvement, and cardiac conduction abnormalities. Although mild myocardial dysfunction may be detected in this syndrome with age, overt myocardial dysfunction with heart failure is not frequent. Cardiac resynchronization therapy is an effective treatment to improve morbidity and reduce mortality in patients with DM1 showing intra-ventricular conduction delay and/or congestive heart failure. We report the case of a patient with Steinert disease showing an early onset ventricular dysfunction due to chronic right ventricular apical pacing, in which an epicardial left ventricular lead implantation was performed following the failure of the percutaneous attempt. As no relief in symptoms of heart failure, nor an improvement of left ventricular ejection fraction and reverse remodelling was observed six months later, the patient was addressed to the heart transplantation.

Association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment in type 2 diabetic patients

PubMed Central

Huang, Rong; Han, Jing; Tian, Sai; Cai, Rongrong; Sun, Jie; Shen, Yanjue; Wang, Shaohua

2017-01-01

Background and aims People with insulin resistance and type 2 diabetes mellitus (T2DM) are at increased risks of cognitive impairment. We aimed to investigate the association of plasma ghrelin levels and ghrelin rs4684677 polymorphism with mild cognitive impairment (MCI) in T2DM patients. Results In addition to elevated glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG) and homeostasis model assessment of insulin resistance (HOMA-IR), T2DM patients with MCI had decreased plasma ghrelin levels compared with their healthy-cognition subjects (all p < 0.05). Further logistic regression analysis showed that ghrelin level was one of independent factors for MCI in T2DM patients (p < 0.05). Moreover, partial correlation analysis demonstrated that ghrelin levels were positively associated with the scores of Montreal Cognitive Assessment (r = 0.196, p = 0.041) and Auditory Verbal Learning Test-delayed recall (r = 0.197, p = 0.040) after adjustment for HbA1c, FBG and HOMA-IR, wherein the latter represented episodic memory functions. No significant differences were found for the distributions of genotype and allele of ghrelin rs4684677 polymorphism between MCI and control group. Materials and methods A total of 218 T2DM patients, with 112 patients who satisfied the MCI diagnostic criteria and 106 who exhibited healthy cognition, were enrolled in this study. Demographic characteristics, clinical variables and cognitive performances were extensively assessed. Plasma ghrelin levels and ghrelin rs4684677 polymorphism were also determined. Conclusions Our results suggest that decreased ghrelin levels are associated with MCI, especially with episodic memory dysfunction in T2DM populations. PMID:28146431

Comparison of Low Resolution Electromagnetic Tomography Imaging Between Subjects With Mild and Severe Obstructive Sleep Apnea Syndrome: A Preliminary Study

PubMed Central

Lee, Hyun-Kwon; Shin, Hyun-Sil; Hong, Seok-Chan

2008-01-01

Objective The purpose of this study was to identify the regions of the brain associated with recurrent nocturnal chronic hypoxic episodes in patients with untreated obstructive sleep apnea syndrome (OSAS) using low-resolution electromagnetic tomography (LORETA) and quantitative electroencephalography (QEEG). Methods Nocturnal polysomnograph (NPSG) and subsequent morning electroencephalograph (EEG) were measured in 20 subjects with OSAS. Mild (n=10 ages 39.5±12.1 years) and severe (n=10 ages 41.7±13.6 years) right-handed male OSAS subjects were selected by interview and questionnaires including the NPSG, Beck Depression Inventory, Beck Anxiety Inventory, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index. The LORETA and QEEG were compared between the severe and mild OSAS groups by frequency bands (delta 1-3 Hz, theta 4-7 Hz, alpha 8-12 Hz, beta1 13-18 Hz, beta2 19-21 Hz, beta3 22-30 Hz, and total 1-30 Hz) made by spectral analysis during resting with the eyes closed. Results The LORETA analysis showed decreased alpha activity at the right posterior cingulate gyrus (Brodmann area 23) in cases with severe OSAS compared to mild OSAS (p<0.05). For the QEEG, the absolute power of the alpha activity (8-12 Hz) was decreased in P3 (p=0.047), PZ (p=0.039) and O2 (p=0.04) in cases with severe OSAS compared to mild OSAS cases. The LORETA and QEEG analyses had similar results with regard to band, activation and location. Conclusion The decreased activity of the alpha frequency in the right posterior cingulate gyrus, in patients with severe OSAS compared to those with mild OSAS, suggests that chronic repeated short-term hypoxia during sleep, in OSAS, could provoke cortical brain dysfunction associated with cognitive dysfunction such as memory and attention. PMID:20046408

A review of mild traumatic brain injury diagnostics: current perspectives, limitations, and emerging technology.

PubMed

Cook, Glen A; Hawley, Jason S

2014-10-01

Mild traumatic brain injury (mTBI) or concussion is a common battlefield and in-garrison injury caused by transmission of mechanical forces to the head. The energy transferred in such events can cause structural and/or functional changes in the brain that manifest as focal neurological, cognitive, or behavioral dysfunction. Current diagnostic criteria for mTBI are highly limited, variable, and based on subjective self-report. The subjective nature of the symptoms, both in quantity and quality, together with their large overlap in other physical and behavioral maladies, limit the clinician's ability to accurately diagnose, treat, and make prognostic decisions after such injuries. These diagnostic challenges are magnified in an operational environment as well. The Department of Defense has invested significant resources into improving the diagnostic tools and accuracy for mTBI. This focus has been to supplement the clinician's examination with technology that is better able to objectify brain dysfunction after mTBI. Through this review, we discuss the current state of three promising technologies--soluble protein biomarkers, advanced neuroimaging, and quantitative electroencephalography--that are of particular interest within military medicine. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

The Hachinski ischemic scale and cognition: the influence of ethnicity.

PubMed

Johnson, Leigh A; Cushing, Blair; Rohlfing, Geoffrey; Edwards, Melissa; Davenloo, Hedieh; D'Agostino, Darrin; Hall, James R; O'Bryant, Sid E

2014-05-01

cardiovascular burden is considered a risk factor for the development of cognitive dysfunction and dementia. While this link is well established in the literature, implementing this work in primary care settings remains a challenge. The goal of this study is to examine the utility of the Hachinski Ischemic Scale (HIS) in identifying cognitive dysfunction and diagnosis of mild cognitive impairment (MCI) in an ethnically diverse sample. data were analysed on 517 participants (211 Mexican Americans and 306 non-Hispanic Whites) recruited from Project FRONTIER, a study of rural health. Neuropsychological measures were utilised to assess for cognitive functioning. among non-Hispanic Whites, HIS scores were significantly related to poorer performance on tasks of global cognition [B (SE) = -0.13 (0.06), P = 0.02], immediate memory [B (SE) = -0.85 (0.26), P < 0.001], attention [B (SE) = -1.6 (0.36), P < 0.001] and executive functioning [B (SE) = 0.46 (0.12), P < 0.001], and significantly predicted diagnosis of MCI [odds ratio (OR) = 1.4; 95% confidence interval (CI) = 1.2-1.6]. For Mexican Americans, HIS scores were significantly related to immediate memory [B (SE) = -0.78 (0.28), P = 0.01], attention [B (SE) = -0.74 (0.36), P = 0.04] and executive functioning [B (SE) = 0.37 (0.14), P = 0.01]; however, HIS scores were not significantly related to diagnosis of MCI in Mexican Americans (OR = 1.2, 95% CI = 0.96-1.4, P = 0.116). HIS scores were related to cognitive functioning; however, these results differed by ethnicity. It is possible that these findings indicate that vascular factors may increase risk for MCI among non-Hispanic Whites but not for Mexican Americans. These findings are consistent with past research that suggests risk factors for MCI may differ by ethnicity.

The impact of subjective cognitive fatigue and depression on cognitive function in patients with multiple sclerosis.

PubMed

Golan, Daniel; Doniger, Glen M; Wissemann, Karl; Zarif, Myassar; Bumstead, Barbara; Buhse, Marijean; Fafard, Lori; Lavi, Idit; Wilken, Jeffrey; Gudesblatt, Mark

2018-02-01

The association between subjective cognitive fatigue and objective cognitive dysfunction in patients with multiple sclerosis (PwMS) has been studied, with conflicting results. To explore the impact of fatigue on cognitive function, while controlling for the influence of depression, disability, comorbidities, and psychotropic medications. PwMS completed a computerized cognitive testing battery with age- and education-adjusted cognitive domain scores. Disability (Expanded Disability Status Scale (EDSS)), cognitive fatigue, and depression were concurrently evaluated. In all, 699 PwMS were included. Both cognitive fatigue and depression were significantly and negatively correlated with the same cognitive domains: information processing speed, executive function, attention, motor function, and memory (-0.15 ⩽ r ⩽ -0.14 for cognitive fatigue; -0.24 ⩽ r ⩽ -0.19 for depression). Multivariate analysis revealed significant but small independent correlations only between depression and neuropsychological test results, while cognitive fatigue had no independent correlation with objective cognitive function except for a trend toward impaired motor function in highly fatigued PwMS. Depression and cognitive fatigue accounted for no more than 6% of the variance in objective cognitive domain scores. Cognitive fatigue is not independently related to objective cognitive impairment. Depression may influence cognitive function of PwMS primarily when it is severe. Cognitive impairment in PwMS should not be ascribed to fatigue or mild depression.

Evolution of diagnostic criteria and assessments for Parkinson's disease mild cognitive impairment.

PubMed

Goldman, Jennifer G; Holden, Samantha K; Litvan, Irene; McKeith, Ian; Stebbins, Glenn T; Taylor, John-Paul

2018-04-01

Mild cognitive impairment has gained recognition as a construct and a potential prodromal stage to dementia in both Alzheimer's disease and Parkinson's disease (PD). Although mild cognitive impairment has been recognized in the Alzheimer's disease field, it is a relatively more recent topic of interest in PD. Recent advances include the development of diagnostic criteria for PD mild cognitive impairment to provide more uniform definitions for clinical and research use. Studies reveal that mild cognitive impairment in PD is frequent, but also heterogeneous, with variable clinical presentations, differences in its progression to dementia, and likely differences in underlying pathophysiology. Application of the International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment Task Force diagnostic criteria has provided insights regarding cognitive measures, functional assessments, and other key topics that may require additional refinement. Furthermore, it is important to consider definitions of PD mild cognitive impairment in the landscape of other related Lewy body disorders, such as dementia with Lewy bodies, and in the context of prodromal and early-stage PD. This article examines the evolution of mild cognitive impairment in concept and definition, particularly in PD, but also in related disorders such as Alzheimer's disease and dementia with Lewy bodies; the development and application of International Parkinson and Movement Disorder Society PD Mild Cognitive Impairment diagnostic criteria; and insights and future directions for the field of PD mild cognitive impairment. © 2018 International Parkinson and Movement Disorder Society. © 2018 International Parkinson and Movement Disorder Society.

Abnormal amyloid β42 expression and increased oxidative stress in plasma of CKD patients with cognitive dysfunction: A small scale case control study comparison with Alzheimer's disease.

PubMed

Vinothkumar, G; Kedharnath, C; Krishnakumar, S; Sreedhar, S; Preethikrishnan, K; Dinesh, S; Sundaram, A; Balakrishnan, D; Shivashekar, G; Sureshkumar; Venkataraman, P

2017-12-01

Cognitive dysfunction has been increasingly recognized in chronic kidney disease (CKD) patients. Senile plaques are important pathophysiological characteristic of cognitive dysfunction. The major component of plaques is the amyloid β (Aβ) peptide released from proteolytic cleavage of amyloid precursor protein (APP). Plasma Aβ has been a focus of the growing literature on blood based biomarkers for cognitive dysfunction. Oxidative stress is prevalent in CKD and it plays an important role in cognitive dysfunction. Increased oxidative stress leads to cause cleavage of APP and Aβ production. The aim of this study is to assess the antioxidant status and Aβ 42 levels in plasma of CKD patients with cognitive dysfunction compared to CKD without cognitive dysfunction. A total of 60 subjects divided into 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction based on neuropsychological assessment tests. To compare antioxidant status and Aβ 42 levels in plasma, the following groups such as healthy subjects (n = 30), normocytic normochromic anemia (n = 30) and Alzheimer's disease (AD, n = 10) patients were also maintained. Plasma Superoxide dismutase (SOD), Catalase (CAT), Glutathione peroxidase (GPx), Reduced glutathione (GSH) and lipid peroxidation (LPO) were determined by spectrophotometrically. Aβ level was determined by immunoblotting method. The parameters were statistically compared with healthy, normocytic normochromic anemia and AD subjects. Like AD subjects, significantly increased Aβ and LPO level while decreased SOD, CAT, GPx and GSH levels were observed in plasma of CKD patients with cognitive dysfunction when compared to healthy, CKD without cognitive dysfunction and normocytic normochromic anemic subjects. Results suggest that elevated plasma oxidative stress and Aβ were seen in CKD patients with cognitive dysfunction may be attributed to pathological changes within the brain.

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.

Increased hippocampal activation in ApoE-4 carriers and non-carriers with amnestic mild cognitive impairment.

PubMed

Tran, Tammy T; Speck, Caroline L; Pisupati, Aparna; Gallagher, Michela; Bakker, Arnold

2017-01-01

Increased fMRI activation in the hippocampus is recognized as a signature characteristic of the amnestic mild cognitive impairment (aMCI) stage of Alzheimer's disease (AD). Previous work has localized this increased activation to the dentate gyrus/CA3 subregion of the hippocampus and showed a correlation with memory impairments in those patients. Increased hippocampal activation has also been reported in carriers of the ApoE-4 allelic variation independently of mild cognitive impairment although these findings were not localized to a hippocampal subregion. To assess the ApoE-4 contribution to increased hippocampal fMRI activation, patients with aMCI genotyped for ApoE-4 status and healthy age-matched control participants completed a high-resolution fMRI scan while performing a memory task designed to tax hippocampal subregion specific functions. Consistent with previous reports, patients with aMCI showed increased hippocampal activation in the left dentate gyrus/CA3 region of the hippocampus as well as memory task errors attributable to this subregion. However, this increased fMRI activation in the hippocampus did not differ between ApoE-4 carriers and ApoE-4 non-carriers and the proportion of memory errors attributable to dentate gyrus/CA3 function did not differ between ApoE-4 carriers and ApoE-4 non-carriers. These results indicate that increased fMRI activation of the hippocampus observed in patients with aMCI is independent of ApoE-4 status and that ApoE-4 does not contribute to the dysfunctional hippocampal activation or the memory errors attributable to this subregion in these patients.

Making sense of mild cognitive impairment: a qualitative exploration of the patient's experience.

PubMed

Lingler, Jennifer Hagerty; Nightingale, Marcie C; Erlen, Judith A; Kane, April L; Reynolds, Charles F; Schulz, Richard; DeKosky, Steven T

2006-12-01

The proposed dementia precursor state of mild cognitive impairment is emerging as a primary target of aging research. Yet, little is known about the subjective experience of living with a diagnosis of mild cognitive impairment. This study examines, from the patient's perspective, the experience of living with and making sense of the diagnosis. We recruited 12 older adults with amnestic or nonamnestic mild cognitive impairment from a university-based memory disorders clinic. We conducted in-home, semistructured interviews in order to elicit rich descriptions of the personal experience of having mild cognitive impairment. We used the qualitative method of grounded theory to analyze narrative data. Understanding and coming to terms with the syndrome, or assigning meaning, constituted a fundamental aspect of living with a diagnosis of mild cognitive impairment. This process comprised interrelated emotional and cognitive dimensions. Participants employed a range of positive, neutral, and negative phrasing in order to depict their emotional reactions to receiving a diagnosis. Cognitive representations of mild cognitive impairment included both prognosis-focused and face-value appraisals. Expectations of normal aging, personal experience with dementia, and concurrent health problems were key contextual factors that provided the backdrop against which participants assigned meaning to a diagnosis of mild cognitive impairment. Clinicians who disclose diagnoses of mild cognitive impairment need to be mindful of the potential for varying interpretations of the information that is conveyed. Future research needs to include systematic, longitudinal investigations of illness representation and its impact on health behaviors among individuals with mild cognitive impairment.

Mild Cognitive Impairment in Parkinson's Disease-What Is It?

PubMed

Weil, Rimona S; Costantini, Alyssa A; Schrag, Anette E

2018-03-10

Mild cognitive impairment is a common feature of Parkinson's disease, even at the earliest disease stages, but there is variation in the nature and severity of cognitive involvement and in the risk of conversion to Parkinson's disease dementia. This review aims to summarise current understanding of mild cognitive impairment in Parkinson's disease. We consider the presentation, rate of conversion to dementia, underlying pathophysiology and potential biomarkers of mild cognitive impairment in Parkinson's disease. Finally, we discuss challenges and controversies of mild cognitive impairment in Parkinson's disease. Large-scale longitudinal studies have shown that cognitive involvement is important and common in Parkinson's disease and can present early in the disease course. Recent criteria for mild cognitive impairment in Parkinson's provide the basis for further study of cognitive decline and for the progression of different cognitive phenotypes and risk of conversion to dementia. Improved understanding of the underlying pathology and progression of cognitive change are likely to lead to opportunities for early intervention for this important aspect of Parkinson's disease.

Efficacy of a Multimodal Cognitive Rehabilitation Including Psychomotor and Endurance Training in Parkinson's Disease

PubMed Central

Reuter, I.; Mehnert, S.; Sammer, G.; Oechsner, M.; Engelhardt, M.

2012-01-01

Mild cognitive impairment, especially executive dysfunction might occur early in the course of Parkinson's disease. Cognitive training is thought to improve cognitive performance. However, transfer of improvements achieved in paper and pencil tests into daily life has been difficult. The aim of the current study was to investigate whether a multimodal cognitive rehabilitation programme including physical exercises might be more successful than cognitive training programmes without motor training. 240 PD-patients were included in the study and randomly allocated to three treatment arms, group A cognitive training, group B cognitive training and transfer training and group C cognitive training, transfer training and psychomotor and endurance training. The primary outcome measure was the ADAS-Cog. The secondary outcome measure was the SCOPA-Cog. Training was conducted for 4 weeks on a rehabilitation unit, followed by 6 months training at home. Caregivers received an education programme. The combination of cognitive training using paper and pencil and the computer, transfer training and physical training seems to have the greatest effect on cognitive function. Thus, patients of group C showed the greatest improvement on the ADAS-Cog and SCOPA-COG and were more likely to continue with the training programme after the study. PMID:23008772

Nose-to-Brain Delivery of Peptide Drugs Enhanced by Coadministration of Cell-penetrating Peptides: Therapeutic Potential for Dementia.

PubMed

Kamei, Noriyasu

2017-01-01

Recent reports suggest that peptide drugs such as insulin have the potential to serve as therapeutics in neurodegenerative diseases such as Alzheimer's disease. However, the transport of these drugs to the therapeutic target, the brain, is significantly hindered by the blood-brain barrier (BBB). Intranasal administration appears to be an ideal solution for drug delivery to the brain, bypassing the BBB, however the entry of peptide drugs into neuronal and epithelial cells in the olfactory mucosa remains low. In this study, we therefore examined whether intranasal coadministration of cell-penetrating peptides (CPPs) could improve nose-to-brain drug transport. In both mice and rats, we found that direct transport of insulin into the brain was significantly facilitated when coadministered with amphipathic CPP penetratin, and eventually insulin reached the deeper regions of the brain such as the hippocampus. In the mouse line senescence-accelerated mouse prone-8 (SAMP8), spatial learning tests demonstrated that long-term intranasal coadministration of insulin with penetratin improved mild memory loss in the early stages of dementia. In contrast, the severe cognitive dysfunction in the aged SAMP8 mice was preserved despite intranasal coadministration of insulin with penetratin. The immunohistological examination of the hippocampus suggested that enhanced nose-to-brain delivery of insulin had a partial neuroprotective effect but unexpectedly increased amyloid β plaque deposition. In conclusion, intranasal coadministration of insulin with CPPs has the potential to serve as a therapeutic for mild cognitive dysfunction. To identify suitable pharmacotherapy for dementia with severe pathology, further studies of nose-to-brain delivery of molecularly appropriate biopharmaceuticals are necessary.

A longitudinal analysis of cognitive dysfunction, coping, and depression in multiple sclerosis.

PubMed

Rabinowitz, Amanda R; Arnett, Peter A

2009-09-01

Using a longitudinal design, the authors examined coping and cognitive functioning in the development of depression in individuals with multiple sclerosis (MS). Coping style was evaluated in 2 conceptually distinct roles: as moderator and mediator of the impact of cognitive dysfunction on depression. Using indices derived from the COPE (C. S. Carver, M. F. Scheier, & J. K. Weintraub, 1989), the authors operationalized coping in 3 ways-as active, avoidant, and an index accounting for relative levels of both. Coping both moderated and partially mediated the relationship between cognitive dysfunction and depression. Moderation results suggest that the relationship between cognitive dysfunction and depression is dependent on coping style-adaptive coping protects individuals from experiencing depression related to their cognitive deficits; however, when individuals use maladaptive coping, cognitive dysfunction puts them at risk for depression. Mediational results suggest that cognitive dysfunction leads to depression partially due to cognitive dysfunction's effects on coping. That is, cognitive deficits may impair individuals' ability to use adaptive coping strategies, leaving them more likely to use maladaptive strategies. Clinical and theoretical implications of these findings are discussed.

Acute caffeine administration effect on brain activation patterns in mild cognitive impairment.

PubMed

Haller, Sven; Montandon, Marie-Louise; Rodriguez, Cristelle; Moser, Dominik; Toma, Simona; Hofmeister, Jeremy; Sinanaj, Indrit; Lovblad, Karl-Olof; Giannakopoulos, Panteleimon

2014-01-01

Previous studies showed that acute caffeine administration enhances task-related brain activation in elderly individuals with preserved cognition. To explore the effects of this widely used agent on cognition and brain activation in early phases of cognitive decline, we performed a double-blinded, placebo-controlled functional magnetic resonance imaging (fMRI) study during an n-back working memory task in 17 individuals with mild cognitive impairment (MCI) compared to 17 age-matched healthy controls (HC). All individuals were regular caffeine consumers with an overnight abstinence and given 200 mg caffeine versus placebo tablets 30 minutes before testing. Analyses included assessment of task-related activation (general linear model), functional connectivity (tensorial-independent component analysis, TICA), baseline perfusion (arterial spin labeling, ASL), grey matter density (voxel-based morphometry, VBM), and white matter microstructure (tract-based spatial statistics, TBSS). Acute caffeine administration induced a focal activation of the prefrontal areas in HC with a more diffuse and posteromedial activation pattern in MCI individuals. In MCI, TICA documented a significant caffeine-related enhancement in the prefrontal cortex, supplementary motor area, ventral premotor and parietal cortex as well as the basal ganglia and cerebellum. The absence of significant group differences in baseline ASL perfusion patterns supports a neuronal rather than a purely vascular origin of these differences. The VBM and TBSS analyses excluded potentially confounding differences in grey matter density and white matter microstructure between MCI and HC. The present findings suggest a posterior displacement of working memory-related brain activation patterns after caffeine administration in MCI that may represent a compensatory mechanism to counterbalance a frontal lobe dysfunction.

Association of Pesticide Exposure with Neurologic Dysfunction and Disease

PubMed Central

Kamel, Freya; Hoppin, Jane A.

2004-01-01

Poisoning by acute high-level exposure to certain pesticides has well-known neurotoxic effects, but whether chronic exposure to moderate levels of pesticides is also neurotoxic is more controversial. Most studies of moderate pesticide exposure have found increased prevalence of neurologic symptoms and changes in neurobehavioral performance, reflecting cognitive and psychomotor dysfunction. There is less evidence that moderate exposure is related to deficits in sensory or motor function or peripheral nerve conduction, but fewer studies have considered these outcomes. It is possible that the most sensitive manifestation of pesticide neurotoxicity is a general malaise lacking in specificity and related to mild cognitive dysfunction, similar to that described for Gulf War syndrome. Most studies have focused on organophosphate insecticides, but some found neuro-toxic effects from other pesticides, including fungicides, fumigants, and organochlorine and carbamate insecticides. Pesticide exposure may also be associated with increased risk of Parkinson disease; several classes of pesticides, including insecticides, herbicides, and fungicides, have been implicated. Studies of other neurodegenerative diseases are limited and inconclusive. Future studies will need to improve assessment of pesticide exposure in individuals and consider the role of genetic susceptibility. More studies of pesticides other than organophosphates are needed. Major unresolved issues include the relative importance of acute and chronic exposure, the effect of moderate exposure in the absence of poisoning, and the relationship of pesticide-related neurotoxicity to neurodegenerative disease. PMID:15198914

Exploring correlation between perceived parenting styles, early maladaptive schemas, and depression among women with depressive symptoms in iran and India- role of early maladaptive schemas as mediators and moderatos.

PubMed

Khajouei Nia, Maryam; Sovani, Anuradha; Sarami Forooshani, Gholam Reza

2014-12-01

Many studies have reported that inadequate parental styles can contribute to depressive symptoms through dysfunctional cognitive styles. This study aimed to investigate the association of dysfunctional schemas and parenting style with depression, as well as the role of maladaptive schemas such as moderators and mediators in Iran and India. The study sample was selected randomly and consisted of 200 (age group 16-60 y) depressed females (mild to moderate); 100 from Tehran (Iran) and another 100 from Pune (India). The type of the research was causal-comparative. The data collection took place in hospitals and clinics in the targeted cities. Descriptive statistic tests and hierarchical multiple regression were executed (for the purpose of analyzing data) by SPSS 17. It was demonstrated that the association between parenting and depression was not moderated by early maladaptive schemas. On the contrary, the results supported meditational models in which parenting styles are associated with the cognitive schemas, and these in turn are related to depressive symptoms. It was also found that abandonment mediates the impacts of maternal style on depression in Iran. On the other hand, abandonment and punitiveness schemas mediated the relation between paternal style and depression in India. These findings suggest that the correlation between childhood experiences and depression in adulthood are mediated by dysfunctional schemas.

Processing complex pseudo-words in mild cognitive impairment: The interaction of preserved morphological rule knowledge with compromised cognitive ability.

PubMed

Manouilidou, Christina; Dolenc, Barbara; Marvin, Tatjana; Pirtošek, Zvezdan

2016-01-01

Mild cognitive impairment (MCI) affects the cognitive performance of elderly adults. However, the level of severity is not high enough to be diagnosed with dementia. Previous research reports subtle language impairments in individuals with MCI specifically in domains related to lexical meaning. The present study used both off-line (grammaticality judgment) and on-line (lexical decision) tasks to examine aspects of lexical processing and how they are affected by MCI. 21 healthy older adults and 23 individuals with MCI saw complex pseudo-words that violated various principles of word formation in Slovenian and decided if each letter string was an actual word of their language. The pseudo-words ranged in their degree of violability. A task effect was found, with MCI performance to be similar to that of healthy controls in the off-line task but different in the on-line task. Overall, the MCI group responded slower than the elderly controls. No significant differences were observed in the off-line task, while the on-line task revealed a main effect of Violation type, a main effect of Group and a significant Violation × Group interaction reflecting a difficulty for the MCI group to process pseudo-words in real time. That is, while individuals with MCI seem to preserve morphological rule knowledge, they experience additional difficulties while processing complex pseudo-words. This was attributed to an executive dysfunction associated with MCI that delays the recognition of ungrammatical formations.

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).

Gray matter volume and dual-task gait performance in mild cognitive impairment.

PubMed

Doi, Takehiko; Blumen, Helena M; Verghese, Joe; Shimada, Hiroyuki; Makizako, Hyuma; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Suzuki, Takao

2017-06-01

Dual-task gait performance is impaired in older adults with mild cognitive impairment, but the brain substrates associated with dual-task gait performance are not well-established. The relationship between gray matter and gait speed under single-task and dual-task conditions (walking while counting backward) was examined in 560 seniors with mild cognitive impairment (non-amnestic mild cognitive impairment: n = 270; mean age = 72.4 yrs., 63.6 % women; amnestic mild cognitive impairment: n = 290; mean age = 73.4 yrs., 45.4 % women). Multivariate covariance-based analyses of magnetic resonance imaging data, adjusted for potential confounders including single-task gait speed, were performed to identify gray matter patterns associated with dual-task gait speed. There were no differences in gait speed or cognitive performance during dual-task gait between individuals with non-amnestic mild cognitive impairment and amnestic mild cognitive impairment. Overall, increased dual-task gait speed was associated with a gray matter pattern of increased volume in medial frontal gyrus, superior frontal gyrus, anterior cingulate, cingulate, precuneus, fusiform gyrus, middle occipital gyrus, inferior temporal gyrus and middle temporal gyrus. The relationship between dual-task gait speed and brain substrates also differed by mild cognitive impairment subtype. Our study revealed a pattern of gray matter regions associated with dual-task performance. Although dual-task gait performance was similar in amnestic and non-amnestic mild cognitive impairment, the gray matter patterns associated with dual-task gait performance differed by mild cognitive impairment subtype. These findings suggest that the brain substrates supporting dual-task gait performance in amnestic and non-amnestic subtypes are different, and consequently may respond differently to interventions, or require different interventions.

Gray matter volume and dual-task gait performance in mild cognitive impairment

PubMed Central

Blumen, Helena M.; Verghese, Joe; Shimada, Hiroyuki; Makizako, Hyuma; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Suzuki, Takao

2017-01-01

Dual-task gait performance is impaired in older adults with mild cognitive impairment, but the brain substrates associated with dual-task gait performance are not well-established. The relationship between gray matter and gait speed under single-task and dual-task conditions (walking while counting backward) was examined in 560 seniors with mild cognitive impairment (non-amnestic mild cognitive impairment: n = 270; mean age = 72.4 yrs., 63.6 % women; amnestic mild cognitive impairment: n = 290; mean age = 73.4 yrs., 45.4 % women). Multivariate covariance-based analyses of magnetic resonance imaging data, adjusted for potential confounders including single-task gait speed, were performed to identify gray matter patterns associated with dual-task gait speed. There were no differences in gait speed or cognitive performance during dual-task gait between individuals with non-amnestic mild cognitive impairment and amnestic mild cognitive impairment. Overall, increased dual-task gait speed was associated with a gray matter pattern of increased volume in medial frontal gyrus, superior frontal gyrus, anterior cingulate, cingulate, precuneus, fusiform gyrus, middle occipital gyrus, inferior temporal gyrus and middle temporal gyrus. The relationship between dual-task gait speed and brain substrates also differed by mild cognitive impairment subtype. Our study revealed a pattern of gray matter regions associated with dual-task performance. Although dual-task gait performance was similar in amnestic and non-amnestic mild cognitive impairment, the gray matter patterns associated with dual-task gait performance differed by mild cognitive impairment subtype. These findings suggest that the brain substrates supporting dual-task gait performance in amnestic and non-amnestic subtypes are different, and consequently may respond differently to interventions, or require different interventions. PMID:27392792

Gait, dual task and history of falls in elderly with preserved cognition, mild cognitive impairment, and mild Alzheimer's disease.

PubMed

Ansai, Juliana H; Andrade, Larissa P; Rossi, Paulo G; Takahashi, Anielle C M; Vale, Francisco A C; Rebelatto, José R

Studies with functional and applicable methods and new cognitive demands involving executive function are needed to improve screening, prevention and rehabilitation of cognitive impairment and falls. to identify differences in gait, dual task performances, and history of falls between elderly people with preserved cognition, mild cognitive impairment and mild Alzheimer's disease. A cross-sectional study was conducted. The sample consisted of 40 community-dwelling older adults with preserved cognition, 40 older adults with mild cognitive impairment, and 38 older adults with mild Alzheimer's disease. The assessment consisted of anamneses, gait (measured by the 10-meter walk test), dual task (measured by the Timed Up and Go Test associated with the motor-cognitive task of calling a phone number), and history of falls in the past year. There were no differences among all groups for all variables. However, the Alzheimer's disease Group performed significantly worse in the dual task than the other groups. No item of dual task could distinguish people with preserved cognition from those with mild cognitive impairment. The groups with cognitive impairment included more fallers, and specific characteristics in history of falls between groups were identified. Dual task could distinguish Alzheimer's disease patients specifically from other cognitive profiles. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Normative Values for the German Version of the Montreal Cognitive Assessment (MoCA)

ClinicalTrials.gov

2018-05-30

Cognitive Impairment; Cognitive Decline; Cognition Disorders; Cognitive Symptom; Cognitive Change; Cognitive Deterioration; Cognitive Abnormality; Cognitive Impairment, Mild; Cognition Disorders in Old Age; Dementia; Dementia Alzheimers; Dementia, Alzheimer Type; Dementia, Mild; Dementia of Alzheimer Type

Executive dysfunction affects word list recall performance: Evidence from amyotrophic lateral sclerosis and other neurodegenerative diseases.

PubMed

Consonni, Monica; Rossi, Stefania; Cerami, Chiara; Marcone, Alessandra; Iannaccone, Sandro; Francesco Cappa, Stefano; Perani, Daniela

2017-03-01

The Rey Auditory Verbal Learning Test (RAVLT) is widely used in clinical practice to evaluate verbal episodic memory. While there is evidence that RAVLT performance can be influenced by executive dysfunction, the way executive disorders affect the serial position curve (SPC) has not been yet explored. To this aim, we analysed immediate and delayed recall performances of 13 non-demented amyotrophic lateral sclerosis (ALS) patients with a specific mild executive dysfunction (ALSci) and compared their performances to those of 48 healthy controls (HC) and 13 cognitively normal patients with ALS. Moreover, to control for the impact of a severe dysexecutive syndrome and a genuine episodic memory deficit on the SPC, we enrolled 15 patients with a diagnosis of behavioural variant of frontotemporal dementia (bvFTD) and 18 patients with probable Alzheimer's disease (AD). Results documented that, compared to cognitively normal subjects, ALSci patients had a selective mid-list impairment for immediate recall scores. The bvFTD group obtained low performances with a selectively increased forgetting rate for terminal items, whereas the AD group showed a disproportionately large memory loss on the primary and middle part of the SPC for immediate recall scores and were severely impaired in the delayed recall trial. These results suggested that subtle executive dysfunctions might influence the recall of mid-list items, possibly reflecting deficiency in control strategies at retrieval of word lists, whereas severer dysexecutive syndrome might also affect the recall of terminal items possibly due to attention deficit or retroactive interference. © 2015 The British Psychological Society.

Salience Network and Parahippocampal Dopamine Dysfunction in Memory-Impaired Parkinson Disease

PubMed Central

Christopher, Leigh; Duff-Canning, Sarah; Koshimori, Yuko; Segura, Barbara; Boileau, Isabelle; Chen, Robert; Lang, Anthony E.; Houle, Sylvain; Rusjan, Pablo; Strafella, Antonio P.

2016-01-01

Objective Patients with Parkinson disease (PD) and mild cognitive impairment (MCI) are vulnerable to dementia and frequently experience memory deficits. This could be the result of dopamine dysfunction in corticostriatal networks (salience, central executive networks, and striatum) and/or the medial temporal lobe. Our aim was to investigate whether dopamine dysfunction in these regions contributes to memory impairment in PD. Methods We used positron emission tomography imaging to compare D2 receptor availability in the cortex and striatal (limbic and associative) dopamine neuron integrity in 4 groups: memory-impaired PD (amnestic MCI; n=9), PD with nonamnestic MCI (n=10), PD without MCI (n=11), and healthy controls (n=14). Subjects were administered a full neuropsychological test battery for cognitive performance. Results Memory-impaired patients demonstrated more significant reductions in D2 receptor binding in the salience network (insular cortex and anterior cingulate cortex [ACC] and the right parahippocampal gyrus [PHG]) compared to healthy controls and patients with no MCI. They also presented reductions in the right insula and right ACC compared to nonamnestic MCI patients. D2 levels were correlated with memory performance in the right PHG and left insula of amnestic patients and with executive performance in the bilateral insula and left ACC of all MCI patients. Associative striatal dopamine denervation was significant in all PD patients. Interpretation Dopaminergic differences in the salience network and the medial temporal lobe contribute to memory impairment in PD. Furthermore, these findings indicate the vulnerability of the salience network in PD and its potential role in memory and executive dysfunction. PMID:25448687

Occurrence of pituitary dysfunction following traumatic brain injury.

PubMed

Bondanelli, Marta; De Marinis, Laura; Ambrosio, Maria Rosaria; Monesi, Marcello; Valle, Domenico; Zatelli, Maria Chiara; Fusco, Alessandra; Bianchi, Antonio; Farneti, Marco; degli Uberti, Ettore C I

2004-06-01

Traumatic brain injury (TBI) may be associated with impairment of pituitary hormone secretion, which may contribute to long-term physical, cognitive, and psychological disability. We studied the occurrence and risk factors of pituitary dysfunction, including growth hormone deficiency (GHD) in 50 patients (mean age 37.6 +/- 2.4 years; 40 males, age 20-60 years; 10 females, age 23-87 years) with TBI over 5 years. Cranial or facial fractures were documented in 12 patients, and neurosurgery was performed in 14. According to the Glasgow Coma Scale (GCS), 16 patients had suffered from mild, 7 moderate, and 27 severe TBI. Glasgow Outcome Scale (GOS) indicated severe disability in 5, moderate disability in 11, and good recovery in 34 cases. Basal pituitary hormone evaluation, performed once at times variable from 12 to 64 months after TBI, showed hypogonadotrophic hypogonadism in 7 (14%), central hypothyroidism in 5 (10%), low prolactin (PRL) levels in 4 (8%), and high PRL levels in 4 (8%) cases. All subjects had normal corticotrophic and posterior pituitary function. Seven patients showed low insulin-like growth factor-I (IGF-I) levels for age and sex. Results of GHRH plus arginine testing indicated partial GHD in 10 (20%) and severe GHD in 4 (8%) cases. Patients with GHD were older (p <0.05) than patients with normal GH secretion. Magnetic resonance imaging demonstrated pituitary abnormalities in 2 patients; altogether pituitary dysfunction was observed in 27 (54%) patients. Six patients (12%) showed a combination of multiple abnormalities. Occurrence of pituitary dysfunction was 37.5%, 57.1%, and 59.3% in the patients with mild, moderate, and severe TBI, respectively. GCS scores were significantly (p <0.02) lower in patients with pituitary dysfunction compared to those with normal pituitary function (8.3 +/- 0.5 vs. 10.2 +/- 0.6). No relationship was detected between pituitary dysfunction and years since TBI, type of injury, and outcome from TBI. In conclusion, subjects with a history of TBI frequently develop pituitary dysfunction, especially GHD. Therefore, evaluation of pituitary hormone secretion, including GH, should be included in the long-term follow-up of all TBI patients so that adequate hormone replacement therapy may be administered.

Memory performance on the story recall test and prediction of cognitive dysfunction progression in mild cognitive impairment and Alzheimer's dementia.

PubMed

Park, Jong-Hwan; Park, Hyuntae; Sohn, Sang Wuk; Kim, Sungjae; Park, Kyung Won

2017-10-01

To determine the factors that influence diagnosis and differentiation of patients with mild cognitive impairment (MCI) and Alzheimer's dementia (AD) by comparing memory test results at baseline with those at 1-2-year follow up. We consecutively recruited 23 healthy participants, 44 MCI patients and 27 patients with very mild AD according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorder Association criteria for probable Alzheimer's disease and Petersen's clinical diagnostic criteria. We carried out detailed neuropsychological tests, including the Story Recall Test (SRT) and the Seoul Verbal Learning Test, for all participants. We defined study participants as the "progression group" as follows: (i) participants who showed conversion to dementia from the MCI state; and (ii) those with dementia who showed more than a three-point decrement in their Mini-Mental State Examination scores with accompanying functional decline from baseline status, which were ascertained by physician's clinical judgment. The SRT delayed recall scores were significantly lower in the patients with mild AD than in those with MCI and after progression. Lower (relative risk 1.1, 95% confidence interval 0.1-1.6) and higher SRT delayed recall scores (relative risk 2.1, confidence interval 1.0-2.8), and two-test combined immediate and delayed recall scores (relative risk 2.0, confidence interval 0.9-2.3; and relative risk 2.8, confidence interval 1.1-4.2, respectively) were independent predictors of progression in a stepwise multiple adjusted Cox proportional hazards model, with age, sex, depression and educational level forced into the model. The present study suggests that the SRT delayed recall score independently predicts progression to dementia in patients with MCI. Geriatr Gerontol Int 2017; 17: 1603-1609. © 2016 Japan Geriatrics Society.

Dual-task as a predictor of falls in older people with mild cognitive impairment and mild Alzheimer's disease: a prospective cohort study.

PubMed

Gonçalves, Jessica; Ansai, Juliana Hotta; Masse, Fernando Arturo Arriagada; Vale, Francisco Assis Carvalho; Takahashi, Anielle Cristhine de Medeiros; Andrade, Larissa Pires de

2018-04-04

A dual-task tool with a challenging and daily secondary task, which involves executive functions, could facilitate the screening for risk of falls in older people with mild cognitive impairment or mild Alzheimer's disease. To verify if a motor-cognitive dual-task test could predict falls in older people with mild cognitive impairment or mild Alzheimer's disease, and to establish cutoff scores for the tool for both groups. A prospective study was conducted with community-dwelling older adults, including 40 with mild cognitive impairment and 38 with mild Alzheimer's disease. The dual-task test consisted of the Timed up and Go Test associated with a motor-cognitive task using a phone to call. Falls were recorded during six months by calendar and monthly telephone calls and the participants were categorized as fallers or non-fallers. In the Mild cognitive impairment Group, fallers presented higher values in time (35.2s), number of steps (33.7 steps) and motor task cost (116%) on dual-task compared to non-fallers. Time, number of steps and motor task cost were significantly associated with falls in people with mild cognitive impairment. Multivariate analysis identified higher number of steps spent on the test to be independently associated with falls. A time greater than 23.88s (sensitivity=80%; specificity=61%) and a number of steps over 29.50 (sensitivity=65%; specificity=83%) indicated prediction of risk of falls in the Mild cognitive impairment Group. Among people with Alzheimer's disease, no differences in dual-task between fallers and non-fallers were found and no variable of the tool was able to predict falls. The dual-task predicts falls only in older people with mild cognitive impairment. Copyright © 2018 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Recollection and familiarity in amnesic mild cognitive impairment.

PubMed

Serra, Laura; Bozzali, Marco; Cercignani, Mara; Perri, Roberta; Fadda, Lucia; Caltagirone, Carlo; Carlesimo, Giovanni A

2010-05-01

To investigate whether, in patients with amnesic mild cognitive impairment (a-MCI), recognition deficits are mainly due to a selective impairment of recollection rather than familiarity. Nineteen patients with a-MCI and 23 sex-, age-, and education-matched healthy controls underwent two experimental investigations, using the Process Dissociation Procedure (PDP) and the Remember/Know (R/K) procedure, to assess the differential contribution of recollection and familiarity to their recognition performance. Both experimental procedures revealed a selective preservation of familiarity in a-MCI patients. Moreover, the R/K procedure showed a statistically significant impairment of recollection in a-MCI patients for words that were either read or anagrammed during the study phase. A-MCI is known to be commonly associated with a high risk of conversion to Alzheimer's disease (AD). Several previous studies have demonstrated a characteristic impairment of episodic memory in a-MCI, with an early dysfunction of recognition. Our findings are consistent with the knowledge of neurodegeneration occurring in AD, which is characterized, at the earliest disease stages, by a selective involvement of the entorhinal cortex. Moreover, the current study supports the dual process model of recognition, which hypothesizes recollection and familiarity to be independent processes associated with distinct anatomical substrates.

Oxidative stress in Alzheimer disease and mild cognitive impairment: evidence from human data provided by redox proteomics.

PubMed

Swomley, Aaron M; Butterfield, D Allan

2015-10-01

Alzheimer disease (AD) is a neurodegenerative disease with many known pathological features, yet there is still much debate into the exact cause and mechanisms for progression of this degenerative disorder. The amyloid-beta (Aβ)-induced oxidative stress hypothesis postulates that it is the oligomeric Aβ that inserts into membrane systems to initiate much of the oxidative stress observed in brain during the progression of the disease. In order to study the effects of oxidative stress on tissue from patients with AD and amnestic mild cognitive impairment (MCI), we have developed a method called redox proteomics that identifies specific brain proteins found to be selectively oxidized. Here, we discuss experimental findings of oxidatively modified proteins involved in three key cellular processes implicated in the pathogenesis of AD progression: energy metabolism, cell signaling and neurotransmission, as well as the proteasomal degradation pathways and antioxidant response systems. These proteomics studies conducted by our laboratory and others in the field shed light on the molecular changes imposed on the cells of AD and MCI brain, through the deregulated increase in oxidative/nitrosative stress inflicted by Aβ and mitochondrial dysfunction.

The cognitive profile of occipital lobe epilepsy and the selective association of left temporal lobe hypometabolism with verbal memory impairment.

PubMed

Knopman, Alex A; Wong, Chong H; Stevenson, Richard J; Homewood, Judi; Mohamed, Armin; Somerville, Ernest; Eberl, Stefan; Wen, Lingfeng; Fulham, Michael; Bleasel, Andrew F

2014-08-01

We investigated the cognitive profile of structural occipital lobe epilepsy (OLE) and whether verbal memory impairment is selectively associated with left temporal lobe hypometabolism on [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). Nine patients with OLE, ages 8-29 years, completed presurgical neuropsychological assessment. Composite measures were calculated for intelligence quotient (IQ), speed, attention, verbal memory, nonverbal memory, and executive functioning. In addition, the Wisconsin Card Sorting Test (WCST) was used as a specific measure of frontal lobe functioning. Presurgical FDG-PET was analyzed with statistical parametric mapping in 8 patients relative to 16 healthy volunteers. Mild impairments were evident for IQ, speed, attention, and executive functioning. Four patients demonstrated moderate or severe verbal memory impairment. Temporal lobe hypometabolism was found in seven of eight patients. Poorer verbal memory was associated with left temporal lobe hypometabolism (p = 0.002), which was stronger (p = 0.03 and p = 0.005, respectively) than the association of left temporal lobe hypometabolism with executive functioning or with performance on the WCST. OLE is associated with widespread cognitive comorbidity, suggesting cortical dysfunction beyond the occipital lobe. Verbal memory impairment is selectively associated with left temporal lobe hypometabolism in OLE, supporting a link between neuropsychological dysfunction and remote hypometabolism in focal epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Impaired Verb Fluency: A Sign of Mild Cognitive Impairment

ERIC Educational Resources Information Center

Ostberg, Per; Fernaeus, Sven-Erik; Hellstrom, Ake; Bogdanovic, Nenad; Wahlund, Lars Olof

2005-01-01

We assessed verb fluency vs. noun and letter-based fluency in 199 subjects referred for cognitive complaints including Subjective Cognitive Impairment, Mild Cognitive Impairment, and Alzheimer's disease. ANCOVAs and factor analyses identified verb, noun, and letter-based fluency as distinct tasks. Verb fluency performance in Mild Cognitive…

Hearing Impairment, Mild Cognitive Impairment, and Dementia: A Meta-Analysis of Cohort Studies.

PubMed

Wei, Jingkai; Hu, Yirui; Zhang, Li; Hao, Qiang; Yang, Ruowei; Lu, Haidong; Zhang, Xuan; Chandrasekar, Eeshwar K

2017-01-01

To estimate a pooled association between hearing impairment and risk of mild cognitive impairment and dementia. PubMed, Embase, and Web of Science were searched for prospective cohort studies that examined the association between hearing impairment and risk of mild cognitive impairment and/or dementia. Random-effects models were fitted to estimate the summary risk ratios (RRs) and 95% confidence interval (CIs), which represents the pooled association between hearing impairment with risk of mild cognitive impairment and dementia, compared to subjects free of hearing impairment. Four studies on hearing impairment with mild cognitive impairment and 7 studies on hearing impairment with dementia were included in the meta-analysis. A total of 15,521 subjects were studied with follow-up periods between 2 and 16.8 years. Hearing impairment was associated with a greater risk of mild cognitive impairment (RR = 1.30, 95% CI: 1.12, 1.51) and dementia (RR = 2.39, 95% CI: 1.58, 3.61). The meta-analysis showed that hearing impairment is associated with a higher risk of mild cognitive impairment and dementia among older adults.

Reduced global brain metabolism but maintained vascular function in amnestic mild cognitive impairment.

PubMed

Thomas, Binu P; Sheng, Min; Tseng, Benjamin Y; Tarumi, Takashi; Martin-Cook, Kristen; Womack, Kyle B; Cullum, Munro C; Levine, Benjamin D; Zhang, Rong; Lu, Hanzhang

2017-04-01

Amnestic mild cognitive impairment represents an early stage of Alzheimer's disease, and characterization of physiological alterations in mild cognitive impairment is an important step toward accurate diagnosis and intervention of this condition. To investigate the extent of neurodegeneration in patients with mild cognitive impairment, whole-brain cerebral metabolic rate of oxygen in absolute units of µmol O 2 /min/100 g was quantified in 44 amnestic mild cognitive impairment and 28 elderly controls using a novel, non-invasive magnetic resonance imaging method. We found a 12.9% reduction ( p = 0.004) in cerebral metabolic rate of oxygen in mild cognitive impairment, which was primarily attributed to a reduction in the oxygen extraction fraction, by 10% ( p = 0.016). Global cerebral blood flow was not found to be different between groups. Another aspect of vascular function, cerebrovascular reactivity, was measured by CO 2 -inhalation magnetic resonance imaging and was found to be equivalent between groups. Therefore, there seems to be a global, diffuse diminishment in neural function in mild cognitive impairment, while their vascular function did not show a significant reduction.

The boundaries of the cognitive phenotype of autism: theory of mind, central coherence and ambiguous figure perception in young people with autistic traits.

PubMed

Best, Catherine S; Moffat, Vivien J; Power, Michael J; Owens, David G C; Johnstone, Eve C

2008-05-01

Theory of Mind, Weak Central Coherence and executive dysfunction, were investigated as a function of behavioural markers of autism. This was irrespective of the presence or absence of a diagnosis of an autistic spectrum disorder. Sixty young people completed the Social Communication Questionnaire (SCQ), false belief tests, the block design test, viewed visual illusions and an ambiguous figure. A logistic regression was performed and it was found that Theory of Mind, central coherence and ambiguous figure variables significantly contributed to prediction of behavioural markers of autism. These findings provide support for the continuum hypothesis of autism. That is, mild autistic behavioural traits are distributed through the population and these behavioural traits may have the same underlying cognitive determinants as autistic disorder.

Effect of physical activity on memory function in older adults with mild Alzheimer's disease and mild cognitive impairment.

PubMed

Tanigawa, Takanori; Takechi, Hajime; Arai, Hidenori; Yamada, Minoru; Nishiguchi, Shu; Aoyama, Tomoki

2014-10-01

It is very important to maintain cognitive function in patients with mild cognitive disorder. The aim of the present study was to determine whether the amount of physical activity is associated with memory function in older adults with mild cognitive disorder. A total of 47 older adults with mild cognitive disorder were studied; 30 were diagnosed with mild Alzheimer's disease and 17 with mild cognitive impairment. The global cognitive function, memory function, physical performance and amount of physical activity were measured in these patients. We divided these patients according to their walking speed (<1 m/s or >1 m/s). A total of 26 elderly patients were classified as the slow walking group, whereas 21 were classified as the normal walking group. The normal walking group was younger and had significantly better scores than the slow walking group in physical performance. Stepwise multiple linear regression analysis showed that only the daily step counts were associated with the Scenery Picture Memory Test in patients of the slow walking group (β=0.471, P=0.031), but not other variables. No variable was significantly associated with the Scenery Picture Memory Test in the normal walking group. Memory function was strongly associated with the amount of physical activity in patients with mild cognitive disorder who showed slow walking speed. The results show that lower physical activities could be a risk factor for cognitive decline, and that cognitive function in the elderly whose motor function and cognitive function are declining can be improved by increasing the amount of physical activity. © 2014 Japan Geriatrics Society.

On Swedish women's distressing sexual dysfunctions: some concomitant conditions and life satisfaction.

PubMed

Oberg, Katarina; Sjögren Fugl-Meyer, Kerstin

2005-03-01

To explore the associations between women's distressing sexual dysfunctions and different aspects of life satisfaction together with women's concomitant socio-psychological characteristics. Thus, this descriptive article does not discuss causalities. A nationally representative sample of sexually active Swedish women aged 18-65 years in a heterosexual steady partner relationship participated in 1996 in a combined structured interview/questionnaire investigation. Personal sexual distress caused by low sexual interest, insufficient lubrication, orgasm dysfunction, dyspareunia, and vaginism was classified as manifest and mild. Concomitant conditions explored were perceived health, stability of domestic situation, perception of male partner's sexual functions/dysfunctions per se, and some socio-demographic factors. Satisfaction with life as a whole and with 10 different domains of life were reported by using the LiSat-11 checklist. Main results were that a multitude of the independent variables were univariately associated with manifest and, to a lesser extent, mild distressing sexual dysfunctions. This was particularly true for satisfaction with partner relationship and for male's sexual dysfunctions. By performing multiple logistic regressions, the numbers were markedly reduced. The resulting statistical models still contained sexual partner's sexual dysfunctions and satisfaction with partner relationship as dominant covariants of most distressing sexual dysfunctions. Reported low level of satisfaction with partner relationship and male sexual dysfunctions per se are likely to co-occur with manifest but, to a lesser extent, mild distressing sexual dysfunctions in Swedish women aged 18-65 years.

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.

Cognitive reserve as a moderator of postconcussive symptoms in children with complicated and uncomplicated mild traumatic brain injury

PubMed Central

Fay, Taryn B.; Yeates, Keith Owen; Taylor, H. Gerry; Bangert, Barbara; Dietrich, Ann; Nuss, Kathryn E.; Rusin, Jerome; Wright, Martha

2010-01-01

The occurrenceof postconcussive symptoms (PCS) following mild traumatic brain injury (TBI) in children may depend on cognitive reserve capacity. This prospective, longitudinal study examined whether the relationship between mild TBI and PCS is moderated by cognitive ability, which served as a proxy for cognitive reserve. Participants included 182 children with mild TBI and 99 children with orthopedic injuries (OI), ranging from 8 to 15 years of age when injured. Mild TBI were classified as complicated (n = 32) or uncomplicated (n = 150) depending on whether they were associated with trauma-related intracranial abnormalities on magnetic resonance imaging. PCS were assessed initially within 3 weeks of injury, and again at 1, 3, and 12 months post injury. The initial assessment also included standardized tests of children’s cognitive skills and retrospective parent ratings of pre-injury symptoms. Hierarchical linear modeling indicated that ratings of PCS were moderated jointly by cognitive ability and injury severity. Children of lower cognitive ability with a complicated mild TBI were especially prone to cognitive symptoms across time according to parents and to high acute levels of PCS according to children’s self-ratings. Cognitive reserve is an important moderator of the outcomes of mild TBI in children and adolescents. PMID:19835663

Vascular endothelial dysfunction in patients with mild obstructive sleep apnea syndrome.

PubMed

Duchna, Hans-Werner; Stoohs, Riccardo; Guilleminault, Christian; Christine Anspach, Marie; Schultze-Werninghaus, Gerhard; Orth, Maritta

2006-11-01

We investigated endothelial dysfunction, an early manifestation of atherosclerosis, in patients with mild obstructive sleep apnea syndrome (OSAS) (5/h < AHI < 15/h). Endothelium-dependent and -independent vasodilatory function was tested in 10 patients with mild OSAS, 12 healthy controls and 20 subjects with moderate to severe OSAS using the hand vein compliance technique. Maximum endothelium-dependent vasodilation to bradykinin (Emax) was significantly blunted in patients with mild OSAS (68.6 +/- 30.2 %) compared to healthy controls (94.8 +/- 9.5 %; p < 0.05; moderate to severe OSAS: 57.1 +/- 23.4 %; p = 0.33). Mean endothelium-independent venodilation was not altered. After 160.7 +/- 82.2 nights of CPAP therapy, mean Emax was significantly improved to 90.8 +/- 23.8 % (p < 0.01 vs. baseline; p = 0.7 vs. healthy controls) in 7 patients with mild OSAS. Systemic endothelium-dependent venodilation is markedly reduced in subjects with mild OSAS, which may imply adverse cardiovascular consequences. CPAP-treatment leads to a sustained restoration of endothelial dysfunction in these patients and is thus highly recommended.

Predictors and assessment of cognitive dysfunction resulting from ischaemic stroke

PubMed Central

Gottesman, Rebecca F; Hillis, Argye E

2013-01-01

Stroke remains a primary cause of morbidity throughout the world mainly because of its effect on cognition. Individuals can recover from physical disability resulting from stroke, but might be unable to return to their previous occupations or independent life because of cognitive impairments. Cognitive dysfunction ranges from focal deficits, resulting directly from an area of infarction or from hypoperfusion in adjacent tissue, to more global cognitive dysfunction. Global dysfunction is likely to be related to other underlying subclinical cerebrovascular disease, such as white-matter disease or subclinical infarcts. Study of cognitive dysfunction after stroke is complicated by varying definitions and lack of measurement of cognition before stroke. Additionally, stroke can affect white-matter connectivity, so newer imaging techniques, such as diffusion-tensor imaging and magnetisation transfer imaging, that can be used to assess this subclinical injury are important tools in the assessment of cognitive dysfunction after stroke. As research is increasingly focused on the role of preventable risk factors in the development of dementia, the role of stroke in the development of cognitive impairment and dementia could be another target for prevention. PMID:20723846

Relationships between gross- and fine motor functions, cognitive abilities, and self-regulatory aspects of students with physical disabilities.

PubMed

Varsamis, Panagiotis; Agaliotis, Ioannis

2015-12-01

This article reports research on self-regulatory aspects (i.e., goal-setting, self-efficacy and self-evaluation) of secondary and post-secondary students with congenital motor disabilities, who performed a ball-throwing-at-a-target task. Participants were divided into four subgroups presenting distinct combinations of motor and cognitive abilities (i.e., normal cognitive development and mild physical disabilities, normal cognitive development and severe physical disabilities, mild-to-moderate intellectual disability and mild physical disabilities, and mild-to-moderate intellectual disability and severe physical disabilities). Results showed that students presenting mild motor disabilities exhibited a positive self-concept and self-regulation profile, irrespective of their cognitive functioning. Students with considerable motor disabilities, but without cognitive challenges, presented a negative, though realistic self-concept and self-regulation profile. Finally, students with considerable motor disabilities and mild-to-moderate cognitive disabilities showed a positive, though unrealistic, self-regulation profile. The nature of the diverse relationship of motor and cognitive (dis)abilities to specific self-regulatory aspects are discussed, and important instructional implications are mentioned. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparison of two commonly used clinical cognitive screening tests to diagnose mild cognitive impairment in heart failure with the golden standard European Consortium Criteria.

PubMed

Alagiakrishnan, Kannayiram; Mah, Darren; Dyck, Jason R B; Senthilselvan, Ambikaipakan; Ezekowitz, Justin

2017-02-01

This study on mild cognitive impairment (MCI) in heart failure (HF) compares the utility of Montreal Cognitive Assessment (MoCA) to the Mini-Mental Status Exam (MMSE) for diagnosing MCI in a HF population when compared to the golden standard European Consortium Criteria (ECC). Participants were recruited from the Alberta HEART study at the Mazankowski Alberta Heart Institute in Edmonton and St. Mary's hospital in Camrose. This study enrolled 53 community adults aged>50years: 33 HF and 20 controls. Participants were assessed using both the MMSE and MoCA for MCI. MCI was diagnosed using the golden standard, European Consortium Criteria. Sensitivity and specificity analysis, positive and negative predictive values, likelihood ratios and kappa statistic were calculated. The mean age was 72.8years (SD 8.4), 60.4% were females and 34% had underlying ischemic heart disease. Overall, two thirds of patients (22/33, 66%) with HF had MCI. In comparison to European Consortium Criteria, the sensitivity and specificity of MoCA were 82% and 91% in identifying individuals with MCI, and MMSE were 9% and 91%, respectively. The positive and negative predictive values for MoCA were 95% and 71%, and for MMSE were 67% and 33%, respectively. Kappa statistics showed good agreement between MoCA and consortium criteria (kappa=0.68) and a low agreement between MMSE and consortium criteria (kappa=0.07). Cognitive dysfunction is common in patients with HF. Overall, the MoCA seems to be a better screening tool than MMSE for MCI in HF patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

ERIC Educational Resources Information Center

Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

2009-01-01

Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

Developing Interventions for Cancer-Related Cognitive Dysfunction in Childhood Cancer Survivors

PubMed Central

Ullrich, Nicole J.; Whelen, Megan J.; Lange, Beverly J.

2014-01-01

Survivors of childhood cancer frequently experience cancer-related cognitive dysfunction, commonly months to years after treatment for pediatric brain tumors, acute lymphoblastic leukemia (ALL), or tumors involving the head and neck. Risk factors for cancer-related cognitive dysfunction include young age at diagnosis, treatment with cranial irradiation, use of parenteral or intrathecal methotrexate, female sex, and pre-existing comorbidities. Limiting use and reducing doses and volume of cranial irradiation while intensifying chemotherapy have improved survival and reduced the severity of cognitive dysfunction, especially in leukemia. Nonetheless, problems in core functional domains of attention, processing speed, working memory and visual-motor integration continue to compromise quality of life and performance. We review the epidemiology, pathophysiology and assessment of cancer-related cognitive dysfunction, the impact of treatment changes for prevention, and the broad strategies for educational and pharmacological interventions to remediate established cognitive dysfunction following childhood cancer. The increased years of life saved after childhood cancer warrants continued study toward the prevention and remediation of cancer-related cognitive dysfunction, using uniform assessments anchored in functional outcomes. PMID:25080574

PAK Inactivation Impairs Social Recognition in 3xTg-AD Mice without Increasing Brain Deposition of Tau and Aβ

PubMed Central

Arsenault, Dany; Dal-Pan, Alexandre; Tremblay, Cyntia; Bennett, David A.; Guitton, Matthieu J.; De Koninck, Yves; Tonegawa, Susumu

2013-01-01

Defects in p21-activated kinase (PAK) are suspected to play a role in cognitive symptoms of Alzheimer's disease (AD). Dysfunction in PAK leads to cofilin activation, drebrin displacement from its actin-binding site, actin depolymerization/severing, and, ultimately, defects in spine dynamics and cognitive impairment in mice. To determine the role of PAK in AD, we first quantified PAK by immunoblotting in homogenates from the parietal neocortex of subjects with a clinical diagnosis of no cognitive impairment (n = 12), mild cognitive impairment (n = 12), or AD (n = 12). A loss of total PAK, detected in the cortex of AD patients (−39% versus controls), was correlated with cognitive impairment (r2 = 0.148, p = 0.027) and deposition of total and phosphorylated tau (r2 = 0.235 and r2 = 0.206, respectively), but not with Aβ42 (r2 = 0.056). Accordingly, we found a decrease of total PAK in the cortex of 12- and 20-month-old 3xTg-AD mice, an animal model of AD-like Aβ and tau neuropathologies. To determine whether PAK dysfunction aggravates AD phenotype, 3xTg-AD mice were crossed with dominant-negative PAK mice. PAK inactivation led to obliteration of social recognition in old 3xTg-AD mice, which was associated with a decrease in cortical drebrin (−25%), but without enhancement of Aβ/tau pathology or any clear electrophysiological signature. Overall, our data suggest that PAK decrease is a consequence of AD neuropathology and that therapeutic activation of PAK may exert symptomatic benefits on high brain function. PMID:23804095

Abnormal functional connectivity of hippocampus during episodic memory retrieval processing network in amnestic mild cognitive impairment.

PubMed

Bai, Feng; Zhang, Zhijun; Watson, David R; Yu, Hui; Shi, Yongmei; Yuan, Yonggui; Zang, Yufeng; Zhu, Chaozhe; Qian, Yun

2009-06-01

Functional connectivity magnetic resonance imaging technique has revealed the importance of distributed network structures in higher cognitive processes in the human brain. The hippocampus has a key role in a distributed network supporting memory encoding and retrieval. Hippocampal dysfunction is a recurrent finding in memory disorders of aging such as amnestic mild cognitive impairment (aMCI) in which learning- and memory-related cognitive abilities are the predominant impairment. The functional connectivity method provides a novel approach in our attempts to better understand the changes occurring in this structure in aMCI patients. Functional connectivity analysis was used to examine episodic memory retrieval networks in vivo in twenty 28 aMCI patients and 23 well-matched control subjects, specifically between the hippocampal structures and other brain regions. Compared with control subjects, aMCI patients showed significantly lower hippocampus functional connectivity in a network involving prefrontal lobe, temporal lobe, parietal lobe, and cerebellum, and higher functional connectivity to more diffuse areas of the brain than normal aging control subjects. In addition, those regions associated with increased functional connectivity with the hippocampus demonstrated a significantly negative correlation to episodic memory performance. aMCI patients displayed altered patterns of functional connectivity during memory retrieval. The degree of this disturbance appears to be related to level of impairment of processes involved in memory function. Because aMCI is a putative prodromal syndrome to Alzheimer's disease (AD), these early changes in functional connectivity involving the hippocampus may yield important new data to predict whether a patient will eventually develop AD.

Different Functional and Microstructural Changes Depending on Duration of Mild Cognitive Impairment in Parkinson Disease.

PubMed

Shin, N-Y; Shin, Y S; Lee, P H; Yoon, U; Han, S; Kim, D J; Lee, S-K

2016-05-01

The higher cortical burden of Lewy body and Alzheimer disease-type pathology has been reported to be associated with a faster onset of cognitive impairment of Parkinson disease. So far, there has been a few studies only about the changes of gray matter volume depending on duration of cognitive impairment in Parkinson disease. Therefore, our aim was to evaluate the different patterns of structural and functional changes in Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. Fifty-nine patients with Parkinson disease with mild cognitive impairment were classified into 2 groups on the basis of shorter (<1 year, n = 16) and longer (≥1 year, n = 43) durations of parkinsonism before mild cognitive impairment. Fifteen drug-naïve patients with de novo Parkinson disease with intact cognition were included for comparison. Cortical thickness, Tract-Based Spatial Statistics, and seed-based resting-state functional connectivity analyses were performed. Age, sex, years of education, age at onset of parkinsonism, and levodopa-equivalent dose were included as covariates. The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased fractional anisotropy and increased mean and radial diffusivity values in the frontal areas compared with the group with longer duration of parkinsonism before mild cognitive impairment (corrected P < .05). The group with shorter duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity in the default mode network area when the left or right posterior cingulate was used as a seed, and in the dorsolateral prefrontal areas when the left or right caudate was used as a seed (corrected P < .05). The group with longer duration of parkinsonism before mild cognitive impairment showed decreased resting-state functional connectivity mainly in the medial prefrontal cortex when the left or right posterior cingulate was used as a seed, and in the parieto-occipital areas when the left or right caudate was used as a seed (corrected P < .05). No differences in cortical thickness were found in all group contrasts. Resting-state functional connectivity and WM alterations might be useful imaging biomarkers for identifying changes in patients with Parkinson disease with mild cognitive impairment according to the duration of parkinsonism before mild cognitive impairment. The functional and microstructural substrates may topographically differ depending on the rate of cognitive decline in these patients. © 2016 by American Journal of Neuroradiology.

Brain perfusion correlates of visuoperceptual deficits in Mild Cognitive Impairment and mild Alzheimer’s disease

PubMed Central

Alegret, Montserrat; Vinyes-Junqué, Georgina; Boada, Mercè; Martínez-Lage, Pablo; Cuberas, Gemma; Espinosa, Ana; Roca, Isabel; Hernández, Isabel; Valero, Sergi; Rosende-Roca, Maitée; Mauleón, Ana; Becker, James T.; Tárraga, Lluís

2012-01-01

Background Visuoperceptual processing is impaired early in the clinical course of Alzheimer’s disease (AD). The 15-Objects Test (15-OT) detects such subtle performance deficits in Mild Cognitive Impairment (MCI) and mild AD. Reduced brain perfusion in the temporal, parietal and prefrontal regions have been found in early AD and MCI patients. Objectives To confirm the role of the 15-OT in the diagnosis of MCI and AD, and to investigate the brain perfusion correlates of visuoperceptual dysfunction (15-OT) in subjects with MCI, AD and normal aging. Methods Forty-two AD, 42 MCI and 42 healthy elderly control (EC) subjects underwent a brain Single Photon Emission Tomography (SPECT) and separately completed the 15-OT. An analysis of variance compared 15-OT scores between groups. SPM5 was used to analyse the SPECT data. Results 15-OT performace was impaired in the MCI and AD patients. In terms of the SPECT scans, AD patients showed reduced perfusion in temporal-parietal regions, while the MCI subjects had decreased perfusion in the middle and posterior cingulate. When MCI and AD groups were compared, a significant brain perfusion reduction was found in temporo-parietal regions. In the whole sample, 15-OT performance was significantly correlated with the clinical dementia rating scores, and with the perfusion in the bilateral posterior cingulate and the right temporal pole, with no significant correlation in each separate group. Conclusion Our findings suggest that the 15-OT performance provides a useful gradation of impairment from normal aging to AD, and it seems to be related to perfusion in the bilateral posterior cingulate and the right temporal pole. PMID:20555146

The use of the Modified Telephone Interview for Cognitive Status (TICS-M) in the detection of amnestic mild cognitive impairment.

PubMed

Cook, Sarah E; Marsiske, Michael; McCoy, Karin J M

2009-06-01

Many screening tools for detecting cognitive decline require in-person assessment, which is often not cost-effective or feasible for those with physical limitations. The Modified Telephone Interview for Cognitive Status has been used for screening dementia, but little is known about its usefulness in detecting amnestic mild cognitive impairment. Community-dwelling participants (mean age=74.9, mean education = 16.1 years) were administered the Modified Telephone Interview for Cognitive Status during initial screening and subsequently given a multidomain neuropsychological battery. Participants were classified by consensus panel as cognitively normal older adult (noMCI, N=54) or amnestic mild cognitive impairment (N=17) based on neuropsychological performance and Clinical Dementia Rating Scale interview, but independent of Modified Telephone Interview for Cognitive Status score. There was a significant difference between groups in Modified Telephone Interview for Cognitive Status score (t=8.04, P<.01, noMCI range 32-43, mean [SD]=37.4 [2.5], amnestic mild cognitive impairment range 25-37, mean [SD]=31.2 [3.5]). Discriminant function analysis revealed that TICS-M alone correctly classified 85.9% of participants into their respective diagnostic classification (sensitivity=82.4%, specificity=87.0%). Receiver operating characteristics analysis resulted in cutoff score of 34 that optimized sensitivity and specificity of amnestic mild cognitive impairment classification. The Modified Telephone Interview for Cognitive Status is a brief, cost-effective screening measure for identifying those with and without amnestic mild cognitive impairment.

Angiotensin-converting enzyme activity and cognitive impairment during hypoglycaemia in healthy humans.

PubMed

Pedersen-Bjergaard, Ulrik; Thomsen, Carsten E; Høgenhaven, Hans; Smed, Annelise; Kjaer, Troels W; Holst, Jens J; Dela, Flemming; Hilsted, Linda; Frandsen, Erik; Pramming, Stig; Thorsteinsson, Birger

2008-03-01

In type 1 diabetes increased risk of severe hypoglycaemia is associated with high angiotensin-converting enzyme (ACE) activity. We tested in healthy humans the hypothesis that this association is explained by the reduced ability of subjects with high ACE activity to maintain normal cognitive function during hypoglycaemia. Sixteen healthy volunteers selected by either particularly high or low serum ACE activity were subjected to hypoglycaemia (plasma glucose 2.7 mmol/L). Cognitive function was assessed by choice reaction tests. Despite a similar hypoglycaemic stimulus in the two groups, only the group with high ACE activity showed significant deterioration in cognitive performance during hypoglycaemia. In the high ACE group mean reaction time (MRT) in the most complex choice reaction task was prolonged and error rate (ER) was increased in contrast to the low ACE group. The total hypoglycaemic symptom response was greater in the high ACE group than in the low ACE group (p=0.031). There were no differences in responses of counterregulatory hormones or in concentrations of substrates between the groups. Healthy humans with high ACE activity are more susceptible to cognitive dysfunction and report higher symptom scores during mild hypoglycaemia than subjects with low ACE activity.

Association of neuropsychiatric symptoms and sub-syndromes with cognitive impairment in community-dwelling Asian elderly.

PubMed

Xu, Xin; Ang, Seow Li; Hilal, Saima; Chan, Qun Lin; Wong, Tien Yin; Venketasubramanian, Narayanaswamy; Ikram, Mohammad Kamran; Chen, Christopher Li-Hsian

2015-11-01

To investigate the presence of neuropsychiatric symptoms (NPS) and sub-syndromes in elderly community-dwelling Asians with varying severity of cognitive impairment. Chinese and Malay participants (n = 613) from the Epidemiology of Dementia in Singapore (EDIS) Study aged ≥ 60 years underwent clinical examination, neuropsychological testing, and NPS assessment using the Neuropsychiatric Inventory (NPI). Diagnosis of no cognitive impairment (NCI), cognitive impairment-no dementia (CIND), including CIND-mild and CIND-moderate, and dementia were made using established criteria. A significant increase in the numbers of NPS was observed accompanying with increasing severity of cognitive impairment (p < 0.001). Compared to those with NCI/CIND-mild, participants with CIND-moderate [Odds ratio (OR): 4.2, 95% confidence interval (CI): 1.8-10.0] or dementia [OR: 9.2, 95% CI: 2.3-36.0] were more likely to have two or more neuropsychiatric sub-syndromes. Participants with CIND-moderate were more likely to have hyperactivity [OR: 2.0, 95% CI: 1.0-3.8] and apathy [OR: 2.9, 95% CI: 1.0-8.4] sub-syndromes, whereas patients with dementia were more likely to have psychosis [OR: 6.9, 95% CI: 2.4-20.1], affective (OR: 8.7, 95% CI: 1.8-42.9), and hyperactivity (OR: 5.4, 95% CI: 1.8-16.1). Furthermore, executive dysfunction and visual memory impairment were associated with the presence of three neuropsychiatric sub-syndromes; whist language and visuomotor speed impairment were related to the presence of two sub-syndromes. By contrast, impairment in attention, verbal memory, and visuoconstruction were not associated with any of the sub-syndromes. The presence of NPS and sub-syndromes increase with increasing severities of cognitive impairment, and different neuropsychiatric syndromes are associated with specific impairment on cognitive domains in community-dwelling Asian elderly.

The Hachinski Ischemic Scale and cognition: the influence of ethnicity

PubMed Central

Johnson, Leigh A.; Cushing, Blair; Rohlfing, Geoffrey; Edwards, Melissa; Davenloo, Hedieh; D'Agostino, Darrin; Hall, James R.; O'Bryant, Sid E.

2014-01-01

Objective: cardiovascular burden is considered a risk factor for the development of cognitive dysfunction and dementia. While this link is well established in the literature, implementing this work in primary care settings remains a challenge. The goal of this study is to examine the utility of the Hachinski Ischemic Scale (HIS) in identifying cognitive dysfunction and diagnosis of mild cognitive impairment (MCI) in an ethnically diverse sample. Methods: data were analysed on 517 participants (211 Mexican Americans and 306 non-Hispanic Whites) recruited from Project FRONTIER, a study of rural health. Neuropsychological measures were utilised to assess for cognitive functioning. Results: among non-Hispanic Whites, HIS scores were significantly related to poorer performance on tasks of global cognition [B (SE) = −0.13 (0.06), P = 0.02], immediate memory [B (SE) = −0.85 (0.26), P < 0.001], attention [B (SE) = −1.6 (0.36), P < 0.001] and executive functioning [B (SE) = 0.46 (0.12), P < 0.001], and significantly predicted diagnosis of MCI [odds ratio (OR) = 1.4; 95% confidence interval (CI) = 1.2–1.6]. For Mexican Americans, HIS scores were significantly related to immediate memory [B (SE) = −0.78 (0.28), P = 0.01], attention [B (SE) = −0.74 (0.36), P = 0.04] and executive functioning [B (SE) = 0.37 (0.14), P = 0.01]; however, HIS scores were not significantly related to diagnosis of MCI in Mexican Americans (OR = 1.2, 95% CI = 0.96–1.4, P = 0.116). Conclusion: HIS scores were related to cognitive functioning; however, these results differed by ethnicity. It is possible that these findings indicate that vascular factors may increase risk for MCI among non-Hispanic Whites but not for Mexican Americans. These findings are consistent with past research that suggests risk factors for MCI may differ by ethnicity. PMID:24321843

Informant Perceptions of the Cause of Activities of Daily Living Difficulties in Parkinson's Disease.

PubMed

Benge, Jared F; Balsis, Steve

2016-01-01

Individuals with Parkinson's disease (PD) can have difficulties with activities of daily living (ADL) that stem from cognitive, motor, or affective manifestations of the disease. Accurately attributing ADL difficulty specifically to cognitive decline is critical when conducting a neuropsychological evaluation of a person with PD. Informant description of ADL performance is frequently used for this purpose, but there has been little work assessing informants' ability to attribute ADL dysfunction to a specific symptom source in PD. Fifty community dwelling individuals with PD completed cognitive, motor, and affective measures. A knowledgeable informant completed an ADL scale that asked about degree and perceived source of difficulty (cognitive, motor, affective) for each task. Informants indicated that motor dysfunction was the most common source of ADL difficulty, but the informants viewed difficulty with certain tasks, such as financial management, as particularly related to cognitive dysfunction. Informant reports of the source of ADL dysfunction (cognitive, motor, affective) were consistent with clinical measures of those specific dysfunctions. ADL dysfunction attributed to cognition specifically (χ(2) = 9.80, p = .01) was higher in those with measurable cognitive impairment. Informant reports of the sources of ADL dysfunction correlate with clinical measures of these symptoms, suggesting that informants may provide useful clinical information about the cause of ADL dysfunction in persons with PD.

Analysing UK clinicians' understanding of cognitive symptoms in major depression: A survey of primary care physicians and psychiatrists.

PubMed

McAllister-Williams, R Hamish; Bones, Kate; Goodwin, Guy M; Harrison, John; Katona, Cornelius; Rasmussen, Jill; Strong, Sarah; Young, Allan H

2017-01-01

Cognitive dysfunction occurs in depression and can persist into remission. It impacts on patient functioning but remains largely unrecognised, unmonitored and untreated. We explored understanding of cognitive dysfunction in depression among UK clinicians. A multi-step consultation process. Step 1: a multi-stakeholder steering committee identified key themes of burden, detection and management of cognitive dysfunction in depression, and developed statements on each to explore understanding and degree of agreement among clinicians. Step 2: 100 general practitioners (GPs) and 100 psychiatrists indicated their level of agreement with these statements. Step 3: the steering committee reviewed responses and highlighted priority areas for future education and research. There was agreement that clinicians are not fully aware of cognitive dysfunction in depression. Views of the relationship between cognitive dysfunction and other depressive symptom severities was not consistent with the literature. In particular, there was a lack of recognition that some cognitive dysfunction can persist into remission. There was understandable uncertainty around treatment options, given the current limited evidence base. However, it was recognised that cognitive dysfunction is an area of unmet need and that there is a lack of objective tests of cognition appropriate for depressed patients that can be easily implemented in the clinic. Respondents are likely to be 'led' by the direction of the statements they reviewed. The study did not involve patients and carers. UK clinicians should undergo training regarding cognitive dysfunction in depression, and further research is needed into its assessment, treatment and monitoring. Copyright © 2016 Elsevier B.V. All rights reserved.

Evaluating sub-clinical cognitive dysfunction and event-related potentials (P300) in clinically isolated syndrome.

PubMed

Kocer, Belgin; Unal, Tugba; Nazliel, Bijen; Biyikli, Zeynep; Yesilbudak, Zulal; Karakas, Sirel; Irkec, Ceyla

2008-12-01

This study investigated the presence of sub-clinical cognitive dysfunction in patients with clinically isolated syndrome (CIS) and the abnormalities of cognitive event-related potentials (ERPs). Subclinical cognitive dysfunction was assessed in 20 patients with CIS and in 20 healthy controls. Patients had impairments in verbal learning and long-term memory, evaluating attention, executive function and visuospatial skills, in decreasing order of frequency. SDLT and SIT were the most, and COWAT and BNT were the least affected tests. The N200 and P200 latencies were prolonged, and N100, N200 and P200 amplitudes were reduced in the patients relative to the controls, from the Fz, Cz and Pz electrode positions (p<0.05). Detailed cognitive testing is valuable in determining subclinical cognitive dysfunction in CIS patients. ERP abnormalities as well as abnormalities in detailed cognitivetesting in patients with CIS are helpful in the diagnosis of sub-clinical cognitive dysfunction.

Multifactorial determinants of cognition — Thyroid function is not the only one

PubMed Central

Moncayo, Roy; Ortner, Karina

2015-01-01

Background Since the 1960s hypothyroidism together with iodine deficiency have been considered to be a principal determinant of cognition development. Following iodine supplementation programs and improved treatment options for hypothyroidism this relation might not be valid in 2015. On the other hand neurosciences have added different inputs also related to cognition. Scope of review We will examine the characteristics of the original and current publications on thyroid function and cognition and also add some general determinants of intelligence and cognition. One central issue for us is the relation of stress to cognition knowing that both physical and psychological stress, are frequent elements in subjects with thyroid dysfunction. We have considered a special type of stress called pre-natal stress which can influence cognitive functions. Fear and anxiety can be intermingled requiring mechanisms of fear extinction. Major conclusions Recent studies have failed to show an influence of thyroid medication during pregnancy on intellectual development. Neuroscience offers a better explanation of cognition than hypothyroidism and iodine deficiency. Additional factors relevant to cognition are nutrition, infection, prenatal stress, and early life stress. In turn stress is related to low magnesium levels. Magnesium supplementation can correct both latent hypothyroidism and acquired mild cognitive deficits. General significance Cognition is a complex process that depends on many determinants and not only on thyroid function. Magnesium deficiency appears to be a basic mechanism for changes in thyroid function as well as of cognition. PMID:26672993

Executive Functions, Memory, and Social Cognitive Deficits and Recovery in Chronic Alcoholism: A Critical Review to Inform Future Research.

PubMed

Le Berre, Anne-Pascale; Fama, Rosemary; Sullivan, Edith V

2017-08-01

Alcoholism is a complex and dynamic disease, punctuated by periods of abstinence and relapse, and influenced by a multitude of vulnerability factors. Chronic excessive alcohol consumption is associated with cognitive deficits, ranging from mild to severe, in executive functions, memory, and metacognitive abilities, with associated impairment in emotional processes and social cognition. These deficits can compromise efforts in initiating and sustaining abstinence by hampering efficacy of clinical treatment and can obstruct efforts in enabling good decision making success in interpersonal/social interactions, and awareness of cognitive and behavioral dysfunctions. Despite evidence for differences in recovery levels of selective cognitive processes, certain deficits can persist even with prolonged sobriety. Herein is presented a review of alcohol-related cognitive impairments affecting component processes of executive functioning, memory, and the recently investigated cognitive domains of metamemory, social cognition, and emotional processing; also considered are trajectories of cognitive recovery with abstinence. Finally, in the spirit of critical review, limitations of current knowledge are noted and avenues for new research efforts are proposed that focus on (i) the interaction among emotion-cognition processes and identification of vulnerability factors contributing to the development of emotional and social processing deficits and (ii) the time line of cognitive recovery by tracking alcoholism's dynamic course of sobriety and relapse. Knowledge about the heterochronicity of cognitive recovery in alcoholism has the potential of indicating at which points during recovery intervention may be most beneficial. Copyright © 2017 by the Research Society on Alcoholism.

Transitions to Mild Cognitive Impairments, Dementia, and Death: Findings from the Nun Study

PubMed Central

Tyas, Suzanne L.; Salazar, Juan Carlos; Snowdon, David A.; Desrosiers, Mark F.; Riley, Kathryn P.; Mendiondo, Marta S.; Kryscio, Richard J.

2007-01-01

The potential of early interventions for dementia has increased interest in cognitive impairments less severe than dementia. However, predictors of the trajectory from intact cognition to dementia have not yet been clearly identified. The purpose of this study was to determine whether known risk factors for dementia increased the risk of mild cognitive impairments or progression from mild cognitive impairments to dementia. A polytomous logistic regression model was used, with parameters governing transitions within transient states (intact cognition, mild cognitive impairments, global impairment) estimated separately from parameters governing the transition from transient to absorbing state (dementia or death). Analyses were based on seven annual examinations (1991–2002) of 470 Nun Study participants aged ≥75 years at baseline and living in the United States. Odds of developing dementia increased with age primarily for those with low educational levels. In these women, presence of an apolipoprotein E gene *E4 allele increased the odds more than fourfold by age 95 years. Age, education, and the apolipoprotein E gene were all significantly associated with mild cognitive impairments. Only age, however, was associated with progression to dementia. Thus, risk factors for dementia may operate primarily by predisposing individuals to develop mild cognitive impairments; subsequent progression to dementia then depends on only time and competing mortality. PMID:17431012

Transitions to mild cognitive impairments, dementia, and death: findings from the Nun Study.

PubMed

Tyas, Suzanne L; Salazar, Juan Carlos; Snowdon, David A; Desrosiers, Mark F; Riley, Kathryn P; Mendiondo, Marta S; Kryscio, Richard J

2007-06-01

The potential of early interventions for dementia has increased interest in cognitive impairments less severe than dementia. However, predictors of the trajectory from intact cognition to dementia have not yet been clearly identified. The purpose of this study was to determine whether known risk factors for dementia increased the risk of mild cognitive impairments or progression from mild cognitive impairments to dementia. A polytomous logistic regression model was used, with parameters governing transitions within transient states (intact cognition, mild cognitive impairments, global impairment) estimated separately from parameters governing the transition from transient to absorbing state (dementia or death). Analyses were based on seven annual examinations (1991-2002) of 470 Nun Study participants aged > or = 75 years at baseline and living in the United States. Odds of developing dementia increased with age primarily for those with low educational levels. In these women, presence of an apolipoprotein E gene *E4 allele increased the odds more than fourfold by age 95 years. Age, education, and the apolipoprotein E gene were all significantly associated with mild cognitive impairments. Only age, however, was associated with progression to dementia. Thus, risk factors for dementia may operate primarily by predisposing individuals to develop mild cognitive impairments; subsequent progression to dementia then depends on only time and competing mortality.

Hypometabolism as a therapeutic target in Alzheimer's disease.

PubMed

Costantini, Lauren C; Barr, Linda J; Vogel, Janet L; Henderson, Samuel T

2008-12-03

The pathology of Alzheimer's disease (AD) is characterized by cerebral atrophy in frontal, temporal, and parietal regions, with senile plaques, dystrophic neurites, and neurofibrillar tangles within defined areas of the brain. Another characteristic of AD is regional hypometabolism in the brain. This decline in cerebral glucose metabolism occurs before pathology and symptoms manifest, continues as symptoms progress, and is more severe than that of normal aging. Ketone bodies are an efficient alternative fuel for cells that are unable to metabolize glucose or are 'starved' of glucose. AC-1202 is designed to elevate serum ketone levels safely. We previously showed that treatment with AC-1202 in patients with mild-to-moderate AD improves memory and cognition. Treatment outcomes were influenced by apolipoprotein E genotype status. These data suggest that AC-1202 may be an effective treatment for cognitive dysfunction by providing an alternative substrate for use by glucose-compromised neurons.

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.

Cognitive remission: a novel objective for the treatment of major depression?

PubMed

Bortolato, Beatrice; Miskowiak, Kamilla W; Köhler, Cristiano A; Maes, Michael; Fernandes, Brisa S; Berk, Michael; Carvalho, André F

2016-01-22

Cognitive dysfunction in major depressive disorder (MDD) encompasses several domains, including but not limited to executive function, verbal memory, and attention. Furthermore, cognitive dysfunction is a frequent residual manifestation in depression and may persist during the remitted phase. Cognitive deficits may also impede functional recovery, including workforce performance, in patients with MDD. The overarching aims of this opinion article are to critically evaluate the effects of available antidepressants as well as novel therapeutic targets on neurocognitive dysfunction in MDD. Conventional antidepressant drugs mitigate cognitive dysfunction in some people with MDD. However, a significant proportion of MDD patients continue to experience significant cognitive impairment. Two multicenter randomized controlled trials (RCTs) reported that vortioxetine, a multimodal antidepressant, has significant precognitive effects in MDD unrelated to mood improvement. Lisdexamfetamine dimesylate was shown to alleviate executive dysfunction in an RCT of adults after full or partial remission of MDD. Preliminary evidence also indicates that erythropoietin may alleviate cognitive dysfunction in MDD. Several other novel agents may be repurposed as cognitive enhancers for MDD treatment, including minocycline, insulin, antidiabetic agents, angiotensin-converting enzyme inhibitors, S-adenosyl methionine, acetyl-L-carnitine, alpha lipoic acid, omega-3 fatty acids, melatonin, modafinil, galantamine, scopolamine, N-acetylcysteine, curcumin, statins, and coenzyme Q10. The management of cognitive dysfunction remains an unmet need in the treatment of MDD. However, it is hoped that the development of novel therapeutic targets will contribute to 'cognitive remission', which may aid functional recovery in MDD.

Cognitive Training Using a Novel Memory Game on an iPad in Patients with Amnestic Mild Cognitive Impairment (aMCI)

PubMed Central

Savulich, George; Piercy, Thomas; Fox, Chris; Suckling, John; Rowe, James B; O’Brien, John T

2017-01-01

Abstract Background Cognitive training is effective in patients with mild cognitive impairment but does not typically address the motivational deficits associated with older populations with memory difficulties. Methods We conducted a randomized controlled trial of cognitive training using a novel memory game on an iPad in 42 patients with a diagnosis of amnestic mild cognitive impairment assigned to either the cognitive training (n=21; 8 hours of gameplay over 4 weeks) or control (n=21; clinic visits as usual) groups. Results Significant time-by-pattern-by-group interactions were found for cognitive performance in terms of the number of errors made and trials needed on the Cambridge Neuropsychological Test Automated Battery Paired Associates Learning task (P=.044; P=.027). Significant time-by-group interactions were also found for the Cambridge Neuropsychological Test Automated Battery Paired Associates Learning first trial memory score (P=.002), Mini-Mental State Examination (P=.036), the Brief Visuospatial Memory Test (P=.032), and the Apathy Evaluation Scale (P=.026). Within-group comparisons revealed highly specific effects of cognitive training on episodic memory. The cognitive training group maintained high levels of enjoyment and motivation to continue after each hour of gameplay, with self-confidence and self-rated memory ability improving over time. Conclusions Episodic memory robustly improved in the cognitive training group. “Gamified” cognitive training may also enhance visuospatial abilities in patients with amnestic mild cognitive impairment. Gamification maximizes engagement with cognitive training by increasing motivation and could complement pharmacological treatments for amnestic mild cognitive impairment and mild Alzheimer’s disease. Larger, more controlled trials are needed to replicate and extend these findings. PMID:28898959

Cognitive Training Using a Novel Memory Game on an iPad in Patients with Amnestic Mild Cognitive Impairment (aMCI).

PubMed

Savulich, George; Piercy, Thomas; Fox, Chris; Suckling, John; Rowe, James B; O'Brien, John T; Sahakian, Barbara J

2017-08-01

Cognitive training is effective in patients with mild cognitive impairment but does not typically address the motivational deficits associated with older populations with memory difficulties. We conducted a randomized controlled trial of cognitive training using a novel memory game on an iPad in 42 patients with a diagnosis of amnestic mild cognitive impairment assigned to either the cognitive training (n=21; 8 hours of gameplay over 4 weeks) or control (n=21; clinic visits as usual) groups. Significant time-by-pattern-by-group interactions were found for cognitive performance in terms of the number of errors made and trials needed on the Cambridge Neuropsychological Test Automated Battery Paired Associates Learning task (P=.044; P=.027). Significant time-by-group interactions were also found for the Cambridge Neuropsychological Test Automated Battery Paired Associates Learning first trial memory score (P=.002), Mini-Mental State Examination (P=.036), the Brief Visuospatial Memory Test (P=.032), and the Apathy Evaluation Scale (P=.026). Within-group comparisons revealed highly specific effects of cognitive training on episodic memory. The cognitive training group maintained high levels of enjoyment and motivation to continue after each hour of gameplay, with self-confidence and self-rated memory ability improving over time. Episodic memory robustly improved in the cognitive training group. "Gamified" cognitive training may also enhance visuospatial abilities in patients with amnestic mild cognitive impairment. Gamification maximizes engagement with cognitive training by increasing motivation and could complement pharmacological treatments for amnestic mild cognitive impairment and mild Alzheimer's disease. Larger, more controlled trials are needed to replicate and extend these findings. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Olfaction and apathy in Alzheimer's disease, mild cognitive impairment, and healthy older adults.

PubMed

Seligman, Sarah C; Kamath, Vidyulata; Giovannetti, Tania; Arnold, Steven E; Moberg, Paul J

2013-01-01

Apathy is a prevalent neuropsychiatric manifestation in individuals with Alzheimer's disease (AD) that is associated with decreased social functioning and increased caregiver burden. Olfactory deficits are also commonly observed in AD, and prior work has indicated a link between increased apathy and olfactory dysfunction in individuals with Parkinson's disease. Here, we examined odor identification performance in patients with probable AD (n = 172), individuals with mild cognitive impairment (MCI; n = 112), and neurologically and psychiatrically healthy older adults (n = 132) and its relation to apathy, depression, and overall psychopathology. Participants were administered the Sniffin' Sticks odor identification test and measures assessing severity of apathy, depression, and overall neuropsychiatric symptomatology. Consistent with previous research, AD and MCI patients were significantly worse at identifying odors than healthy older adults. Additionally, a sex by diagnosis interaction was observed. AD patients had significantly higher levels of apathy relative to MCI and control participants. Of note, across the entire sample odor identification deficits were correlated with level of apathy at the level of p < 0.01, but not with depression or neuropsychiatric symptom severity, when controlling for Mini-Mental State Examination (MMSE) score. Collectively, these data suggest that olfactory disturbance and apathy in AD may result from the progression of disease pathology in shared neural substrates.

Cell cycle proteins in brain in mild cognitive impairment: insights into progression to Alzheimer disease.

PubMed

Keeney, Jeriel T R; Swomley, Aaron M; Harris, Jessica L; Fiorini, Ada; Mitov, Mihail I; Perluigi, Marzia; Sultana, Rukhsana; Butterfield, D Allan

2012-10-01

Recent studies have demonstrated the re-emergence of cell cycle proteins in brain as patients progress from the early stages of mild cognitive impairment (MCI) into Alzheimer's disease (AD). Oxidative stress markers present in AD have also been shown to be present in MCI brain suggesting that these events occur in early stages of the disease. The levels of key cell cycle proteins, such as CDK2, CDK5, cyclin G1, and BRAC1 have all been found to be elevated in MCI brain compared to age-matched control. Further, peptidyl prolyl cis-trans isomerase (Pin1), a protein that plays an important role in regulating the activity of key proteins, such as CDK5, GSK3-β, and PP2A that are involved in both the phosphorylation state of Tau and in the cell cycle, has been found to be oxidatively modified and downregulated in both AD and MCI brain. Hyperphosphorylation of Tau then results in synapse loss and the characteristic Tau aggregation as neurofibrillary tangles, an AD hallmark. In this review, we summarized the role of cell cycle dysregulation in the progression of disease from MCI to AD. Based on the current literature, it is tempting to speculate that a combination of oxidative stress and cell cycle dysfunction conceivably leads to neurodegeneration.

Quantitative assessment of finger tapping characteristics in mild cognitive impairment, Alzheimer's disease, and Parkinson's disease.

PubMed

Roalf, David R; Rupert, Petra; Mechanic-Hamilton, Dawn; Brennan, Laura; Duda, John E; Weintraub, Daniel; Trojanowski, John Q; Wolk, David; Moberg, Paul J

2018-06-01

Fine motor impairments are common in neurodegenerative disorders, yet standardized, quantitative measurements of motor abilities are uncommonly used in neurological practice. Thus, understanding and comparing fine motor abilities across disorders have been limited. The current study compared differences in finger tapping, inter-tap interval, and variability in Alzheimer's disease (AD), Parkinson's disease (PD), mild cognitive impairment (MCI), and healthy older adults (HOA). Finger tapping was measured using a highly sensitive light-diode finger tapper. Total number of finger taps, inter-tap interval, and intra-individual variability (IIV) of finger tapping was measured and compared in AD (n = 131), PD (n = 63), MCI (n = 46), and HOA (n = 62), controlling for age and sex. All patient groups had fine motor impairments relative to HOA. AD and MCI groups produced fewer taps with longer inter-tap interval and higher IIV compared to HOA. The PD group, however, produced more taps with shorter inter-tap interval and higher IIV compared to HOA. Disease-specific changes in fine motor function occur in the most common neurodegenerative diseases. The findings suggest that alterations in finger tapping patterns are common in AD, MCI, and PD. In addition, the present results underscore the importance of motor dysfunction even in neurodegenerative disorders without primary motor symptoms.

Donepezil for treatment of cognitive dysfunction in children with Down syndrome aged 10-17.

PubMed

Kishnani, Priya S; Heller, James H; Spiridigliozzi, Gail A; Lott, Ira; Escobar, Luis; Richardson, Sharon; Zhang, Richard; McRae, Thomas

2010-12-01

The objective of this 10-week, randomized, double-blind, placebo-controlled multicenter study was to assess the efficacy and safety of donepezil for the treatment of cognitive dysfunction exhibited by children with Down syndrome (DS). Intervention comprised donepezil (2.5-10 mg/day) in children (aged 10-17 years) with DS of mild-to-moderate severity. The primary measures were the Vineland-II Adaptive Behavior Scales (VABS-II) Parent/Caregiver Rating Form (PCRF) the sum of nine subdomain standardized scores and standard safety measures. Secondary measures included the VABS-II/PCRF scores on the following domains and their respective individual subdomains: Communication (receptive, expressive, and written); Daily Living Skills (personal, domestic, and community); Socialization (interpersonal relationships, play and leisure time, and coping skills), and scores on the Test of Verbal Expression and Reasoning, a subject-performance-based measure of expressive language. At baseline, 129 participants were assigned treatment with donepezil or placebo. During the double-blind phase, VABS II/PCRF sum of the nine subdomain standardized scores, called v-scores, improved significantly from baseline in both groups (P < 0.0001), with no significant between-group differences. This trial failed to demonstrate any benefit for donepezil versus placebo in children and adolescents with DS, although donepezil appeared to be well tolerated. © 2010 Wiley-Liss, Inc.

Therapeutic impact of rHuEPO on abnormal platelet APP, BACE 1, presenilin 1, ADAM 10 and Aβ expressions in chronic kidney disease patients with cognitive dysfunction like Alzheimer's disease: A pilot study.

PubMed

G, Vinothkumar; S, Krishnakumar; Sureshkumar; G, Shivashekar; S, Sreedhar; Preethikrishnan; S, Dinesh; A, Sundaram; D, Balakrishnan; Riya; P, Venkataraman

2018-08-01

Cognitive dysfunction is reported to be a major cause of morbidity in chronic kidney disease (CKD). The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases . Platelets contain more than 95% of the circulating APP and implicate as a candidate biomarker for cognitive decline. Recombinant human erythropoietin (rHuEPO) is a standard therapy for anemia in CKD and also acts as a neuroprotective agent. The aim of the study is to determine the impact of rHuEPO therapy on platelet APP processing in CKD with Cognitive Dysfunction. A total of 60 subjects comprising of 30 CKD without cognitive dysfunction and 30 CKD with cognitive dysfunction based on neuropsychological assessment. APP, BACE1, Presenilin 1, ADAM 10 (α secretase) and Aβ expressions in platelets were determined by western blotting and lipid peroxidation (LPO) in platelet rich plasma (PRP) was done by spectrophotometrically. The parameters were statistically compared with Alzheimer's disease (AD), Normocytic normochromic anemic and healthy subjects. Significantly (p < 0.05) decreased APP, ADAM 10 while increased BACE1, Presenilin 1, Aβ and LPO were observed in CKD with cognitive dysfunction like AD subjects compared to other groups. The parameters were reassessed in CKD with cognitive dysfunction subjects after rHuEPO (100 IU/ kg, weekly twice, 6 months) therapy. All the parameters were retrieved significantly (p < 0.05) along with improved neuropsychological tests scoring after rHuEPO therapy. This study demonstrated that rHuEPO is an effective neuroprotective agent in the context of CKD associated cognitive dysfunction and proved its clinical usefulness. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Green tea consumption affects cognitive dysfunction in the elderly: a pilot study.

PubMed

Ide, Kazuki; Yamada, Hiroshi; Takuma, Norikata; Park, Mijong; Wakamiya, Noriko; Nakase, Junpei; Ukawa, Yuuichi; Sagesaka, Yuko M

2014-09-29

Green tea is known to have various health benefits for humans. However, the effect of green tea consumption on cognitive dysfunction remains to be clinically verified. We conducted a clinical study to investigate the effects of green tea consumption on cognitive dysfunction. Twelve elderly nursing home residents with cognitive dysfunction (Mini-Mental State Examination Japanese version (MMSE-J) score: <28) participated in the study (2 men, 10 women; mean age, 88 years). The participants consumed green tea powder 2 g/day for 3 months. After three months of green tea consumption, the participants' MMSE-J scores were significantly improved (before, 15.3 ± 7.7; after, 17.0 ± 8.2; p = 0.03). This result suggests that green tea consumption may be effective in improving cognitive function or reducing the progression of cognitive dysfunction; however, long-term large-scale controlled studies are needed to further clarify the effect.

Cognitive-Behavioral Erectile Dysfunction Treatment for Gay Men

ERIC Educational Resources Information Center

Hart, Trevor A.; Schwartz, Danielle R.

2010-01-01

The purpose of the present paper is to assist cognitive-behavioral therapists who are treating erectile dysfunction among gay men. Little information is available to cognitive-behavioral therapists about the psychological and social effects of erectile dysfunction in this population, or how to incorporate the concerns of gay men with erectile…

Cognitive function affects trainability for physical performance in exercise intervention among older adults with mild cognitive impairment.

PubMed

Uemura, Kazuki; Shimada, Hiroyuki; Makizako, Hyuma; Doi, Takehiko; Yoshida, Daisuke; Tsutsumimoto, Kota; Anan, Yuya; Suzuki, Takao

2013-01-01

Although much evidence supports the hypothesis that cognitive function and physical function are interrelated, it is unclear whether cognitive decline with mild cognitive impairment influences trainability of physical performance in exercise intervention. The purpose of this study was to examine the association between cognitive function at baseline and change in physical performance after exercise intervention in older adults with mild cognitive impairment. Forty-four older adults diagnosed with mild cognitive impairment based on the Peterson criteria (mean age 74.8 years) consented to and completed a 6-month twice weekly exercise intervention. The Timed Up and Go (TUG) test was used as a measure of physical performance. The Mini-Mental State Examination (MMSE), Trail Making Test Part B, Geriatric Depression Scale, baseline muscle strength of knee extension, and attendance rate of intervention, were measured as factors for predicting trainability. In the correlation analysis, the change in TUG showed modest correlations with attendance rate in the exercise program (r = -0.354, P = 0.027) and MMSE at baseline (r = -0.321, P = 0.034). A multiple regression analysis revealed that change in TUG was independently associated with attendance rate (β = -0.322, P = 0.026) and MMSE score (β = -0.295, P = 0.041), controlling for age and gender. General cognitive function was associated with improvements in physical performance after exercise intervention in subjects with mild cognitive impairment. Further research is needed to examine the effects of exercise programs designed to address cognitive obstacles in older adults with mild cognitive impairment.

Cognitive dysfunction in multiple sclerosis: a review of recent developments.

PubMed

Bobholz, Julie A; Rao, Stephen M

2003-06-01

Nearly half of all patients diagnosed with multiple sclerosis will develop cognitive dysfunction, a symptom associated with significant decline in activities of daily living. The purpose of this review is to discuss recent literature investigating issues related to cognitive dysfunction in multiple sclerosis. Recent studies, examined in this review, have provided increased understanding regarding specific cognitive processes affected in multiple sclerosis, as well as a characterization of its natural history. Studies have also continued to emphasize the extent to which cognitive deficits in the condition are associated with decline in daily living skills. Recent concerns regarding driving performance have been documented among cognitively impaired individuals. Studies have also examined correlates of cognitive dysfunction, with particular emphasis on neuroimaging techniques reflecting disease activity or lesion burden. With increased understanding of neurobiological correlates of cognitive deficits, investigators have begun to examine potential treatments for managing cognitive dysfunction. This area of research has suggested that disease modifying medications can have an impact on magnetic resonance imaging disease activity by altering the cerebral demyelinating process resulting in a slower decline in cognitive functions over time and improved activities of daily living for patients with multiple sclerosis.

Positive Effects of Computer-Based Cognitive Training in Adults with Mild Cognitive Impairment

ERIC Educational Resources Information Center

Herrera, C.; Chambon, C.; Michel, B. F.; Paban, V.; Alescio-Lautier, B.

2012-01-01

Considering the high risk for individuals with amnestic Mild Cognitive Impairment (A-MCI) to progress towards Alzheimer's disease (AD), we investigated the efficacy of a non-pharmacological intervention, that is, cognitive training that could reduce cognitive difficulties and delay the cognitive decline. For this, we evaluated the efficacy of a…

The role of molecular testing and enzyme analysis in the management of hypomorphic citrullinemia.

PubMed

Dimmock, David P; Trapane, Pamela; Feigenbaum, Annette; Keegan, Catherine E; Cederbaum, Stephen; Gibson, James; Gambello, Michael J; Vaux, Keith; Ward, Patricia; Rice, Gregory M; Wolff, Jon A; O'Brien, William E; Fang, Ping

2008-11-15

Expanded newborn screening detects patients with modest elevations in citrulline; however it is currently unclear how to treat these patients and how to counsel their parents. In order to begin to address these issues, we compared the clinical, biochemical, and molecular features of 10 patients with mildly elevated citrulline levels. Three patients presented with clinical illness whereas seven came to attention as a result of expanded newborn screening. One patient presented during pregnancy and responded promptly to IV sodium phenylacetate/sodium benzoate and arginine therapy with no long-term adverse effects on mother or fetus. Two children presented with neurocognitive dysfunction, one of these responded dramatically to dietary protein reduction. ASS enzyme activity was not deficient in all patients with biallelic mutations suggesting this test cannot exclude the ASS1 locus in patients with mildly elevated plasma citrulline. Conversely, all symptomatic patients who were tested had deficient activity. We describe four unreported mutations (p.Y291S, p.R272H, p.F72L, and p.L88I), as well as the common p.W179R mutation. In silico algorithms were inconsistent in predicting the pathogenicity of mutations. The cognitive benefit in one patient of protein restriction and the lack of adverse outcome in seven others restricted from birth, suggest a role for protein restriction and continued monitoring to prevent neurocognitive dysfunction. (c) 2008 Wiley-Liss, Inc.

Cognitive dysfunction in depression - pathophysiology and novel targets.

PubMed

Carvalho, Andre F; Miskowiak, Kamilla K; Hyphantis, Thomas N; Kohler, Cristiano A; Alves, Gilberto S; Bortolato, Beatrice; G Sales, Paulo Marcelo; Machado-Vieira, Rodrigo; Berk, Michael; McIntyre, Roger S

2014-01-01

Major depressive disorder (MDD) is associated with cognitive dysfunction encompassing several domains, including memory, executive function, processing speed and attention. Cognitive deficits persist in a significant proportion of patients even in remission, compromising psychosocial functioning and workforce performance. While monoaminergic antidepressants may improve cognitive performance in MDD, most antidepressants have limited clinical efficacy. The overarching aims of this review were: (1) to synthesize extant literature on putative biological pathways related to cognitive dysfunction in MDD and (2) to review novel neurotherapeutic targets for cognitive enhancement in MDD. We found that reciprocal and overlapping biological pathways may contribute to cognitive dysfunction in MDD, including an hyperactive hypothalamic-pituitary-adrenal axis, an increase in oxidative and nitrosative stress, inflammation (e.g., enhanced production of pro-inflammatory cytokines), mitochondrial dysfunction, increased apoptosis as well as a diminished neurotrophic support. Several promising neurotherapeutic targets were identified such as minocycline, statins, anti-inflammatory compounds, N-acetylcysteine, omega-3 poliunsaturated fatty acids, erythropoietin, thiazolidinediones, glucagon-like peptide-1 analogues, S-adenosyl-l-methionine (SAMe), cocoa flavonols, creatine monohydrate and lithium. Erythropoietin and SAMe had pro-cognitive effects in randomized controlled trials (RCT) involving MDD patients. Despite having preclinical and/or preliminary evidences from trials suggesting possible efficacy as novel cognitive enhancing agents for MDD, no RCT to date was performed for most of the other therapeutic targets reviewed herein. In conclusion, multiple biological pathways are involved in cognitive dysfunction in MDD. RCTs testing genuinely novel pro-cognitive compounds for MDD are warranted.

Cognitive dysfunction and functional magnetic resonance imaging in systemic lupus erythematosus.

PubMed

Barraclough, M; Elliott, R; McKie, S; Parker, B; Bruce, I N

2015-10-01

Cognitive dysfunction is a common aspect of systemic lupus erythematosus (SLE) and is increasingly reported as a problem by patients. In many cases the exact cause is unclear. Limited correlations between specific autoantibodies or structural brain abnormalities and cognitive dysfunction in SLE have been reported. It may be that the most appropriate biomarkers have yet to be found. Functional magnetic resonance imaging (fMRI) is a technique used in many other conditions and provides sensitive measures of brain functionality during cognitive tasks. It is now beginning to be employed in SLE studies. These studies have shown that patients with SLE often perform similarly to healthy controls in terms of behavioural measures on cognitive tasks. However, SLE patients appear to employ compensatory brain mechanisms, such as increased response in fronto-parietal regions, to maintain adequate cognitive performance. As there have been only a few studies using fMRI in SLE to investigate cognitive dysfunction, many questions remain unanswered. Further research could, however, help to identify biomarkers for cognitive dysfunction in SLE. © The Author(s) 2015.

Social cognition and underlying cognitive mechanisms in children with an extra X chromosome: a comparison with autism spectrum disorder.

PubMed

van Rijn, S; Stockmann, L; van Buggenhout, G; van Ravenswaaij-Arts, C; Swaab, H

2014-06-01

Individuals with an extra X chromosome are at increased risk for autism symptoms. This study is the first to assess theory of mind and facial affect labeling in children with an extra X chromosome. Forty-six children with an extra X chromosome (29 boys with Klinefelter syndrome and 17 girls with Trisomy X), 56 children with autism spectrum disorder (ASD) and 88 non-clinical controls, aged 9-18 years, were included. Similar to children with ASD, children with an extra X chromosome showed significant impairments in social cognition. Regression analyses showed that different cognitive functions predicted social cognitive skills in the extra X and ASD groups. The social cognitive deficits were similar for boys and girls with an extra X chromosome, and not specific for a subgroup with high Autism Diagnostic Interview Revised autism scores. Thus, children with an extra X chromosome show social cognitive deficits, which may contribute to social dysfunction, not only in children showing a developmental pattern that is 'typical' for autism but also in those showing mild or late presenting autism symptoms. Our findings may also help explain variance in type of social deficit: children may show similar social difficulties, but these may arise as a consequence of different underlying information processing deficits. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Tests of Dorsolateral Frontal Function Correlate with Objective Tests of Postural Stability in Early to Moderate Stage Parkinson’s Disease

PubMed Central

Nocera, Joe R.; Price, Catherine; Fernandez, Hubert H.; Amano, Shinichi; Vallabhajosula, Srikant; Okun, Michael S.; Hwynn, Nelson; Hass, Chris J.

2010-01-01

A substantial number of individuals with Parkinson’s disease who display impaired postural stability experience accelerated cognitive decline and an increased prevalence of dementia. To date, studies suggest that this relationship, believed to be due to involvement of nondopaminergic circuitry, occurs later in the disease process. Research has yet to adequately investigate this cognitive-posturomotor relationship especially when examining earlier disease states. To gain greater understanding of the relationship between postural stability and cognitive function/dysfunction we evaluated a more stringent, objective measure of postural stability (center of pressure displacement), and also more specific measures of cognition in twenty-two patients with early to moderate stage Parkinson’s disease. The magnitude of the center of pressure displacement in this cohort was negatively correlated with performance on tests known to activate dorsolateral frontal regions. Additionally, the postural stability item of the UPDRS exhibited poor correlation with the more objective measure of center of pressure displacement and all specific measures of cognition. These results may serve as rationale for a more thorough evaluation of postural stability and cognition especially in individuals with mild Parkinson’s disease. Greater understanding of the relationship between motor and cognitive processes in Parkinson’s disease will be critical for understanding the disease process and its potential therapeutic possibilities. PMID:20829093

The role of human cognitive neuroscience in drug discovery for the dementias.

PubMed

Wesnes, Keith A; Edgar, Chris J

2014-02-01

Cognitive dysfunction characterizes all the various forms of dementia. Evidence is accumulating that all of the progressive neurodegenerative dementias, such as Alzheimer's disease (AD), are preceded by years, if not decades, of pathological cognitive decline. The limited effectiveness of the four current medications registered for AD together with the failure of dozens of programmes over the last decade has influenced the decision to evaluate treatment at earlier stages of the disease; even before any cognitive symptoms have appeared. However, it has to be acknowledged that treating mild cognitive impairment (MCI) as a prodrome for AD has also had very limited success. Nonetheless a more important problem in MCI research, and dementia in general, has to be laid at the door of the limited effectiveness of the cognitive tests employed. This problem will become even more severe for the latest research direction of treating preclinical AD because such individuals will have levels of cognitive abilities which are in the normal range; and thus many of the scales currently used in dementia research will not be sufficiently demanding to identify change over time. This paper reviews and discusses the methodology and instruments available for research and clinical practice in this major area; with a focus on the challenges involved in test selection and evaluation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Making Sense of Mild Cognitive Impairment: A Qualitative Exploration of the Patient's Experience

ERIC Educational Resources Information Center

Lingler, Jennifer Hagerty; Nightingale, Marcie C.; Erlen, Judith A.; Kane, April L.; Reynolds, Charles F.; Schulz, Richard; DeKosky, Steven T.

2006-01-01

Purpose: The proposed dementia precursor state of mild cognitive impairment is emerging as a primary target of aging research. Yet, little is known about the subjective experience of living with a diagnosis of mild cognitive impairment. This study examines, from the patient's perspective, the experience of living with and making sense of the…

Intraindividual Stepping Reaction Time Variability Predicts Falls in Older Adults With Mild Cognitive Impairment.

PubMed

Bunce, David; Haynes, Becky I; Lord, Stephen R; Gschwind, Yves J; Kochan, Nicole A; Reppermund, Simone; Brodaty, Henry; Sachdev, Perminder S; Delbaere, Kim

2017-06-01

Reaction time measures have considerable potential to aid neuropsychological assessment in a variety of health care settings. One such measure, the intraindividual reaction time variability (IIV), is of particular interest as it is thought to reflect neurobiological disturbance. IIV is associated with a variety of age-related neurological disorders, as well as gait impairment and future falls in older adults. However, although persons diagnosed with Mild Cognitive Impairment (MCI) are at high risk of falling, the association between IIV and prospective falls is unknown. We conducted a longitudinal cohort study in cognitively intact (n = 271) and MCI (n = 154) community-dwelling adults aged 70-90 years. IIV was assessed through a variety of measures including simple and choice hand reaction time and choice stepping reaction time tasks (CSRT), the latter administered as a single task and also with a secondary working memory task. Logistic regression did not show an association between IIV on the hand-held tasks and falls. Greater IIV in both CSRT tasks, however, did significantly increase the risk of future falls. This effect was specific to the MCI group, with a stronger effect in persons exhibiting gait, posture, or physiological impairment. The findings suggest that increased stepping IIV may indicate compromised neural circuitry involved in executive function, gait, and posture in persons with MCI increasing their risk of falling. IIV measures have potential to assess neurobiological disturbance underlying physical and cognitive dysfunction in old age, and aid fall risk assessment and routine care in community and health care settings. © 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.

Acute Affective Reactivity and Quality of Life in Older Adults with Amnestic Mild Cognitive Impairment: A Functional MRI Study.

PubMed

Ren, Ping; Heffner, Kathi L; Jacobs, Alanna; Lin, Feng

2017-11-01

Poor quality of life (QoL) is a major concern among older adults with amnestic mild cognitive impairment (MCI). Maladaptive affective regulation and its relevant frontal dysfunction that are often observed in older adults with MCI may provide an insight into the understanding of their QoL. In this case-controlled study, participants (MCI patients, N = 18; healthy comparisons [HC], N = 21) completed cognitive tasks, and underwent resting-state functional magnetic resonance imaging (rs-fMRI) immediately before and after the tasks. The amplitude of low-frequency fluctuations (ALFF) of rs-fMRI signals was calculated to examine the brain's spontaneous activity. The change in valence from the Self-Assessment Manikin indexed affective reactivity. QoL was assessed using Quality of Life-AD measure. Multiple mediator model was used to examine the mediating effect of frontal regions' ALFF reactivity between the affective reactivity and QoL. The MCI group had significantly worse QoL and more negative affective reactivity than HC group. Less negative affective reactivity was significantly associated with better QoL in MCI not HC. ALFF in the anterior cingulate cortex, medial prefrontal cortex (MPFC), and superior frontal gyrus (SFG) increased significantly less after cognitive tasks in MCI than HC. For the entire sample, greater increases of ALFF in MPFC and SFG were significantly associated with better QoL, and SFG alone significantly mediated the association between affective reactivity and QoL. Enhancing SFG activation, especially among those with MCI, may provide a therapeutic target for addressing the negative impact of maladaptive affective regulation on QoL. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

The dual task-cost of standing balance affects quality of life in mildly disabled MS people.

PubMed

Castelli, Letizia; De Luca, Francesca; Marchetti, Maria Rita; Sellitto, Giovanni; Fanelli, Fulvia; Prosperini, Luca

2016-05-01

The aim of this study was to explore the correlations between the dual-task cost (DTC) of standing balance and quality of life (QoL) in mildly disabled patients with multiple sclerosis (MS). In this cross-sectional study, patients affected by MS with an expanded disability status scale (EDSS) score of 3.0 or less and without an overt balance impairment were tested by means of static posturography under eyes-opened (single-task condition) and while performing the Stroop word-color test (dual-task condition), to estimate the DTC of standing balance. The self-reported 54-item MS quality of life questionnaire (MSQoL-54) was also administered to obtain a MS-specific assessment of health-related QoL. Among the 120 screened patients, 75 (53 women, 22 men) were tested. Although there was no impact of the DTC of standing balance on the physical and mental composite scores of MSQoL-54, patients who had a greater DTC of standing balance scored worse on role limitations due to physical problems (p = 0.007) and social function (p < 0.001), irrespective of demographic and other clinical characteristics including walking performance and cognitive status. However, the EDSS step and fatigue also contributed to reduced scores in these two QoL domains (p-values < 0.01). In conclusion, the phenomenon of cognitive-motor interference, investigated as DTC of standing balance, may affect specific QoL domains even in mildly disabled patients with MS and in the absence of an overt balance dysfunction.

Maternal Depressive Symptoms, Dysfunctional Cognitions, and Infant Night Waking: The Role of Maternal Nighttime Behavior

ERIC Educational Resources Information Center

Teti, Douglas M.; Crosby, Brian

2012-01-01

Mechanisms were examined to clarify relations between maternal depressive symptoms, dysfunctional cognitions, and infant night waking among 45 infants (1-24 months) and their mothers. A mother-driven mediational model was tested in which maternal depressive symptoms and dysfunctional cognitions about infant sleep predicted infant night waking via…

Dysfunctional Cognitions among Offspring of Individuals with Bipolar Disorder.

PubMed

Ruggero, Camilo J; Bain, Kathleen M; Smith, Patrick M; Kilmer, Jared N

2015-07-01

Individuals with bipolar disorder often endorse dysfunctional beliefs consistent with cognitive models of bipolar disorder (Beck, 1976; Mansell, 2007). The present study sought to assess whether young adult offspring of those with bipolar disorder would also endorse these beliefs, independent of their own mood episode history. Participants (N = 89) were young adult college students with a parent with bipolar disorder (n = 27), major depressive disorder (MDD; n = 30), or no mood disorder (n = 32). Semi-structured interviews of the offspring were used to assess diagnoses. Dysfunctional beliefs related to Beck and colleagues' (2006) and Mansell's (2007) cognitive models were assessed. Unlike offspring of parents with MDD or no mood disorder, those with a parent with bipolar disorder endorsed significantly more dysfunctional cognitions associated with extreme appraisal of mood states, even after controlling for their own mood diagnosis. Once affected by a bipolar or depressive disorder, offspring endorsed dysfunctional cognitions across measures. Dysfunctional cognitions, particularly those related to appraisals of mood states and their potential consequences, are evident in young adults with a parent who has bipolar disorder and may represent targets for psychotherapeutic intervention.

The neuropsychology and neurobiology of late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: A critical review.

PubMed

Van Assche, Lies; Morrens, Manuel; Luyten, Patrick; Van de Ven, Luc; Vandenbulcke, Mathieu

2017-12-01

The current review discusses neuropsychological profiles and the longitudinal course of cognitive dysfunction in Late Onset Schizophrenia (LOS) and Very-late-onset schizophrenia-like psychosis (VLOSLP), and attempts to clarify its neurobiological underpinnings. A systematic literature search resulted in 29 publications describing original research on the neuropsychology of LOS/VLOSLP and 46 studies focussing on neurobiology. Although mildly progressive cognitive impairment is usually present, only a subgroup of LOS/VLOSLP develops dementia during a 10-year follow-up succeeding the onset of psychosis. This coincides with the absence of neuropathological evidence for neurodegeneration in many cases. Cognitive deterioration is characterized by deficits in (working) memory, language, psychomotor speed and executive functioning. Underlying neurobiological changes encompass white matter pathology, increased ventricle-to-brain ratio (VBR) with coinciding atrophy and hypo-metabolism of frontal, temporal and subcortical areas. Multiple changes in neurobiology and cognition contributing to LOS/VLOSLP may reflect stress-related accelerated brain aging rather than neurodegenerative pathology. Their involvement in the onset of illness, however, might be inversely proportional to pre-existing (psychosocial and/or genetic) vulnerability to psychosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sleep deprivation reduces perceived emotional intelligence and constructive thinking skills.

PubMed

Killgore, William D S; Kahn-Greene, Ellen T; Lipizzi, Erica L; Newman, Rachel A; Kamimori, Gary H; Balkin, Thomas J

2008-07-01

Insufficient sleep can adversely affect a variety of cognitive abilities, ranging from simple alertness to higher-order executive functions. Although the effects of sleep loss on mood and cognition are well documented, there have been no controlled studies examining its effects on perceived emotional intelligence (EQ) and constructive thinking, abilities that require the integration of affect and cognition and are central to adaptive functioning. Twenty-six healthy volunteers completed the Bar-On Emotional Quotient Inventory (EQi) and the Constructive Thinking Inventory (CTI) at rested baseline and again after 55.5 and 58 h of continuous wakefulness, respectively. Relative to baseline, sleep deprivation was associated with lower scores on Total EQ (decreased global emotional intelligence), Intrapersonal functioning (reduced self-regard, assertiveness, sense of independence, and self-actualization), Interpersonal functioning (reduced empathy toward others and quality of interpersonal relationships), Stress Management skills (reduced impulse control and difficulty with delay of gratification), and Behavioral Coping (reduced positive thinking and action orientation). Esoteric Thinking (greater reliance on formal superstitions and magical thinking processes) was increased. These findings are consistent with the neurobehavioral model suggesting that sleep loss produces temporary changes in cerebral metabolism, cognition, emotion, and behavior consistent with mild prefrontal lobe dysfunction.

An fMRI study into emotional processing in Parkinson's disease: Does increased medial prefrontal activation compensate for striatal dysfunction?

PubMed

Moonen, Anja J H; Weiss, Peter H; Wiesing, Michael; Weidner, Ralph; Fink, Gereon R; Reijnders, Jennifer S A M; Weber, Wim M; Leentjens, Albert F G

2017-01-01

Apart from a progressive decline of motor functions, Parkinson's disease (PD) is also characterized by non-motor symptoms, including disturbed processing of emotions. This study aims at assessing emotional processing and its neurobiological correlates in PD with the focus on how medicated Parkinson patients may achieve normal emotional responsiveness despite basal ganglia dysfunction. Nineteen medicated patients with mild to moderate PD (without dementia or depression) and 19 matched healthy controls passively viewed positive, negative, and neutral pictures in an event-related blood oxygen level-dependent functional magnetic resonance imaging study (BOLD-fMRI). Individual subjective ratings of valence and arousal levels for these pictures were obtained right after the scanning. Parkinson patients showed similar valence and arousal ratings as controls, denoting intact emotional processing at the behavioral level. Yet, Parkinson patients showed decreased bilateral putaminal activation and increased activation in the right dorsomedial prefrontal cortex (PFC), compared to controls, both most pronounced for highly arousing emotional stimuli. Our findings revealed for the first time a possible compensatory neural mechanism in Parkinson patients during emotional processing. The increased medial PFC activity may have modulated emotional responsiveness in patients via top-down cognitive control, therewith restoring emotional processing at the behavioral level, despite striatal dysfunction. These results may impact upon current treatment strategies of affective disorders in PD as patients may benefit from this intact or even compensatory influence of prefrontal areas when therapeutic strategies are applied that rely on cognitive control to modulate disturbed processing of emotions.

Executive Function and Personality Predict Instrumental Activities of Daily Living in Alzheimer Disease.

PubMed

Roy, Shumita; Ficarro, Stephanie; Duberstein, Paul; Chapman, Benjamin P; Dubovsky, Steven; Paroski, Margaret; Szigeti, Kinga; Benedict, Ralph H B

2016-11-01

Previous research shows that executive function (EF) and personality independently predict functional decline. Our objective was to determine whether personality traits predict independence with instrumental activities of daily living (IADLs), after accounting for executive dysfunction, in a mixed sample of patients with amnestic mild cognitive impairment (MCI) and Alzheimer disease (AD). In a cross-sectional analysis at a university medical center, 63 healthy older adults (median age: 67.6 years; 71% women) and 119 patients (median age: 75.0 years; 58% women) with varying degrees of AD (probable AD: 85; possible AD: 3; amnestic MCI: 31) were studied. Standardized neuropsychological measures, NEO Five-Factor Inventory (NEO-FFI), and informant-report Lawton and Brody IADL scales were used. All participants underwent neuropsychological evaluation, including administration of self- and informant-report NEO-FFI. Patients additionally underwent neurologic examination, and their informants completed the Lawton and Brody IADL scale. When testing the association between EF and personality on IADLs in the patient sample, conceptual card sorting, informant-report Openness, and informant-report Conscientiousness all significantly predicted IADLs, after accounting for age, education, and depression. In addition, a significant interaction showed that low Conscientiousness and executive dysfunction, in combination, can predict impairment of IADLs. Personality has a unique association with IADLs in patients with AD pathology that is not explained by EF. The findings confirm prior speculation that personality, in addition to cognitive dysfunction, is a risk factor for functional decline. Early identification of vulnerable individuals may allow for intervention to prolong functional independence. Copyright © 2016 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

An item response theory analysis of the Executive Interview and development of the EXIT8: A Project FRONTIER Study.

PubMed

Jahn, Danielle R; Dressel, Jeffrey A; Gavett, Brandon E; O'Bryant, Sid E

2015-01-01

The Executive Interview (EXIT25) is an effective measure of executive dysfunction, but may be inefficient due to the time it takes to complete 25 interview-based items. The current study aimed to examine psychometric properties of the EXIT25, with a specific focus on determining whether a briefer version of the measure could comprehensively assess executive dysfunction. The current study applied a graded response model (a type of item response theory model for polytomous categorical data) to identify items that were most closely related to the underlying construct of executive functioning and best discriminated between varying levels of executive functioning. Participants were 660 adults ages 40 to 96 years living in West Texas, who were recruited through an ongoing epidemiological study of rural health and aging, called Project FRONTIER. The EXIT25 was the primary measure examined. Participants also completed the Trail Making Test and Controlled Oral Word Association Test, among other measures, to examine the convergent validity of a brief form of the EXIT25. Eight items were identified that provided the majority of the information about the underlying construct of executive functioning; total scores on these items were associated with total scores on other measures of executive functioning and were able to differentiate between cognitively healthy, mildly cognitively impaired, and demented participants. In addition, cutoff scores were recommended based on sensitivity and specificity of scores. A brief, eight-item version of the EXIT25 may be an effective and efficient screening for executive dysfunction among older adults.

The mediational effects of FDG hypometabolism on the association between cerebrospinal fluid biomarkers and neurocognitive function.

PubMed

Dowling, N Maritza; Johnson, Sterling C; Gleason, Carey E; Jagust, William J

2015-01-15

Positive cerebrospinal fluid (CSF) biomarkers of tau and amyloid beta42 suggest possible active underlying Alzheimer's disease (AD) including neurometabolic dysfunction and neurodegeneration leading to eventual cognitive decline. But the temporal relationship between CSF, imaging markers of neural function, and cognition has not been described. Using a statistical mediation model, we examined relationships between cerebrospinal fluid (CSF) analytes (hyperphosphorylated tau (p-Tau(181p)), β-amyloid peptides 1-42 (Aβ(1-42)), total tau (t-Tau), and their ratios); change in cognitive function; and change in [18F]fluorodeoxyglucose (FDG) uptake using positron emission tomography (PET). We hypothesized that a) abnormal CSF protein values at baseline, result in cognitive declines by decreasing neuronal glucose metabolism across time, and b) the role of altered glucose metabolism in the assumed causal chain varies by brain region and the nature of CSF protein alteration. Data from 412 individuals participating in Alzheimer's Disease Neuroimaging (ADNI) cohort studies were included in analyses. At baseline, individuals were cognitively normal (N = 82), or impaired: 241 with mild cognitive impairment, and 89 with Alzheimer's disease. A parallel-process latent growth curve model was used to test mediational effects of changes in regional FDG-PET uptake over time in relation to baseline CSF biomarkers and changes in cognition, measured with the 13-item Alzheimer Disease's Assessment Scale-cognitive subscale (ADAS-Cog). Findings suggested a causal sequence of events; specifically, FDG hypometabolism acted as a mediator between antecedent CSF biomarker alterations and subsequent cognitive impairment. Higher baseline concentrations of t-Tau, and p-Tau(181p) were more predictive of decline in cerebral glucose metabolism than lower baseline concentrations of Aβ(1-42). FDG-PET changes appeared to mediate t-Tau or t-Tau/Aβ(1-42)-associated cognitive change across all brain regions examined. Significant direct effects of alterations in Aβ(1-42) levels on hypometabolism were observed in a single brain region: middle/inferior temporal gyrus. Results support a temporal framework model in which reduced CSF amyloid-related biomarkers occur earlier in the pathogenic pathway, ultimately leading to detrimental cognitive effects. Also consistent with this temporal framework model, baseline markers of neurofibrillary degeneration predicted changes in brain glucose metabolism in turn causing longitudinal cognitive changes, suggesting that tau-related burden precedes neurometabolic dysfunction. While intriguing, the hypothesized mediational relationships require further validation. Published by Elsevier Inc.

Neuronal loss associated with cognitive performance in amyotrophic lateral sclerosis: an (11C)-flumazenil PET study.

PubMed

Wicks, Paul; Turner, Martin R; Abrahams, Sharon; Hammers, Alexander; Brooks, David J; Leigh, P Nigel; Goldstein, Laura H

2008-02-01

Amyotrophic lateral sclerosis (ALS) is a multi-system disorder. Mild cognitive deficits are present in a subgroup of non-demented patients with ALS. Detailed neuropsychological assessments reveal deficits of word retrieval including impairments on tests of verbal fluency and confrontation naming. The PET GABA(A) receptor ligand [11C]-flumazenil is a marker of neuronal dysfunction in ALS. This study used [11C]-flumazenil PET to identify correlations between cortical regions and impairments in word retrieval. Twelve patients with ALS underwent [11C]-flumazenil PET and neuropsychological assessment, including tests of written letter fluency and confrontation naming. Poorer performance on verbal fluency correlated with decreased [11C]-flumazenil binding in a region including the right inferior frontal gyrus, superior temporal gyrus, and anterior insula. Poorer performance on a test of confrontation naming correlated with decreased binding in the left middle frontal gyrus (extending to Broca's area) and left cuneus. This study indicates that [11C]-flumazenil PET can be used to help localize cortical regions associated with cognitive deficits in ALS.

Comparisons of Korsakoff and Non-Korsakoff Alcoholics on Neuropsychological Tests of Prefrontal Brain Functioning

PubMed Central

Oscar-Berman, Marlene; Kirkley, Shalene M.; Gansler, David A.; Couture, Ashley

2014-01-01

Background Evidence suggests that alcoholics exhibit particular deficits in brain systems involving the prefrontal cortex, but few studies have directly compared patients with and without Korsakoff’s syndrome on measures of prefrontal integrity. Methods Neuropsychological tasks sensitive to dysfunction of frontal brain systems were administered, along with standard tests of memory, intelligence, and visuospatial abilities, to 50 healthy, abstinent, nonamnesic alcoholics, 6 patients with alcohol-induced persisting amnestic disorder (Korsakoff’s syndrome), 6 brain-damaged controls with right hemisphere lesions, and 82 healthy nonalcoholic controls. Results Korsakoff patients were impaired on tests of memory, fluency, cognitive flexibility, and perseveration. Non-Korsakoff alcoholics showed some frontal system deficits as well, but these were mild. Cognitive deficits in non-Korsakoff alcoholics were related to age, duration of abstinence (less than 5 years), duration of abuse (more than 20 years), and amount of alcohol intake. Conclusions Abnormalities of frontal system functioning are most apparent in alcoholics with Korsakoff’s syndrome. In non-Korsakoff alcoholics, factors contributing to cognitive performance are age, duration of abstinence, duration of alcoholism, and amount of alcohol consumed. PMID:15100620

Associations between recent severe hypoglycemia, retinal vessel diameters, and cognition in adults with type 1 diabetes.

PubMed

Ryan, Christopher M; Klein, Barbara E K; Lee, Kristine E; Cruickshanks, Karen J; Klein, Ronald

Mild cognitive dysfunction has been identified in children and adults with type 1 diabetes, but most studies have failed to find a relationship between severe hypoglycemia and cognition, despite reports of such associations in older adults with type 2 diabetes. Focusing on older adults with type 1 diabetes, we examined the associations between cognitive performance and recent episodes of severe hypoglycemia, retinal vessel diameters and the presence of micro- and macrovascular complications. Cognitive functioning was assessed in 244 participants enrolled in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. The mean (SD; range) age at assessment in 2012-14 was 55.2 (8.3; 37-82) years and the mean (SD) duration of diabetes was 41.1 (5.6) years. Three cognitive domains were assessed in this cross-sectional study: mental efficiency and executive function, nonverbal memory, and verbal memory. Multivariate modeling demonstrated that although age and/or education are most strongly associated with performance on measures of mental efficiency, three diabetes-related variables were also associated with poorer test scores: an episode of severe hypoglycemia in the past year (β=-0.360 [95% CI, -0.672, -0.047]), retinal arteriolar and venular diameters (β=0.140 [95% CI, 0.062, 0.219]; β=-0.127 [95% CI -0.207, -0.047]), and carotid artery plaque (β=-0.372 [95% CI -0.741, -0.003]). In addition, recent severe hypoglycemia was associated with poorer nonverbal memory (β=-0.522 [95% CI, -0.849, -0.194]). For middle-aged and older adults with long-duration type 1 diabetes, poorer cognition was associated with a recent episode of severe hypoglycemia as well as with the presence of micro- and/or macrovascular conditions. Given the increasing numbers of aging adults with type 1 diabetes, future longitudinal studies are needed to identify causality and to determine whether diabetes management techniques that reduce the onset or severity of vascular complications and hypoglycemia can also reduce the risk of cognitive dysfunction in this population. Copyright © 2016 Elsevier Inc. All rights reserved.

[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.

Effects of Computer Cognitive Training on Depression in Cognitively Impaired Seniors

ERIC Educational Resources Information Center

Allen, Nara L.

2016-01-01

The aim of the present study was to investigate the effects of a computer cognitive training program on depression levels in older mildly cognitive impaired individuals. Peterson et al. (1999), defines mild cognitive impairment (MCI) as a transitional stage in which an individual's memory deteriorates and his likelihood of developing Alzheimer's…

Early Detection of Cognitive-Linguistic Change Associated with Mild Cognitive Impairment

ERIC Educational Resources Information Center

Fleming, Valarie B.

2014-01-01

Individuals with mild cognitive impairment (MCI) may present with subtle declines in linguistic ability that go undetected by tasks not challenging enough to tax a relatively intact cognitive-linguistic system. This study was designed to replicate and extend a previous study of cognitive-linguistic ability in MCI using a complex discourse…

Profiles and Cognitive Predictors of Motor Functions among Early School-Age Children with Mild Intellectual Disabilities

ERIC Educational Resources Information Center

Wuang, Y.-P.; Wang, C.-C.; Huang, M.-H.; Su, C.-Y.

2008-01-01

Background: The purpose of the study was to describe sensorimotor profile in children with mild intellectual disability (ID), and to examine the association between cognitive and motor function. Methods: A total of 233 children with mild ID aged 7 to 8 years were evaluated with measures of cognitive, motor and sensory integrative functioning.…

Mild to moderate cognitive impairment is a major risk factor for mortality and nursing home admission in the first year after hip fracture

USDA-ARS?s Scientific Manuscript database

It is not well established if and to what extent mild to moderate cognitive impairment predicts mortality and risk of nursing home admission after hip fracture. To investigate prospectively whether and to what extent mild to moderate cognitive impairment, contributes to mortality and admission to nu...

[Psychotherapy with mild cognitive impairment and dementia].

PubMed

Linnemann, A; Fellgiebel, A

2017-11-01

Despite evidence for psychotherapy (PT) in elderly patients, it is not standard care in patients with mild cognitive impairment and dementia. Although neuropsychiatric symptoms are frequent in these patients, there is a lack of studies investigating the importance and efficiency of PT. Can patients with mild cognitive impairment and dementia benefit from PT? If so, which modifications of therapeutic strategies are necessary for treating elderly patients with mild cognitive impairments? Evaluation of empirical evidence on the efficiency of PT for patients with mild cognitive impairment and dementia. Presentation of interventions and modifications of therapeutic strategies. Empirical evidence points towards beneficial effects of PT on depressive symptoms and quality of life. The treatment of anxiety disorders has so far been broadly neglected. Modifications of therapeutic strategies include simplification of content, repetitions, implementation of external memory aids and inclusion of caregivers into therapeutic process. Psychotherapy can be effective in patients with mild cognitive impairment and early stages of dementia. When practicing PT, an adaptation of therapeutic strategies is necessary. Nevertheless, there is a need for further studies investigating the benefits and implementation of PT into standard care, especially as pharmacological interventions are very limited in their efficiency and tolerability in this patient population.

Subjective cognitive dysfunction in rehabilitation outpatients with musculoskeletal disorders or chronic pain.

PubMed

Schrier, Ernst; Geertzen, Jan H; Dijkstra, Pieter U

2017-08-01

Rehabilitation patients, without brain damage, sometimes complain about poor concentration and problems with their memory. The magnitude and associations, of this cognitive dysfunction, with different factors is unclear. To determine the magnitude of cognitive dysfunction in rehabilitation outpatient and to explore its associations with patient characteristics, diagnosis, surgery, pain, stress, anxiety and depression. Cross-sectional. Rehabilitation outpatients. Between July 2009 and January 2012, 274 rehabilitation outpatients were included and divided in 8 different groups through diagnosis. Cognitive functioning was assessed using the cognitive failure questionnaire and compared with the general Dutch population. Associations of gender, age, diagnosis, recent surgery, pain and stress coping ability with cognitive function was explored. Mediation of depression and anxiety was explored. The rehabilitation patients had a significantly higher score on the CFQ (mean 35.9±13.4) when compared to the general Dutch population (mean 31.8±11.1). Mean difference is 4.1, 95% confidence interval 2.60 to 5.60. In the stepwise linear regression analysis only gender, diagnosis and stress coping ability were significantly associated. A significant mediation effect was found of anxiety (P≤0.001) and depression (P≤0.005) between stress coping ability and cognitive function. Rehabilitation outpatients experience more cognitive problems in comparison to the general Dutch population. Reported dysfunction of cognition in rehabilitation outpatients are associated with stress coping ability and for a small amount to gender and diagnosis. The association of stress coping ability and cognitive dysfunction is mediated by depression and anxiety. Women tend to report more dysfunctional cognition compared to men. Patient characteristics, surgery and experienced pain have no significant influence on the experienced cognitive dysfunction. Cognitive problems reported by patients should be addressed by adapting the rehabilitation program, for instance write down instructions, repeat explanations and take more time for instructions. Cognitive problems in rehabilitation patients without brain damage is probably a stress coping problem and can be addressed by boosting resilience. Targeting depression or anxiety is another option of treatment cognition if those are mediating between stress coping and cognitive problems.

Carbohydrates for improving the cognitive performance of independent-living older adults with normal cognition or mild cognitive impairment.

PubMed

Ooi, Cheow Peng; Loke, Seng Cheong; Yassin, Zaitun; Hamid, Tengku-Aizan

2011-04-13

Mild cognitive impairment (MCI) is an intermediate state between normal cognition and dementia in which daily function is largely intact. This condition may present an opportunity for research into the prevention of dementia. Carbohydrate is an essential and easily accessible macronutrient which influences cognitive performance. A better understanding of carbohydrate-driven cognitive changes in normal cognition and mild cognitive impairment may suggest ways to prevent or reduce cognitive decline. To assess the effectiveness of carbohydrates in improving cognitive function in older adults. We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register on 22 June 2010 using the terms: carbohydrates OR carbohydrate OR monosaccharides OR disaccharides OR oligosaccharides OR polysaccharides OR CARBS. ALOIS contains records from all major healthcare databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trial databases and grey literature sources. All randomised controlled trials (RCT) that have examined the efficacy of any form of carbohydrates in normal cognition and MCI. One review author selected and retrieved relevant articles for further assessment. The remaining authors independently assessed whether any of the retrieved trials should be included. Disagreements were resolved by discussion.  There is no suitable RCT of any form of carbohydrates involving independent-living older adults with normal cognition or mild cognitive impairment. There are no suitable RCTs on which to base any recommendations about the use of any form of carbohydrate for enhancing cognitive performance in older adults with normal cognition or mild cognitive impairment. More studies of many different carbohydrates are needed to tease out complex nutritional issues and further evaluate memory improvement.

Neural correlates of true and false memory in mild cognitive impairment.

PubMed

Sweeney-Reed, Catherine M; Riddell, Patricia M; Ellis, Judi A; Freeman, Jayne E; Nasuto, Slawomir J

2012-01-01

The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer's disease, which has been described as a 'disconnection syndrome'.

Aspartic acid in the hippocampus: a biomarker for postoperative cognitive dysfunction

PubMed Central

Hu, Rong; Huang, Dong; Tong, Jianbin; Liao, Qin; Hu, Zhonghua; Ouyang, Wen

2014-01-01

This study established an aged rat model of cognitive dysfunction using anesthesia with 2% isoflurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethylacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid (100 μmol/L). Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction. PMID:25206795

Aspartic acid in the hippocampus: a biomarker for postoperative cognitive dysfunction.

PubMed

Hu, Rong; Huang, Dong; Tong, Jianbin; Liao, Qin; Hu, Zhonghua; Ouyang, Wen

2014-01-15

This study established an aged rat model of cognitive dysfunction using anesthesia with 2% isoflurane and 80% oxygen for 2 hours. Twenty-four hours later, Y-maze test results showed that isoflurane significantly impaired cognitive function in aged rats. Gas chromatography-mass spectrometry results showed that isoflurane also significantly increased the levels of N,N-diethylacetamide, n-ethylacetamide, aspartic acid, malic acid and arabinonic acid in the hippocampus of isoflurane-treated rats. Moreover, aspartic acid, N,N-diethylacetamide, n-ethylacetamide and malic acid concentration was positively correlated with the degree of cognitive dysfunction in the isoflurane-treated rats. It is evident that hippocampal metabolite changes are involved in the formation of cognitive dysfunction after isoflurane anesthesia. To further verify these results, this study cultured hippocampal neurons in vitro, which were then treated with aspartic acid (100 μmol/L). Results suggested that aspartic acid concentration in the hippocampus may be a biomarker for predicting the occurrence and disease progress of cognitive dysfunction.

Clinical Epidemiology, Evaluation, and Management of Dementia in Parkinson Disease.

PubMed

Safarpour, Delaram; Willis, Allison W

2016-11-01

The prevalence of neurodegenerative diseases such as Parkinson disease (PD) will increase substantially, due to the aging of the population and improved treatments leading to better disease-related outcomes. Dementia is the most common nonmotor symptom in PD, and most patients with PD will have cognitive dysfunction and cognitive decline in the course of their disease. The development of cognitive dysfunction in PD greatly limits the ability to participate in activities of daily living and can be a tipping point for nursing home placement or major caregiver stress. Understanding the different causes of dementia and how to reduce the incidence and impact of secondary cognitive dysfunction in PD are necessary skills for primary care physicians and neurologists. In this review, we discuss the clinical epidemiology of dementia in PD with an emphasis on preventable cognitive dysfunction, present tools for outpatient evaluation of cognitive dysfunction, and describe current pharmacological treatments for dementia in PD. © The Author(s) 2016.

Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia

PubMed Central

Roberts, Rosebud O.; Christianson, Teresa J. H.; Kremers, Walter K.; Mielke, Michelle M.; Machulda, Mary M.; Vassilaki, Maria; Alhurani, Rabe E.; Geda, Yonas E.; Knopman, David S.; Petersen, Ronald C.

2015-01-01

IMPORTANCE To increase the opportunity to delay or prevent mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD), markers of early detection are essential. Olfactory impairment may be an important clinical marker and predictor of these conditions and may help identify persons at increased risk. OBJECTIVE To examine associations of impaired olfaction with incident MCI subtypes, and progression from MCI subtypes to AD dementia. DESIGN, SETTING, AND PARTICIPANTS Participants enrolled in the population-based, prospective Mayo Clinic Study of Aging were clinically evaluated at baseline and every 15-months thereafter, and classified as having normal cognition, MCI (amnestic, aMCI and nonamnestic, naMCI), and dementia. We administered the Brief Smell Identification Test (B-SIT) to assess olfactory function. MAIN OUTCOMES AND MEASURES Mild cognitive impairment, AD dementia, longitudinal change in cognitive performance measures. RESULTS Over a mean 3.5 years of follow-up, there were 250 incident cases of MCI among 1430 cognitively normal participants. We observed an association between decreasing olfactory identification, as measured by decrease in number of correct responses in B-SIT score, and an increased risk of aMCI. Compared to the upper B-SIT quartile (Q4, best scores), hazard ratios (HR) were 1.12; P = 0.68 for Q3; HR, 1.95; P =0.003 for Q2; and HR, 2.18; P = 0.001 (worst scores; p for trend <0.001) after adjustment for sex and education, with age as the time scale. There was no association with naMCI. There were 64 incident dementia cases among 221 prevalent MCI cases. The B-SIT score also predicted progression from aMCI to AD, with a significant dose-response with worsening B-SIT quartiles. Compared to Q4, HR estimates were 3.02, P = 0.038 for Q3; HR, 3.63; P = 0.024 for Q2; and HR, 5.20; P = 0.001 for Q1. After adjusting for key predictors of MCI risk, B-SIT (as a continuous measure) remained a significant predictor of MCI (HR, 1.10; p < 0.001), and improved the model concordance. CONCLUSIONS AND RELEVANCE Olfactory impairment predicts incident aMCI and progression from aMCI to AD. These findings are consistent with previous studies that have reported associations of olfactory impairment with cognitive impairment in late life, and suggest that olfactory tests have potential utility for screening for MCI and MCI that is likely to progress. PMID:26569387

Association Between Cognitive Function and Health Care Costs 3 Months and 6 Months After Initiating Antidepressant Medication for Depressive Disorders.

PubMed

Walker, Valery; Patel, Haridarshan; Kurlander, Jonathan L; Essoi, Breanna; Yang, Jiao; Mahableshwarkar, Atul R; Samp, Jennifer C; Akhras, Kasem S

2015-09-01

Major depressive disorder is one of the most common and disabling mental health disorders and is associated with substantial costs in terms of direct health care utilization and workplace productivity. Cognitive dysfunction, which alone substantially increases health care costs, is commonly associated with major depressive disorder. However, the health care costs of cognitive dysfunction in the context of depressive disorder are unknown. Recovery from mood symptoms is not always associated with resolution of cognitive dysfunction. Thus, cognitive dysfunction may contribute to health care burden even with successful antidepressant therapy.  To compare health care utilization and costs for patients with a depressive disorder with and without cognitive dysfunction, at 3 and 6 months after initiation of antidepressant medication.  This was an observational study, combining a cross-sectional patient survey, administered during a telephone interview, with health care claims data from a large, geographically diverse U.S. health plan. Included patients had at least 1 pharmacy claim for an antidepressant medication between August 1 and September 30, 2012, and no claim for any antidepressant during the 6 months prior to the index date. In addition to other criteria assessed in the claims data, patients confirmed a diagnosis of depression or major depressive disorder and the absence of any exclusionary neurological diagnoses possibly associated with cognitive impairment. Eligible patients were administered validated cognitive function assessments of verbal episodic memory (Hopkins Verbal Learning Test-Revised, Delayed and Total); attention (Digit Span Forward Maximum Sequence Length); working memory (Digit Span Backward Maximum Sequence Length); and executive function (D-KEFS-Letter Fluency Test). Based on comparison of scores with normative data, patients were assigned to cognitive dysfunction or cognitive normal cohorts. All-cause (all diagnoses) and depressive disorder-related health care utilization and costs (all from a payer perspective) were assessed 6 months prior (baseline) to antidepressant initiation and 3 months and 6 months after (follow-up) initiation of antidepressant medication. Health care utilization and costs included ambulatory (office and hospital outpatient), emergency room, inpatient hospital, pharmacy, other medical (e.g., laboratory and diagnostics), and total (all categories combined). All-cause and depressive disorder-related total costs during the 3- and 6-month follow-up periods were modeled with generalized linear modeling with gamma distribution and log link, while adjusting for potential confounders (age, race, gender, education, employment, and comorbidities). Of the 13,537 patients who were mailed an invitation, 824 (6%) were eligible and agreed to participate. Of these, 563 patients provided informed consent, completed the interview, maintained eligibility, and were included in the 3-month calculations. Among these, 255 (45%) were classified as having cognitive dysfunction. Mean patient age was 41.3 (± 12.5) years; 80% were female. Most patients were white and employed. More patients in the cognitive normal cohort were white (P  less than  0.001) and employed full time (P = 0.029), had higher education attainment (P  less than    0.001), and had fewer comorbidities (P = 0.007) than those in the cognitive dysfunction cohort. Over the first 3 months, patients with cognitive dysfunction had higher adjusted all-cause costs ($3,309 vs. $2,157, P = 0.002) and higher adjusted depressive disorder-related costs ($718 vs. $406, P  less than  0.001) than patients without cognitive dysfunction. At 6 months, data from 4 patients were removed from the analysis because of exclusionary diagnoses. Over 6 months, patients with cognitive dysfunction had higher adjusted all-cause costs ($4,793) than patients without cognitive dysfunction ($3,683, P = 0.034). Over 6 months, depressive disorder-related costs did not significantly differ between patients with ($771) and without cognitive dysfunction ($594, P = 0.071). The main drivers of all-cause costs were office visits, outpatient hospital visits, and inpatient costs, and the main driver of depressive disorder-related costs was inpatient costs. Cognitive dysfunction was associated with higher adjusted all-cause and depressive disorder-related costs 3 months after initiation of an antidepressant medication. This difference persisted for all-cause costs through 6 months. Identification and treatment of cognitive dysfunction in patients with depressive disorder might reduce health care costs.

Emerging pharmacotherapy for cancer patients with cognitive dysfunction

PubMed Central

2013-01-01

Advances in the diagnosis and multi-modality treatment of cancer have increased survival rates for many cancer types leading to an increasing load of long-term sequelae of therapy, including that of cognitive dysfunction. The cytotoxic nature of chemotherapeutic agents may also reduce neurogenesis, a key component of the physiology of memory and cognition, with ramifications for the patient’s mood and other cognition disorders. Similarly radiotherapy employed as a therapeutic or prophylactic tool in the treatment of primary or metastatic disease may significantly affect cognition. A number of emerging pharmacotherapies are under investigation for the treatment of cognitive dysfunction experienced by cancer patients. Recent data from clinical trials is reviewed involving the stimulants modafinil and methylphenidate, mood stabiliser lithium, anti-Alzheimer’s drugs memantine and donepezil, as well as other agents which are currently being explored within dementia, animal, and cell culture models to evaluate their use in treating cognitive dysfunction. PMID:24156319

Patients With Very Mild Dementia May Confuse Objective Cognitive Impairments With Subjective Physical Health of Quality of Life: The Tome City Project in Japan.

PubMed

Kasai, Mari; Meguro, Kenichi

2018-01-01

Many elderly people with cognitive dysfunction may observe a decrease in their health levels and quality of life (QOL). The basic concept of QOL consists of several categories including physical functions and mental health. The QOL domain that is most important for elderly people is physical health and, to a lesser extent, psychological health, social relationships, and/ or the environment. Our aim was to explore the relationships between the subjective measure of QOL, an abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF) scale, and the objective measure of impairment, Clinical Dementia Rating (CDR), among elderly people in a community. Totally, 178 community dwellers aged 75 years and above agreed to participate and completed the WHOQOL-BREF; 66 (32 males, 34 females) scored a CDR of 0 (healthy), 86 (33, 53) scored a CDR of 0.5 (questionable dementia or very mild dementia), and 26 (12, 14) scored a CDR of 1 and above (dementia). According to Pearson's correlation coefficient analysis (significance level, p < 0.05), the physical domain of the WHOQOL-BREF had significant statistical negative correlations with all CDR subscales. The CDR subscale of memory impairment had a significant statistical negative correlation with the WHOQOL-BREF subscales of the physical ( r = -0.151, p = 0.044) and psychological ( r = -0.232, p < 0.002) domains. The CDR subscale of home and hobbies impairment had significant statistical negative correlations with all WHOQOL-BREF subscales including the physical ( r = -0.226, p = 0.002), psychological ( r = -0.226, p = 0.002), social ( r = -0.167, p = 0.026), and environmental ( r = -0.204, p = 0.006) domains. Patients with very mild dementia may confuse cognitive impairment and physical disabilities. In the future, we need to systematically combine memory clinics and all departments related to the elderly for the successful early detection and rehabilitation of, and long-term care for, dementia.

Patients With Very Mild Dementia May Confuse Objective Cognitive Impairments With Subjective Physical Health of Quality of Life: The Tome City Project in Japan

PubMed Central

Kasai, Mari; Meguro, Kenichi

2018-01-01

Many elderly people with cognitive dysfunction may observe a decrease in their health levels and quality of life (QOL). The basic concept of QOL consists of several categories including physical functions and mental health. The QOL domain that is most important for elderly people is physical health and, to a lesser extent, psychological health, social relationships, and/ or the environment. Our aim was to explore the relationships between the subjective measure of QOL, an abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF) scale, and the objective measure of impairment, Clinical Dementia Rating (CDR), among elderly people in a community. Totally, 178 community dwellers aged 75 years and above agreed to participate and completed the WHOQOL-BREF; 66 (32 males, 34 females) scored a CDR of 0 (healthy), 86 (33, 53) scored a CDR of 0.5 (questionable dementia or very mild dementia), and 26 (12, 14) scored a CDR of 1 and above (dementia). According to Pearson’s correlation coefficient analysis (significance level, p < 0.05), the physical domain of the WHOQOL-BREF had significant statistical negative correlations with all CDR subscales. The CDR subscale of memory impairment had a significant statistical negative correlation with the WHOQOL-BREF subscales of the physical (r = -0.151, p = 0.044) and psychological (r = -0.232, p < 0.002) domains. The CDR subscale of home and hobbies impairment had significant statistical negative correlations with all WHOQOL-BREF subscales including the physical (r = -0.226, p = 0.002), psychological (r = -0.226, p = 0.002), social (r = -0.167, p = 0.026), and environmental (r = -0.204, p = 0.006) domains. Patients with very mild dementia may confuse cognitive impairment and physical disabilities. In the future, we need to systematically combine memory clinics and all departments related to the elderly for the successful early detection and rehabilitation of, and long-term care for, dementia. PMID:29706921

Differential SPECT activation patterns associated with PASAT performance may indicate frontocerebellar functional dissociation in chronic mild traumatic brain injury.

PubMed

Hattori, Naoya; Swan, Megan; Stobbe, Gary A; Uomoto, Jay M; Minoshima, Satoshi; Djang, David; Krishnananthan, Ruben; Lewis, David H

2009-07-01

Patients with mild traumatic brain injury (TBI) often complain of cognitive fatigue during the chronic recovery phase. The Paced Auditory Serial Addition Test (PASAT) is a complex psychologic measure that may demonstrate subtle deficiencies in higher cognitive functions. The purpose of this study was to investigate the brain activation of regional cerebral blood flow (rCBF) with PASAT in patients with mild TBI to explore mechanisms for the cognitive fatigue. Two groups consisting of 15 patients with mild TBI and 15 healthy control subjects underwent (99m)Tc-ethylene cysteine dimer SPECT at rest and during PASAT on a separate day. Cortical rCBF was extracted using a 3-dimensional stereotactic surface projection and statistically analyzed to identify areas of activation, which were compared with PASAT performance scores. Image analysis demonstrated a difference in the pattern of activation between patients with mild TBI and healthy control subjects. Healthy control subjects activated the superior temporal cortex (Brodmann area [BA] 22) bilaterally, the precentral gyrus (BA 9) on the left, and the precentral gyrus (BA 6) and cerebellum bilaterally. Patients with mild TBI demonstrated a larger area of supratentorial activation (BAs 9, 10, 13, and 46) but a smaller area of activation in the cerebellum, indicating frontocerebellar dissociation. Patients with mild TBI and cognitive fatigue demonstrated a different pattern of activation during PASAT. Frontocerebellar dissociation may explain cognitive impairment and cognitive fatigue in the chronic recovery phase of mild traumatic brain injury.

Cognitive Impairment Precedes and Predicts Functional Impairment in Mild Alzheimer's Disease.

PubMed

Liu-Seifert, Hong; Siemers, Eric; Price, Karen; Han, Baoguang; Selzler, Katherine J; Henley, David; Sundell, Karen; Aisen, Paul; Cummings, Jeffrey; Raskin, Joel; Mohs, Richard

2015-01-01

The temporal relationship of cognitive deficit and functional impairment in Alzheimer's disease (AD) is not well characterized. Recent analyses suggest cognitive decline predicts subsequent functional decline throughout AD progression. To better understand the relationship between cognitive and functional decline in mild AD using autoregressive cross-lagged (ARCL) panel analyses in several clinical trials. Data included placebo patients with mild AD pooled from two multicenter, double-blind, Phase 3 solanezumab (EXPEDITION/2) or semagacestat (IDENTITY/2) studies, and from AD patients participating in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Cognitive and functional outcomes were assessed using AD Assessment Scale-Cognitive subscale (ADAS-Cog), AD Cooperative Study-Activities of Daily Living instrumental subscale (ADCS-iADL), or Functional Activities Questionnaire (FAQ), respectively. ARCL panel analyses evaluated relationships between cognitive and functional impairment over time. In EXPEDITION, ARCL panel analyses demonstrated cognitive scores significantly predicted future functional impairment at 5 of 6 time points, while functional scores predicted subsequent cognitive scores in only 1 of 6 time points. Data from IDENTITY and ADNI programs yielded consistent results whereby cognition predicted subsequent function, but not vice-versa. Analyses from three databases indicated cognitive decline precedes and predicts subsequent functional decline in mild AD dementia, consistent with previously proposed hypotheses, and corroborate recent publications using similar methodologies. Cognitive impairment may be used as a predictor of future functional impairment in mild AD dementia and can be considered a critical target for prevention strategies to limit future functional decline in the dementia process.

Cognitive medicine - a new approach in health care science.

PubMed

Wallin, Anders; Kettunen, Petronella; Johansson, Per M; Jonsdottir, Ingibjörg H; Nilsson, Christer; Nilsson, Michael; Eckerström, Marie; Nordlund, Arto; Nyberg, Lars; Sunnerhagen, Katharina S; Svensson, Johan; Terzis, Beata; Wahlund, Lars-Olof; Georg Kuhn, H

2018-02-08

The challenges of today's society call for more knowledge about how to maintain all aspects of cognitive health, such as speed/attention, memory/learning, visuospatial ability, language, executive capacity and social cognition during the life course. Medical advances have improved treatments of numerous diseases, but the cognitive implications have not been sufficiently addressed. Disability induced by cognitive dysfunction is also a major issue in groups of patients not suffering from Alzheimer's disease or related disorders. Recent studies indicate that several negative lifestyle factors can contribute to the development of cognitive impairment, but intervention and prevention strategies have not been implemented. Disability due to cognitive failure among the workforce has become a major challenge. Globally, the changing aging pyramid results in increased prevalence of cognitive disorders, and the diversity of cultures influences the expression, manifestation and consequences of cognitive dysfunction. Major tasks in the field of cognitive medicine are basic neuroscience research to uncover diverse disease mechanisms, determinations of the prevalence of cognitive dysfunction, health-economical evaluations, and intervention studies. Raising awareness for cognitive medicine as a clinical topic would also highlight the importance of specialized health care units for an integrative approach to the treatment of cognitive dysfunctions.

Early Maladaptive Schemas and Cognitive Distortions in Adults with Morbid Obesity: Relationships with Mental Health Status.

PubMed

da Luz, Felipe Q; Sainsbury, Amanda; Hay, Phillipa; Roekenes, Jessica A; Swinbourne, Jessica; da Silva, Dhiordan C; da S Oliveira, Margareth

2017-02-28

Dysfunctional cognitions may be associated with unhealthy eating behaviors seen in individuals with obesity. However, dysfunctional cognitions commonly occur in individuals with poor mental health independently of weight. We examined whether individuals with morbid obesity differed with regard to dysfunctional cognitions when compared to individuals of normal weight, when mental health status was controlled for. 111 participants-53 with morbid obesity and 58 of normal weight-were assessed with the Mini-Mental State Examination, Young Schema Questionnaire, Cognitive Distortions Questionnaire, Depression, Anxiety and Stress Scale, and a Demographic and Clinical Questionnaire. Participants with morbid obesity showed higher scores in one (insufficient self-control/self-discipline) of 15 early maladaptive schemas and in one (labeling) of 15 cognitive distortions compared to participants of normal weight. The difference between groups for insufficient self-control/self-discipline was not significant when mental health status was controlled for. Participants with morbid obesity showed more severe anxiety than participants of normal weight. Our findings did not show clinically meaningful differences in dysfunctional cognitions between participants with morbid obesity or of normal weight. Dysfunctional cognitions presented by individuals with morbid obesity are likely related to their individual mental health and not to their weight.

Influence of Educational Attainment on Cognition-Based Intervention Programs for Persons with Mild Alzheimer's Disease.

PubMed

Contador, Israel; Fernández-Calvo, Bernardino; Ramos, Francisco; Olazarán, Javier

2016-05-01

This research retrospectively analyzed the effect of education on cognitive interventions carried out in patients with mild Alzheimer's disease (AD). The total sample consisted of 75 patients with mild AD receiving treatment with cholinesterase inhibitors. The participants were divided into two groups: cognitive intervention (IG; n=45) and waiting list (WLG; n=30). Patients in the IG received either the Big Brain Academy (n=15) or the Integrated Psychostimulation Program (n=30) during 12 weeks. The influence of education on intervention effect was analyzed comparing mean change scores of the two study groups in the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), stratified by educational level. The potential effect of age, sex, cognitive status, and type of intervention was examined using post hoc stratification analyses. Higher education was associated with faster cognitive decline in the WLG (effect size=0.51; p<.01). However, cognitive evolution was not influenced by education in the IG (effect size=0.12; p=.42). Our results suggest that cognitive intervention might delay accelerated cognitive decline in higher educated individuals with mild AD.

Informed Consent and Cognitive Dysfunction After Noncardiac Surgery in the Elderly.

PubMed

Hogan, Kirk J; Bratzke, Lisa C; Hogan, Kendra L

2018-02-01

Cognitive dysfunction 3 months after noncardiac surgery in the elderly satisfies informed consent thresholds of foreseeability in 10%-15% of patients, and materiality with new deficits observed in memory and executive function in patients with normal test performance beforehand. At present, the only safety step to avoid cognitive dysfunction after surgery is to forego surgery, thereby precluding the benefits of surgery with removal of pain and inflammation, and resumption of normal nutrition, physical activity, and sleep. To assure that consent for surgery is properly informed, risks of both cognitive dysfunction and alternative management strategies must be discussed with patients by the surgery team before a procedure is scheduled.

Adaptive and regulatory mechanisms in aged rats with postoperative cognitive dysfunction

PubMed Central

Bi, Yanlin; Liu, Shuyun; Yu, Xinjuan; Wang, Mingshan; Wang, Yuelan

2014-01-01

Inflammation may play a role in postoperative cognitive dysfunction. 5′ Adenosine monophosphate-activated protein kinase, nuclear factor-kappa B, interleukin-1β, and tumor necrosis factor-α are involved in inflammation. Therefore, these inflammatory mediators may be involved in postoperative cognitive dysfunction. Western immunoblot analysis revealed 5′ adenosine monophosphate-activated protein kinase and nuclear factor-kappa B in the hippocampus of aged rats were increased 1–7 days after splenectomy. Moreover, interleukin-1β and tumor necrosis factor-α were upregulated and gradually decreased. Therefore, these inflammatory mediators may participate in the splenectomy model of postoperative cognitive dysfunction in aged rats. PMID:25206851

Pathogenesis of Cognitive Dysfunction in Patients with Obstructive Sleep Apnea: A Hypothesis with Emphasis on the Nucleus Tractus Solitarius

PubMed Central

Daulatzai, Mak Adam

2012-01-01

OSA is characterized by the quintessential triad of intermittent apnea, hypoxia, and hypoxemia due to pharyngeal collapse. This paper highlights the upstream mechanisms that may trigger cognitive decline in OSA. Three interrelated steps underpin cognitive dysfunction in OSA patients. First, several risk factors upregulate peripheral inflammation; these crucial factors promote neuroinflammation, cerebrovascular endothelial dysfunction, and oxidative stress in OSA. Secondly, the neuroinflammation exerts negative impact globally on the CNS, and thirdly, important foci in the neocortex and brainstem are rendered inflamed and dysfunctional. A strong link is known to exist between neuroinflammation and neurodegeneration. A unique perspective delineated here underscores the importance of dysfunctional brainstem nuclei in etiopathogenesis of cognitive decline in OSA patients. Nucleus tractus solitarius (NTS) is the central integration hub for afferents from upper airway (somatosensory/gustatory), respiratory, gastrointestinal, cardiovascular (baroreceptor and chemoreceptor) and other systems. The NTS has an essential role in sympathetic and parasympathetic systems also; it projects to most key brain regions and modulates numerous physiological functions. Inflamed and dysfunctional NTS and other key brainstem nuclei may play a pivotal role in triggering memory and cognitive dysfunction in OSA. Attenuation of upstream factors and amelioration of the NTS dysfunction remain important challenges. PMID:23470865

Cognitive dysfunction in patients with Systemic Lupus Erythematosus.

PubMed

Butt, Bilal Azeem; Farman, Sumaira; Khan, Saira Elaine Anwer; Saeed, Muhammad Ahmed; Ahmad, Nighat Mir

2017-01-01

To determine the frequency of cognitive dysfunction in patients with Systemic Lupus Erythematosus in a Pakistani population, presenting at a tertiary care Rheumatology setting. This cross-sectional study was conducted at the Division of Rheumatology, Fatima Memorial Hospital, Lahore, from March to June 2016. A total of 43 consecutive patients, who fulfilled the 2012 SLICC (Systemic Lupus International Collaborating Clinics) classification criteria for Systemic Lupus Erythematosus (SLE), were enrolled. Cognitive function was assessed using Montréal Cognitive Assessment (MoCA) questionnaire. Demographic data and disease dynamics were collected in a proforma. Cognitive dysfunction was defined as score < 26/30, adjusted for duration of formal education. SPSS version 16.0 for windows was used to analyse data and to calculate frequency of cognitive dysfunction. Out of 43 enrolled patients, 95.3% were females and 4.7% were males, with mean age of 28.72 ± 9.25 years and mean formal education duration of 10.98 ± 3.29 years. The mean disease duration was 24.21 ± 30.46 months. Anti-nuclear antibodies (ANA) were present in all patients and anti-ds DNA in 93% patients. Cognitive dysfunction according to MoCA score was found in 65.1% (n=28) patients. For patients with disease duration more than two years, cognitive dysfunction was found in 60% patients [p>0.05] and for duration of formal education less than 12 years in 74.1% patients [p>0.05]. In this study, two third of SLE patients had Cognitive dysfunction. Hence, there is an increasing need to recognise and initiate early therapy for this overlooked aspect of SLE with an aim to achieve better quality of life.

Cognition following bilateral deep brain stimulation surgery of the subthalamic nucleus for Parkinson's disease.

PubMed

Halpern, Casey H; Rick, Jacqueline H; Danish, Shabbar F; Grossman, Murray; Baltuch, Gordon H

2009-05-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by significant motor dysfunction and various non-motor disturbances, including cognitive alterations. Deep brain stimulation (DBS) is an increasingly utilized therapeutic option for patients with PD that yields remarkable success in alleviating disabling motor symptoms. DBS has additionally been associated with changes in cognition, yet the evidence is not consistent across studies. The following review sought to provide a clearer understanding of the various cognitive sequelae of bilateral subthalamic nucleus (STN) DBS while taking into account corresponding neuroanatomy and potential confounding variables. A literature search was performed using the following inclusion criteria: (1) at least five subjects followed for a mean of at least 3 months after surgery; (2) pre- and postoperative cognitive data using at least one standardized measure; (3) adequate report of study results using means and standard deviations. Two recent meta-analyses found mild post-operative impairments in verbal learning and executive function in patients who underwent DBS surgery. However, studies have revealed improved working memory and psychomotor speed in the 'on' vs 'off' stimulation state. A deficit in language may be a consequence of the surgical procedure. While cognitive decline has been observed in some domains, our review of the data suggests that STN DBS is a worthwhile and safe method to treat PD. (c) 2008 John Wiley & Sons, Ltd.

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.

Memory deficits for facial identity in patients with amnestic mild cognitive impairment (MCI).

PubMed

Savaskan, Egemen; Summermatter, Daniel; Schroeder, Clemens; Schächinger, Hartmut

2018-01-01

Faces are among the most relevant social stimuli revealing an encounter's identity and actual emotional state. Deficits in facial recognition may be an early sign of cognitive decline leading to social deficits. The main objective of the present study is to investigate if individuals with amnestic mild cognitive impairment show recognition deficits in facial identity. Thirty-seven individuals with amnestic mild cognitive impairment, multiple-domain (15 female; age: 75±8 yrs.) and forty-one healthy volunteers (24 female; age 71±6 yrs.) participated. All participants completed a human portrait memory test presenting unfamiliar faces with happy and angry emotional expressions. Five and thirty minutes later, old and new neutral faces were presented, and discrimination sensitivity (d') and response bias (C) were assessed as signal detection parameters of cued facial identity recognition. Memory performance was lower in amnestic mild cognitive impairment as compared to control subjects, mainly because of an altered response bias towards an increased false alarm rate (favoring false OLD ascription of NEW items). In both groups, memory performance declined between the early and later testing session, and was always better for acquired happy than angry faces. Facial identity memory is impaired in patients with amnestic mild cognitive impairment. Liberalization of the response bias may reflect a socially motivated compensatory mechanism maintaining an almost identical recognition hit rate of OLD faces in individuals with amnestic mild cognitive impairment.

A cross-sectional study of functional disabilities and perceived cognitive dysfunction in patients with major depressive disorder in South Korea: The PERFORM-K study.

PubMed

Kim, Jae Min; Chalem, Ylana; di Nicola, Sylvia; Hong, Jin Pyo; Won, Seung Hee; Milea, Dominique

2016-05-30

PERFORM-K was a cross-sectional observational study that investigated functional disability, productivity and quality of life in MDD outpatients in South Korea, and the associations of these with depressive symptoms, perceived cognitive dysfunction and other factors. A total of 312 outpatients who started antidepressant monotherapy underwent a single study interview. Physicians and patients assessed depression severity. Patients also assessed: perceived cognitive dysfunction, functional disability, impaired productivity and quality of life. Patients had moderate to severe depression (MADRS mean total score: 28.9±7.3), and reported marked functional disability (SDS mean total score: 16.7±8.6), impaired productivity (WPAI mean overall work productivity loss: 52.4±31.8%), perceived cognitive dysfunction (PDQ-D mean total score: 29.9±18.6) and impaired quality of life (EQ-5D mean utility index score of 0.726±0.192). Greater functional disability and impairment in daily activities were associated with more severe depression and greater perceived cognitive dysfunction. Irrespective of depression severity, patients with more severe perceived cognitive dysfunction reported worse work-related productivity outcomes (higher presenteeism and greater overall work productivity loss). PERFORM-K confirms the impact of MDD on functional status and well-being in South Korean patients, and highlights the importance of recognising cognitive dysfunction in clinical practice. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Association of social and cognitive impairment and biomarkers in autism spectrum disorders

PubMed Central

2014-01-01

Objectives The neurological basis for autism is still not fully understood, and the role of the interaction between neuro-inflammation and neurotransmission impairment needs to be clearer. This study aims to test the possible association between impaired levels of gamma aminobutyric acid (GABA), serotonin, dopamine, oxytocin, and interferon-γ-induced protein-16 (IFI16) and the severity of social and cognitive dysfunctions in individuals with autism spectrum disorders. Materials and methods GABA, serotonin, dopamine, oxytocin, and IFI16 as biochemical parameters related to neurochemistry and inflammation were determined in the plasma of 52 Saudi autistic male patients, categorized as mild-moderate and severe as indicated by their Childhood Autism Rating Scale (CARS) or social responsiveness scale (SRS), and compared to 30 age- and gender-matched control samples. Results The data indicated that Saudi patients with autism have remarkably impaired plasma levels of the measured parameters compared to age and gender-matched controls. While serotonin in platelet-free plasma and dopamine did not correlated with the severity in social and cognitive dysfunction, GABA, oxytocin, and IFI16 were remarkably associated with the severity of both tested scores (SRS and CARS). Conclusions The relationship between the selected parameters confirms the role of impaired neurochemistry and neuro-inflammation in the etiology of autism spectrum disorders and the possibility of using GABA, oxytocin, and IFI16 as markers of autism severity. Receiver operating characteristic analysis together with predictiveness diagrams proved that the measured parameters could be used as predictive biomarkers of clinical symptoms and provide significant guidance for future therapeutic strategy to re-establish physiological homeostasis. PMID:24400970

The safety, tolerability, pharmacokinetics and cognitive effects of GSK239512, a selective histamine H₃ receptor antagonist in patients with mild to moderate Alzheimer's disease: a preliminary investigation.

PubMed

Nathan, Pradeep J; Boardley, Rebecca; Scott, Nicola; Berges, Alienor; Maruff, Paul; Sivananthan, Tharani; Upton, Neil; Lowy, Martin T; Nestor, Peter J; Lai, Robert

2013-03-01

The histamine H3 receptor plays a critical role in the negative neuromodulation of neurotransmitters involved in cognitive function. H3 receptor antagonists/inverse agonists have been shown to exert pro-cognitive effects in pre-clinical models. GSK239512 is a potent and selective H₃ receptor antagonist developed for the treatment of cognitive dysfunction in neurodegenerative disorders. In this study we examined the safety, tolerability, pharmacokinetics and pro-cognitive effects of GSK239512 (oral) in patients with mild to moderate Alzheimer's disease using ascending dose titration regimens. The study was conducted in two parts. Part A was a single-blind, placebo run-in, flexible dose titration over 9 days in two cohorts, each consisting of two patients. Part B was a double-blind, randomised, placebo controlled, parallel group, which investigated 3 flexible dose titration regimens over 4 weeks in 3 cohorts, each consisting of eight patients. Overall, the 5/10/20/40 μg and 10/20/40/80 μg regimens were well-tolerated. The regimen of 20/40/80/150 μg showed the poorest tolerability likely due to the higher starting dose. There were no clinically significant abnormalities in haematology, clinical chemistry, urinalysis parameters and cardiovascular parameters. GSK239512 had positive effects on tasks of attention and memory with effect sizes between 0.56 and 1.37. GSK239512 displayed asatisfactory level of tolerability in patients with Alzheimer's disease with evidence for positive effects on attention and memory. The findings suggest that a titration regimen with a starting dose of 5-10 μg and a maximum dose of 80 μg is likely to be a well-tolerated and potentially efficacious regimen for future clinical trials in patients with Alzheimer's disease. These findings await replication in a larger study.

Neural Correlates of True and False Memory in Mild Cognitive Impairment

PubMed Central

Sweeney-Reed, Catherine M.; Riddell, Patricia M.; Ellis, Judi A.; Freeman, Jayne E.; Nasuto, Slawomir J.

2012-01-01

The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer’s disease, which has been described as a ‘disconnection syndrome’. PMID:23118992

Ginkgo Biloba for Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Yang, Guoyan; Wang, Yuyi; Sun, Jin; Zhang, Kang; Liu, Jianping

2016-01-01

Ginkgo biloba is a natural medicine used for cognitive impairment and Alzheimer's disease. The objective of this review is to explore the effectiveness and safety of Ginkgo biloba in treating mild cognitive impairment and Alzheimer's disease. Electronic search was conducted from PubMed, Cochrane Library, and four major Chinese databases from their inception up to 1(st) December, 2014 for randomized clinical trials on Ginkgo biloba in treating mild cognitive impairment or Alzheimer's disease. Meta-analyses were performed by RevMan 5.2 software. 21 trials with 2608 patients met the inclusion criteria. The general methodological quality of included trials was moderate to poor. Compared with conventional medicine alone, Ginkgo biboba in combination with conventional medicine was superior in improving Mini-Mental State Examination (MMSE) scores at 24 weeks for patients with Alzheimer's disease (MD 2.39, 95% CI 1.28 to 3.50, P<0.0001) and mild cognitive impairment (MD 1.90, 95% CI 1.41 to 2.39, P<0.00001), and Activity of Daily Living (ADL) scores at 24 weeks for Alzheimer's disease (MD -3.72, 95% CI -5.68 to -1.76, P=0.0002). When compared with placebo or conventional medicine in individual trials, Ginkgo biboba demonstrated similar but inconsistent findings. Adverse events were mild. Ginkgo biloba is potentially beneficial for the improvement of cognitive function, activities of daily living, and global clinical assessment in patients with mild cognitive impairment or Alzheimer's disease. However, due to limited sample size, inconsistent findings and methodological quality of included trials, more research are warranted to confirm the effectiveness and safety of ginkgo biloba in treating mild cognitive impairment and Alzheimer's disease.

On categorization and quantification of women's sexual dysfunctions: an epidemiological approach.

PubMed

Oberg, K; Fugl-Meyer, A R; Fugl-Meyer, K S

2004-06-01

The objectives of this study are to compare the two definitions of female sexual dysfunction, namely dysfunction per se (A category) and personal distress caused by dysfunction (B category), and to gauge their associations with some sociodemographic aspects and level of sexual well-being. The subjects were a nationally representative sample of sexually active Swedish women (n: 1056) aged 18-65 y, who participated in a combined structured interview/questionnaire investigation. The functions analysed were: self-reported sexual desire, interest, lubrication, orgasm, genital pain and vaginism, which were subclassified for the A and B categories into no, mild (sporadically occurring) and manifest dysfunction. Sexual well-being was reported along a six-grade scale ranging from very satisfied to very dissatisfied. The sociodemographic items registered were: education, occupation, financial situation, social group, immigrant status, location of domicile and church-going. Aggregated mild and manifest dysfunction per se of sexual interest, orgasm and vaginal lubrication were reported by about 60-90%. More than one-third had dyspareunia, but few reported vaginism. Mild dysfunctions were clearly more common than manifest dysfunctions. Not fully 45% of those with manifest low interest and orgasm perceived these dysfunctions as manifestly distressing, while in 60-70% lubricational insufficiency of dyspareunia led to manifest distress. Age and the included sociodemographic variables had marginal or no influence on sexual functions. A four-factor sexual function pattern was identified, closely linking A and B categories in a pairwise manner. Three factors, labelled sexual desire, orgasm and genital function were powerful classifiers (discriminant analysis) of level of sexual well-being. Hence, it is a matter of taste whether to use the A or the B category. Together, they can explain the gross level of satisfaction with sexual life to an adequate extent.

Difficulty with learning of exercise instructions associated with 'working memory' dysfunction and frontal glucose hypometabolism in a patient with very mild subcortical vascular dementia with knee osteoarthritis.

PubMed

Takeda, Kenji; Meguro, Kenichi; Tanaka, Naofumi; Nakatsuka, Masahiro

2013-07-25

We present a patient with no dementia, depression or apathy, who had difficulty in learning self-exercise instructions. The patient was an 80-year-old right-handed woman who was admitted to a rehabilitation unit to receive postoperative rehabilitation after a femoral neck fracture. She was instructed quadriceps isometric exercises to perform 10 repetitions and to hold each stretch for 10 s. She performed the exercise correctly with motivation, but she had difficulty in learning the number of repetitions and the duration of each stretch. She had no history of cerebrovascular accident and the neurological examination was normal. Neuropsychological testing, MRI and (18)F-fluoro- D-glucose-positron emission tomography (FDG-PET) were performed to examine the neural mechanisms associated with this difficulty in learning instructions. Neuropsychological tests revealed dysfunction of working memory while other cognitive domains were relatively preserved. Her neuropsychological tests scores were (1) Mini-Mental State Examination: 24 (mild cognitive impairment), (2) Geriatric Depression Scale-15: 2 (no depression), (3) Apathy Scale: 2 (no apathy), (4) digit span forward: 5 (normal), (5) digit span backward: 2 (impaired), (6) visuospatial span forward: 4 (normal), (7) visuospatial span backward: 2 (impaired), (8) frontal assessment battery: 11 (normal), (9) Weigl test: 0 (impaired), (10) trail making test A: 52 s (normal), (11) train making test B: failed (impaired). T2-weighted and fluid-attenuated inversion recovery MRI showed high signal-intensity lesions in the cerebral deep white matter. FDG-PET revealed hypometabolic areas in the bilateral frontal lobes, particularly in the bilateral dorsolateral frontal area, anterior cingulate cortex and orbitofrontal cortex. One of the possible neural mechanisms underlying the learning difficulties in this patient may have been partial blockage of the cingulofrontal network by deep white matter lesions.

Anosognosia in mild cognitive impairment and mild Alzheimer's disease: frequency and neuropsychological correlates.

PubMed

Orfei, Maria Donata; Varsi, Ambra Erika; Blundo, Carlo; Celia, Elisabetta; Casini, Anna Rosa; Caltagirone, Carlo; Spalletta, Gianfranco

2010-12-01

To evaluate severity of anosognosia and to identify its neuropsychological correlates in preclinical and clinical Alzheimer's Disease (AD). The Clinical Insight Rating Scale, the Anosognosia Questionnaire for Dementia (AQ-D), and the Mental Deterioration Battery were used to assess anosognosia and cognitive performances in mild AD (N = 38), amnesic mild cognitive impairment (a-MCI; N = 35), and multiple domain MCI (md-MCI; N = 38). Patients with mild AD were more anosognosic than both MCI groups, which, however, did not differ from one other. A categorical diagnosis of anosognosia was made in 42% of patients with mild AD, 3% of md-MCI, but in no subjects with a-MCI. Reduced verbal episodic memory raw score was associated with decreased awareness of cognitive difficulties (AQ-D total and intellectual functioning scores) only in MCI. In mild AD, anosognosia was linked only to increased age and reduced basic activities of daily living performances. The diagnosis of anosognosia is frequent in patients with mild AD but not in those with MCI. In the latter case, the authors cannot speak of true anosognosia but only of decreased awareness of illness. Furthermore, reduced awareness of cognitive difficulties is linked with verbal memory performances in patients with MCI but not in those with AD, suggesting for the latter the involvement of factors other than neuropsychological. Thus, neuropsychiatric dimensions commonly present in patients with AD should be investigated along with anosognosia.

Multimodal Cognitive Enhancement Therapy for Patients with Mild Cognitive Impairment and Mild Dementia: A Multi- Center, Randomized, Controlled, Double-Blind, Crossover Trial.

PubMed

Han, Ji Won; Lee, Hyeonggon; Hong, Jong Woo; Kim, Kayoung; Kim, Taehyun; Byun, Hye Jin; Ko, Ji Won; Youn, Jong Chul; Ryu, Seung-Ho; Lee, Nam-Jin; Pae, Chi-Un; Kim, Ki Woong

2017-01-01

We developed and evaluated the effect of Multimodal Cognitive Enhancement Therapy (MCET) consisting of cognitive training, cognitive stimulations, reality orientation, physical therapy, reminiscence therapy, and music therapy in combination in older people with mild cognitive impairment (MCI) or mild dementia. This study was a multi-center, double-blind, randomized, placebo-controlled, two-period cross-over study (two 8-week treatment phases separated by a 4-week wash-out period). Sixty-four participants with MCI or dementia whose Clinical Dementia Rating was 0.5 or 1 were randomized to the MCET group or the mock-therapy (placebo) group. Outcomes were measured at baseline, week 9, and week 21. Fifty-five patients completed the study. Mini-Mental State Examination (effect size = 0.47, p = 0.013) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (effect size = 0.35, p = 0.045) scores were significantly improved in the MCET compared with mock-therapy group. Revised Memory and Behavior Problems Checklist frequency (effect size = 0.38, p = 0.046) and self-rated Quality of Life - Alzheimer's Disease (effect size = 0.39, p = 0.047) scores were significantly improved in the MCET compared with mock-therapy. MCET improved cognition, behavior, and quality of life in people with MCI or mild dementia more effectively than conventional cognitive enhancing activities did.

Cognitive Rehabilitation for Executive Dysfunction in Parkinson's Disease: Application and Current Directions

PubMed Central

Calleo, Jessica; Burrows, Cristina; Levin, Harvey; Marsh, Laura; Lai, Eugene; York, Michele K.

2012-01-01

Cognitive dysfunction in Parkinson's disease contributes to disability, caregiver strain, and diminished quality of life. Cognitive rehabilitation, a behavioral approach to improve cognitive skills, has potential as a treatment option to improve and maintain cognitive skills and increase quality of life for those with Parkinson's disease-related cognitive dysfunction. Four cognitive rehabilitation programs in individuals with PD are identified from the literature. Characteristics of the programs and outcomes are reviewed and critiqued. Current studies on cognitive rehabilitation in PD demonstrate feasibility and acceptability of a cognitive rehabilitation program for patients with PD, but are limited by their small sample size and data regarding generalization of effects over the long term. Because PD involves progressive heterogeneous physical, neurological, and affective difficulties, future cognitive rehabilitation programs should aim for flexibility and individualization, according to each patient's strengths and deficits. PMID:22135762

Oxygen cost of treadmill and over-ground walking in mildly disabled persons with multiple sclerosis

PubMed Central

Suh, Yoojin; Dlugonski, Deirdre; Weikert, Madeline; Agiovlasitis, Stamatis; Fernhall, Bo; Goldman, Myla

2011-01-01

Walking impairment is a ubiquitous feature of multiple sclerosis (MS) and the O2 cost of walking might quantify this dysfunction in mild MS. This paper examined the difference in O2 cost of walking between persons with MS who have mild disability and healthy controls and the correlation between the O2 cost of walking and disability. Study 1 included 18 persons with mild MS and 18 controls and indicated that the O2 cost of walking was significantly higher in MS than controls and that disability was significantly associated with the O2 cost of slow, moderate, and fast treadmill walking. Study 2 included 24 persons with mild MS and indicated that disability was significantly correlated with O2 cost of comfortable, fast, and slow over-ground walking. We provide evidence that the O2 cost of walking is an indicator of walking dysfunction in mildly disabled persons with MS and should be considered in clinical research and practice. PMID:20798968

Oxygen cost of treadmill and over-ground walking in mildly disabled persons with multiple sclerosis.

PubMed

Motl, Robert W; Suh, Yoojin; Dlugonski, Deirdre; Weikert, Madeline; Agiovlasitis, Stamatis; Fernhall, Bo; Goldman, Myla

2011-04-01

Walking impairment is a ubiquitous feature of multiple sclerosis (MS) and the O(2) cost of walking might quantify this dysfunction in mild MS. This paper examined the difference in O(2) cost of walking between persons with MS who have mild disability and healthy controls and the correlation between the O(2) cost of walking and disability. Study 1 included 18 persons with mild MS and 18 controls and indicated that the O(2) cost of walking was significantly higher in MS than controls and that disability was significantly associated with the O(2) cost of slow, moderate, and fast treadmill walking. Study 2 included 24 persons with mild MS and indicated that disability was significantly correlated with O(2) cost of comfortable, fast, and slow over-ground walking. We provide evidence that the O(2) cost of walking is an indicator of walking dysfunction in mildly disabled persons with MS and should be considered in clinical research and practice.

The process of disclosing a diagnosis of dementia and mild cognitive impairment: A national survey of specialist physicians in Denmark.

PubMed

Nielsen, T Rune; Svensson, Birthe Hjorth; Rohr, Gitte; Gottrup, Hanne; Vestergaard, Karsten; Høgh, Peter; Waldemar, Gunhild

2018-01-01

Background Although general recommendations for diagnostic disclosure of dementia are available, little is known about how these recommendations are implemented. The aim of the current study was to investigate the process and content of dementia diagnostic disclosure meetings, and to compare key aspects of disclosing a diagnosis of dementia and mild cognitive impairment. Method A total of 54 specialist physicians in Danish dementia diagnostic departments completed an online survey on their practices regarding diagnostic disclosure of dementia and mild cognitive impairment. The influence of respondent characteristics was assessed, and differences on key aspects of disclosing a diagnosis of dementia and mild cognitive impairment were analyzed. Results The results suggest that among Danish specialist physicians, there is a general consensus regarding the organization of diagnostic disclosure meetings. However, differences in employed terminology and information provided when disclosing a dementia diagnosis were evident. Significant differences were present on key aspects of the diagnostic disclosure of dementia and mild cognitive impairment. For instance, 91% would use the term dementia during diagnostic disclosures compared to just 72% for mild cognitive impairment. Conclusion The range of practices reflected in the present study confirms the complexity of diagnostic disclosure and highlights the importance of preparation and follow-up strategies to tailor the disclosure process to the needs of individual patients with dementia and their caregivers. Due to earlier diagnosis of neurodegenerative disorders, more research is urgently needed on this aspect of the diagnostic process, especially to develop evidence-based models for the disclosure of mild cognitive impairment.

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.

[Cognitive dysfunction in schizophrenic psychoses. Drug and psychological treatment choices].

PubMed

Sachs, G; Katschnig, H

2001-03-01

Primarily from the perspective of psychopharmacology, schizophrenic symptomatology has recently been dichotomized into "plus" and "minus" symptoms, although the role of cognitive dysfunctions has been regarded as particularly important for the diagnosis since the time of Eugen Bleuler. Many studies show that schizophrenic patients suffer consistently from cognitive dysfunction. Among these, are impairments of attention and memory functions as well as executive functions such as planning and problem solving. These impairments are stable or progressive and often continue into the remission phase of schizophrenia and impair both social integration as well as occupational performance. In this overview, research results on cognitive dysfunction in patients with schizophrenic illnesses and their relation to psychosocial disabilities are described first. The therapeutic value and possible clinical-practice implications of atypical anti-psychotics and various cognitive therapy methods are then presented. Methodological weaknesses and open questions, both pharmacological and with regard to cognitive interventions, are discussed.

The impact of cognitive impairment on self-management in chronic obstructive pulmonary disease: A systematic review.

PubMed

Baird, Chelsea; Lovell, Janaka; Johnson, Marilyn; Shiell, Kerrie; Ibrahim, Joseph E

2017-08-01

To determine the characteristics of persons with cognitive impairment being able to self-manage in chronic obstructive pulmonary disease (COPD). In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance this systematic review examined all studies in English from 1st January 2000 to 20 February 2016, describing the relationship between cognition and COPD self-management domains in older community dwelling persons with dementia or cognitive impairment. Of 4474 studies identified, thirteen studies were eligible for inclusion. No studies differentiated populations into recognized dementia subtypes. Study aims were variable; most (n = 7) examined inhaler competency alone. Studies identified a link between worsening cognition and the need for assistance in activities of daily living. Only one study evaluated the impact of cognition on overall self-management and found no association between cognitive impairment and self-rated self-management. Mild degrees of cognitive impairment were associated with reduced symptom recall. Cognitive impairment in COPD was associated with high degrees of inhaler incompetency. Basic cognitive screening tests were able to predict inhaler incompetence with reduced overall cognitive function, dyspraxia, and/or executive function identified as predictors of incompetency. Multiple measures of disability consistently demonstrated that cognitive impairment in COPD significantly increased the need for assistance in many aspects of daily living, treatment adherence, and effective self-management. Given the nature of neuropsychological deficits seen in COPD, dedicated screening tools are required. Future research should investigate the impact of cognitive dysfunction in COPD and identify how to support those that lack capacity to self-manage. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early differentiation of dementia with Lewy bodies and Alzheimer's disease: Heart rate variability at mild cognitive impairment stage.

PubMed

Kim, Min Seung; Yoon, Jung Han; Hong, Ji Man

2018-05-29

Our study aimed to investigate whether heart rate variability (HRV) could be a useful diagnostic screening tool at MCI (mild cognitive impairment) stage of Dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). This retrospective study used a selected sample from Ajou neurological registry. We identified MCI patients who underwent HRV testing at baseline, and who developed probable DLB (MCI-DLB: n = 23) or AD (MCI-AD: n = 32). The MCI-DLB group exhibited significantly lower levels of almost all HRV parameters compared with the MCI-AD group. Fronto-executive function and visuospatial abilities were poorer in the MCI-DLB group, whereas the extent of verbal memory impairment was greater in the MCI-AD. Verbal memory score was negatively correlated with overall HRV parameters, and visuospatial function was positively correlated with the frequency domain of HRV. Receiver operating curve area under the curve (AUC) analysis revealed that the low frequency component was the best potential diagnostic marker (AUC = 0.88). MCI-DLB patients exhibited greater cardiac autonomic dysfunction (as measured by HRV) and greater fronto-executive and visuospatial deficit compared with MCI-AD patients. HRV may be useful method to differentiate DLB from AD in patients with MCI; this would facilitate early disease-specific intervention. Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

MEG Working Memory N-Back Task Reveals Functional Deficits in Combat-Related Mild Traumatic Brain Injury.

PubMed

Huang, Ming-Xiong; Nichols, Sharon; Robb-Swan, Ashley; Angeles-Quinto, Annemarie; Harrington, Deborah L; Drake, Angela; Huang, Charles W; Song, Tao; Diwakar, Mithun; Risbrough, Victoria B; Matthews, Scott; Clifford, Royce; Cheng, Chung-Kuan; Huang, Jeffrey W; Sinha, Anusha; Yurgil, Kate A; Ji, Zhengwei; Lerman, Imanuel; Lee, Roland R; Baker, Dewleen G

2018-04-13

Combat-related mild traumatic brain injury (mTBI) is a leading cause of sustained cognitive impairment in military service members and Veterans. However, the mechanism of persistent cognitive deficits including working memory (WM) dysfunction is not fully understood in mTBI. Few studies of WM deficits in mTBI have taken advantage of the temporal and frequency resolution afforded by electromagnetic measurements. Using magnetoencephalography (MEG) and an N-back WM task, we investigated functional abnormalities in combat-related mTBI. Study participants included 25 symptomatic active-duty service members or Veterans with combat-related mTBI and 20 healthy controls with similar combat experiences. MEG source-magnitude images were obtained for alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), and low-frequency (1-7 Hz) bands. Compared with healthy combat controls, mTBI participants showed increased MEG signals across frequency bands in frontal pole (FP), ventromedial prefrontal cortex, orbitofrontal cortex (OFC), and anterior dorsolateral prefrontal cortex (dlPFC), but decreased MEG signals in anterior cingulate cortex. Hyperactivations in FP, OFC, and anterior dlPFC were associated with slower reaction times. MEG activations in lateral FP also negatively correlated with performance on tests of letter sequencing, verbal fluency, and digit symbol coding. The profound hyperactivations from FP suggest that FP is particularly vulnerable to combat-related mTBI.

Frontal Assessment Battery as a Useful Tool to Differentiate Mild Cognitive Impairment due to Subcortical Ischemic Vascular Disease from Alzheimer Disease.

PubMed

Hsu, Yen-Hsuan; Huang, Ching-Feng; Lo, Chung-Ping; Wang, Tzu-Lan; Yang, Chi-Cheng; Tu, Min-Chien

2016-01-01

Prominent executive dysfunction can differentiate vascular dementia from Alzheimer disease (AD). However, it is unclear whether the Frontal Assessment Battery (FAB) screening tool can differentiate subcortical ischemic vascular disease (SIVD) from AD at the pre-dementia stage. In addition, the neural correlates of FAB performance have yet to be clarified. Patients with mild cognitive impairment (MCI) due to SIVD (MCI-V), MCI due to AD (MCI-A), and demographically matched controls completed the Mini-Mental State Examination, Taiwanese FAB (TFAB), Category Fluency, and Chinese Version of the Verbal Learning Test, and underwent magnetic resonance imaging. White matter hyperintensities were rated according to the Scheltens scale. TFAB total scale and its Orthographical Fluency subtest were the only measures that could differentiate MCI-V from MCI-A. Discriminative analysis showed that Orthographical Fluency scores successfully identified 73.2% of the cases with MCI-V, with 85.0% sensitivity. Orthographical Fluency scores were specifically associated with lesion load within frontal periventricular, frontal deep white matter, and basal ganglia regions. The TFAB, and especially its 1-min Orthographical Fluency subtest, is a useful screening procedure to differentiate MCI due to SIVD from MCI due to AD. The discriminative ability is probably due to frontosubcortical white matter pathologies disproportionately involved in the two disease entities. © 2016 S. Karger AG, Basel.

Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

PubMed

Schneider, Christine B; Donix, Markus; Linse, Katharina; Werner, Annett; Fauser, Mareike; Klingelhoefer, Lisa; Löhle, Matthias; von Kummer, Rüdiger; Reichmann, Heinz; Storch, Alexander

2017-09-01

Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

Assessment and clinical implications of cognitive impairment in acutely ill geriatric patients using a revised simplified short-term memory recall test (STMT-R).

PubMed

Yamamoto, Hiroshi; Ogawa, Kenichi; Huaman Battifora, Henry; Yamamuro, Kaori; Ishitake, Tatsuya

2018-05-24

Cognitive dysfunction due to delirium or dementia is a common finding in acutely ill geriatric patients, but often remains undetected. A brief and sensitive clinical identification method could prevent errors or complications while evaluating the mental status of elderly patients. To evaluate the usefulness and clinical implications of the revised simplified short-term memory recall test (STMT-R) in geriatric patients admitted in the emergency department; with age, gender, dementia history, serum albumin, underlying diseases and clinical outcome used as comparative factors. Mini-mental state examination and STMT-R scores were initially compared and a positive correlation was observed (r = 0.66, p < 0.001). Subsequently, 885 inpatients aged over 50 years underwent STMT-R evaluation between October 2014 and September 2015. We considered as cognitive dysfunction STMT-R scores ≤ 4 of a maximum score of 8. Among enrolled patients, 52.2% were female and the mean age was 78.9 years. There were 159 patients who were unable to complete the test (incomplete testing group). We observed cognitive dysfunction in 460 patients, while 266 did not have cognitive dysfunction. There were significant differences between those with and without cognitive dysfunction in terms of age, dementia history, underlying respiratory diseases, and hospital outcome. Cognitive dysfunction at admission can have a negative effect on the hospital outcomes of elderly patients. Age, a history of dementia and underlying respiratory diseases may also influence cognitive functional decline.

Linking Essential Tremor to the Cerebellum: Clinical Evidence.

PubMed

Benito-León, Julián; Labiano-Fontcuberta, Andrés

2016-06-01

Essential tremor (ET) might be a family of diseases unified by the presence of kinetic tremor, but also showing etiological, pathological, and clinical heterogeneity. In this review, we will describe the most significant clinical evidence, which suggests that ET is linked to the cerebellum. Data for this review were identified by searching PUBMED (January 1966 to May 2015) crossing the terms "essential tremor" (ET) and "cerebellum," which yielded 201 entries, 11 of which included the term "cerebellum" in the article title. This was supplemented by articles in the author's files that pertained to this topic. The wide spectrum of clinical features of ET that suggest that it originates as a cerebellar or cerebellar outflow problem include the presence of intentional tremor, gait and balance abnormalities, subtle features of dysarthria, and oculomotor abnormalities, as well as deficits in eye-hand coordination, motor learning deficits, incoordination during spiral drawing task, abnormalities in motor timing and visual reaction time, impairment of social abilities, improvement in tremor after cerebellar stroke, efficacy of deep brain stimulation (which blocks cerebellar outflow), and cognitive dysfunction. It is unlikely, however, that cerebellar dysfunction, per se, fully explains ET-associated dementia, because the cognitive deficits that have been described in patients with cerebellar lesions are generally mild. Overall, a variety of clinical findings suggest that in at least a sizable proportion of patients with ET, there is an underlying abnormality of the cerebellum and/or its pathways.

Early Maladaptive Schemas and Cognitive Distortions in Adults with Morbid Obesity: Relationships with Mental Health Status

PubMed Central

da Luz, Felipe Q.; Sainsbury, Amanda; Hay, Phillipa; Roekenes, Jessica A.; Swinbourne, Jessica; da Silva, Dhiordan C.; da S. Oliveira, Margareth

2017-01-01

Dysfunctional cognitions may be associated with unhealthy eating behaviors seen in individuals with obesity. However, dysfunctional cognitions commonly occur in individuals with poor mental health independently of weight. We examined whether individuals with morbid obesity differed with regard to dysfunctional cognitions when compared to individuals of normal weight, when mental health status was controlled for. 111 participants—53 with morbid obesity and 58 of normal weight—were assessed with the Mini-Mental State Examination, Young Schema Questionnaire, Cognitive Distortions Questionnaire, Depression, Anxiety and Stress Scale, and a Demographic and Clinical Questionnaire. Participants with morbid obesity showed higher scores in one (insufficient self-control/self-discipline) of 15 early maladaptive schemas and in one (labeling) of 15 cognitive distortions compared to participants of normal weight. The difference between groups for insufficient self-control/self-discipline was not significant when mental health status was controlled for. Participants with morbid obesity showed more severe anxiety than participants of normal weight. Our findings did not show clinically meaningful differences in dysfunctional cognitions between participants with morbid obesity or of normal weight. Dysfunctional cognitions presented by individuals with morbid obesity are likely related to their individual mental health and not to their weight. PMID:28264484

Curcumin attenuates surgery-induced cognitive dysfunction in aged mice.

PubMed

Wu, Xiang; Chen, Huixin; Huang, Chunhui; Gu, Xinmei; Wang, Jialing; Xu, Dilin; Yu, Xin; Shuai, Chu; Chen, Liping; Li, Shun; Xu, Yiguo; Gao, Tao; Ye, Mingrui; Su, Wei; Liu, Haixiong; Zhang, Jinrong; Wang, Chuang; Chen, Junping; Wang, Qinwen; Cui, Wei

2017-06-01

Post-operative cognitive dysfunction (POCD) is associated with elderly patients undergoing surgery. However, pharmacological treatments for POCD are limited. In this study, we found that curcumin, an active compound derived from Curcuma longa, ameliorated the cognitive dysfunction following abdominal surgery in aged mice. Further, curcumin prevented surgery-induced anti-oxidant enzyme activity. Curcumin also increased brain-derived neurotrophic factor (BDNF)-positive area and expression of pAkt in the brain, suggesting that curcumin activated BDNF signaling in aged mice. Furthermore, curcumin neutralized cholinergic dysfunction involving choline acetyltransferase expression induced by surgery. These results strongly suggested that curcumin prevented cognitive impairments via multiple targets, possibly by increasing the activity of anti-oxidant enzymes, activation of BDNF signaling, and neutralization of cholinergic dysfunction, concurrently. Based on these novel findings, curcumin might be a potential agent in POCD prophylaxis and treatment.

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.

Beneficial effects of dexmedetomidine on early postoperative cognitive dysfunction in pediatric patients with tonsillectomy.

PubMed

Han, Chuanlai; Fu, Rong; Lei, Weifu

2018-07-01

According to clinical investigations, early postoperative cognitive dysfunction is the most common adverse event in pediatric patients after tonsillectomy. A previous study has indicated that dexmedetomidine (DEX) is an efficient drug for the treatment of postoperative cognitive dysfunction. However, the efficacy of DEX in alleviating early postoperative cognitive dysfunction in pediatric patients following tonsillectomy has remained elusive, which was therefore assessed in the present study. A total of 186 children presenting with cognitive dysfunction subsequent to tonsillectomy were recruited to analyze the efficacy of DEX. Patients were randomly divided into two groups and received intravenous treatment with DEX (n=112) or placebo (n=74). Duration of treatment, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of DEX were evaluated in a preliminary experiment. The improvement of postoperative cognitive function in children with tonsillectomy was analyzed with a Mini-Mental State Examination (MMSE) following treatment with DEX. A 40-item quality of life (MONEX-40) questionnaire was used to assess the efficacy of DEX. The plasma levels of interleukin (IL)-6, IL-1, tumor necrosis factor (TNF)-α, superoxide dismutase (SOD), neuron-specific enolase (NSE), C-reactive protein (CRP), cortisol and melatonin were also analyzed. The preliminary experiment determined that the DLT was 10 mg/kg and the MTD was 15 mg/kg. In the major clinical trial, it was revealed that MMSE scores in the DEX treatment group were markedly improved, indicating that DEX had a beneficial effect in pediatric patients with early postoperative cognitive dysfunction after tonsillectomy. In addition, IL-1and TNF-α were downregulated, while IL-6 and SOD were upregulated in patients with cognitive dysfunction after treatment with DEX compared with those in the placebo group. Furthermore, DEX treatment markedly decreased the serum levels of CRP, NSE cortisol and melatonin, which are associated with the occurrence of postoperative cognitive dysfunction in pediatric patients following tonsillectomy. In conclusion, intravenous administration of DEX at a dose of 10 mg/kg improves postoperative cognitive function in pediatric patients with tonsillectomy by decreasing the serum levels of inflammatory factors and stress-associated signaling molecules. Trial registration no. QLSDHOS0200810102C (Qilu Hospital of Shandong University, Jinan, China).

Effects of Combined Physical and Cognitive Exercises on Cognition and Mobility in Patients With Mild Cognitive Impairment: A Randomized Clinical Trial.

PubMed

Shimada, Hiroyuki; Makizako, Hyuma; Doi, Takehiko; Park, Hyuntae; Tsutsumimoto, Kota; Verghese, Joe; Suzuki, Takao

2017-11-17

Although participation in physical and cognitive activities is encouraged to reduce the risk of dementia, the preventive efficacy of these activities for patients with mild cognitive impairment is unestablished. To compare the cognitive and mobility effects of a 40-week program of combined cognitive and physical activity with those of a health education program. A randomized, parallel, single-blind controlled trial. A population-based study of participants recruited from Obu, a residential suburb of Nagoya, Japan. Between August 2011 and February 2012, we evaluated 945 adults 65 years or older with mild cognitive impairment, enrolled 308, and randomly assigned them to the combined activity group (n = 154) or the health education control group (n = 154). The combined activity program involved weekly 90-minute sessions for 40 weeks focused on physical and cognitive activities. The control group attended 90-minute health promotion classes thrice during the 40-week trial period. The outcome measures were assessed at the study's beginning and end by personnel blinded to mild cognitive impairment subtype and group. The primary endpoints were postintervention changes in scores on (1) the Mini-Mental State Examination as a measure of general cognitive status and memory, (2) the Wechsler Memory Scale-Revised-Logical Memory II, and (3) the Rey Auditory Verbal Learning Test. We applied mobility assessments and assessed brain atrophy with magnetic resonance imaging. Compared with the control group, the combined activity group showed significantly greater scores on the Mini-Mental State Examination (difference = 0.8 points, P = .012) and Wechsler Memory Scale-Revised-Logical Memory II (difference = 1.0, P = .004), significant improvements in mobility and the nonmemory domains and reduced left medial temporal lobe atrophy in amnestic mild cognitive impairment (Z-score difference = -31.3, P < .05). Combined physical and cognitive activity improves or maintains cognitive and physical performance in older adults with mild cognitive impairment, especially the amnestic type. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Parkinsonism due to manganism in a welder: neurological and neuropsychological sequelae.

PubMed

Bowler, Rosemarie M; Koller, William; Schulz, Paul E

2006-05-01

A 33-year-old welder with 3 years of exposure to manganese (Mn) bearing welding fumes was seen by neurologists for cognitive and motor complaints. He exhibited signs and symptoms of Parkinson's disease, including tremor, bradykinesia, gait disturbance and cogwheel rigidity. However, he was young and had significant inattention and forgetfulness, had found levodopa unhelpful and moved with a cock-walk gait, all of which suggested manganism. His serum and urine levels of Mn were, in fact, elevated, and his brain MRI had increased T1-weighted signal intensities in the basal ganglia bilaterally (globus pallidus) consistent with Mn deposition. Two years later, he underwent comprehensive neuropsychological testing. Clinical history indicated a mild tremor and emotional dysfunction with irritability, anxiety, and depression with psychotic features. He showed deficits in cognitive flexibility, information processing and speed, and greatly reduced motor speed, which are consistent with a fronto-subcortical process. These findings support a diagnosis of early onset parkinsonism from welding.

De novo artistic behaviour following brain injury.

PubMed

Pollak, Thomas A; Mulvenna, Catherine M; Lythgoe, Mark F

2007-01-01

The effect of brain injury and disease on the output of established artists is an object of much study and debate. The emergence of de novo artistic behaviour following such injury or disease, while very rare, has been recorded in cases of frontotemporal dementia, epilepsy, subarachnoid haemorrhage and Parkinson's disease. This may be an underdiagnosed phenomenon and may represent an opportunity to further understand the neural bases of creative thought and behaviour in man and those of cognitive change after brain injury. There is clearly an important role for hemispheric localization of pathology, which is usually within the temporal cortex, upon the medium of artistic expression, and a likely role for mild frontal cortical dysfunction in producing certain behavioural and cognitive characteristics that may be conducive to the production of art. Possible mechanisms of 'artistic drive' and 'creative idea generation' in these patients are also considered. The increased recognition and responsible nurturing of this behaviour in patients may serve as a source of great comfort to individuals and their families at an otherwise difficult time.

Anti-N-methyl-D-aspartate receptor and anti-ribosomal-P autoantibodies contribute to cognitive dysfunction in systemic lupus erythematosus.

PubMed

Massardo, L; Bravo-Zehnder, M; Calderón, J; Flores, P; Padilla, O; Aguirre, J M; Scoriels, L; González, A

2015-05-01

Autoantibodies against N-methyl-D-aspartate receptor (anti-NMDAR) and ribosomal-P (anti-P) antigens are potential pathogenic factors in the frequently observed diffuse brain dysfunctions in patients with systemic lupus erythematosus (SLE). Although studies have been conducted in this area, the role of anti-NMDAR antibodies in SLE cognitive dysfunction remains elusive. Moreover, the specific contribution of anti-P antibodies has not been reported yet. The present study attempts to clarify the contribution of anti-NMDAR and anti-P antibodies to cognitive dysfunction in SLE. The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to assess a wide range of cognitive function areas in 133 Chilean women with SLE. ANCOVA models included autoantibodies, patient and disease features. Cognitive deficit was found in 20%. Higher SLEDAI-2K scores were associated with impairment in spatial memory and learning abilities, whereas both anti-NMDAR and anti-P antibodies contributed to deficits in attention and spatial planning abilities, which reflect fronto-parietal cortex dysfunctions. These results reveal an association of active disease together with specific circulating autoantibodies, such as anti-NMDAR and anti-P, with cognitive dysfunction in SLE patients. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Aphasia and unilateral spatial neglect due to acute thalamic hemorrhage: clinical correlations and outcomes.

PubMed

Osawa, Aiko; Maeshima, Shinichiro

2016-04-01

Thalamic hemorrhages are associated with a variety of cognitive dysfunctions, and it is well known that such cognitive changes constitute a limiting factor of recovery of the activities of daily living (ADL). The relationship between cognitive dysfunction and hematomas is unclear. In this study, we investigated the relationship between aphasia/neglect and hematoma volume, hematoma type, and the ADL. One hundred fifteen patients with thalamic hemorrhage (70 men and 45 women) were studied. Their mean age was 68.9 ± 10.3 years, and patients with both left and right lesions were included. We calculated hematoma volume and examined the presence or absence of aphasia/neglect and the relationships between these dysfunctions and hematoma volume, hematoma type, and the ADL. Fifty-nine patients were found to have aphasia and 35 were found to have neglect. Although there was no relationship between hematoma type and cognitive dysfunction, hematoma volume showed a correlation with the severity of cognitive dysfunction. The ADL score and ratio of patient discharge for patients with aphasia/neglect were lower than those for patients without aphasia/neglect. We observed a correlation between the hematoma volume in thalamic hemorrhage and cognitive dysfunction. Aphasia/neglect is found frequently in patients with acute thalamic hemorrhage and may influence the ADL.

Undiagnosed long-term cognitive impairment in acutely hospitalised older medical patients with delirium: a prospective cohort study.

PubMed

Jackson, Thomas A; MacLullich, Alasdair M J; Gladman, John R F; Lord, Janet M; Sheehan, Bart

2016-07-01

delirium and dementia are common in the general hospital, being present in nearly 50% of older unselected admissions to hospital. Cognitive impairment is a risk factor for delirium, but the prevalence of previously undiagnosed cognitive impairment (dementia or mild cognitive impairment) in patients with delirium is unknown. we performed a prospective cohort study of people over 70 years admitted to hospital with delirium to establish the prevalence of previously unrecognised prior cognitive impairment. Delirium was diagnosed at baseline using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Mild cognitive impairment and dementia were diagnosed 3 months following recruitment in survivors using the International Working Group on Mild Cognitive Impairment criteria and DSM-IV criteria, respectively. delirium was identified in 17.9% of older patients, and 82 participants with delirium were assessed at 3 months: 5 (6%) had persistent delirium, 14 (17%) had mild cognitive impairment and 47 (57%) had dementia. In 17 participants with prior dementia and 14 with prior mild cognitive impairment, the diagnosis had been unrecognised, amounting to 31/82 (38%) of all patients with delirium having some form of previously undiagnosed cognitive impairment. given that over 1/3 of older patients with delirium were found to have a previously undiagnosed cognitive impairment, the development and evaluation of services to follow-up and manage patients with delirium are warranted. © The Author 2016. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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.

Alzheimer's Disease Assessment Scale-Cognitive subscale variants in mild cognitive impairment and mild Alzheimer's disease: change over time and the effect of enrichment strategies.

PubMed

Podhorna, Jana; Krahnke, Tillmann; Shear, Michael; Harrison, John E

2016-02-12

Development of new treatments for Alzheimer's disease (AD) has broadened into early interventions in individuals with modest cognitive impairment and a slow decline. The 11-item version of the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) was originally developed to measure cognition in patients with mild to moderate AD. Attempts to improve its properties for early AD by removing items prone to ceiling and/or by adding cognitive measures known to be impaired early have yielded a number of ADAS-Cog variants. Using Alzheimer's Disease Neuroimaging Initiative data, we compared the performance of the 3-, 5-, 11- and 13-item ADAS-Cog variants in subjects with early AD. Given the interest in enrichment strategies, we also examined this aspect with a focus on cerebrospinal fluid (CSF) markers. Subjects with mild cognitive impairment (MCI) and mild AD with available ADAS-Cog 13 and CSF data were analysed. The decline over time was defined by change from baseline. Direct cross-comparison of the ADAS-Cog variants was performed using the signal-to-noise ratio (SNR), with higher values reflecting increased sensitivity to detect change over time. The decline over time on any of the ADAS-Cog variants was minimal in subjects with MCI. Approximately half of subjects with MCI fulfilled enrichment criteria for positive AD pathology. The impact of enrichment was detectable but subtle in MCI. The annual decline in mild AD was more pronounced but still modest. More than 90 % of subjects with mild AD had positive AD pathology. SNRs were low in MCI but greater in mild AD. The numerically largest SNRs were seen for the ADAS-Cog 5 in MCI and for both the 5- and 13-item ADAS-Cog variants in mild AD, although associated confidence intervals were large. The possible value of ADAS-Cog expansion or reduction is less than compelling, particularly in MCI. In mild AD, adding items known to be impaired at early stages seems to provide more benefit than removing items on which subjects score close to ceiling.

Effects of white matter lesions on brain perfusion in patients with mild cognitive impairment.

PubMed

Ishibashi, Masato; Kimura, Noriyuki; Aso, Yasuhiro; Matsubara, Etsuro

2018-05-01

To evaluate the effects of white matter lesions on regional cerebral blood flow in subjects with amnestic mild cognitive impairment. Seventy-five subjects with mild cognitive impairment (36 men and 39 women; mean age, 78.1 years) were included in the study. We used the Mini-Mental State Examination to assess cognitive function. All subjects underwent brain magnetic resonance imaging and 99m Tc ethylcysteinate dimer single photon emission computed tomography. Subjects were stratified based on the presence or absence of white matter lesions on magnetic resonance imaging. Statistical parametric mapping of differences in regional cerebral blood flow between the two groups were assessed by voxel-by-voxel group analysis using SPM8. Of all 75 subjects with mild cognitive impairment, 46 (61.3%) had mild to moderate white matter lesions. The prevalence of hypertension tended to be higher in subjects with white matter lesions than in those without white matter lesions. Mini-Mental State Examination scores were significantly lower in subjects with white matter lesions than in those without white matter lesions. Subjects with white matter lesions had decreased regional cerebral blood flow mainly in the frontal, parietal, and medial temporal lobes, as well as the putamen, compared to those without white matter lesions. In subjects with mild cognitive impairment, white matter lesions were associated with cognitive impairment and mainly frontal lobe brain function. Copyright © 2018 Elsevier B.V. All rights reserved.

Raven's Coloured Progressive Matrices as a Measure of Cognitive Functioning in Cerebral Palsy

ERIC Educational Resources Information Center

Pueyo, R.; Junque, C.; Vendrell, P.; Narberhaus, A.; Segarra, D.

2008-01-01

Background: Cognitive dysfunction is frequent in Cerebral Palsy (CP). CP motor impairment and associated speech deficits often hinder cognitive assessment, with the result being that not all CP studies consider cognitive dysfunction. Raven's Coloured Progressive Matrices is a simple, rapid test which can be used in persons with severe motor…

Should general anaesthesia be avoided in the elderly?

PubMed Central

Strøm, C.; Rasmussen, L. S.; Sieber, F. E.

2016-01-01

Summary Surgery and anaesthesia exert comparatively greater adverse effects on the elderly than on the younger brain, manifest by the higher prevalence of postoperative delirium and cognitive dysfunction. Postoperative delirium and cognitive dysfunction delay rehabilitation, and are associated with increases in morbidity and mortality among elderly surgical patients. We review the aetiology of postoperative delirium and cognitive dysfunction in the elderly with a particular focus on anaesthesia and sedation, discuss methods of diagnosing and monitoring postoperative cognitive decline, and describe the treatment strategies by which such decline may be prevented. PMID:24303859

Cognitive disorders in children's hydrocephalus.

PubMed

Zielińska, Dorota; Rajtar-Zembaty, Anna; Starowicz-Filip, Anna

Hydrocephalus is defined as an increase of volume of cerebrospinal fluid in the ventricular system of the brain. It develops as a result of cerebrospinal fluid flow disorder due to dysfunctions of absorption or, less frequently, as a result of the increase of its production. Hydrocephalus may lead to various cognitive dysfunctions in children. In order to determine cognitive functioning in children with hydrocephalus, the authors reviewed available literature while investigating this subject. The profile of cognitive disorders in children with hydrocephalus may include a wide spectrum of dysfunctions and the process of neuropsychological assessment may be very demanding. The most frequently described cognitive disorders within children's hydrocephalus include attention, executive, memory, visual, spatial or linguistic dysfunctions, as well as behavioral problems. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Mild traumatic brain injury: a neuropsychiatric approach to diagnosis, evaluation, and treatment

PubMed Central

Arciniegas, David B; Anderson, C Alan; Topkoff, Jeannie; McAllister, Thomas W

2005-01-01

Traumatic brain injury (TBI) is a common occurrence in the United States, with an estimated incidence exceeding 1 million injuries per year. Cognitive, emotional, behavioral, and physical impairments are common sequelae of TBI and may, in a significant minority of patients, persist well into the late period following injury. The etiology of these symptoms in individuals with mild TBI is controversial, with hypotheses of postconcussive symptom formation variously ascribing greater or lesser weight to neural damage, pre- and/or post-injury psychological or psychiatric factors, somatization, malingering, or some combination of these. Some of these hypotheses reflect biases common to medicolegal or compensation-related contexts, whereas others are derived from recent neuroimaging and electrophysiology studies. Studies of the latter sort suggest that many of the typical postconcussive symptoms are associated with neurobiological dysfunction in one or more areas of the central nervous system. Whether these symptoms constitute a postconcussive syndrome per se is debatable. Instead, it may be more accurate to describe them as commonly co-occurring symptoms rather than as a syndromal sequela of TBI. The present review addresses these issues including the epidemiology and course of recovery from mild TBI and the validity of the postconcussive syndrome. Suggestions regarding the assessment and treatment of individuals with post-concussive symptoms are offered. PMID:18568112

Analysis of macrolinguistic aspects of narratives from individuals with Alzheimer's disease, mild cognitive impairment, and no cognitive impairment.

PubMed

Toledo, Cíntia Matsuda; Aluísio, Sandra Maria; Dos Santos, Leandro Borges; Brucki, Sonia Maria Dozzi; Trés, Eduardo Sturzeneker; de Oliveira, Maira Okada; Mansur, Letícia Lessa

2018-01-01

The depiction of features in discourse production promotes accurate diagnosis and helps to establish the therapeutic intervention in cognitive impairment and dementia. We aimed to identify alterations in the macrolinguistic aspects of discourse using a new computational tool. Sixty individuals, aged 60 years and older, were distributed in three different groups: mild Alzheimer's disease (mAD), amnestic mild cognitive impairment, and healthy controls. A narrative created by individuals was analyzed through the Coh-Metrix-Dementia program, extracting the features of interest automatically. mAD showed worse overall performance compared to the other groups: less informative discourse, greater impairment in global coherence, greater modalization, and inferior narrative structure. It was not possible to discriminate between amnestic mild cognitive impairment and healthy controls. Our results are in line with the literature, verifying a pathological change in the macrostructure of discourse in mAD.

[Two cases of Duchenne muscular dystrophy over 40 years after onset].

PubMed

Ishizaki, Masatoshi; Ueyama, Hidetsugu; Masuda, Teruaki; Nishida, Yasuto; Imamura, Shigehiro; Ando, Yukio

2013-01-01

We report two 45 year old men with Duchenne muscular dystrophy. Case 1 showed a deleted exon 50 of the dystrophin gene by MLPA analysis, and Case 2 showed deleted exons 46-52. Both patients presented with severe weakness of the skeletal muscles and respiratory dysfunction, while cardiac involvement was mild and cognitive function was almost normal. The patients are able to shop at a mall, participate in activities, and attend hobbies, although they are bedridden with artificial respiration through tracheotomy. With the progress of the respiratory care and cardiac protective therapy, the prognosis of Duchenne muscular dystrophy has improved remarkably. At present, it is possible to survive over 40 years with maintenance of quality of life, if cardiac damage is not severe.

The clinical utility of naturalistic action test in differentiating mild cognitive impairment from early dementia in memory clinic.

PubMed

Bruce, Irene; Ntlholang, Ontefetse; Crosby, Lisa; Cunningham, Conal; Lawlor, Brian

2016-03-01

This study aimed to examine the validity of the Naturalistic Action Test in differentiating Mild Cognitive Impairment from early dementia compared to clinical diagnosis and ascertain Naturalistic Action Test cut-off points. This was a cross-sectional study of 70 consecutive patients diagnosed with Mild Cognitive Impairment attending the memory clinic in St James's Hospital, Dublin, Ireland. Patients with a diagnosis of Mild Cognitive Impairment who attended for routine annual assessment were asked to participate in the study. The Naturalistic Action Test was carried out after the patient had completed their routine assessment in the clinic. The Area under the Curve, AUC ± SE was 0.808 ± 0.058, p < 0.001 with 95% CI (0.695-0.922). There was concordance in 40 and discrepancy in 30 patients between the NAT and the gold standard consensus diagnosis (PPV 38%, NPV 96%, sensitivity 94%, specificity 46% and accuracy 59%) using cut-off point of ≥14 for normal function on Naturalistic Action Test. The difference was not related to age, sex, level of education or informant. Using the Youden index, we determined a Naturalistic Action Test cut-off score of ≥11 for Mild Cognitive Impairment in our study (PPV 50%, NPV 91%, sensitivity 78%, specificity 73% and accuracy of 74%). There was discrepancy in 18 patients using the new cut-off point (≥11 for Mild Cognitive Impairment vs ≤10 for dementia). The Naturalistic Action Test is a useful tool that can increase diagnostic accuracy in differentiating Mild Cognitive Impairment from early dementia. Copyright © 2015 John Wiley & Sons, Ltd.

A Reanalysis of Cognitive-Functional Performance in Older Adults: Investigating the Interaction Between Normal Aging, Mild Cognitive Impairment, Mild Alzheimer's Disease Dementia, and Depression

PubMed Central

de Paula, Jonas J.; Bicalho, Maria A.; Ávila, Rafaela T.; Cintra, Marco T. G.; Diniz, Breno S.; Romano-Silva, Marco A.; Malloy-Diniz, Leandro F.

2016-01-01

Depressive symptoms are associated with cognitive-functional impairment in normal aging older adults (NA). However, less is known about this effect on people with mild Cognitive Impairment (MCI) and mild Alzheimer's disease dementia (AD). We investigated this relationship along with the NA-MCI-AD continuum by reanalyzing a previously published dataset. Participants (N = 274) underwent comprehensive neuropsychological assessment including measures of Executive Function, Language/Semantic Memory, Episodic Memory, Visuospatial Abilities, Activities of Daily Living (ADL), and the Geriatric Depression Scale. MANOVA, logistic regression and chi-square tests were performed to assess the association between depression and cognitive-functional performance in each group. In the NA group, depressed participants had a lower performance compared to non-depressed participants in all cognitive and functional domains. However, the same pattern was not observed in the MCI group or in AD. The results suggest a progressive loss of association between depression and worse cognitive-functional performance along the NA-MCI-AD continuum. PMID:26858666

[Effectiveness of a cognitive-motorphysiotherapeutical therapy intervention in institutionalized older adults with mild cognitive impairment and mild dementia].

PubMed

Menezes, Alessandra Vieira; Aguiar, Alessandra da Silva de; Alves, Elysama Fernandes; Quadros, Layse Biz de; Bezerra, Poliana Penasso

2016-11-01

The aim of this study was to investigate the effectiveness of four months of cognitive-motor physiotherapy intervention, with a single weekly visit, on cognitive function, mobility and functional independence of institutionalized elderly individuals with mild cognitive impairment and mild dementia. In a controlled clinical trial, 15 subjects were allocated to experimental and control groups. Regarding the assessment of the subjects the following instruments were applied: Mini-Mental State Examination, Clinical Dementia Rating Scale, Verbal Fluency Test and Frontal Assessment Battery for analyzing cognitive functions; Berg Balance Scale and Timed Up and Go Test to verify mobility, and; Barthel Scale and Pfeffer Index for measurement of functional independence. The statistical procedures involved the application of Student's t-test with a 5% significance threshold. With respect to the results, the experimental group performed better only in mobility-related tests at the end of the intervention (p < 0.05). The proposed intervention showed efficacy on mobility, but not on cognition and functional independence. The short period of time and low weekly basis may be related to the results obtained.

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.

Immune function and brain abnormalities in patients with systemic lupus erythematosus without overt neuropsychiatric manifestations.

PubMed

Kozora, E; Filley, C M; Zhang, L; Brown, M S; Miller, D E; Arciniegas, D B; Pelzman, J L; West, S G

2012-04-01

This study examined the relationship between immune, cognitive and neuroimaging assessments in subjects with systemic lupus erythematosus (SLE) without histories of overt neuropsychiatric (NP) disorders. In total, 84 subjects with nonNPSLE and 37 healthy controls completed neuropsychological testing from the American College of Rheumatology SLE battery. Serum autoantibody and cytokine measures, volumetric magnetic resonance imaging, and magnetic resonance spectroscopy data were collected on a subset of subjects. NonNPSLE subjects had lower scores on measures of visual/complex attention, visuomotor speed and verbal memory compared with controls. No clinically significant differences between nonNPSLE patients and controls were found on serum measures of lupus anticoagulant, anticardiolipin antibodies, beta 2-glycoproteins, or pro-inflammatory cytokines (interleukin (IL)-1, IL-6, interferon alpha (IFN-alpha), and interferon gamma (IFN-gamma)). Higher scores on a global cognitive impairment index and a memory impairment index were correlated with lower IFN-alpha. Few associations between immune functions and neuroimaging parameters were found. Results indicated that nonNPSLE patients demonstrated cognitive impairment but not immune differences compared with controls. In these subjects, who were relatively young and with mild disease, no relationship between cognitive dysfunction, immune parameters, or previously documented neuroimaging abnormalities were noted. Immune measures acquired from cerebrospinal fluid instead of serum may yield stronger associations.

Neurodevelopment of children under 3 years of age with Smith-Magenis syndrome.

PubMed

Wolters, Pamela L; Gropman, Andrea L; Martin, Staci C; Smith, Michaele R; Hildenbrand, Hanna L; Brewer, Carmen C; Smith, Ann C M

2009-10-01

Systematic data regarding early neurodevelopmental functioning in Smith-Magenis syndrome are limited. Eleven children with Smith-Magenis syndrome less than 3 years of age (mean, 19 months; range, 5-34 months) received prospective multidisciplinary assessments using standardized measures. The total sample scored in the moderately to severely delayed range in cognitive functioning, expressive language, and motor skills and exhibited generalized hypotonia, oral-motor abnormalities, and middle ear dysfunction. Socialization skills were average, and significantly higher than daily living, communication, and motor abilities, which were below average. Mean behavior ratings were in the nonautistic range. According to exploratory analyses, the toddler subgroup scored significantly lower than the infant subgroup in cognition, expressive language, and adaptive behavior, suggesting that the toddlers were more delayed than the infants relative to their respective peers. Infants aged approximately 1 year or younger exhibited cognitive, language, and motor skills that ranged from average to delayed, but with age-appropriate social skills and minimal maladaptive behaviors. At ages 2 to 3 years, the toddlers consistently exhibited cognitive, expressive language, adaptive behavior, and motor delays and mildly to moderately autistic behaviors. Combining age groups in studies may mask developmental and behavioral differences. Increased knowledge of these early neurodevelopmental characteristics should facilitate diagnosis and appropriate intervention.

Predictors of cognitive and physical fatigue in post-acute mild-moderate traumatic brain injury.

PubMed

Schiehser, Dawn M; Delano-Wood, Lisa; Jak, Amy J; Hanson, Karen L; Sorg, Scott F; Orff, Henry; Clark, Alexandra L

2017-10-01

Post-traumatic fatigue (PTF) is a common, disabling, and often chronic symptom following traumatic brain injury (TBI). Yet, the impact of chronic cognitive and physical fatigue and their associations with psychiatric, sleep, cognitive, and psychosocial sequelae in mild-moderate TBI remain poorly understood. Sixty Veterans with a history of mild-moderate TBI and 40 Veteran controls (VC) were administered the Modified Fatigue Impact Scale, a validated measure of TBI-related cognitive and physical fatigue as well as measures of neuropsychiatric, psychosocial, sleep, and objective cognitive functioning. Compared to VC, TBI Veterans endorsed significantly greater levels of cognitive and physical fatigue. In TBI, psychiatric symptoms, sleep disturbance, and post-traumatic amnesia (PTA) were associated with both cognitive and physical fatigue, while loss of consciousness (LOC) and poor attention/processing speed were related to elevations in cognitive fatigue only. In regression analyses, anxiety, sleep disturbance, and LOC significantly predicted cognitive fatigue, while only post-traumatic stress symptoms and PTA contributed to physical fatigue. Cognitive and physical fatigue are problematic symptoms following mild-moderate TBI that are differentially associated with specific injury and psychiatric sequelae. Findings provide potential symptom targets for interventions aimed at ameliorating fatigue, and further underscore the importance of assessing and treating fatigue as a multi-dimensional symptom following TBI.

Physiologic Dysfunction Scores and Cognitive Function Test Performance in United States Adults

PubMed Central

Kobrosly, Roni W; Seplaki, Christopher L; Jones, Courtney M; van Wijngaarden, Edwin

2013-01-01

Objective To investigate the relationship between a measure of cumulative physiologic dysfunction and specific domains of cognitive function. Methods We examined a summary score measuring physiological dysfunction, a multisystem measure of the body’s ability to effectively adapt to physical and psychological demands, in relation to cognitive function deficits in a population of 4511 adults aged 20 to 59 who participated in the third National Health and Nutrition Examination Survey (1988–1994). Measures of cognitive function comprised three domains: working memory, visuomotor speed, and perceptual-motor speed. ‘Physiologic dysfunction’ scores summarizing measures of cardiovascular, immunologic, kidney, and liver function were explored. We used multiple linear regression models to estimate associations between cognitive function measures and physiological dysfunction scores, adjusting for socioeconomic factors, test conditions, and self-reported health factors. Results We noted a dose-response relationship between physiologic dysfunction and working memory (coefficient = 0.207, 95% CI = (0.066, 0.348), p < 0.0001) that persisted after adjustment for all covariates (p = 0.03). We did not observe any significant relationships between dysfunction scores and visuomotor (p = 0.37) or perceptual-motor ability (p = 0.33). Conclusions Our findings suggest that multisystem physiologic dysfunction is associated with working memory. Future longitudinal studies are needed to clarify the underlying mechanisms and explore the persistency of this association into later life. We suggest that such studies should incorporate physiologic data, neuroendocrine parameters, and a wide range of specific cognitive domains. PMID:22155941

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.

78 FR 78504 - Reports, Forms, and Record Keeping Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-26

... requirements, NHTSA asks public comment on the following proposed collection of information: Mild Cognitive... to determine whether they are eligible to participate in a study of the effects of mild cognitive... rehabilitation specialist (DRS) referrals of drivers suspected of having some degree of cognitive impairment by...

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.

Measurement of Functional Cognition and Complex Everyday Activities in Older Adults with Mild Cognitive Impairment and Mild Dementia: Validity of the Large Allen's Cognitive Level Screen.

PubMed

Wesson, Jacqueline; Clemson, Lindy; Crawford, John D; Kochan, Nicole A; Brodaty, Henry; Reppermund, Simone

2017-05-01

To explore the validity of the Large Allen's Cognitive Level Screen-5 (LACLS-5) as a performance-based measure of functional cognition, representing an ability to perform complex everyday activities in older adults with mild cognitive impairment (MCI) and mild dementia living in the community. Using cross-sectional data from the Sydney Memory and Ageing Study, 160 community-dwelling older adults with normal cognition (CN; N = 87), MCI (N = 43), or dementia (N = 30) were studied. Functional cognition (LACLS-5), complex everyday activities (Disability Assessment for Dementia [DAD]), Assessment of Motor and Process Skills [AMPS]), and neuropsychological measures were used. Participants with dementia performed worse than CN on all clinical measures, and MCI participants were intermediate. Correlational analyses showed that LACLS-5 was most strongly related to AMPS Process scores, DAD instrumental activities of daily living subscale, Mini-Mental State Exam, Block Design, Logical Memory, and Trail Making Test B. Multiple regression analysis indicated that both cognitive (Block Design) and functional measures (AMPS Process score) and sex predicted LACLS-5 performance. Finally, LACLS-5 was able to adequately discriminate between CN and dementia and between MCI and dementia but was unable to reliably distinguish between CN and MCI. Construct validity, including convergent and discriminative validity, was supported. LACLS-5 is a valid performance-based measure for evaluating functional cognition. Discriminativevalidity is acceptable for identifying mild dementia but requires further refinement for detecting MCI. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

Disruption of hippocampus-regulated behavioural and cognitive processes by heterozygous constitutive deletion of SynGAP.

PubMed

Muhia, Mary; Yee, Benjamin K; Feldon, Joram; Markopoulos, Foivos; Knuesel, Irene

2010-02-01

The brain-specific Ras/Rap-GTPase activating protein (SynGAP) is a prime candidate linking N-methyl-d-aspartate receptors to the regulation of the ERK/MAP kinase signalling cascade, suggested to be essential for experience-dependent synaptic plasticity. Here, we evaluated the behavioural phenotype of SynGAP heterozygous knockout mice (SG(+/-)), expressing roughly half the normal levels of SynGAP. In the cognitive domain, SG(+/-) mice demonstrated severe working and reference memory deficits in the radial arm maze task, a mild impairment early in the transfer test of the water maze task, and a deficiency in spontaneous alternation in an elevated T-maze. In the non-cognitive domain, SG(+/-) mice were hyperactive in the open field and appeared less anxious in the elevated plus maze test. In contrast, object recognition memory performance was not impaired in SG(+/-) mice. The reduction in SynGAP thus resulted in multiple behavioural traits suggestive of aberrant cognitive and non-cognitive processes normally mediated by the hippocampus. Immunohistochemical evaluation further revealed a significant reduction in calbindin-positive interneurons in the hippocampus and doublecortin-positive neurons in the dentate gyrus of adult SG(+/-) mice. Heterozygous constitutive deletion of SynGAP is therefore associated with notable behavioural as well as morphological phenotypes indicative of hippocampal dysfunction. Any suggestion of a possible causal link between them however remains a matter for further investigation.

Activity restriction in mild COPD: a challenging clinical problem

PubMed Central

O’Donnell, Denis E; Gebke, Kevin B

2014-01-01

Dyspnea, exercise intolerance, and activity restriction are already apparent in mild chronic obstructive pulmonary disease (COPD). However, patients may not seek medical help until their symptoms become troublesome and persistent and significant respiratory impairment is already present; as a consequence, further sustained physical inactivity may contribute to disease progression. Ventilatory and gas exchange impairment, cardiac dysfunction, and skeletal muscle dysfunction are present to a variable degree in patients with mild COPD, and collectively may contribute to exercise intolerance. As such, there is increasing interest in evaluating exercise tolerance and physical activity in symptomatic patients with COPD who have mild airway obstruction, as defined by spirometry. Simple questionnaires, eg, the modified British Medical Research Council dyspnea scale and the COPD Assessment Test, or exercise tests, eg, the 6-minute or incremental and endurance exercise tests can be used to assess exercise performance and functional status. Pedometers and accelerometers are used to evaluate physical activity, and endurance tests (cycle or treadmill) using constant work rate protocols are used to assess the effects of interventions such as pulmonary rehabilitation. In addition, alternative outcome measurements, such as tests of small airway dysfunction and laboratory-based exercise tests, are used to measure the extent of physiological impairment in individuals with persistent dyspnea. This review describes the mechanisms of exercise limitation in patients with mild COPD and the interventions that can potentially improve exercise tolerance. Also discussed are the benefits of pulmonary rehabilitation and the potential role of pharmacologic treatment in symptomatic patients with mild COPD. PMID:24940054

A Behavioural Approach to Helping an Older Adult with a Learning Disability and Mild Cognitive Impairment Overcome Depression

ERIC Educational Resources Information Center

Green, Paul

2017-01-01

Background: There is a considerable body of evidence to suggest that behavioural activation for depression is an equally effective but less complex treatment than cognitive behavioural therapy. It may therefore be more suitable for those who are cognitively impaired (i.e. early-stage dementia or mild cognitive impairment) or have a learning…

Association between academic performance and cognitive dysfunction in patients with juvenile systemic lupus erythematosus.

PubMed

Frittoli, Renan Bazuco; de Oliveira Peliçari, Karina; Bellini, Bruna Siqueira; Marini, Roberto; Fernandes, Paula Teixeira; Appenzeller, Simone

2016-01-01

To determine whether there is an association between the profile of cognitive dysfunction and academic outcomes in patients with juvenile systemic lupus erythematosus (JSLE). Patients aged ≤18 years at the onset of the disease and education level at or above the fifth grade of elementary school were selected. Cognitive evaluation was performed according to the American College of Rheumatology (ACR) recommendations. Symptoms of anxiety and depression were assessed by Beck scales; disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and cumulative damage was assessed by Systemic Lupus International Collaborating Clinics (SLICC). The presence of autoantibodies and medication use were also assessed. A significance level of 5% (p<0.05) was adopted. 41 patients with a mean age of 14.5±2.84 years were included. Cognitive dysfunction was noted in 17 (41.46%) patients. There was a significant worsening in mathematical performance in patients with cognitive dysfunction (p=0.039). Anxiety symptoms were observed in 8 patients (19.51%) and were associated with visual perception (p=0.037) and symptoms of depression were observed in 1 patient (2.43%). Patients with JSLE concomitantly with cognitive dysfunction showed worse academic performance in mathematics compared to patients without cognitive impairment. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Heading in Soccer: Integral Skill or Grounds for Cognitive Dysfunction?

ERIC Educational Resources Information Center

Kirkendall, Donald T.; Garrett, William E., Jr.

2001-01-01

Discusses how purposeful heading of soccer balls and head injuries affect soccer players' cognitive dysfunction. Cognitive deficits may occur for many reasons. Heading cannot be blamed when details of the actual event and impact are unknown. Concussions are the most common head injury in soccer and a factor in cognitive deficits and are probably…

Auditory Processing of Older Adults with Probable Mild Cognitive Impairment

ERIC Educational Resources Information Center

Edwards, Jerri D.; Lister, Jennifer J.; Elias, Maya N.; Tetlow, Amber M.; Sardina, Angela L.; Sadeq, Nasreen A.; Brandino, Amanda D.; Bush, Aryn L. Harrison

2017-01-01

Purpose: Studies suggest that deficits in auditory processing predict cognitive decline and dementia, but those studies included limited measures of auditory processing. The purpose of this study was to compare older adults with and without probable mild cognitive impairment (MCI) across two domains of auditory processing (auditory performance in…

Cholinergic Enhancement of Frontal Lobe Activity in Mild Cognitive Impairment

ERIC Educational Resources Information Center

Saykin, Andrew J.; Wishart, Heather A.; Rabin, Laura A.; Flashman, Laura A.; McHugh, Tara L.; Mamourian, Alexander C.; Santulli, Robert B.

2004-01-01

Cholinesterase inhibitors positively affect cognition in Alzheimer's disease (AD) and other conditions, but no controlled functional MRI studies have examined where their effects occur in the brain. We examined the effects of donepezil hydrochloride (Aricept[Registered sign]) on cognition and brain activity in patients with amnestic mild cognitive…

Salience and Default Mode Network Coupling Predicts Cognition in Aging and Parkinson's Disease.

PubMed

Putcha, Deepti; Ross, Robert S; Cronin-Golomb, Alice; Janes, Amy C; Stern, Chantal E

2016-02-01

Cognitive impairment is common in Parkinson's disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants. We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains. PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson's disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling. Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson's disease.

Remote thalamic microstructural abnormalities related to cognitive function in ischemic stroke patients.

PubMed

Fernández-Andújar, Marina; Doornink, Fleur; Dacosta-Aguayo, Rosalía; Soriano-Raya, Juan José; Miralbell, Júlia; Bargalló, Núria; López-Cancio, Elena; Pérez de la Ossa, Natalia; Gomis, Meritxell; Millán, Mònica; Barrios, Maite; Cáceres, Cynthia; Pera, Guillem; Forés, Rosa; Clemente, Imma; Dávalos, Antoni; Mataró, Maria

2014-11-01

Ischemic stroke can lead to a continuum of cognitive sequelae, ranging from mild vascular cognitive impairment to vascular dementia. These cognitive deficits can be influenced by the disruption of cortico-subcortical circuits. We sought to explore remote thalamic microstructural abnormalities and their association with cognitive function after ischemic stroke. Seventeen patients with right hemispheric ischemic stroke and 17 controls matched for age, sex, and years of education were included. All participants underwent neurological, neuropsychological, and diffusion tensor image examination. Patients were assessed 3 months poststroke. Voxel-wise analysis was used to study thalamic diffusion differences between groups. Mean fractional anisotropy (FA) and mean diffusivity (MD) values in significant thalamic areas were calculated for each subject and correlated with cognitive performance. Stroke patients showed lower FA values and higher MD values in specific areas of both the left and right thalamus compared with controls. In patients, decreased FA values were associated with lower verbal fluency performance in the right thalamus (R(2) = 0.45, β = 0.74) and the left thalamus (R(2) = 0.57, β = 0.77) after adjusting for diabetes mellitus. Moreover, increased MD values were associated with lower verbal fluency performance in the right thalamus (R(2) = 0.27, β = -0.54) after adjusting for diabetes mellitus. In controls, thalamic FA and MD values were not related to any cognitive function. Our findings support the hypothesis that ischemic stroke lesions are associated with remote thalamic diffusion abnormalities, and that these abnormalities can contribute to cognitive dysfunction 3 months after a cerebrovascular event. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Cognitive impairment in progressive supranuclear palsy-Richardson's syndrome is related to white matter damage.

PubMed

Caso, Francesca; Agosta, Federica; Volonté, Maria Antonietta; Ferraro, Pilar M; Tiraboschi, Pietro; Copetti, Massimiliano; Valsasina, Paola; Falautano, Monica; Comi, Giancarlo; Falini, Andrea; Filippi, Massimo

2016-10-01

Beside motor symptoms, patients with progressive supranuclear palsy syndrome (PSPs) commonly present cognitive and behavioral disorders. In this study we aimed to assess the structural brain correlates of cognitive impairment in PSPs. We enrolled 23 patients with probable PSP Richardson's syndrome and 15 matched healthy controls. Patients underwent an extensive clinical and neuropsychological evaluation. Cortical thickness measures and diffusion tensor metrics of white matter tracts were obtained. Random forest analysis was used to identify the strongest MRI predictors of cognitive impairment in PSPs at an individual patient level. PSPs patients were in a moderate stage of the disease showing mild cognitive deficits with prominent executive dysfunction. Relative to controls, PSPs patients had a focal, bilateral cortical thinning mainly located in the prefrontal/precentral cortex and temporal pole. PSPs patients also showed a distributed white matter damage involving the main tracts including the superior cerebellar peduncle, corpus callosum, corticospinal tract, and extramotor tracts, such as the inferior fronto-occipital, superior longitudinal and uncinate fasciculi, and cingulum, bilaterally. Regional cortical thinning measures did not relate with cognitive features, while white matter damage showed a significant impact on cognitive impairment (r values ranging from -0.80 to 0.74). PSPs patients show both focal cortical thinning in dorsolateral anterior regions and a distributed white matter damage involving the main motor and extramotor tracts. White matter measures are highly associated with cognitive deficits. Diffusion tensor MRI metrics are likely to be the most sensitive markers of extramotor deficits in PSPs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alzheimer Disease: Pharmacologic and Nonpharmacologic Therapies for Cognitive and Functional Symptoms.

PubMed

Epperly, Ted; Dunay, Megan A; Boice, Jack L

2017-06-15

Alzheimer disease comprises a syndrome of progressive cognitive and functional decline. Treatments should target cognitive and functional symptoms. Cholinesterase inhibitors, memantine, and a combination of a cholinesterase inhibitor and memantine have produced statistically significant but clinically small delays in various domains of cognitive and functional decline in select patients with Alzheimer disease. Vitamin E has been shown to delay functional decline in patients with mild to moderate Alzheimer disease, especially when taken in combination with a cholinesterase inhibitor. Structured programs of physical exercise improve physical function and reduce rates of neuropsychiatric symptoms in patients with mild to severe Alzheimer disease. Cognitive stimulation programs show benefit in maintenance of cognitive function and improved self-reported quality of life in patients with mild to moderate Alzheimer disease.

Change in Dysfunctional Beliefs About Sleep in Behavior Therapy, Cognitive Therapy, and Cognitive-Behavioral Therapy for Insomnia.

PubMed

Eidelman, Polina; Talbot, Lisa; Ivers, Hans; Bélanger, Lynda; Morin, Charles M; Harvey, Allison G

2016-01-01

As part of a larger randomized controlled trial, 188 participants were randomized to behavior therapy (BT), cognitive therapy (CT), or cognitive-behavioral therapy (CBT) for insomnia. The aims of this study were threefold: (a) to determine whether change in dysfunctional beliefs about sleep was related to change in sleep, insomnia symptoms, and impairment following treatment; (b) to determine whether BT, CT, and CBT differ in their effects on dysfunctional beliefs; and (c) to determine whether the treatments differ in their effects on particular kinds of dysfunctional beliefs. Beliefs, sleep, insomnia symptoms, and sleep-related psychosocial impairment were assessed at pretreatment, posttreatment, and 6- and 12-month follow-up. Greater change in dysfunctional beliefs occurring over the course of BT, CT, or CBT was associated with greater improvement in insomnia symptoms and impairment at posttreatment and both follow-ups. All groups experienced a significant decrease in dysfunctional beliefs during treatment, which were sustained through 6- and 12-month follow-up. Compared with the BT group, a greater proportion of participants in the CT and/or CBT groups endorsed dysfunctional beliefs below a level considered clinically significant at posttreatment and 12-month follow-up. The results demonstrate the importance of targeting dysfunctional beliefs in insomnia treatment, suggest that beliefs may be significantly modified with BT alone, and indicate that cognitive interventions may be particularly powerful in enhancing belief change. Copyright © 2016. Published by Elsevier Ltd.

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

Innate Immune Signalling Genetics of Pain, Cognitive Dysfunction and Sickness Symptoms in Cancer Pain Patients Treated with Transdermal Fentanyl

PubMed Central

Barratt, Daniel T.; Klepstad, Pål; Dale, Ola; Kaasa, Stein; Somogyi, Andrew A.

2015-01-01

Common adverse symptoms of cancer and chemotherapy are a major health burden; chief among these is pain, with opioids including transdermal fentanyl the mainstay of treatment. Innate immune activation has been implicated generally in pain, opioid analgesia, cognitive dysfunction, and sickness type symptoms reported by cancer patients. We aimed to determine if genetic polymorphisms in neuroimmune activation pathways alter the serum fentanyl concentration-response relationships for pain control, cognitive dysfunction, and other adverse symptoms, in cancer pain patients. Cancer pain patients (468) receiving transdermal fentanyl were genotyped for 31 single nucleotide polymorphisms in 19 genes: CASP1, BDNF, CRP, LY96, IL6, IL1B, TGFB1, TNF, IL10, IL2, TLR2, TLR4, MYD88, IL6R, OPRM1, ARRB2, COMT, STAT6 and ABCB1. Lasso and backward stepwise generalised linear regression were used to identify non-genetic and genetic predictors, respectively, of pain control (average Brief Pain Inventory < 4), cognitive dysfunction (Mini-Mental State Examination ≤ 23), sickness response and opioid adverse event complaint. Serum fentanyl concentrations did not predict between-patient variability in these outcomes, nor did genetic factors predict pain control, sickness response or opioid adverse event complaint. Carriers of the MYD88 rs6853 variant were half as likely to have cognitive dysfunction (11/111) than wild-type patients (69/325), with a relative risk of 0.45 (95% CI: 0.27 to 0.76) when accounting for major non-genetic predictors (age, Karnofsky functional score). This supports the involvement of innate immune signalling in cognitive dysfunction, and identifies MyD88 signalling pathways as a potential focus for predicting and reducing the burden of cognitive dysfunction in cancer pain patients. PMID:26332828

Mild Cognitive Impairment

MedlinePlus

... people their age. This condition is called mild cognitive impairment, or MCI. People with MCI can take care of themselves and do their normal activities. MCI memory problems may include Losing things often Forgetting to ...

Are all models susceptible to dysfunctional cognitions about eating and body image? The moderating role of personality styles.

PubMed

Blasczyk-Schiep, Sybilla; Sokoła, Kaja; Fila-Witecka, Karolina; Kazén, Miguel

2016-06-01

We investigated dysfunctional cognitions about eating and body image in relation to personality styles in a group of professional models. Dysfunctional cognitions in professional models (n = 43) and a control group (n = 43) were assessed with the 'Eating Disorder Cognition Questionnaire' (EDCQ), eating attitudes with the 'Eating Attitudes Test' (EAT), and personality with the 'Personality Styles and Disorders Inventory' (PSDI-S). Models had higher scores than controls on the EDCQ and EAT and on nine scales of the PSDI-S. Moderation analyses showed significant interactions between groups and personality styles in predicting EDCQ scales: The ambitious/narcissistic style was related to "negative body and self-esteem", the conscientious/compulsive style to "dietary restraint", and the spontaneous/borderline style to "loss of control in eating". The results indicate that not all models are susceptible to dysfunctional cognitions about eating and body image. Models are at a higher risk of developing negative automatic thoughts and dysfunctional assumptions relating to body size, shape and weight, especially if they have high scores on the above personality styles.

Urtica dioica extract attenuates depressive like behavior and associative memory dysfunction in dexamethasone induced diabetic mice.

PubMed

Patel, Sita Sharan; Udayabanu, Malairaman

2014-03-01

Evidences suggest that glucocorticoids results in depression and is a risk factor for type 2 diabetes. Further diabetes induces oxidative stress and hippocampal dysfunction resulting in cognitive decline. Traditionally Urtica dioica has been used for diabetes mellitus and cognitive dysfunction. The present study investigated the effect of the hydroalcoholic extract of Urtica dioica leaves (50 and 100 mg/kg, p.o.) in dexamethasone (1 mg/kg, i.m.) induced diabetes and its associated complications such as depressive like behavior and cognitive dysfunction. We observed that mice administered with chronic dexamethasone resulted in hypercortisolemia, oxidative stress, depressive like behavior, cognitive impairment, hyperglycemia with reduced body weight, increased water intake and decreased hippocampal glucose transporter-4 (GLUT4) mRNA expression. Urtica dioica significantly reduced hyperglycemia, plasma corticosterone, oxidative stress and depressive like behavior as well as improved associative memory and hippocampal GLUT4 mRNA expression comparable to rosiglitazone (5 mg/kg, p.o.). Further, Urtica dioica insignificantly improved spatial memory and serum insulin. In conclusion, Urtica dioica reversed dexamethasone induced hyperglycemia and its associated complications such as depressive like behavior and cognitive dysfunction.

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.

Neuroanatomical Substrates of Social Cognition Dysfunction in Autism

ERIC Educational Resources Information Center

Pelphrey, Kevin; Adolphs, Ralph; Morris, James P.

2004-01-01

In this review article, we summarize recent progress toward understanding the neural structures and circuitry underlying dysfunctional social cognition in autism. We review selected studies from the growing literature that has used the functional neuroimaging techniques of cognitive neuroscience to map out the neuroanatomical substrates of social…

Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer's disease.

PubMed

Jack, Clifford R; Wiste, Heather J; Vemuri, Prashanthi; Weigand, Stephen D; Senjem, Matthew L; Zeng, Guang; Bernstein, Matt A; Gunter, Jeffrey L; Pankratz, Vernon S; Aisen, Paul S; Weiner, Michael W; Petersen, Ronald C; Shaw, Leslie M; Trojanowski, John Q; Knopman, David S

2010-11-01

Biomarkers of brain Aβ amyloid deposition can be measured either by cerebrospinal fluid Aβ42 or Pittsburgh compound B positron emission tomography imaging. Our objective was to evaluate the ability of Aβ load and neurodegenerative atrophy on magnetic resonance imaging to predict shorter time-to-progression from mild cognitive impairment to Alzheimer's dementia and to characterize the effect of these biomarkers on the risk of progression as they become increasingly abnormal. A total of 218 subjects with mild cognitive impairment were identified from the Alzheimer's Disease Neuroimaging Initiative. The primary outcome was time-to-progression to Alzheimer's dementia. Hippocampal volumes were measured and adjusted for intracranial volume. We used a new method of pooling cerebrospinal fluid Aβ42 and Pittsburgh compound B positron emission tomography measures to produce equivalent measures of brain Aβ load from either source and analysed the results using multiple imputation methods. We performed our analyses in two phases. First, we grouped our subjects into those who were 'amyloid positive' (n = 165, with the assumption that Alzheimer's pathology is dominant in this group) and those who were 'amyloid negative' (n = 53). In the second phase, we included all 218 subjects with mild cognitive impairment to evaluate the biomarkers in a sample that we assumed to contain a full spectrum of expected pathologies. In a Kaplan-Meier analysis, amyloid positive subjects with mild cognitive impairment were much more likely to progress to dementia within 2 years than amyloid negative subjects with mild cognitive impairment (50 versus 19%). Among amyloid positive subjects with mild cognitive impairment only, hippocampal atrophy predicted shorter time-to-progression (P < 0.001) while Aβ load did not (P = 0.44). In contrast, when all 218 subjects with mild cognitive impairment were combined (amyloid positive and negative), hippocampal atrophy and Aβ load predicted shorter time-to-progression with comparable power (hazard ratio for an inter-quartile difference of 2.6 for both); however, the risk profile was linear throughout the range of hippocampal atrophy values but reached a ceiling at higher values of brain Aβ load. Our results are consistent with a model of Alzheimer's disease in which Aβ deposition initiates the pathological cascade but is not the direct cause of cognitive impairment as evidenced by the fact that Aβ load severity is decoupled from risk of progression at high levels. In contrast, hippocampal atrophy indicates how far along the neurodegenerative path one is, and hence how close to progressing to dementia. Possible explanations for our finding that many subjects with mild cognitive impairment have intermediate levels of Aβ load include: (i) individual subjects may reach an Aβ load plateau at varying absolute levels; (ii) some subjects may be more biologically susceptible to Aβ than others; and (iii) subjects with mild cognitive impairment with intermediate levels of Aβ may represent individuals with Alzheimer's disease co-existent with other pathologies.

Masked Hypertension is Associated With Cognitive Decline in Geriatric Age-Geriatric MASked Hypertension and Cognition (G-MASH-cog) Study.

PubMed

Esme, Mert; Yavuz, Burcu Balam; Yavuz, Bunyamin; Asil, Serkan; Tuna Dogrul, Rana; Sumer, Fatih; Kilic, Mustafa Kemal; Kizilarslanoglu, Muhammet Cemal; Varan, Hacer Dogan; Sagir, Aykut; Balci, Cafer; Halil, Meltem; Cankurtaran, Mustafa

2018-01-16

Masked hypertension is described as high ambulatory blood pressure measurements (ABPM) where office blood pressure measurements are normal. Effect of hypertension on cognitive functions is well known. However, the effect of masked hypertension on cognitive functions is unclear. The aim of this study is to examine the relationship between masked hypertension and cognitive functions. One hundred-two normotensive patients admitted to the Geriatric Medicine outpatient clinic were included. Exclusion criteria were hypertension, dementia, major depression, and usage of antihypertensive medication. All patients underwent ABPM procedures and average daytime blood pressure, mean blood pressure at night and the 24-hour average blood pressure measurements were recorded. Comprehensive geriatric assessment tests and neuropsychological tests were administered. The diagnosis of masked hypertension was based on the definitions in the 2013 guideline of the European Society of Cardiology. Forty-four patients (43%) were diagnosed with masked hypertension. Patients with masked hypertension had significantly lower scores on Mini-Mental State Examination (MMSE) test, Quick Mild Cognitive Impairment Test (QMCI), and Categorical Fluency Test than the normotensive patients (p = .011; p = .046; and p = .004; respectively). Montreal Cognitive Assessment Scale test score was lower in masked hypertension, although this was not statistically significant. This study may indicate that geriatric patients with masked hypertension, compared to normotensive patients have decreased cognitive functions. Masked hypertension should be kept in mind while assessing older adults. When masked hypertension is detected, cognitive assessment is essential to diagnose possible cognitive dysfunction at early stage. © The Author 2017. 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.

Anxiety is associated with cognitive impairment in newly-diagnosed Parkinson's disease.

PubMed

Dissanayaka, Nadeeka N W; Lawson, Rachael A; Yarnall, Alison J; Duncan, Gordon W; Breen, David P; Khoo, Tien K; Barker, Roger A; Burn, David J

2017-03-01

Anxiety and mild cognitive impairment (MCI) are prevalent non-motor manifestations of Parkinson's disease (PD). While few studies have demonstrated a possible link between cognitive dysfunction and anxiety in PD, to our knowledge, no studies have directly examined the association between them. This study investigated the association between anxiety and cognitive deficits in newly diagnosed PD patients. Patients with newly diagnosed PD (N = 185) were recruited from community and outpatient clinics. Anxiety was assessed using the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) clinician rated anxiety item, which has previously been validated against a standardized criteria for the diagnosis of anxiety disorders in PD. Participants scoring ≥2 were classified as anxious. A threshold of 1 SD below normative values (obtained from controls) was used to define cognitive impairment. Impairments in specific cognitive domains were identified as being >1 SD below controls in ≥1 test per domain. After controlling for age, education and motor severity, patients with anxiety were three times more likely to have cognitive impairment compared to those without anxiety (OR = 3.0, 95% CI = 1.2-7.3, p < 0.05). Patients with anxiety were more than twice as likely to be classified as having cognitive impairment due to impairment in the memory domain compared with PD without anxiety (OR = 2.3, 95% CI = 1.0-5.1, p < 0.05), whilst no associations were found between anxiety and performance on other cognitive domains. This study shows an association between anxiety and cognitive impairment (specifically memory impairment). Examining the neural basis of this association warrants future research in this developing field. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Different cognitive functions discriminate gait performance in younger and older women: A pilot study.

PubMed

Gonzales, Joaquin U; James, C Roger; Yang, Hyung Suk; Jensen, Daniel; Atkins, Lee; Thompson, Brennan J; Al-Khalil, Kareem; O'Boyle, Michael

2016-10-01

Cognitive dysfunction is associated with slower gait speed in older women, but whether cognitive function affects gait performance earlier in life has yet to be investigated. Thus, the objective of this study was to test the hypothesis that cognitive function will discriminate gait performance in healthy younger women. Fast-pace and dual-task gait speed were measured in 30 young to middle-aged (30-45y) and 26 older (61-80y) women without mild cognitive impairment. Visuoperceptual ability, working memory, executive function, and learning ability were assessed using neuropsychological tests. Within each age group, women were divided by the median into lower and higher cognitive function groups to compare gait performance. Younger women with higher visuoperceptual ability had faster fast-pace (2.25±0.30 vs. 1.98±0.18m/s, p≤0.01) and dual-task gait speed (2.02±0.27 vs. 1.69±0.25m/s, p≤0.01) than women with lower visuoperceptual ability. The difference in dual-task gait speed remained significant (p=0.02) after adjusting for age, years of education, and other covariates. Dividing younger women based on other cognitive domains showed no difference in gait performance. In contrast, working memory and executive function discriminated dual-task gait speed (p<0.05) in older women after adjusting for age and education. To our knowledge, this is the first study to show that poorer cognitive function even at a relatively young age can negatively impact mobility. Different cognitive functions discriminated gait performance based on age, highlighting a possible influence of aging in the relationship between cognitive function and mobility in women. Copyright © 2016 Elsevier B.V. All rights reserved.

Slowing down after a mild traumatic brain injury: a strategy to improve cognitive task performance?

PubMed

Ozen, Lana J; Fernandes, Myra A

2012-01-01

Long-term persistent attention and memory difficulties following a mild traumatic brain injury (TBI) often go undetected on standard neuropsychological tests, despite complaints by mild TBI individuals. We conducted a visual Repetition Detection working memory task to digits, in which we manipulated task difficulty by increasing cognitive load, to identify subtle deficits long after a mild TBI. Twenty-six undergraduate students with a self-report of one mild TBI, which occurred at least 6 months prior, and 31 non-head-injured controls took part in the study. Participants were not informed until study completion that the study's purpose was to examine cognitive changes following a mild TBI, to reduce the influence of "diagnosis threat" on performance. Neuropsychological tasks did not differentiate the groups, though mild TBI participants reported higher state anxiety levels. On our working memory task, the mild TBI group took significantly longer to accurately detect repeated targets on our task, suggesting that slowed information processing is a long-term consequence of mild TBI. Accuracy was comparable in the low-load condition and, unexpectedly, mild TBI performance surpassed that of controls in the high-load condition. Temporal analysis of target identification suggested a strategy difference between groups: mild TBI participants made a significantly greater number of accurate responses following the target's offset, and significantly fewer erroneous distracter responses prior to target onset, compared with controls. Results suggest that long after a mild TBI, high-functioning young adults invoke a strategy of delaying their identification of targets in order to maintain, and facilitate, accuracy on cognitively demanding tasks. © The Author 2011. Published by Oxford University Press. All rights reserved.

Reduced Frontal Activations at High Working Memory Load in Mild Cognitive Impairment: Near-Infrared Spectroscopy.

PubMed

Yeung, Michael K; Sze, Sophia L; Woo, Jean; Kwok, Timothy; Shum, David H K; Yu, Ruby; Chan, Agnes S

2016-01-01

Some functional magnetic resonance imaging studies have reported altered activations in the frontal cortex during working memory (WM) performance in individuals with mild cognitive impairment (MCI), but the findings have been mixed. The objective of the present study was to utilize near-infrared spectroscopy (NIRS), an alternative imaging technique, to examine neural processing during WM performance in individuals with MCI. Twenty-six older adults with MCI (7 males; mean age 69.15 years) were compared with 26 age-, gender-, handedness-, and education-matched older adults with normal cognition (NC; 7 males; mean age 68.87 years). All of the participants undertook an n-back task with a low (i.e., 0-back) and a high (i.e., 2-back) WM load condition while their prefrontal dynamics were recorded by a 16-channel NIRS system. Although behavioral results showed that the two groups had comparable task performance, neuroimaging results showed that the MCI group, unlike the NC group, did not exhibit significantly increased frontal activations bilaterally when WM load increased. Compared to the NC group, the MCI group had similar frontal activations at low load (p > 0.05 on all channels) but reduced activations at high load (p < 0.05 on 4 channels), thus failing to demonstrate WM-related frontal activations (p < 0.05 on 9 channels). In addition, we found a positive correlation between the left WM-related frontal activations and WM ability primarily in the NC group (rs = 0.42, p = 0.035), suggesting a relationship between frontal hypoactivation and WM difficulties. The present findings suggest the presence of frontal dysfunction that is dependent on WM load in individuals with MCI. © 2016 S. Karger AG, Basel.

Development and Evaluation of Cognitive Games to Promote Health and Wellbeing in Elderly People with Mild Cognitive Impairment.

PubMed

Scase, Mark; Kreiner, Karl; Ascolese, Antonio

2018-01-01

In Europe the number of elderly people is increasing. This population growth has resulted in higher healthcare costs. The purpose of this project was to try to promote active ageing in people aged 65-80 with mild cognitive impairment through cognitive games delivered via a tablet computer. Age-appropriate cognitive games were developed targeting different aspects of cognition and then experiences of elderly people using these games were evaluated. The design of games was developed through iterative user-centered design focus groups with elderly people as participants. The experiences of participants playing the games over a 47 day period were explored through semi-structured interviews. Four games were developed that addressed a range of cognitive functions such as perception, attention, memory, language, comprehension and executive function. The participants were able to play these games without external intervention over an extended period and reported positively on their experiences. Cognitive games can be used successfully by people with mild cognitive impairment to promote active ageing.

Stability of Cognitive Vulnerabilities to Depression: A Short-Term Prospective Multiwave Study

PubMed Central

Hankin, Benjamin L.

2009-01-01

The stability of 3 cognitive vulnerabilities—a negative cognitive style, dysfunctional attitudes, and rumination—as well as depressive symptoms as a benchmark were examined to investigate whether cognitive vulnerabilities are stable, enduring risks for depression. A sample of adolescents (6th–10th graders) completed measures of these 3 cognitive vulnerabilities and depressive symptoms every 5 weeks for 4 waves of data across 5 months. Mean-level and differential stability were examined for the sample overall and by age subgroups. A negative cognitive style exhibited mean-level stability, whereas rumination and dysfunctional attitudes showed some mean-level change. Absolute magnitudes of test–retest reliabilities were strong for depressive symptoms (mean r = .70), moderately high for a negative cognitive style (mean r = .52), and more modest for rumination (mean r = .28) and dysfunctional attitudes (mean r = .26). Structural equation modeling showed that primarily enduring processes, but not contextual forces, contributed to the patterning of these test–retest reliabilities over time for a negative cognitive style and dysfunctional attitudes, whereas both enduring and contextual dynamics appeared to underlie the stability for rumination. Theoretical and clinical implications of these findings are discussed. PMID:18489208

Memory self-awareness in the preclinical and prodromal stages of Alzheimer's disease.

PubMed

Vannini, Patrizia; Amariglio, Rebecca; Hanseeuw, Bernard; Johnson, Keith A; McLaren, Donald G; Chhatwal, Jasmeer; Pascual-Leone, Alvaro; Rentz, Dorene; Sperling, Reisa A

2017-05-01

While loss of insight of cognitive deficits, anosognosia, is a common symptom in Alzheimer's disease dementia, there is a lack of consensus regarding the presence of altered awareness of memory function in the preclinical and prodromal stages of the disease. Paradoxically, very early in the Alzheimer's disease process, individuals may experience heightened awareness of memory changes before any objective cognitive deficits can be detected, here referred to as hypernosognosia. In contrast, awareness of memory dysfunction shown by individuals with mild cognitive impairment (MCI) is very variable, ranging from marked concern to severe lack of insight. This study aims at improving our mechanistic understanding of how alterations in memory self-awareness are related to pathological changes in clinically normal (CN) adults and MCI patients. 297 CN and MCI patients underwent PiB-PET (Positron Emission Tomography using Pittsburgh Compound B) in vivo amyloid imaging. Amyloid burden was estimated from Alzheimer's disease vulnerable regions, including the frontal, lateral parietal and lateral temporal, and retrosplenial cortex. Memory self-awareness was assessed using discrepancy scores between subjective and objective measures of memory function. A set of univariate analysis of variance were performed to assess the relationship between self-awareness of memory and amyloid pathology. Whereas CN individuals harboring amyloid pathology demonstrated hypernosognosia, MCI patients with increased amyloid pathology demonstrated anosognosia. In contrast, MCI patients with low amounts of amyloid were observed to have normal insight into their memory functions. Altered self-awareness of memory tracks with amyloid pathology. The findings of variability of awareness may have important implications for the reliability of self-report of dysfunction across the spectrum of preclinical and prodromal Alzheimer's disease. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transcranial LED therapy for cognitive dysfunction in chronic, mild traumatic brain injury: two case reports

NASA Astrophysics Data System (ADS)

Naeser, Margaret A.; Saltmarche, Anita; Krengel, Maxine H.; Hamblin, Michael R.; Knight, Jeffrey A.

2010-02-01

Two chronic, traumatic brain injury (TBI) cases are presented, where cognitive function improved following treatment with transcranial light emitting diodes (LEDs). At age 59, P1 had closed-head injury from a motor vehicle accident (MVA) without loss of consciousness and normal MRI, but unable to return to work as development specialist in internet marketing, due to cognitive dysfunction. At 7 years post-MVA, she began transcranial LED treatments with cluster heads (2.1" diameter with 61 diodes each - 9x633nm, 52x870nm; 12-15mW per diode; total power, 500mW; 22.2 mW/cm2) on bilateral frontal, temporal, parietal, occipital and midline sagittal areas (13.3 J/cm2 at scalp, estimated 0.4 J/cm2 to brain cortex per area). Prior to transcranial LED, focused time on computer was 20 minutes. After 2 months of weekly, transcranial LED treatments, increased to 3 hours on computer. Performs nightly home treatments (now, 5 years, age 72); if stops treating >2 weeks, regresses. P2 (age 52F) had history of closed-head injuries related to sports/military training and recent fall. MRI shows fronto-parietal cortical atrophy. Pre-LED, was not able to work for 6 months and scored below average on attention, memory and executive function. Performed nightly transcranial LED treatments at home (9 months) with similar LED device, on frontal and parietal areas. After 4 months of LED treatments, returned to work as executive consultant, international technology consulting firm. Neuropsychological testing (post- 9 months of transcranial LED) showed significant improvement in memory and executive functioning (range, +1 to +2 SD improvement). Case 2 reported reduction in PTSD symptoms.

Clinical significance of circulating vascular cell adhesion molecule-1 to white matter disintegrity in Alzheimer's dementia.

PubMed

Huang, Chi-Wei; Tsai, Meng-Han; Chen, Nai-Ching; Chen, Wei-Hsi; Lu, Yan-Ting; Lui, Chun-Chung; Chang, Ya-Ting; Chang, Wen-Neng; Chang, Alice Y W; Chang, Chiung-Chih

2015-11-25

Endothelial dysfunction leads to worse cognitive performance in Alzheimer's dementia (AD). While both cerebrovascular risk factors and endothelial dysfunction lead to activation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin, it is not known whether these biomarkers extend the diagnostic repertoire in reflecting intracerebral structural damage or cognitive performance. A total of 110 AD patients and 50 age-matched controls were enrolled. Plasma levels of VCAM-1, ICAM-1 and E-selectin were measured and correlated with the cognitive performance, white matter macro-structural changes, and major tract-specific fractional anisotropy quantification. The AD patients were further stratified by clinical dementia rating score (mild dementia, n=60; moderate-to-severe dementia, n=50). Compared with the controls, plasma levels of VCAM-1 (p< 0.001), ICAM-1 (p=0.028) and E-selectin (p=0.016) were significantly higher in the patients, but only VCAM-1 levels significantly reflected the severity of dementia (p< 0.001). In addition, only VCAM-1 levels showed an association with macro- and micro- white matter changes especially in the superior longitudinal fasciculus (p< 0.001), posterior thalamic radiation (p=0.002), stria terminalis (p=0.002) and corpus callosum (p=0.009), and were independent of, age and cortical volume. These tracts show significant association with MMSE, short term memory and visuospatial function. Meanwhile, while VCAM-1 level correlated significantly with short-term memory (p=0.026) and drawing (p=0.025) scores in the AD patients after adjusting for age and education, the significance disappeared after adjusting for global FA. Endothelial activation, especially VCAM-1, was of clinical significance in AD that reflects macro- and micro-structural changes and poor short term memory and visuospatial function.

General anesthetic and the risk of dementia in elderly patients: current insights

PubMed Central

Hussain, Maria; Berger, Miles; Eckenhoff, Roderic G; Seitz, Dallas P

2014-01-01

In this review, we aim to provide clinical insights into the relationship between surgery, general anesthesia (GA), and dementia, particularly Alzheimer’s disease (AD). The pathogenesis of AD is complex, involving specific disease-linked proteins (amyloid-beta [Aβ] and tau), inflammation, and neurotransmitter dysregulation. Many points in this complex pathogenesis can potentially be influenced by both surgery and anesthetics. It has been demonstrated in some in vitro, animal, and human studies that some anesthetics are associated with increased aggregation and oligomerization of Aβ peptide and enhanced accumulation and hyperphosphorylation of tau protein. Two neurocognitive syndromes that have been studied in relation to surgery and anesthesia are postoperative delirium and postoperative cognitive dysfunction, both of which occur more commonly in older adults after surgery and anesthesia. Neither the route of anesthesia nor the type of anesthetic appears to be significantly associated with the development of postoperative delirium or postoperative cognitive dysfunction. A meta-analysis of case-control studies found no association between prior exposure to surgery utilizing GA and incident AD (pooled odds ratio =1.05, P=0.43). The few cohort studies on this topic have shown varying associations between surgery, GA, and AD, with one showing an increased risk, and another demonstrating a decreased risk. A recent randomized trial has shown that patients who received sevoflurane during spinal surgery were more likely to have progression of preexisting mild cognitive impairment compared to controls and to patients who received propofol or epidural anesthesia. Given the inconsistent evidence on the association between surgery, anesthetic type, and AD, well-designed and adequately powered studies with longer follow-up periods are required to establish a clear causal association between surgery, GA, and AD. PMID:25284995

Memory self-awareness in the preclinical and prodromal stages of Alzheimer’s disease

PubMed Central

Vannini, Patrizia; Amariglio, Rebecca; Hanseeuw, Bernard; Johnson, Keith A.; McLaren, Donald G; Chhatwal, Jasmeer; Pascual-Leone, Alvaro; Rentz, Dorene; Sperling, Reisa A.

2017-01-01

While loss of insight of cognitive deficits, anosognosia, is a common symptom in Alzheimer’s disease dementia, there is a lack of consensus regarding the presence of altered awareness of memory function in the preclinical and prodromal stages of the disease. Paradoxically, very early in the Alzheimer’s disease process, individuals may experience heightened awareness of memory changes before any objective cognitive deficits can be detected, here referred to as hypernosognosia. In contrast, awareness of memory dysfunction shown by individuals with mild cognitive impairment (MCI) is very variable, ranging from marked concern to severe lack of insight. This study aims at improving our mechanistic understanding of how alterations in memory self-awareness are related to pathological changes in clinically normal (CN) adults and MCI patients. 297 CN and MCI patients underwent PiB-PET (Positron Emission Tomography using Pittsburgh Compound B) in vivo amyloid imaging. Amyloid burden was estimated from Alzheimer’s disease vulnerable regions, including the frontal, lateral parietal and lateral temporal, and retrosplenial cortex. Memory self-awareness was assessed using discrepancy scores between subjective and objective measures of memory function. A set of univariate analysis of variance were performed to assess the relationship between self-awareness of memory and amyloid pathology. Whereas CN individuals harboring amyloid pathology demonstrated hypernosognosia, MCI patients with increased amyloid pathology demonstrated anosognosia. In contrast, MCI patients with low amounts of amyloid were observed to have normal insight into their memory functions. Altered self-awareness of memory tracks with amyloid pathology. The findings of variability of awareness may have important implications for the reliability of self-report of dysfunction across the spectrum of preclinical and prodromal Alzheimer’s disease. PMID:28385579

The effect of mild motion sickness and sopite syndrome on multitasking cognitive performance.

PubMed

Matsangas, Panagiotis; McCauley, Michael E; Becker, William

2014-09-01

In this study, we investigated the effects of mild motion sickness and sopite syndrome on multitasking cognitive performance. Despite knowledge on general motion sickness, little is known about the effect of motion sickness and sopite syndrome on multitasking cognitive performance. Specifically, there is a gap in existing knowledge in the gray area of mild motion sickness. Fifty-one healthy individuals performed a multitasking battery. Three independent groups of participants were exposed to two experimental sessions. Two groups received motion only in the first or the second session, whereas the control group did not receive motion. Measurements of motion sickness, sopite syndrome, alertness, and performance were collected during the experiment Only during the second session, motion sickness and sopite syndrome had a significant negative association with cognitive performance. Significant performance differences between symptomatic and asymptomatic participants in the second session were identified in composite (9.43%), memory (31.7%), and arithmetic (14.7%) task scores. The results suggest that performance retention between sessions was not affected by mild motion sickness. Multitasking cognitive performance declined even when motion sickness and soporific symptoms were mild. The results also show an order effect. We postulate that the differential effect of session on the association between symptomatology and multitasking performance may be related to the attentional resources allocated to performing the multiple tasks. Results suggest an inverse relationship between motion sickness effects on performance and the cognitive effort focused on performing a task. Even mild motion sickness has potential implications for multitasking operational performance.

4C.05: PWV IS AN INDEPENDENT DETERMINANT OF COGNITIVE DYSFUNCTION IN CKD PATIENTS.

PubMed

Karasavvidou, D; Pappas, K; Stagikas, D; Makridis, D; Katsinas, C; Kalaitzidis, R

2015-06-01

Cognitive dysfunction has long been recognized as a complication of chronic kidney disease (CKD), through several putative mechanisms, including high BP, large and small artery damage. Our study tests the hypothesis that large artery stiffness and microvascular damage are related to brain microcirculation changes as reflected by impaired cognitive function in CKD patients.(Figure is included in full-text article.) : Two hundred seventeen patients (50 with CKD stage 1; 67 stage 2; 53 stage 3; 47 stage 4), with mean age 58.4 years (64.5% males), were enrolled in a cross-sectional study. Cognitive function was assessed using Mini Mental State Examination (MMSE). Full score on the MMSE is 30; cognitive impairment was defined as <26 and cognitive dysfunction as <19. Educational level was categorized as lower versus higher education. Using the Sphygmocor system and an oscillometric device, we directly measured brachial SBP (bSBP) and pulse pressure (bPP), carotid SBP (cSBP) and pulse pressure (cPP) and estimated aortic SBP (aSBP) and pulse pressure (aPP) from the radial pressure waveform. Pulse Pressure Amplification (PPA), augmentation index (AIx) and carotid-femoral pulse wave velocity (cfPWV) were calculated. The risk of cognitive dysfunction increased significantly from CKD stage 3 to 4 (p < 0.01). Table. In univariate analysis, age (p < 0.001), education level (p < 0.001) stages of CKD (p < 0.004), cfPWV (p < 0.029), AIx (p < 0.03), bSBP (p < 0.002), aSBP (p < 0.012), cSBP (p < 0.015) and cPP (p < 0.002) were significantly and negatively associated with MMSE. In multivariate regression analysis, adjusted for CKD stages, the remaining independent factor significantly (p < 0.02) associated with cognitive dysfunction was cfPWV. Carotid-femoral PWV may be a more sensitive marker of cognitive dysfunction than other parameters of central blood pressure. Since high cfPWV is associated with high pressure pulsatility at the cerebrovascular level, these data suggest that the later could play a pathophysiological role in cognitive dysfunction. In clinical practice, measuring aortic stiffness may help predicting the cognitive decline. Whether, the reduction in aortic stiffness following treatment translates into improved cognitive outcomes remains to be determined.

Role of inflammatory markers in Elderly Type 2 Diabetic Patients with Mild Cognitive Impairment.

PubMed

Hosny, Salwa S; Bahaaeldin, Ahmed M; Khater, Mohamed S; Bekhet, Meram M; Hebah, Hayam A; Hasanin, Ghada A

2018-04-22

Type 2 diabetes (T2DM) is a risk factor for Alzheimer's disease and mild cognitive impairment. The etiology of cognitive impairment in people with T2DM is uncertain but, chronic hyperglycemia, cerebral micro vascular disease, severe hypoglycemia, and increased prevalence of macro vascular disease are implicated. to determine the serum levels of soluble vascular adhesion molecule (sVCAM-1) and highly sensitive C-reactive protein (hs-CRP) in elderly type 2 diabetics with mild cognitive impairment (MCI). Our study was conducted on 90 elderly subjects (aged 60 years old or more). They were divided into Group І, 30 patients with T2DM and mild cognitive impairment, group ІІ, 30 patients with T2DM without cognitive impairment and group III, 30 healthy subjects as a control group. They were subjected to history taking, full clinical examination, anthropometric measurement, the Addenbrooke's Cognitive Examination III (ACE---III 2012), Fasting plasma glucose, 2 hours plasma glucose, HbA1c, lipid profile, protein/creatinine ratio, serum sVCAM-1 and hs-CRP. Serum levels of sVCAM-1 in diabetic elderly patients with MCI were significantly higher (946.7 ± 162.01 ng/ml) than diabetic elderly patients without cognitive impairment (479.06 ± 65.27 ng/ml) and control (263.7 ± 72.05 ng/ml) with (P=0.002). Serum levels of Hs-CRP in diabetic elderly patients with MCI were significantly higher than as diabetic elderly patients without cognitive impairment and control with (P=0.005). Elderly diabetic patients with mild cognitive impairment, have higher levels of soluble adhesion molecules and markers of low-grade systemic inflammation than other groups. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cognitive control dysfunction in emotion dysregulation and psychopathology of major depression (MD): Evidence from transcranial brain stimulation of the dorsolateral prefrontal cortex (DLPFC).

PubMed

Salehinejad, Mohammad Ali; Ghanavai, Elham; Rostami, Reza; Nejati, Vahid

2017-03-01

Previous studies showed that MD is associated with a variety of cognitive deficits and executive dysfunctions which can persist even in remitted states. However, the role of cognitive impairments in MD psychopathology and treatment is not fully understood. This article aims to discuss how executive functions central components (e.g., Working memory and attention) mediate MD psychopathology considering the role of dorsolateral prefrontal cortex (dLPFC) and present findings of a brain stimulation experiment to support this notion. The effect of transcranial direct current stimulation (tDCS) of the dLPFC on enhancing cognitive control functions was investigated. Twenty-four patients with MD (Experimental group=12, Control group=12) received 10 sessions of tDCS (2mA for 30min) over 10 consecutive days. The experimental group received active stimulation and the control group received sham stimulation. Participant's performance on cognitive functions (PAL, SRM, RVP and CRT from CANTAB) and their depression scores were assessed before and after tDCS. Results showed that brain stimulation of the dLPFC improved executive dysfunction in patients and a significant improvement on depression scores was also observed suggesting that cognitive control dysfunction may be a mediator in emotional dysregulation and psychopathology of MD. No follow-up investigation was done in this study which does not allow to infer long-term effect of tDCS. Low-focality of tDCS might have stimulated adjacent areas too. Cognitive components, namely cognitive control dysfunction, play role in MD psychopathology as they are involved in emotion dysregulation in MD. The amount of contribution of cognitive components in MD psychopathology is however, an open question. tDCS can be used as an intervention to improve cognitive dysfunction in MD. Copyright © 2017 Elsevier B.V. All rights reserved.

Discourse changes in early Alzheimer disease, mild cognitive impairment, and normal aging.

PubMed

Chapman, Sandra Bond; Zientz, Jennifer; Weiner, Myron; Rosenberg, Roger; Frawley, William; Burns, Mary Hope

2002-01-01

The purpose of this study was to determine the sensitivity of discourse gist measures to the early cognitive-linguistic changes in Alzheimer disease (AD) and in the preclinical stages. Differences in discourse abilities were examined in 25 cognitively normal adults, 24 adults with mild probable AD, and 20 adults with mild cognitive impairment (MCI) at gist and detail levels of discourse processing. The authors found that gist and detail levels of discourse processing were significantly impaired in persons with AD and MCI as compared with normal control subjects. Gist-level discourse processing abilities showed minimal overlap between cognitively normal control subjects and those with mild AD. Moreover, the majority of the persons with MCI performed in the range of AD on gist measures. These findings indicate that discourse gist measures hold promise as a diagnostic complement to enhance early detection of AD. Further studies are needed to determine how early the discourse gist deficits arise in AD.

Various MRS application tools for Alzheimer disease and mild cognitive impairment.

PubMed

Gao, F; Barker, P B

2014-06-01

MR spectroscopy is a noninvasive technique that allows the detection of several naturally occurring compounds (metabolites) from well-defined regions of interest within the human brain. Alzheimer disease, a progressive neurodegenerative disorder, is the most common cause of dementia in the elderly. During the past 20 years, multiple studies have been performed on MR spectroscopy in patients with both mild cognitive impairment and Alzheimer disease. Generally, MR spectroscopy studies have found decreased N-acetylaspartate and increased myo-inositol in both patients with mild cognitive impairment and Alzheimer disease, with greater changes in Alzheimer disease than in mild cognitive impairment. This review summarizes the information content of proton brain MR spectroscopy and its related technical aspects, as well as applications of MR spectroscopy to mild cognitive impairment and Alzheimer disease. While MR spectroscopy may have some value in the differential diagnosis of dementias and assessing prognosis, more likely its role in the near future will be predominantly as a tool for monitoring disease response or progression in treatment trials. More work is needed to evaluate the role of MR spectroscopy as a biomarker in Alzheimer disease and its relationship to other imaging modalities. © 2014 by American Journal of Neuroradiology.

Japanese and North American Alzheimer's Disease Neuroimaging Initiative studies: Harmonization for international trials.

PubMed

Iwatsubo, Takeshi; Iwata, Atsushi; Suzuki, Kazushi; Ihara, Ryoko; Arai, Hiroyuki; Ishii, Kenji; Senda, Michio; Ito, Kengo; Ikeuchi, Takeshi; Kuwano, Ryozo; Matsuda, Hiroshi; Sun, Chung-Kai; Beckett, Laurel A; Petersen, Ronald C; Weiner, Michael W; Aisen, Paul S; Donohue, Michael C

2018-05-08

We conducted Japanese Alzheimer's Disease Neuroimaging Initiative (J-ADNI) and compared the basic characteristics and progression profiles with those of ADNI in North America. A total of 537 Japanese subjects with normal cognition, late amnestic mild cognitive impairment (LMCI), or mild Alzheimer's disease (AD) were enrolled using the same criteria as ADNI. Rates of changes in representative cognitive or functional measures were compared for amyloid positron emission tomography- or cerebrospinal fluid amyloid β(1-42)-positive LMCI and mild AD between J-ADNI and ADNI. Amyloid positivity rates were significantly higher in normal cognition of ADNI but at similar levels in LMCI and mild AD between J-ADNI and ADNI. Profiles of decline in cognitive or functional measures in amyloid-positive LMCI in J-ADNI (n = 75) and ADNI (n = 269) were remarkably similar, whereas those in mild AD were milder in J-ADNI (n = 73) compared with ADNI (n = 230). These results support the feasibility of bridging of clinical trials in the prodromal stage of AD between Asia and western countries. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Diagnostic accuracy of the MMSE in detecting probable and possible Alzheimer's disease in ethnically diverse highly educated individuals: an analysis of the NACC database.

PubMed

Spering, Cynthia C; Hobson, Valerie; Lucas, John A; Menon, Chloe V; Hall, James R; O'Bryant, Sid E

2012-08-01

To validate and extend the findings of a raised cut score of O'Bryant and colleagues (O'Bryant SE, Humphreys JD, Smith GE, et al. Detecting dementia with the mini-mental state examination in highly educated individuals. Arch Neurol. 2008;65(7):963-967.) for the Mini-Mental State Examination in detecting cognitive dysfunction in a bilingual sample of highly educated ethnically diverse individuals. Archival data were reviewed from participants enrolled in the National Alzheimer's Coordinating Center minimum data set. Data on 7,093 individuals with 16 or more years of education were analyzed, including 2,337 cases with probable and possible Alzheimer's disease, 1,418 mild cognitive impairment patients, and 3,088 nondemented controls. Ethnic composition was characterized as follows: 6,296 Caucasians, 581 African Americans, 4 American Indians or Alaska natives, 2 native Hawaiians or Pacific Islanders, 149 Asians, 43 "Other," and 18 of unknown origin. Diagnostic accuracy estimates (sensitivity, specificity, and likelihood ratio) of Mini-Mental State Examination cut scores in detecting probable and possible Alzheimer's disease were examined. A standard Mini-Mental State Examination cut score of 24 (≤23) yielded a sensitivity of 0.58 and a specificity of 0.98 in detecting probable and possible Alzheimer's disease across ethnicities. A cut score of 27 (≤26) resulted in an improved balance of sensitivity and specificity (0.79 and 0.90, respectively). In the cognitively impaired group (mild cognitive impairment and probable and possible Alzheimer's disease), the standard cut score yielded a sensitivity of 0.38 and a specificity of 1.00 while raising the cut score to 27 resulted in an improved balance of 0.59 and 0.96 of sensitivity and specificity, respectively. These findings cross-validate our previous work and extend them to an ethnically diverse cohort. A higher cut score is needed to maximize diagnostic accuracy of the Mini-Mental State Examination in individuals with college degrees.

Electroencephalographic findings related with mild cognitive impairment in idiopathic rapid eye movement sleep behavior disorder.

PubMed

Sasai, Taeko; Matsuura, Masato; Inoue, Yuichi

2013-12-01

Mild cognitive impairment (MCI) and electroencephalographic (EEG) slowing have been reported as common findings of idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) and α-synucleinopathies. The objective of this study is to clarify the relation between MCI and physiological markers in iRBD. Cross-sectional study. Yoyogi Sleep Disorder Center. Thirty-one patients with iRBD including 17 younger patients with iRBD (younger than 70 y) and 17 control patients for the younger patients with iRBD. N/A. Montreal Cognitive Assessment (MoCA) and n-polysomnogram (PSG) were conducted of all participants. In patients with iRBD, the factors associated with MCI were explored among parameters of REM sleep without atonia (RWA), score of Sniffin' Sticks Test (threshold-discrimination-identification [TDI] score), RBD morbidity, and RBD severity evaluated with the Japanese version of the RBD questionnaire (RBDQ-JP). The younger iRBD group showed significantly lower alpha power during wake and lower MoCA score than the age-matched control group. MCI was detected in 13 of 17 patients (76.5%) on MoCA in this group. Among patients wtih iRBD, the MoCA score negatively correlated with age, proportion of slow wave sleep, TDI score, and EEG spectral power. Multiple regression analysis provided the following equation: MoCA score = 50.871-0.116*age -5.307*log (δ power during REM sleep) + 0.086*TDI score (R² = 0.598, P < 0.01). The standardized partial regression coefficients were -0.558 for age, -0.491 for log (δ power during REM sleep), and 0.357 for TDI score (F = 9.900, P < 0.001). Electroencephalographic slowing, especially during rapid eye movement sleep and olfactory dysfunction, was revealed to be associated with cognitive decline in idiopathic rapid eye movement sleep behavior disorder.

Patterns of effective connectivity during memory encoding and retrieval differ between patients with mild cognitive impairment and healthy older adults.

PubMed

Hampstead, B M; Khoshnoodi, M; Yan, W; Deshpande, G; Sathian, K

2016-01-01

Previous research has shown that there is considerable overlap in the neural networks mediating successful memory encoding and retrieval. However, little is known about how the relevant human brain regions interact during these distinct phases of memory or how such interactions are affected by memory deficits that characterize mild cognitive impairment (MCI), a condition that often precedes dementia due to Alzheimer's disease. Here we employed multivariate Granger causality analysis using autoregressive modeling of inferred neuronal time series obtained by deconvolving the hemodynamic response function from measured blood oxygenation level-dependent (BOLD) time series data, in order to examine the effective connectivity between brain regions during successful encoding and/or retrieval of object location associations in MCI patients and comparable healthy older adults. During encoding, healthy older adults demonstrated a left hemisphere dominant pattern where the inferior frontal junction, anterior intraparietal sulcus (likely involving the parietal eye fields), and posterior cingulate cortex drove activation in most left hemisphere regions and virtually every right hemisphere region tested. These regions are part of a frontoparietal network that mediates top-down cognitive control and is implicated in successful memory formation. In contrast, in the MCI patients, the right frontal eye field drove activation in every left hemisphere region examined, suggesting reliance on more basic visual search processes. Retrieval in the healthy older adults was primarily driven by the right hippocampus with lesser contributions of the right anterior thalamic nuclei and right inferior frontal sulcus, consistent with theoretical models holding the hippocampus as critical for the successful retrieval of memories. The pattern differed in MCI patients, in whom the right inferior frontal junction and right anterior thalamus drove successful memory retrieval, reflecting the characteristic hippocampal dysfunction of these patients. These findings demonstrate that neural network interactions differ markedly between MCI patients and healthy older adults. Future efforts will investigate the impact of cognitive rehabilitation of memory on these connectivity patterns. Published by Elsevier Inc.

Poor balance and lower gray matter volume predict falls in older adults with mild cognitive impairment

PubMed Central

2013-01-01

Background The risk of falling is associated with cognitive dysfunction. Older adults with mild cognitive impairment (MCI) exhibit an accelerated reduction of brain volume, and face an increased risk of falling. The current study examined the relationship between baseline physical performance, baseline gray matter volume and falls during a 12-month follow-up period among community-dwelling older adults with MCI. Methods Forty-two older adults with MCI (75.6 years, 43% women) underwent structural magnetic resonance imaging and baseline physical performance assessment, including knee-extension strength, one-legged standing time, and walking speed with normal pace. ‘Fallers’ were defined as people who had one or more falls during the 12-month follow-up period. Results Of the 42 participants, 26.2% (n = 11) experienced at least one fall during the 12-month follow-up period. Fallers exhibited slower walking speed and shorter one-legged standing time compared with non-fallers (both p < .01). One-legged standing time (sec) (standardized odds ratio [95% confidence interval]: 0.89 [0.81, 0.98], p = .02) was associated with a significantly lower rate of falls during the 12-month follow-up after adjusting for age, sex, body mass index, and history of falling in the past year at baseline. Voxel-based morphometry was used to examine differences in baseline gray matter volume between fallers and non-fallers, revealing that fallers exhibited a significantly greater reduction in the bilateral middle frontal gyrus and superior frontal gyrus. Conclusions Poor balance predicts falls over 12 months, and baseline lower gray matter densities in the middle frontal gyrus and superior frontal gyrus were associated with falls in older adults with MCI. Maintaining physical function, especially balance, and brain structural changes through many sorts of prevention strategies in the early stage of cognitive decline may contribute to decreasing the risk of falls in older adults with MCI. PMID:23915144

Erectile dysfunction and type 2 diabetes mellitus in northern Pakistan.

PubMed

Ahmed, Ibrar; Aamir, Aziz ul Hassan; Anwar, Ejaz; Ali, Sobia Sabir; Ali, Asfhaq; Ali, Amjad

2013-12-01

To determine the frequency of erectile dysfunction in married male Type-2 diabetic patients. The cross-sectional observational study was carried out at the Endocrinology, Diabetes and Metabolic Diseases Unit Hayatabad Medical Complex, Peshawar, from July 2011 to Apr 2012, comprising 217 male married Type-2 diabetic patients. Serum samples were assayed for blood glucose, lipid profile and glycated haemoglobin A1c. Body mass index and waist-to-hip ratio was calculated. Erectile dysfunction was assessed by Sexual Health Inventory for Men questionnaire. SPSS 18 was used for statistical analysis. A total of 217 patients were initially interviewed. The mean age was 43.1 +/- 8.160 years. The frequency of drectile dysfunction increased with age, duration of patients and increased body mass index. Overall, 6 (2.8%) patients had no erectile dysfunction, 37 (17.1%) had mild, 82 (37.8%) mild to moderate; 47 (21.7%) moderate; and 45 (20.7%) severe. Higher HbAlc levels and atherogenic dyslipidaemia were associated with erectile dysfunction. Poor glycaemic control was associated with increased erectile dysfunction risk. Duration of diabetes, older age, increased body mass index are associated with increased incidence of the condition in patients with diabetes. Intensive lifestyle changes in the beginning can add to the better management of Type-2 diabetes and prevention of erectile dysfunction.

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.

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.

Anti-NR2A/B Antibodies and Other Major Molecular Mechanisms in the Pathogenesis of Cognitive Dysfunction in Systemic Lupus Erythematosus

PubMed Central

Tay, Sen Hee; Mak, Anselm

2015-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects approximately 1–45.3 per 100,000 people worldwide. Although deaths as a result of active and renal diseases have been substantially declining amongst SLE patients, disease involving the central nervous system (CNS), collectively termed neuropsychiatric systemic lupus erythematosus (NPSLE), remains one of the important causes of death in these patients. Cognitive dysfunction is one of the most common manifestations of NPSLE, which comprises deficits in information-processing speed, attention and executive function, in conjunction with preservation of speech. Albeit a prevalent manifestation of NPSLE, the pathogenetic mechanisms of cognitive dysfunction remain unclear. Recent advances in genetic studies, molecular techniques, neuropathology, neuroimaging and cognitive science have gleaned valuable insights into the pathophysiology of lupus-related cognitive dysfunction. In recent years, a role for autoantibodies, molecular and cellular mechanisms in cognitive dysfunction, has been emerging, challenging our previous concept of the brain as an immune privileged site. This review will focus on the potential pathogenic factors involved in NPSLE, including anti-N-methyl-d-aspartate receptor subunit NR2A/B (anti-NR2A/B) antibodies, matrix metalloproteinase-9, neutrophil extracellular traps and pro-inflammatory mediators. Better understanding of these mechanistic processes will enhance identification of new therapeutic modalities to halt the progression of cognitive decline in SLE patients. PMID:25955648

Attachment, dysfunctional attitudes, self-esteem, and association to depressive symptoms in patients with mood disorders.

PubMed

Fuhr, Kristina; Reitenbach, Ivanina; Kraemer, Jan; Hautzinger, Martin; Meyer, Thomas D

2017-04-01

Cognitive factors might be the link between early attachment experiences and later depression. Similar cognitive vulnerability factors are discussed as relevant for both unipolar and bipolar disorders. The goals of the study were to test if there are any differences concerning attachment style and cognitive factors between remitted unipolar and bipolar patients compared to controls, and to test if the association between attachment style and depressive symptoms is mediated by cognitive factors. A path model was tested in 182 participants (61 with remitted unipolar and 61 with remitted bipolar disorder, and 60 healthy subjects) in which adult attachment insecurity was hypothesized to affect subsyndromal depressive symptoms through the partial mediation of dysfunctional attitudes and self-esteem. No differences between patients with remitted unipolar and bipolar disorders concerning attachment style, dysfunctional attitudes, self-esteem, and subsyndromal depressive symptoms were found, but both groups reported a more dysfunctional pattern than healthy controls. The path models confirmed that the relationship between attachment style and depressive symptoms was mediated by the cognitive variables 'dysfunctional attitudes' and 'self-esteem'. With the cross-sectional nature of the study, results cannot explain causal development over time. The results emphasize the relevance of a more elaborate understanding of cognitive and interpersonal factors in mood disorders. It is important to address cognitive biases and interpersonal experiences in treatment of mood disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

Prefrontal cortical gamma-aminobutyric acid transmission and cognitive function: drawing links to schizophrenia from preclinical research.

PubMed

Tse, Maric T; Piantadosi, Patrick T; Floresco, Stan B

2015-06-01

Cognitive dysfunction in schizophrenia is one of the most pervasive and debilitating aspects of the disorder. Among the numerous neural abnormalities that may contribute to schizophrenia symptoms, perturbations in markers for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), particularly within the frontal lobes, are some of the most reliable alterations observed at postmortem examination. However, how prefrontal GABA dysfunction contributes to cognitive impairment in schizophrenia remains unclear. We provide an overview of postmortem GABAergic perturbations in the brain affected by schizophrenia and describe circumstantial evidence linking these alterations to cognitive dysfunction. In addition, we conduct a survey of studies using neurodevelopmental, genetic, and pharmacologic rodent models that induce schizophrenia-like cognitive impairments, highlighting the convergence of these mechanistically distinct approaches to prefrontal GABAergic disruption. We review preclinical studies that have directly targeted prefrontal cortical GABAergic transmission using local application of GABAA receptor antagonists. These studies have provided an important link between GABA transmission and cognitive dysfunction in schizophrenia because they show that reducing prefrontal inhibitory transmission induces various cognitive, emotional, and dopaminergic abnormalities that resemble aspects of the disorder. These converging clinical and preclinical findings provide strong support for the idea that perturbations in GABA signaling drive certain forms of cognitive dysfunction in schizophrenia. Future studies using this approach will yield information to refine further a putative "GABA hypothesis" of schizophrenia. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Cognitive Function Before and After Left Heart Catheterization.

PubMed

Scott, David A; Evered, Lisbeth; Maruff, Paul; MacIsaac, Andrew; Maher, Sarah; Silbert, Brendan S

2018-03-10

Hospital procedures have been associated with cognitive change in older patients. This study aimed to document the prevalence of mild cognitive impairment in individuals undergoing left heart catheterization (LHC) before the procedure and the incidence of cognitive decline to 3 months afterwards. We conducted a prospective, observational, clinical investigation of elderly participants undergoing elective LHC. Cognition was assessed using a battery of written tests and a computerized cognitive battery before the LHC and then at 3 months afterwards. The computerized tests were also administered at 24 hours (or discharge) and 7 days after LHC. A control group of 51 community participants was recruited to calculate cognitive decline using the Reliable Change Index. Of 437 participants, mild cognitive impairment was identified in 226 (51.7%) before the procedure. Computerized tests detected an incidence of cognitive decline of 10.0% at 24 hours and 7.5% at 7 days. At 3 months, written tests detected an incidence of cognitive decline of 13.1% and computerized tests detected an incidence of 8.5%. Cognitive decline at 3 months using written tests was associated with increasing age, whereas computerized tests showed cognitive decline was associated with baseline amnestic mild cognitive impairment, diabetes mellitus, and prior coronary stenting. More than half the patients aged >60 years presenting for LHC have mild cognitive impairment. LHC is followed by cognitive decline in 8% to 13% of individuals at 3 months after the procedure. Subtle cognitive decline both before and after LHC is common and may have important clinical implications. URL: www.anzctr.org.au. Unique identifier: ACTRN12607000051448. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Regional analysis of the magnetization transfer ratio of the brain in mild Alzheimer disease and amnestic mild cognitive impairment.

PubMed

Mascalchi, M; Ginestroni, A; Bessi, V; Toschi, N; Padiglioni, S; Ciulli, S; Tessa, C; Giannelli, M; Bracco, L; Diciotti, S

2013-01-01

Manually drawn VOI-based analysis shows a decrease in magnetization transfer ratio in the hippocampus of patients with Alzheimer disease. We investigated with whole-brain voxelwise analysis the regional changes of the magnetization transfer ratio in patients with mild Alzheimer disease and patients with amnestic mild cognitive impairment. Twenty patients with mild Alzheimer disease, 27 patients with amnestic mild cognitive impairment, and 30 healthy elderly control subjects were examined with high-resolution T1WI and 3-mm-thick magnetization transfer images. Whole-brain voxelwise analysis of magnetization transfer ratio maps was performed by use of Statistical Parametric Mapping 8 software and was supplemented by the analysis of the magnetization transfer ratio in FreeSurfer parcellation-derived VOIs. Voxelwise analysis showed 2 clusters of significantly decreased magnetization transfer ratio in the left hippocampus and amygdala and in the left posterior mesial temporal cortex (fusiform gyrus) of patients with Alzheimer disease as compared with control subjects but no difference between patients with amnestic mild cognitive impairment and either patients with Alzheimer disease or control subjects. VOI analysis showed that the magnetization transfer ratio in the hippocampus and amygdala was significantly lower (bilaterally) in patients with Alzheimer disease when compared with control subjects (ANOVA with Bonferroni correction, at P < .05). Mean magnetization transfer ratio values in the hippocampus and amygdala in patients with amnestic mild cognitive impairment were between those of healthy control subjects and those of patients with mild Alzheimer disease. Support vector machine-based classification demonstrated improved classification performance after inclusion of magnetization transfer ratio-related features, especially between patients with Alzheimer disease versus healthy subjects. Bilateral but asymmetric decrease of magnetization transfer ratio reflecting microstructural changes of the residual GM is present not only in the hippocampus but also in the amygdala in patients with mild Alzheimer disease.

Diagnostic utility of Montreal Cognitive Assessment in the Fifth Edition of Diagnostic and Statistical Manual of Mental Disorders: major and mild neurocognitive disorders.

PubMed

Liew, Tau Ming; Feng, Lei; Gao, Qi; Ng, Tze Pin; Yap, Philip

2015-02-01

The Montreal Cognitive Assessment (MOCA) is a screening tool for mild cognitive impairment (MCI) and dementia. The new criteria for Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) mild neurocognitive disorder (NCD) define participants with cognitive decline but no dementia, and major NCD (dementia). We explored the usefulness of MOCA to detect major and mild NCD. Cross-sectional test research. Tertiary hospital memory clinic and community-based Singapore Longitudinal Aging Study (SLAS). Participants with questionable dementia (clinical dementia rating, CDR = 0.5) and early dementia (CDR ≤1) over a period of 1 year were identified from the memory clinic registry. The patient records were reviewed and the diagnostic labels of major and mild NCD were applied accordingly. Healthy controls (HC) (CDR = 0, Mini-Mental State Examination >26) were recruited from the on-going SLAS. Major and mild NCD were diagnosed based on medical history, clinical examination, basic and instrumental activities of daily living, locally validated bedside cognitive tests (Mini-Mental State Examination, Frontal Assessment Battery, and Clock Drawing Test), relevant laboratory investigations and standardized neuropsychological assessment. Two hundred fifty-one participants were included (41 mild NCD, 64 major NCD, 146 HC). On receiver operating characteristic curve analysis, the diagnostic performance by area under the curve (AUC) for MOCA was 0.99 [95% confidence interval (CI) 0.98-1.0] for major NCD and 0.77 (95% CI 0.67-0.86) for mild NCD. For diagnosis of mild NCD, MOCA performed better in those with lower education (primary and below) (AUC 0.90) compared with those with secondary education and beyond (AUC 0.66). MOCA has high diagnostic utility for major NCD but its usefulness in detecting mild NCD is more modest. Possible reasons include greater heterogeneity in participants with mild NCD and how "quantified clinical assessment" in the DSM-5 mild NCD criteria is interpreted and operationalized. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

A milk-based wolfberry preparation prevents prenatal stress-induced cognitive impairment of offspring rats, and inhibits oxidative damage and mitochondrial dysfunction in vitro.

PubMed

Feng, Zhihui; Jia, Haiqun; Li, Xuesen; Bai, Zhuanli; Liu, Zhongbo; Sun, Lijuan; Zhu, Zhongliang; Bucheli, Peter; Ballèvre, Olivier; Wang, Junkuan; Liu, Jiankang

2010-05-01

Lycium barbarum (Fructus Lycii, Wolfberry, or Gouqi) belongs to the Solanaceae. The red-colored fruits of L. barbarum have been used for a long time as an ingredient in Chinese cuisine and brewing, and also in traditional Chinese herbal medicine for improving health. However, its effects on cognitive function have not been well studied. In the present study, prevention of a milk-based wolfberry preparation (WP) on cognitive dysfunction was tested in a prenatal stress model with rats and the antioxidant mechanism was tested by in vitro experiments. We found that prenatal stress caused a significant decrease in cognitive function (Morris water maze test) in female offspring. Pretreatment of the mother rats with WP significantly prevented the prenatal stress-induced cognitive dysfunction. In vitro studies showed that WP dose-dependently scavenged hydroxyl and superoxide radicals (determined by an electron spin resonance spectrometric assay), and inhibited FeCl(2)/ascorbic acid-induced dysfunction in brain tissue and tissue mitochondria, including increases in reactive oxygen species and lipid peroxidation and decreases in the activities of complex I, complex II, and glutamate cysteine ligase. These results suggest that dietary supplementation with WP may be an effective strategy for preventing the brain oxidative mitochondrial damage and cognitive dysfunction associated with prenatal stress.

Neurotransmitter-based strategies for the treatment of cognitive dysfunction in Down syndrome.

PubMed

Das, Devsmita; Phillips, Cristy; Hsieh, Wayne; Sumanth, Krithika; Dang, Van; Salehi, Ahmad

2014-10-03

Down syndrome (DS) is a multisystem disorder affecting the cardiovascular, respiratory, gastrointestinal, neurological, hematopoietic, and musculoskeletal systems and is characterized by significant cognitive disability and a possible common pathogenic mechanism with Alzheimer's disease. During the last decade, numerous studies have supported the notion that the triplication of specific genes on human chromosome 21 plays a significant role in cognitive dysfunction in DS. Here we reviewed studies in trisomic mouse models and humans, including children and adults with DS. In order to identify groups of genes that contribute to cognitive disability in DS, multiple mouse models of DS with segmental trisomy have been generated. Over-expression of these particular genes in DS can lead to dysfunction of several neurotransmitter systems. Therapeutic strategies for DS have either focused on normalizing the expression of triplicated genes with important roles in DS or restoring the function of these systems. Indeed, our extensive review of studies on the pathogenesis of DS suggests that one plausible strategy for the treatment of cognitive dysfunction is to target the cholinergic, serotonergic, GABA-ergic, glutamatergic, and norepinephrinergic system. However, a fundamental strategy for treatment of cognitive dysfunction in DS would include reducing to normal levels the expression of specific triplicated genes in affected systems before the onset of neurodegeneration. Published by Elsevier Inc.

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.

The synergistic effect of acupuncture and computer-based cognitive training on post-stroke cognitive dysfunction: a study protocol for a randomized controlled trial of 2 × 2 factorial design.

PubMed

Yang, Shanli; Ye, Haicheng; Huang, Jia; Tao, Jing; Jiang, Cai; Lin, Zhicheng; Zheng, Guohua; Chen, Lidian

2014-08-07

Stroke is one of the most common causes of cognitive impairment. Up to 75% of stroke survivors may be considered to have cognitive impairment, which severely limit individual autonomy for successful reintegration into family, work and social life. The clinical efficacy of acupuncture with Baihui (DU20) and Shenting (DU24) in stroke and post-stroke cognitive impairment has been previously demonstrated. Computer-assisted cognitive training is part of conventional cognitive rehabilitation and has also shown to be effective in improvement of cognitive function of affected patients. However, the cognitive impairment after stroke is so complexity that one single treatment cannot resolve effectively. Besides, the effects of acupuncture and RehaCom cognitive training have not been systematically compared, nor has the possibility of a synergistic effect of combination of the two therapeutic modalities been evaluated. Our primary aim of this trial is to evaluate the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. A randomized controlled trial of 2 × 2 factorial design will be conducted in the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine. A total of 240 patients with cognitive dysfunction after stroke who meet the eligibility criteria will be recruited and randomized into RehaCom training group, acupuncture group, a combination of both or control group in a 1:1:1:1 ratio. All patients will receive conventional treatment. The interventions will last for 12 weeks (30 min per day, Monday to Friday every week). Evaluations will be conducted by blinded assessors at baseline and again at 4, 8 and 12 weeks. Outcome measurements include mini-mental state examination (MMSE), Montreal cognitive assessments (MoCA), functional independence measure scale (FIM) and adverse events. The results of this trial are expected to clarify the synergistic effect of acupuncture and RehaCom cognitive training on cognitive dysfunction after stroke. Furthermore, to confirm whether combined or alone of acupuncture and RehaCom cognitive training, is more effective than conventional treatment in the management of post-stroke cognitive dysfunction. Chinese Clinical Trial Registry: ChiCTR-TRC-13003704.

Diastolic dysfunction characterizes cirrhotic cardiomyopathy

PubMed Central

Somani, Piyush O.; contractor, Qais; Chaurasia, Ajay S.; Rathi, Pravin M.

2014-01-01

Aim Present study aims to study the occurrence of cirrhotic cardiomyopathy and its correlation to hepatorenal syndrome by assessing the cardiac status in patients with cirrhosis of liver and healthy controls. Methods Thirty alcoholic cirrhotic, thirty non-alcoholic cirrhotic and thirty controls were enrolled for the study. Cardiac parameters were assessed by color doppler echocardiography. Patients were followed up for twelve months period for development of hepatorenal syndrome. Results Mild diastolic dysfunction was present in 18 cirrhotic patients (30%): grade I in fifteen patients and grade II in three. Diastolic dysfunction was unrelated to age; sex and etiology of cirrhosis. Among all the echocardiographic parameters, only deceleration time was found to be statistically significant. Echocardiographic parameters in systolic and diastolic function were not different in compensated vs decompensated patients in different Child-Pugh classes or cirrhosis aetiologies. At one year follow-up, no significant differences were found in survival between patients with or without diastolic dysfunction. Hepatorenal syndrome developed in only two patients and its correlation with diastolic dysfunction was not statistically significant. Conclusions Present study shows that although diastolic dysfunction is a frequent event in cirrhosis, it is usually of mild degree and does not correlate with severity of liver dysfunction. There are no significant differences in echocardiographic parameters between alcoholic and non-alcoholic cirrhosis. HRS is not correlated to diastolic dysfunction in cirrhotic patients. There is no difference in survival at one year between patients with or without diastolic dysfunction. Diastolic dysfunction in cirrhosis is unrelated to circulatory dysfunction, ascites and HRS. PMID:25634400

The Effects of Cognitive Organizers to Facilitate Content-Area Learning for Students with Mild Disabilities: A Pilot Study

ERIC Educational Resources Information Center

Boon, Richard T.; Fore, Cecil, III; Ayres, Kevin; Spencer, Vicky G.

2005-01-01

The purpose of this pilot study was to examine the effects of cognitive organizers using Inspiration 6 software to improve and enhance content-area learning in social studies for students with mild disabilities. Using a one-group, pre-posttest design, ten students with mild disabilities received instruction with the integration of technology-based…

Bipolar Disorder and Cognitive Dysfunction: A Complex Link.

PubMed

Cipriani, Gabriele; Danti, Sabrina; Carlesi, Cecilia; Cammisuli, Davide Maria; Di Fiorino, Mario

2017-10-01

The aim of this article was to describe the current evidence regarding phenomenon of cognitive functioning and dementia in bipolar disorder (BD). Cochrane Library and PubMed searches were conducted for relevant articles, chapters, and books published before 2016. Search terms used included "bipolar disorder," "cognitive dysfunction," and "dementia." At the end of the selection process, 159 studies were included in our qualitative synthesis. As result, cognitive impairments in BD have been previously considered as infrequent and limited to the affective episodes. Nowadays, there is evidence of stable and lasting cognitive dysfunctions in all phases of BD, including remission phase, particularly in the following domains: attention, memory, and executive functions. The cause of cognitive impairment in BD raises the question if it subtends a neurodevelopmental or a neurodegenerative process. Impaired cognitive functioning associated with BD may contribute significantly to functional disability, in addition to the distorted affective component usually emphasized.

"Don't Look Now": The Role of Self-Focus in Sexual Dysfunction.

ERIC Educational Resources Information Center

Wiederman, Michael W.

2001-01-01

Couples and family counselors may aid in the remedy of sexual dysfunction when it has a cognitive or psychological basis. One important source of sexual dysfunction is cognitive distraction that results from certain forms of self-focus during sexual activity with a partner, a phenomenon sex therapists have labeled spectatoring. Introduces sensate…

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

Evidence for neuroinflammation and neuroprotection in HCV infection-associated encephalopathy.

PubMed

Bokemeyer, M; Ding, X-Q; Goldbecker, A; Raab, P; Heeren, M; Arvanitis, D; Tillmann, H L; Lanfermann, H; Weissenborn, K

2011-03-01

Fatigue, mood disturbances and cognitive dysfunction are frequent in patients infected with hepatitis C virus (HCV) who have mild liver disease. The reason is still unclear. The present study aims to gain more insight into the pathomechanism by combining an extensive neuropsychological examination with magnetic resonance spectroscopy in four different brain regions in a patient group covering the whole spectrum of neuropsychiatric findings in patients afflicted with HCV who have only mild liver disease. 53 HCV-positive patients with only mild liver disease and differing degrees of neuropsychiatric symptoms were studied with single-voxel MRS of the parietal white matter, occipital grey matter, basal ganglia and pons. Brain metabolite concentrations were quantitatively analysed by using LCmodel. MRS data were compared to those of 23 healthy controls adjusted for age, and analysed for relationships with the extent of neuropsychiatric symptoms. Choline (p=0.02), creatine (p=0.047) and N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (NN, p=0.02) concentrations in the basal ganglia and choline concentrations in the white matter (p=0.045) were significantly higher in the patients than in controls. Interestingly, the difference was most evident for the patients with low fatigue scores (eg, white matter: choline: p=0.001, creatine: p=0.003, NN: p=0.031). Myo-inositol differed significantly between groups in the white (p=0.001) and grey matter (p=0.003). Fatigue correlated negatively with white matter NN, choline and creatine and myo-inositol levels in white and grey matter and basal ganglia (p<0.01). As the increase of choline, creatine and myo-inositol are usually interpreted to indicate glial activation and macrophage infiltration in chronic inflammation and slow virus infections of the brain the present data endorse the hypothesis, that HCV infection may induce neuroinflammation and brain dysfunction. The concomitant increase of NN and the negative correlation to the extent of fatigue suggest a cerebral compensatory process after HCV infection.

Brain inflammation accompanies amyloid in the majority of mild cognitive impairment cases due to Alzheimer's disease.

PubMed

Parbo, Peter; Ismail, Rola; Hansen, Kim V; Amidi, Ali; Mårup, Frederik H; Gottrup, Hanne; Brændgaard, Hans; Eriksson, Bengt O; Eskildsen, Simon F; Lund, Torben E; Tietze, Anna; Edison, Paul; Pavese, Nicola; Stokholm, Morten G; Borghammer, Per; Hinz, Rainer; Aanerud, Joel; Brooks, David J

2017-07-01

See Kreisl (doi:10.1093/awx151) for a scientific commentary on this article.Subjects with mild cognitive impairment associated with cortical amyloid-β have a greatly increased risk of progressing to Alzheimer's disease. We hypothesized that neuroinflammation occurs early in Alzheimer's disease and would be present in most amyloid-positive mild cognitive impairment cases. 11C-Pittsburgh compound B and 11C-(R)-PK11195 positron emission tomography was used to determine the amyloid load and detect the extent of neuroinflammation (microglial activation) in 42 mild cognitive impairment cases. Twelve age-matched healthy control subjects had 11C-Pittsburgh compound B and 10 healthy control subjects had 11C-(R)-PK11195 positron emission tomography for comparison. Amyloid-positivity was defined as 11C-Pittsburgh compound B target-to-cerebellar ratio above 1.5 within a composite cortical volume of interest. Supervised cluster analysis was used to generate parametric maps of 11C-(R)-PK11195 binding potential. Levels of 11C-(R)-PK11195 binding potential were measured in a selection of cortical volumes of interest and at a voxel level. Twenty-six (62%) of 42 mild cognitive impairment cases showed a raised cortical amyloid load compared to healthy controls. Twenty-two (85%) of the 26 amyloid-positive mild cognitive impairment cases showed clusters of increased cortical microglial activation accompanying the amyloid. There was a positive correlation between levels of amyloid load and 11C-(R)-PK11195 binding potentials at a voxel level within subregions of frontal, parietal and temporal cortices. 11C-(R)-PK11195 positron emission tomography reveals increased inflammation in a majority of amyloid positive mild cognitive impairment cases, its cortical distribution overlapping that of amyloid deposition. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment.

PubMed

Papma, Janne M; Smits, Marion; de Groot, Marius; Mattace Raso, Francesco U; van der Lugt, Aad; Vrooman, Henri A; Niessen, Wiro J; Koudstaal, Peter J; van Swieten, John C; van der Veen, Frederik M; Prins, Niels D

2017-09-01

Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI.

A comprehensive assessment of cognitive function in the common genetic generalized epilepsy syndromes.

PubMed

Loughman, A; Bowden, S C; D'Souza, W J

2017-03-01

Considered to be benign conditions, the common genetic generalized epilepsy (GGE) syndromes are now known to be frequently accompanied by cognitive dysfunction. However, unresolved issues impede clinical management of this common comorbidity, including which cognitive abilities are most affected, whether there are differences between syndromes and how seizure type and mood symptoms affect cognitive dysfunction. We provide a detailed description of cognitive ability and evaluate factors contributing to cognitive dysfunction. A total of 76 adults with GGE were assessed with the Woodcock Johnson III Tests of Cognitive Abilities. Scores on tests of overall cognitive ability, acquired knowledge, long-term retrieval and speed of information processing were significantly below the normative mean. Long-term retrieval was a pronounced weakness with a large reduction in scores (d = 0.84). GGE syndrome, seizure type and the presence of recent psychopathology symptoms were not significantly associated with cognitive function. This study confirms previous meta-analytic findings with a prospective study, offers new insights into the cognitive comorbidity of these common epilepsy syndromes and reinforces the need for cognitive interventions in people with GGE. © 2016 EAN.

[Depression and frontal dysfunction: risks for the elderly?].

PubMed

Thomas, P; Hazif Thomas, C; Billon, R; Peix, R; Faugeron, P; Clément, J-P

2009-09-01

Frontal lobe syndromes include reduced activity, particularly a diminution of spontaneous activity, lack of drive, inability to plan ahead, and induce a lack of concern. These last points constitute the executive dysfunction syndrome. That executive dysfunction could be the core defect in patients with geriatric or vascular depression, and might be related to frontal-subcortical circuit dysfunction. Sometimes frontal lobe syndromes are associated with restless, aimless, uncoordinated behavior or even disinhibition, increasing the risks of falls and of malnutrition. Some authors have distinguished between lesions of the lateral frontal cortex, most closely linked to the motor structures of the brain, which lead to disturbances of movement and action with perseveration and inertia, and lesions of the orbital and medial areas, interlinked with limbic and reticular systems, damage to which leads to disinhibition and changes of affect. The medial frontal syndrome is marked by akinesia, associated with gait disturbances, and loss of autonomy. For these reasons, it has been proposed that a subtype of depression, "depression-executive dysfunction syndrome" could occur in late life. This assertion was based on clinical, neuropathological, and neuroimaging findings suggesting that frontostriatal dysfunctions contribute to the development of both depression and executive dysfunction and influence the course of depression. Depressive symptomatology, and especially psychomotor retardation and loss of interest in activities, contributed to disability in depression-executive dysfunction syndrome patients. This study is not restricted to major depression. It examined the relationship of executive impairment to the course of depressive symptoms among a psychogeriatric population with dementia or depression in order to assess the consequences of these pathologies on disabilities of aged persons. The study was carried out in Limoges (France) during 2006 and 2007. Three hundred and twenty one psychogeriatric outpatients were included after their written agreement. They were assessed using different scales for autonomy, cognition, depression, frontal impairment and these results were compared with the risk of fall, a possible loss of autonomy and a proteino-energical malnutrition. The statistical study was made using the Systat 11 software. The following tests were used: Student Test, Chi(2) test, and the Manova test, which was adjusted to the duration of the disease, the caregiver's age, his/her education level, and level of cognitive impairment. The regression method used was the multiple linear regression method as well as a descending step-by-step analysis. One hundred and thirty six males (77.3+/-7.09 years old) and 185 females (80.4+/-6.5 years old) were recruited. Patients mainly presented with Alzheimer's disease (n=123) and 65 presented an associated depression, 25 presented vascular dementia, 30 a Lewy bodies dementia, 27 a fronto-temporal dementia. Twenty-seven presented psychosis and 40 a Mild Cognitive Impairment. A control group was composed of 33 persons presumed without psychogeriatric pathologies. Depression associated with an executive dysfunction syndrome increased loss of autonomy, the risk of fall and of malnutrition, especially in the case of cognitive impairment. The multivariate regression analysis step-by-step shows an increasing risk of fall in the presence of a depression-executive dysfunction syndrome. Motivation is altered when the patient is depressed. In demented patients, depression significantly increases behavioral disorders, social and familial relationships, and instrumental acts of daily life. It precipitates the risks of falls and of malnutrition. The principal finding of this study is that geriatric depression is characterized by impaired executive functioning. In the present study, depressed patients also had a greater tendency to fall and to suffer from malnutrition. Executive processes are fundamental to the daily functioning of depressed older adults, and dysfunction may lead to a lack of compensatory strategies that would improve the outcomes of late-life depression or of increasing dependency as well. In demented patients, depression triggers loss of motivation and executive dysfunction as well. Depression and executive dysfunction triggers the loss of autonomy, the risk of fall and of malnutrition in elderly patients. The clinical significance of this study is that the delineation of specific executive in depressed elderly patients may facilitate the development of effective treatment interventions, including treatment for geriatric depression.

Cognitive Developmental Therapy: Aiding Adult Children of Dysfunctional Families.

ERIC Educational Resources Information Center

Towers, David A.

The works of Kegan and Guidano have presented cognition and emotion as complementary modes of knowing that develop together. Cognition is conceived of as being concerned with the knowledge of reality, and emotions are conceptualized as people's system for knowing of their relationship to that reality. Adult children of dysfunctional families are a…

Mild Cognitive Impairment and Progession to Dementia: New Findings

MedlinePlus

... MD Mild cognitive impairment and progression to dementia New findings John C.S. Breitner, MD, MPH WHAT WERE ... how different they are. This article offers important new information to answer that question. The study is ...

Effect of Common Neuropathologies on Progression of Late Life Cognitive Impairment

PubMed Central

Yu, Lei; Boyle, Patricia A.; Leurgans, Sue; Schneider, Julie A.; Kryscio, Richard J.; Wilson, Robert S.; Bennett, David A.

2015-01-01

Brain pathologies of Alzheimer’s, cerebrovascular and Lewy body diseases are common in old age, but the relationship of these pathologies with progression from normal cognitive function to the various stages of cognitive impairment is unknown. In this study, we fit latent Markov models from longitudinal cognitive data to empirically derive three latent stages corresponding to no impairment, mild impairment, and moderate impairment; then, we examined the associations of common neuropathologies with the rates of transition among these stages. Cognitive and neuropathological data were available from 653 autopsied participants in two ongoing cohort studies of aging who were cognitively healthy at baseline (mean baseline age 79.1 years) and had longitudinal cognitive data. On average, participants in these analyses developed mild impairment 5 years after enrollment, progressed to moderate impairment after an additional 3.4 years, and stayed impaired for 2.8 years until death. AD and chronic macroscopic infarcts were associated with a higher risk of progression to mild impairment and subsequently to moderate impairment. By contrast, Lewy bodies were associated only with progression from mild to moderate impairment. The 5-year probability of progression to mild or moderate impairment was 20% for persons without any of these three pathologies, 38% for AD only, 51% for AD and macroscopic infarcts, and 56% for AD, infarcts and Lewy bodies. Thus, the presence of AD pathology alone nearly doubles the risk of developing cognitive impairment in late life, and the presence of multiple pathologies further increases this risk over multiple years prior to death. PMID:25976345

[Noopept in the treatment of mild cognitive impairment in patients with stroke].

PubMed

Amelin, A V; Iliukhina, A Iu; Shmonin, A A

2011-01-01

Noopept is a neuroprotector and nootropics. Literature data revealed the treatment effect of noopept on mild cognitive impairment in patients with discirculatory encephalopathy. The present open prospective study included 60 patients with stroke treated with noopept during 12 months. Cognitive functions were assessed before and after treatment using neuropsychological tests. An analysis of MMSE scores and lateral and categorical associations revealed the significant improvement of cognitive functions after 2 months in patients of the main group compared to the controls. The global assessment of efficacy revealed the mild improvement in the main group while no changes were found in the control group. The results have demonstrated that noopept, used in dose 20 mg daily during 2 months, improves cognitive functions in stroke patients and has a high level of safety.

Rational pharmacological approaches for cognitive dysfunction and depression in Parkinson's disease.

PubMed

Sandoval-Rincón, Maritza; Sáenz-Farret, Michel; Miguel-Puga, Adán; Micheli, Federico; Arias-Carrión, Oscar

2015-01-01

Parkinson's disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. The present study aims to conduct a critical systematic review of the literature to describe the main pharmacological strategies to treat cognitive dysfunction and major depressive disorder in PD patients. We performed a search of articles cited in PubMed from 2004 to 2014 using the following MeSH terms (Medical subject headings) "Parkinson disease"; "Delirium," "Dementia," "Amnestic," "Cognitive disorders," and "Parkinson disease"; "depression," "major depressive disorder," "drug therapy." We found a total of 71 studies related to pharmacological treatment in cognitive dysfunction and 279 studies for pharmacological treatment in major depressive disorder. After fulfillment of all the inclusion and exclusion criteria, 13 articles remained for cognitive dysfunction and 11 for major depressive disorder, which are presented and discussed in this study. Further research into non-motor symptoms of PD may provide insights into mechanisms of neurodegeneration, and provide better quality of life by using rational drugs.

The neuropathology of traumatic brain injury.

PubMed

Mckee, Ann C; Daneshvar, Daniel H

2015-01-01

Traumatic brain injury, a leading cause of mortality and morbidity, is divided into three grades of severity: mild, moderate, and severe, based on the Glasgow Coma Scale, the loss of consciousness, and the development of post-traumatic amnesia. Although mild traumatic brain injury, including concussion and subconcussion, is by far the most common, it is also the most difficult to diagnose and the least well understood. Proper recognition, management, and treatment of acute concussion and mild traumatic brain injury are the fundamentals of an emerging clinical discipline. It is also becoming increasingly clear that some mild traumatic brain injuries have persistent, and sometimes progressive, long-term debilitating effects. Evidence indicates that a single traumatic brain injury can precipitate or accelerate multiple age-related neurodegenerations, increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease, and that repetitive mild traumatic brain injuries can provoke the development of a tauopathy, chronic traumatic encephalopathy. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus, septal abnormalities, and abnormal deposits of hyperphosphorylated tau (τ) as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy frequently occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including Alzheimer's disease, Lewy body disease, and motor neuron disease. Currently, chronic traumatic encephalopathy can be diagnosed only at autopsy; however, promising efforts to develop imaging, spinal fluid, and peripheral blood biomarkers are underway to diagnose and monitor the course of disease in living subjects. © 2015 Elsevier B.V. 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.

[Discipline styles and co-morbid disorders of adolescents with attention deficit hyperactivity disorder: a longitudinal study].

PubMed

Colomer-Diago, Carla; Berenguer-Forner, Carmen; Tárraga-Mínguez, Raúl; Miranda-Casas, Ana

2014-02-24

Problems in cognitive functioning, social and educational development of children with attention deficit hyperactivity disorder (ADHD) continue to be present in adolescence and adulthood. Although the literature shows a significant relationship between the use of dysfunctional discipline methods and severity in the course of ADHD, follow-up studies have been rare. To analyze parenting style and ADHD symptomatology assessed in childhood (time 1) to predict the oppositional behavior and cognitive problems in early adolescence (time 2), and to study, depending on the use of dysfunctional parenting style, the course of oppositional behavior and cognitive problems. Forty-five children with ADHD-combined presentation were assessed in two different moments: time 1 (ages: 6-13) and time 2 (ages: 8-16). Oppositionism and cognitive problems in the follow-up were predicted by dysfunctional discipline styles and ADHD severity (assessed in time 1). Oppositional behavior increased between time 1 and time 2 in children with a dysfunctional parenting, whereas a decrease on oppositional symptoms was observed in the functional parenting group (time x discipline interaction effect). Dysfunctional parenting practices in childhood predicted cognitive and behavioral problems associated in adolescence. The findings have implications for the planning of interventions.

Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer’s disease

PubMed Central

Wiste, Heather J.; Vemuri, Prashanthi; Weigand, Stephen D.; Senjem, Matthew L.; Zeng, Guang; Bernstein, Matt A.; Gunter, Jeffrey L.; Pankratz, Vernon S.; Aisen, Paul S.; Weiner, Michael W.; Petersen, Ronald C.; Shaw, Leslie M.; Trojanowski, John Q.; Knopman, David S.

2010-01-01

Biomarkers of brain Aβ amyloid deposition can be measured either by cerebrospinal fluid Aβ42 or Pittsburgh compound B positron emission tomography imaging. Our objective was to evaluate the ability of Aβ load and neurodegenerative atrophy on magnetic resonance imaging to predict shorter time-to-progression from mild cognitive impairment to Alzheimer’s dementia and to characterize the effect of these biomarkers on the risk of progression as they become increasingly abnormal. A total of 218 subjects with mild cognitive impairment were identified from the Alzheimer’s Disease Neuroimaging Initiative. The primary outcome was time-to-progression to Alzheimer’s dementia. Hippocampal volumes were measured and adjusted for intracranial volume. We used a new method of pooling cerebrospinal fluid Aβ42 and Pittsburgh compound B positron emission tomography measures to produce equivalent measures of brain Aβ load from either source and analysed the results using multiple imputation methods. We performed our analyses in two phases. First, we grouped our subjects into those who were ‘amyloid positive’ (n = 165, with the assumption that Alzheimer's pathology is dominant in this group) and those who were ‘amyloid negative’ (n = 53). In the second phase, we included all 218 subjects with mild cognitive impairment to evaluate the biomarkers in a sample that we assumed to contain a full spectrum of expected pathologies. In a Kaplan–Meier analysis, amyloid positive subjects with mild cognitive impairment were much more likely to progress to dementia within 2 years than amyloid negative subjects with mild cognitive impairment (50 versus 19%). Among amyloid positive subjects with mild cognitive impairment only, hippocampal atrophy predicted shorter time-to-progression (P < 0.001) while Aβ load did not (P = 0.44). In contrast, when all 218 subjects with mild cognitive impairment were combined (amyloid positive and negative), hippocampal atrophy and Aβ load predicted shorter time-to-progression with comparable power (hazard ratio for an inter-quartile difference of 2.6 for both); however, the risk profile was linear throughout the range of hippocampal atrophy values but reached a ceiling at higher values of brain Aβ load. Our results are consistent with a model of Alzheimer’s disease in which Aβ deposition initiates the pathological cascade but is not the direct cause of cognitive impairment as evidenced by the fact that Aβ load severity is decoupled from risk of progression at high levels. In contrast, hippocampal atrophy indicates how far along the neurodegenerative path one is, and hence how close to progressing to dementia. Possible explanations for our finding that many subjects with mild cognitive impairment have intermediate levels of Aβ load include: (i) individual subjects may reach an Aβ load plateau at varying absolute levels; (ii) some subjects may be more biologically susceptible to Aβ than others; and (iii) subjects with mild cognitive impairment with intermediate levels of Aβ may represent individuals with Alzheimer’s disease co-existent with other pathologies. PMID:20935035

The effectiveness of ICT-based neurocognitive and psychosocial rehabilitation programmes in people with mild dementia and mild cognitive impairment using GRADIOR and ehcoBUTLER: study protocol for a randomised controlled trial.

PubMed

Vanova, Martina; Irazoki, Eider; García-Casal, J Antonio; Martínez-Abad, Fernando; Botella, Cristina; Shiells, Kate R; Franco-Martín, Manuel A

2018-02-12

Cognitive rehabilitation is a highly individualised, non-pharmacological intervention for people with mild cognitive impairment (MCI) and dementia, which in recent years has also been developed for various IT platforms. In this study, we aim to evaluate the effectiveness of the cognitive rehabilitation software GRADIOR in a multi-centre, single-blinded randomised controlled trial with people with MCI and mild dementia. A total of 400 people with MCI and mild dementia will be randomly allocated to one of four groups. This trial will compare the cognitive rehabilitation treatment using the GRADIOR programme with a psychosocial stimulation intervention (PSS) using the ehcoBUTLER platform, with a combined treatment consisting of GRADIOR and ehcoBUTLER, and with a group receiving treatment as usual during a period of 1 year. The outcomes of this clinical trial will be to determine any relevant changes in cognition, mood, quality of life, activities of daily living and quality of patient-carer relationship after 4 months and 1 year of intervention in a cross-sectional group comparison. Participants will be followed-up for 1 year to investigate potential long-term effects of the conducted treatments. Current Controlled Trials ISRCTN, ID: 15742788 . Registered on 12 June 2017.

Efficiently Assessing Negative Cognition in Depression: An Item Response Theory Analysis of the Dysfunctional Attitude Scale

ERIC Educational Resources Information Center

Beevers, Christopher G.; Strong, David R.; Meyer, Bjorn; Pilkonis, Paul A.; Miller, Ivan R.

2007-01-01

Despite a central role for dysfunctional attitudes in cognitive theories of depression and the widespread use of the Dysfunctional Attitude Scale, form A (DAS-A; A. Weissman, 1979), the psychometric development of the DAS-A has been relatively limited. The authors used nonparametric item response theory methods to examine the DAS-A items and…

Creativity on tap? Effects of alcohol intoxication on creative cognition

PubMed Central

Benedek, Mathias; Panzierer, Lisa; Jauk, Emanuel; Neubauer, Aljoscha C.

2017-01-01

Anecdotal reports link alcohol intoxication to creativity, while cognitive research highlights the crucial role of cognitive control for creative thought. This study examined the effects of mild alcohol intoxication on creative cognition in a placebo-controlled design. Participants completed executive and creative cognition tasks before and after consuming either alcoholic beer (BAC of 0.03) or non-alcoholic beer (placebo). Alcohol impaired executive control, but improved performance in the Remote Associates Test, and did not affect divergent thinking ability. The findings indicate that certain aspects of creative cognition benefit from mild attenuations of cognitive control, and contribute to the growing evidence that higher cognitive control is not always associated with better cognitive performance. PMID:28705663

Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms.

PubMed

Skelly, Donal T; Griffin, Éadaoin W; Murray, Carol L; Harney, Sarah; O'Boyle, Conor; Hennessy, Edel; Dansereau, Marc-Andre; Nazmi, Arshed; Tortorelli, Lucas; Rawlins, J Nicholas; Bannerman, David M; Cunningham, Colm

2018-06-06

Systemic inflammation can impair cognition with relevance to dementia, delirium and post-operative cognitive dysfunction. Episodes of delirium also contribute to rates of long-term cognitive decline, implying that these acute events induce injury. Whether systemic inflammation-induced acute dysfunction and acute brain injury occur by overlapping or discrete mechanisms remains unexplored. Here we show that systemic inflammation, induced by bacterial LPS, produces both working-memory deficits and acute brain injury in the degenerating brain and that these occur by dissociable IL-1-dependent processes. In normal C57BL/6 mice, LPS (100 µg/kg) did not affect working memory but impaired long-term memory consoliodation. However prior hippocampal synaptic loss left mice selectively vulnerable to LPS-induced working memory deficits. Systemically administered IL-1 receptor antagonist (IL-1RA) was protective against, and systemic IL-1β replicated, these working memory deficits. Dexamethasone abolished systemic cytokine synthesis and was protective against working memory deficits, without blocking brain IL-1β synthesis. Direct application of IL-1β to ex vivo hippocampal slices induced non-synaptic depolarisation and irrevesible loss of membrane potential in CA1 neurons from diseased animals and systemic LPS increased apoptosis in the degenerating brain, in an IL-1RI -/- -dependent fashion. The data suggest that LPS induces working memory dysfunction via circulating IL-1β but direct hippocampal action of IL-1β causes neuronal dysfunction and may drive neuronal death. The data suggest that acute systemic inflammation produces both reversible cognitive deficits, resembling delirium, and acute brain injury contributing to long-term cognitive impairment but that these events are mechanistically dissociable. These data have significant implications for management of cognitive dysfunction during acute illness.

Dysfunctions of decision-making and cognitive control as transdiagnostic mechanisms of mental disorders: advances, gaps, and needs in current research.

PubMed

Goschke, Thomas

2014-01-01

Disadvantageous decision-making and impaired volitional control over actions, thoughts, and emotions are characteristics of a wide range of mental disorders such as addiction, eating disorders, depression, and anxiety disorders and may reflect transdiagnostic core mechanisms and possibly vulnerability factors. Elucidating the underlying neurocognitive mechanisms is a precondition for moving from symptom-based to mechanism-based disorder classifications and ultimately mechanism-targeted interventions. However, despite substantial advances in basic research on decision-making and cognitive control, there are still profound gaps in our current understanding of dysfunctions of these processes in mental disorders. Central unresolved questions are: (i) to which degree such dysfunctions reflect transdiagnostic mechanisms or disorder-specific patterns of impairment; (ii) how phenotypical features of mental disorders relate to dysfunctional control parameter settings and aberrant interactions between large-scale brain systems involved in habit and reward-based learning, performance monitoring, emotion regulation, and cognitive control; (iii) whether cognitive control impairments are consequences or antecedent vulnerability factors of mental disorders; (iv) whether they reflect generalized competence impairments or context-specific performance failures; (v) whether not only impaired but also chronic over-control contributes to mental disorders. In the light of these gaps, needs for future research are: (i) an increased focus on basic cognitive-affective mechanisms underlying decision and control dysfunctions across disorders; (ii) longitudinal-prospective studies systematically incorporating theory-driven behavioural tasks and neuroimaging protocols to assess decision-making and control dysfunctions and aberrant interactions between underlying large-scale brain systems; (iii) use of latent-variable models of cognitive control rather than single tasks; (iv) increased focus on the interplay of implicit and explicit cognitive-affective processes; (v) stronger focus on computational models specifying neurocognitive mechanisms underlying phenotypical expressions of mental disorders. Copyright © 2013 John Wiley & Sons, Ltd.

Visualizing Hyperactivation in Neurodegeneration Based on Prefrontal Oxygenation: A Comparative Study of Mild Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Controls

PubMed Central

Yap, Kah Hui; Ung, Wei Chun; Ebenezer, Esther G. M.; Nordin, Nadira; Chin, Pui See; Sugathan, Sandheep; Chan, Sook Ching; Yip, Hung Loong; Kiguchi, Masashi; Tang, Tong Boon

2017-01-01

Background: Cognitive performance is relatively well preserved during early cognitive impairment owing to compensatory mechanisms. Methods: We explored functional near-infrared spectroscopy (fNIRS) alongside a semantic verbal fluency task (SVFT) to investigate any compensation exhibited by the prefrontal cortex (PFC) in Mild Cognitive Impairment (MCI) and mild Alzheimer's disease (AD). In addition, a group of healthy controls (HC) was studied. A total of 61 volunteers (31 HC, 12 patients with MCI and 18 patients with mild AD) took part in the present study. Results: Although not statistically significant, MCI exhibited a greater mean activation of both the right and left PFC, followed by HC and mild AD. Analysis showed that in the left PFC, the time taken for HC to achieve the activation level was shorter than MCI and mild AD (p = 0.0047 and 0.0498, respectively); in the right PFC, mild AD took a longer time to achieve the activation level than HC and MCI (p = 0.0469 and 0.0335, respectively); in the right PFC, HC, and MCI demonstrated a steeper slope compared to mild AD (p = 0.0432 and 0. 0107, respectively). The results were, however, not significant when corrected by the Bonferroni-Holm method. There was also found to be a moderately positive correlation (R = 0.5886) between the oxygenation levels in the left PFC and a clinical measure [Mini-Mental State Examination (MMSE) score] in MCI subjects uniquely. Discussion: The hyperactivation in MCI coupled with a better SVFT performance may suggest neural compensation, although it is not known to what degree hyperactivation manifests as a potential indicator of compensatory mechanisms. However, hypoactivation plus a poorer SVFT performance in mild AD might indicate an inability to compensate due to the degree of structural impairment. Conclusion: Consistent with the scaffolding theory of aging and cognition, the task-elicited hyperactivation in MCI might reflect the presence of compensatory mechanisms and hypoactivation in mild AD could reflect an inability to compensate. Future studies will investigate the fNIRS parameters with a larger sample size, and their validity as prognostic biomarkers of neurodegeneration. PMID:28919856

Anosognosia for cognitive and behavioral symptoms in Parkinson's disease with mild dementia and mild cognitive impairment: Frequency and neuropsychological/neuropsychiatric correlates.

PubMed

Orfei, Maria Donata; Assogna, Francesca; Pellicano, Clelia; Pontieri, Francesco Ernesto; Caltagirone, Carlo; Pierantozzi, Mariangela; Stefani, Alessandro; Spalletta, Gianfranco

2018-04-17

Anosognosia is a multidimensional phenomenon with detrimental effects on patients' illness course, therapy compliance and quality of life. We aimed at investigating anosognosia for cognitive and behavioral symptoms in Parkinson's Disease (PD) with dementia (PDD) and, for the first time, in PD with Mild Cognitive Impairment (MCI-PD). Community dwelling subjects (47 mild PDD, 136 multidomain MCI-PD (mdMCI-PD), 5 single domain MCI-PD (sdMCI-PD), and 197 PD without cognitive impairment (noCI-PD) were enrolled in a cross-sectional design study. All the subjects were administered the Anosognosia Questionnaire for Dementia, the Mental Deterioration Battery and a number of neuropsychiatric inventories. A diagnosis of anosognosia was made in 36% of patients with mild PDD and 16% with mdMCI-PD, whether it was negligible in sdMCI-PD and noCI-PD. Higher severity of anosognosia for cognitive impairment was also found in PDD and in mdMCI-PD. SdMCI-PD had the lower severity of anosognosia for cognitive impairment. Higher anosognosia for cognitive impairment was associated to lower depression in noCI-PD (r = -0.227, p = 0.0013) and mdMCI-PD (r = -0.266, p = 0.0016), and to reduced hedonic tone in noCI-PD (r = -0.191, p = 0.0071). Greater anosognosia was associated to lower executive performances in PDD (r = 0.424, p = 0.0074). Anosognosia for non-motor symptoms is frequent in PD patients with mild dementia or mdMCI. Results confirm the role of neuropsychiatric characteristics in anosognosia also in PD, the high prevalence of anosognosia in neurodegenerative illnesses and suggest a common pathogenic path for anosognosia in different neurodegenerative and psychiatric disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Maternal depressive symptoms, dysfunctional cognitions, and infant night waking: the role of maternal nighttime behavior.

PubMed

Teti, Douglas M; Crosby, Brian

2012-01-01

Mechanisms were examined to clarify relations between maternal depressive symptoms, dysfunctional cognitions, and infant night waking among 45 infants (1-24 months) and their mothers. A mother-driven mediational model was tested in which maternal depressive symptoms and dysfunctional cognitions about infant sleep predicted infant night waking via their impact on mothers' bedtime and nighttime behavior with infants (from video). Two infant-driven mediational models were also examined, in which infant night waking predicted maternal depressive symptoms, or dysfunctional cognitions, via their impact on nighttime maternal behavior. Stronger support for the mother-driven model was obtained, which was further supported by qualitative observations from video-recordings. This study provides important insights about maternal depression's effects on nighttime parenting, and how such parenting affects infant sleep. © 2012 The Authors. Child Development © 2012 Society for Research in Child Development, Inc.

The Cognitive and Neural Expression of Semantic Memory Impairment in Mild Cognitive Impairment and Early Alzheimer's Disease

ERIC Educational Resources Information Center

Joubert, Sven; Brambati, Simona M.; Ansado, Jennyfer; Barbeau, Emmanuel J.; Felician, Olivier; Didic, Mira; Lacombe, Jacinthe; Goldstein, Rachel; Chayer, Celine; Kergoat, Marie-Jeanne

2010-01-01

Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to…

Validity of dietary eicosapentaenoic acid and docosahexaenoic acid intakes determined by interviewer-administrated food frequency questionnaire among older adults with mild-to-moderate cognitive impairment or dementia

USDA-ARS?s Scientific Manuscript database

Epidemiological research is increasingly focused on elderly populations, many of whom exhibit mild to moderate cognitive impairments. This presents a challenge for collection and interpretation of self-reported dietary data. There are few reports on the impact of cognitive function and dementia o...

Comparison of the MoCA and BEARNI tests for detection of cognitive impairment in in-patients with alcohol use disorders.

PubMed

Pelletier, Stéphanie; Alarcon, Régis; Ewert, Valérie; Forest, Margot; Nalpas, Bertrand; Perney, Pascal

2018-06-01

Screening of cognitive impairment is a major challenge in alcoholics seeking treatment, since cognitive dysfunction may impair the overall efficacy of rehabilitation programs and consequently increase relapse rate. We compared the performance of two screening tools: the MoCA (Montreal Cognitive Assessment), which is widely used in patients with neurological diseases and already used in patients with alcohol use disorder (AUD), and the BEARNI (Brief Evaluation of Alcohol-Related Neuropsychological Impairments), a recent test specifically developed for the alcoholic population. We compared the sensitivity and specificity of the MoCA and the BEARNI in a sample of AUD patients with and without cognitive impairment assessed by a battery of neuropsychological tests. Ninety patients were included. There were 67 men and 23 women aged 48.9 ± 9.6 years. According to the neuropsychological tests, 51.1% of patients had no cognitive impairment, while it was mild or moderate to severe in 31.1 and 17.8%, respectively. The BEARNI sensitivity was extremely high (1.0), since all patients with cognitive impairment were identified, but its specificity was very low (0.04). The MoCA had a lower sensitivity (0.79) than the BEARNI, but its specificity was significantly better (0.65). A detailed analysis of the BEARNI scores showed a discrepancy between the qualitative and quantitative interpretation of the test which could, at least in part, explain its low specificity. Both the MoCA and the BEARNI are screening tools which identified alcoholic patients with cognitive impairment. However, in routine use, the MoCA appeared to be more appropriate given the low specificity of the BEARNI. Copyright © 2018 Elsevier B.V. All rights reserved.

Examination of the Clinicopathologic Continuum of Alzheimer Disease in the Autopsy Cohort of the National Alzheimer Coordinating Center

PubMed Central

Serrano-Pozo, Alberto; Qian, Jing; Monsell, Sarah E.; Frosch, Matthew P.; Betensky, Rebecca A.; Hyman, Bradley T.

2014-01-01

To test the hypothesis that Alzheimer disease (AD) is a clinical and pathologic continuum between normal aging and end-stage dementia, we selected a convenience sample of subjects from the National Alzheimer Coordinating Center 2005 to 2012 autopsy cohort (n = 2,083) with the last clinical evaluation within 2 years before autopsy and no other primary neuropathologic diagnosis. Demographic and neuropathologic characteristics were correlated with the Clinical Dementia Rating–Sum of Boxes in the 835 subjects meeting these criteria. Both neuritic plaques and neurofibrillary tangles independently predicted Clinical Dementia Rating–Sum of Boxes. Severe small-vessel disease, severe amyloid angiopathy, and hippocampal sclerosis were also independently associated with the degree of cognitive impairment. By contrast, education was a strong independent protective factor against cognitive deficits. The cause of mild to moderate dementia remained uncertain in 14% of the patients. Inverse probability weighting suggests the generalizability of these results to nonautopsied cohorts. These data indicate that plaques and tangles independently contribute to cognitive impairment, that concurrent vascular disease strongly correlates with cognitive dysfunction even in a sample selected to represent the AD pathologic continuum, and that education further modifies clinical expression. Thus, multiple concomitant etiologies of brain damage and premorbid characteristics contribute to the uncertainty of AD clinicopathologic correlations based only on tangles and plaques. PMID:24226270

Workers on transformation of the shelter object of the Chernobyl nuclear power plant into an ecologically-safe system show qEEG abnormalities and cognitive dysfunctions: A follow-up study.

PubMed

Loganovsky, Konstantyn; Perchuk, Iryna; Marazziti, Donatella

2016-12-01

The present study aimed at assessing bioelectric activity and cognitive functions in the workers on the conversion project of the "Shelter" object (SO) of the Chernobyl nuclear power plant into an environmentally safe system. A total of 196 men were included and examined before (t0) and after (t1) working on the SO in the period 2004-2008. They underwent a qEEG and a battery of neuropsychological and psychiatric assessments. At t1, the organized type of qEEG shifted towards the disorganized one. An increase of spectral δ-power in the left frontotemporal area, of θ- and α-power in the left temporal area, with redistribution of α-activity to the front and reduction of dominant frequency in the left temporal area, were registered. Further, neurocognitive tests revealed the presence of mild cognitive disorders at t1. Interestingly, those subjects previously exposed to radiation with no consequences, were more resistant to these detrimental effects. Taken together, the disturbances observed may be considered as cognitive symptoms of a chronic fatigue syndrome resulting from the exposure to ionizing radiation. Simple and non-invasive assessments, such as those performed by us, may be helpful to detect early brain changes caused by the presence of radiological risk factors.

Examination of the clinicopathologic continuum of Alzheimer disease in the autopsy cohort of the National Alzheimer Coordinating Center.

PubMed

Serrano-Pozo, Alberto; Qian, Jing; Monsell, Sarah E; Frosch, Matthew P; Betensky, Rebecca A; Hyman, Bradley T

2013-12-01

To test the hypothesis that Alzheimer disease (AD) is a clinical and pathologic continuum between normal aging and end-stage dementia, we selected a convenience sample of subjects from the National Alzheimer Coordinating Center 2005 to 2012 autopsy cohort (n = 2,083) with the last clinical evaluation within 2 years before autopsy and no other primary neuropathologic diagnosis. Demographic and neuropathologic characteristics were correlated with the Clinical Dementia Rating-Sum of Boxes in the 835 subjects meeting these criteria. Both neuritic plaques and neurofibrillary tangles independently predicted Clinical Dementia Rating-Sum of Boxes. Severe small-vessel disease, severe amyloid angiopathy, and hippocampal sclerosis were also independently associated with the degree of cognitive impairment. By contrast, education was a strong independent protective factor against cognitive deficits. The cause of mild to moderate dementia remained uncertain in 14% of the patients. Inverse probability weighting suggests the generalizability of these results to nonautopsied cohorts. These data indicate that plaques and tangles independently contribute to cognitive impairment, that concurrent vascular disease strongly correlates with cognitive dysfunction even in a sample selected to represent the AD pathologic continuum, and that education further modifies clinical expression. Thus, multiple concomitant etiologies of brain damage and premorbid characteristics contribute to the uncertainty of AD clinicopathologic correlations based only on tangles and plaques.

Divergent regional patterns of cerebral hypoperfusion and gray matter atrophy in mild cognitive impairment patients.

PubMed

Wirth, Miranka; Pichet Binette, Alexa; Brunecker, Peter; Köbe, Theresa; Witte, A Veronica; Flöel, Agnes

2017-03-01

Reductions of cerebral blood flow and gray matter structure have been implicated in early pathogenesis of Alzheimer's disease, potentially providing complementary information. The present study evaluated regional patterns of cerebral hypoperfusion and atrophy in patients with mild cognitive impairment and healthy older adults. In each participant, cerebral perfusion and gray matter structure were extracted within selected brain regions vulnerable to Alzheimer's disease using magnetic resonance imaging. Measures were compared between diagnostic groups with/without adjustment for covariates. In mild cognitive impairment patients, cerebral blood flow was significantly reduced in comparison with healthy controls in temporo-parietal regions and the basal ganglia in the absence of local gray matter atrophy. By contrast, gray matter structure was significantly reduced in the hippocampus in the absence of local hypoperfusion. Both, cerebral perfusion and gray matter structure were significantly reduced in the entorhinal and isthmus cingulate cortex in mild cognitive impairment patients compared with healthy older adults. Our results demonstrated partly divergent patterns of temporo-parietal hypoperfusion and medial-temporal atrophy in mild cognitive impairment patients, potentially indicating biomarker sensitivity to dissociable pathological mechanisms. The findings support applicability of cerebral perfusion and gray matter structure as complementary magnetic resonance imaging-based biomarkers in early Alzheimer's disease detection, a hypothesis to be further evaluated in longitudinal studies.

Anxiety symptoms and risk of dementia and mild cognitive impairment in the oldest old women.

PubMed

Kassem, Ahmed M; Ganguli, Mary; Yaffe, Kristine; Hanlon, Joseph T; Lopez, Oscar L; Wilson, John W; Ensrud, Kristine; Cauley, Jane A

2018-04-01

Research is limited and findings conflict regarding anxiety as a predictor of future cognitive decline in the oldest old persons. We examined the relationship between levels of and changes in anxiety symptoms, and subsequent dementia and mild cognitive impairment (MCI) in the oldest old women. We conducted secondary analyses of data collected from 1425 community-dwelling women (mean age = 82.8, SD ±3.1 years) followed on average for five years. The Goldberg Anxiety Scale was used to assess anxiety symptoms at baseline, and an expert clinical panel adjudicated dementia and MCI at follow-up. Participants with probable cognitive impairment at baseline were excluded. At baseline, 190 (13%) women had moderate/severe anxiety symptoms and 403 (28%) had mild anxiety symptoms. Compared with those with no anxiety symptoms at baseline, women with mild anxiety symptoms were more likely to develop dementia at follow-up (multivariable-adjusted odds ratio = 1.66, 95% confidence interval 1.12-2.45). No significant association was observed between anxiety symptoms and MCI. In the oldest old women, our findings suggest that mild anxiety symptoms may predict future risk of dementia, but not MCI. Future studies should explore potential biological mechanisms underlying associations of anxiety with cognitive impairment.

Cognitive Impairment and Pain Among Nursing Home Residents With Cancer.

PubMed

Dubé, Catherine E; Mack, Deborah S; Hunnicutt, Jacob N; Lapane, Kate L

2018-06-01

The prevalence of pain and its management has been shown to be inversely associated with greater levels of cognitive impairment. To evaluate whether the documentation and management of pain varies by level of cognitive impairment among nursing home residents with cancer. Using a cross-sectional study, we identified all newly admitted U.S. nursing home residents with a cancer diagnosis in 2011-2012 (n = 367,462). Minimum Data Set 3.0 admission assessment was used to evaluate pain/pain management in the past five days and cognitive impairment (assessed via the Brief Interview for Mental Status or the Cognitive Performance Scale for 91.6% and 8.4%, respectively). Adjusted prevalence ratios with 95% CI were estimated from robust Poisson regression models. For those with staff-assessed pain, pain prevalence was 55.5% with no/mild cognitive impairment and 50.5% in those severely impaired. Pain was common in those able to self-report (67.9% no/mild, 55.9% moderate, and 41.8% severe cognitive impairment). Greater cognitive impairment was associated with reduced prevalence of any pain (adjusted prevalence ratio severe vs. no/mild cognitive impairment; self-assessed pain 0.77; 95% CI 0.76-0.78; staff-assessed pain 0.96; 95% CI 0.93-0.99). Pharmacologic pain management was less prevalent in those with severe cognitive impairment (59.4% vs. 74.9% in those with no/mild cognitive impairment). In nursing home residents with cancer, pain was less frequently documented in those with severe cognitive impairment, which may lead to less frequent use of treatments for pain. Techniques to improve documentation and treatment of pain in nursing home residents with cognitive impairment are needed. Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.

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.

A unifying theory for cognitive abnormalities in functional neurological disorders, fibromyalgia and chronic fatigue syndrome: systematic review.

PubMed

Teodoro, Tiago; Edwards, Mark J; Isaacs, Jeremy D

2018-05-07

Functional cognitive disorder (FCD) describes cognitive dysfunction in the absence of an organic cause. It is increasingly prevalent in healthcare settings yet its key neuropsychological features have not been reported in large patient cohorts. We hypothesised that cognitive profiles in fibromyalgia (FM), chronic fatigue syndrome (CFS) and functional neurological disorders (FNDs) would provide a template for characterising FCD. We conducted a systematic review of studies with cognition-related outcomes in FM, CFS and FND. We selected 52 studies on FM, 95 on CFS and 39 on FND. We found a general discordance between high rates of subjective cognitive symptoms, including forgetfulness, distractibility and word-finding difficulties, and inconsistent objective neuropsychological deficits. Objective deficits were reported, including poor selective and divided attention, slow information processing and vulnerability to distraction. In some studies, cognitive performance was inversely correlated with pain, exertion and fatigue. Performance validity testing demonstrated poor effort in only a minority of subjects, and patients with CFS showed a heightened perception of effort. The cognitive profiles of FM, CFS and non-cognitive FND are similar to the proposed features of FCD, suggesting common mechanistic underpinnings. Similar findings have been reported in patients with mild traumatic brain injury and whiplash. We hypothesise that pain, fatigue and excessive interoceptive monitoring produce a decrease in externally directed attention. This increases susceptibility to distraction and slows information processing, interfering with cognitive function, in particular multitasking. Routine cognitive processes are experienced as unduly effortful. This may reflect a switch from an automatic to a less efficient controlled or explicit cognitive mode, a mechanism that has also been proposed for impaired motor control in FND. These experiences might then be overinterpreted due to memory perfectionism and heightened self-monitoring of cognitive performance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Olfactory Dysfunction as a Global Biomarker for Sniffing out Alzheimer's Disease: A Meta-Analysis.

PubMed

Kotecha, Alisha M; Corrêa, Angelo D C; Fisher, Kim M; Rushworth, Jo V

2018-04-13

Cases of Alzheimer's disease (AD) are rising exponentially due to increasing global life expectancy. There are approximately 50 million sufferers worldwide, with prevalence rising most rapidly in low-income countries such as Africa and Asia. There is currently no definite diagnosis of AD until after death, thus an early biomarker for AD is urgently required in order to administer timelier and more effective interventions. Olfactory dysfunction (problems with the sense of smell) is one of the earliest, preclinical symptoms observed in AD. Olfaction is a promising early biomarker for use worldwide as it is easy, cheap to measure, and not reliant on specialist clinicians or laboratory analysis. We carried out a meta-analysis to determine the credibility of olfaction in diagnosing AD in the preclinical stages, by comparing olfaction in healthy controls against AD patients and patients with mild cognitive impairment (MCI). Data from 10 articles were subjected to two comparative meta-analyses. In the case of AD, the results illustrated that the overall magnitude of effect size was more apparent, d = -1.63, 95% CI [-1.95, -1.31], in comparison to that of MCI, d = -0.81, 95% CI [-1.08, -0.55]. This shows that olfaction worsens progressively as patients progress from MCI to AD, highlighting the potential for olfactory dysfunction to identify AD in the preclinical stages prior to MCI.

Objective Cognitive Functioning in Self-reported Habitual Short Sleepers not Reporting Daytime Dysfunction: Examination of Impulsivity via Delay Discounting.

PubMed

Curtis, Brian J; Williams, Paula G; Anderson, Jeffrey S

2018-05-30

1) Examine performance on an objective measure of reward-related cognitive impulsivity (delay discounting) among self-reported habitual short sleepers and medium (i.e., recommended 7-9 hours) length sleepers either reporting or not reporting daytime dysfunction; 2) Inform the debate regarding what type and duration of short sleep (e.g., 21 to 24 hours of total sleep deprivation, self-reported habitual short sleep duration) meaningfully influences cognitive impulsivity; 3) Compare the predictive utility of sleep duration and perceived dysfunction to other factors previously shown to influence cognitive impulsivity via delay discounting performance (age, income, education, and fluid intelligence). We analyzed data from 1,190 adults from the Human Connectome Project database. Participants were grouped on whether they reported habitual short (≤ 6 hours) vs. medium length (7-9 hours) sleep duration and whether they perceived daytime dysfunction using the Pittsburgh Sleep Quality Index. All short sleepers exhibited increased delay discounting compared to all medium length sleepers, regardless of perceived dysfunction. Of the variables examined, self-reported sleep duration was the strongest predictor of delay discounting behavior between groups and across all 1,190 participants. Individuals who report habitual short sleep are likely to exhibit increased reward-related cognitive impulsivity regardless of perceived sleep-related daytime impairment. Therefore, there is reason to suspect that these individuals exhibit more daytime dysfunction, in the form of reward-related cognitive impulsivity, than they may assume. Current findings suggest that assessment of sleep duration over the prior month has meaningful predictive utility for human reward-related impulsivity.

Gap junctional intercellular communication dysfunction mediates the cognitive impairment induced by cerebral ischemia-reperfusion injury: PI3K/Akt pathway involved.

PubMed

Zhou, Shujun; Fang, Zheng; Wang, Gui; Wu, Song

2017-01-01

Cerebral ischemia/reperfusion (I/R) injury causes hippocampal apoptosis and cognitive impairment, and the dysfunction of gap junction intercellular communication (GJIC) may contribute to the cognitive impairment. We aim to examine the impact of cerebral I/R injury on cognitive impairment, the role of GJIC dysfunction in the rat hippocampus and the involvement of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) pathway. Rats were subjected to a cerebral I/R procedure and underwent cognitive assessment with the novel object recognition and Morris Water Maze tasks. The distance of Lucifer Yellow dye transfer and the Cx43 protein were examined to measure GJIC. Neural apoptosis was assessed with the terminal deoxynucleotide-transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) method. After rats received inhibitors of the PI3K/Akt pathway, GJIC and cognitive ability were measured again. GJIC promotion by ZP123 significantly reversed cognitive impairment and hippocampal apoptosis induced by cerebral I/R, while the inhibition of GJIC by octanol significantly facilitated cognitive impairment and hippocampal apoptosis. The phosphorylation of Akt was enhanced by cerebral I/R and octanol but inhibited by ZP123. The inhibition of the PI3K/Akt pathway significantly suppressed GJIC and cognitive impairment. The PI3K/Akt pathway is involved in cognitive impairment caused by gap junctional communication dysfunction in the rat hippocampus after ischemia-reperfusion injury.

Facial recognition in primary focal dystonia.

PubMed

Rinnerthaler, Martina; Benecke, Cord; Bartha, Lisa; Entner, Tanja; Poewe, Werner; Mueller, Joerg

2006-01-01

The basal ganglia seem to be involved in emotional processing. Primary dystonia is a movement disorder considered to result from basal ganglia dysfunction, and the aim of the present study was to investigate emotion recognition in patients with primary focal dystonia. Thirty-two patients with primary cranial (n=12) and cervical (n=20) dystonia were compared to 32 healthy controls matched for age, sex, and educational level on the facially expressed emotion labeling (FEEL) test, a computer-based tool measuring a person's ability to recognize facially expressed emotions. Patients with cognitive impairment or depression were excluded. None of the patients received medication with a possible cognitive side effect profile and only those with mild to moderate dystonia were included. Patients with primary dystonia showed isolated deficits in the recognition of disgust (P=0.007), while no differences between patients and controls were found with regard to the other emotions (fear, happiness, surprise, sadness, and anger). The findings of the present study add further evidence to the conception that dystonia is not only a motor but a complex basal ganglia disorder including selective emotion recognition disturbances. Copyright (c) 2005 Movement Disorder Society.

Development of involuntary movements after ventriculoperitoneal shunting for normal pressure hydrocephalus in a patient with chronic-phase thalamic haemorrhage.

PubMed

Shindo, Keiichiro; Kondo, Takeo; Sugiyama, Ken; Nishijima, Kazunori; Furusawa, Yoshihito; Mori, Takayuki; Izumi, Shin-Ichi

2007-10-01

Delayed-onset involuntary movements have been described after thalamic stroke. We treated a patient with involuntary movements that increased after ventriculoperitoneal shunting (VPS) for normal pressure hydrocephalus (NPH) following thalamic haemorrage. One and one-half years after right thalamic and intraventricular haemorrhage, NPH suggested clinical evaluation and neuroimaging studies in a 56-year-old man. Hemidystonia and pseudochoreoathetosis were evident in the left arm, leg and trunk. Proprioceptive impairment and mild cerebellar dysfunction affected the left upper and lower extremity. Yet the patient could walk unassisted and carry out activities of daily living (ADL) rated as 90 points according to the Barthel Index (BI). Lumbar puncture lessened both gait disturbance and cognitive impairment. After VPS, cognition and urinary continence improved, but involuntary movements worsened, precluding unaided ambulation and decreasing the BI score to 65 points. Computed tomography after VPS showed resolution of NPH, while single-photon emission computed tomography showed increased cerebral blood flow after VPS. Increased cerebral blood flow after VPS is suspected to have promoted development of abnormal neuronal circuitry.

Effect of acute mild dehydration on cognitive-motor performance in golf.

PubMed

Smith, Mark F; Newell, Alex J; Baker, Mistrelle R

2012-11-01

Whether mild dehydration (-1 to 3% body mass change [ΔBM]) impairs neurophysiological function during sport-specific cognitive-motor performance has yet to be fully elucidated. To investigate this within a golfing context, 7 low-handicap players (age: 21 ± 1.1 years; mass: 76.1 ± 11.8 kg; stature: 1.77 ± 0.07 m; handicap: 3.0 ± 1.2) completed a golf-specific motor and cognitive performance task in a euhydrated condition (EC) and dehydrated condition (DC) (randomized counterbalanced design; 7-day interval). Dehydration was controlled using a previously effective 12-hour fluid restriction, monitored through ΔBM and urine color assessment (UCOL). Mild dehydration reduced the mean BM by 1.5 ± 0.5% (p = 0.01), with UCOL increasing from 2 (EC) to 4 (DC) (p = 0.02). Mild dehydration significantly impaired motor performance, expressed as shot distance (114.6 vs. 128.6 m; p < 0.001) and off-target accuracy (7.9 vs. 4.1 m; p = 0.001). Cognitive performance, expressed as the mean error in distance judgment to target increased from 4.1 ± 3.0 m (EC) to 8.8 ± 4.7 m (DC) (p < 0.001). The findings support those of previous research that indicates mild dehydration (-1 to 2% ΔBM) significantly impairs cognitive-motor task performance. This study is the first to show that mild dehydration can impair distance, accuracy, and distance judgment during golf performance.

Awareness of Mild Cognitive Impairment and Mild Alzheimer's Disease Dementia Diagnoses Associated With Lower Self-Ratings of Quality of Life in Older Adults.

PubMed

Stites, Shana D; Karlawish, Jason; Harkins, Kristin; Rubright, Jonathan D; Wolk, David

2017-10-01

This study examined how awareness of diagnostic label impacted self-reported quality of life (QOL) in persons with varying degrees of cognitive impairment. Older adults (n = 259) with normal cognition, Mild Cognitive Impairment (MCI), or mild Alzheimer's disease dementia (AD) completed tests of cognition and self-report questionnaires that assessed diagnosis awareness and multiple domains of QOL: cognitive problems, activities of daily living, physical functioning, mental wellbeing, and perceptions of one's daily life. We compared measures of QOL by cognitive performance, diagnosis awareness, and diagnostic group. Persons with MCI or AD who were aware of their diagnosis reported lower average satisfaction with daily life (QOL-AD), basic functioning (BADL Scale), and physical wellbeing (SF-12 PCS), and more difficulties in daily life (DEM-QOL) than those who were unaware (all p ≤ .007). Controlling for gender, those expecting their condition to worsen over time reported greater depression (GDS), higher stress (PSS), lower quality of daily life (QOL-AD, DEM-QOL), and more cognitive difficulties (CDS) compared to others (all p < .05). Persons aware of their diagnostic label-either MCI or AD-and its prognosis report lower QOL than those unaware of these facts about themselves. These relationships are independent of the severity of cognitive impairment. © The Author 2017. 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.

Poor Decision Making Is a Consequence of Cognitive Decline among Older Persons without Alzheimer’s Disease or Mild Cognitive Impairment

PubMed Central

Boyle, Patricia A.; Yu, Lei; Wilson, Robert S.; Gamble, Keith; Buchman, Aron S.; Bennett, David A.

2012-01-01

Objective Decision making is an important determinant of health and well-being across the lifespan but is critical in aging, when many influential decisions are made just as cognitive function declines. Increasing evidence suggests that older adults, even those without dementia, often make poor decisions and are selectively vulnerable to scams. To date, however, the factors associated with poor decision making in old age are unknown. The objective of this study was to test the hypothesis that poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment. Methods Participants were 420 non-demented persons from the Memory and Aging Project, a longitudinal, clinical-pathologic cohort study of aging in the Chicago metropolitan area. All underwent repeated cognitive evaluations and subsequently completed assessments of decision making and susceptibility to scams. Decision making was measured using 12 items from a previously established performance-based measure and a self-report measure of susceptibility to scams. Results Cognitive function data were collected over an average of 5.5 years prior to the decision making assessment. Regression analyses were used to examine whether the prior rate of cognitive decline predicted the level of decision making and susceptibility to scams; analyses controlled for age, sex, education, and starting level of cognition. Among 420 persons without dementia, more rapid cognitive decline predicted poorer decision making and increased susceptibility to scams (p’s<0.001). Further, the relations between cognitive decline, decision making and scams persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or even mild cognitive impairment). Conclusions Poor decision making is a consequence of cognitive decline among older persons without Alzheimer’s disease or mild cognitive impairment, those widely considered “cognitively healthy.” These findings suggest that even very subtle age-related changes in cognition have detrimental effects on judgment. PMID:22916287

Changes in cognitive function and brain glucose metabolism in elderly women with subjective memory impairment: a 24-month prospective pilot study.

PubMed

Jeong, H S; Park, J S; Song, I U; Chung, Y A; Rhie, S J

2017-01-01

Subjective memory impairment (SMI) may precede mild cognitive impairment (MCI) stage and would offer an earlier therapeutic opportunity than MCI would. However, it is not clear whether complaints of forgetfulness are truly reflective of objective memory dysfunction or of impairments in other cognitive domains. The aim of this current longitudinal study was to investigate changes in various cognitive functions and in regional cerebral metabolic rate of glucose (rCMRglc) among elderly women with SMI. Clinical evaluation, comprehensive neuropsychological test, and 18 F-fluoro-2-deoxyglucose positron emission tomography scans were conducted on 24 women with SMI at the baseline and 24-month follow-up. Changes in the cognitive domain scores and rCMRglc were assessed, and the relationships between them were analyzed. All participants stayed in SMI all the way till the follow-up, not converted to MCI or dementia. A significant reduction in executive function was found (mean difference in z-score: -0.21, P = 0.02) without changes in other cognitive domains. Declines in rCMRglc were detected in the left superior temporal gyrus, right posterior cingulate gyrus, left parahippocampal gyrus, right lingual gyrus, and right angular gyrus. The change in executive function had a positive correlation with the percent change of rCMRglc in the right posterior cingulate gyrus (β = 0.43, P = 0.02). Our findings suggest that elderly women with SMI symptoms should be carefully monitored for declines in executive function and related brain glucose metabolism over time. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Analysis of memory deficits following chemotherapy in breast cancer survivors: evidence from the doors and people test.

PubMed

Prokasheva, Svetlana; Faran, Yifat; Cwikel, Julie; Geffen, David B

2011-01-01

Studies of cognitive effects of chemotherapy among breast cancer patients show that not all women who are exposed to chemotherapy develop cognitive dysfunction and that the observed declines in cognitive functioning may be quite subtle. The use of measures that are sensitive to subtle cognitive decline are recommended yet rarely used among clinical populations. The purpose of this study is to specify the types of memory changes observed among breast cancer survivors treated with chemotherapy and tamoxifen, by using an analytic test of memory, the Doors and People test, which uses age-adjusted norms. The participants were 40 women who were survivors of breast cancer, 20 of whom had completed chemotherapy treatment and 20 women who were treated only with tamoxifen. There were no significant differences between the two groups in overall scores and in all four subtests: visual memory, verbal memory, recall, and recognition measured by age-adjusted scores. Forty percent of patients in both of the groups were classified as having mild impairment in episodic memory. No between-group differences were found in the frequency of subjective, cognitive complaints. Subjective complaints were reported by 69% of patients but were unrelated to objective performance. Memory deficits were observed in breast cancer patients who receive either chemotherapy or tamoxifen alone compared to age-adjusted norms. The Doors and People Test is a sensitive measure of memory deficits that is feasible for use with clinical populations of breast cancer patients in order to monitor changes in cognitive function.

Assessment of Alzheimer's disease risk with functional magnetic resonance imaging: an arterial spin labeling study.

PubMed

Bangen, Katherine J; Restom, Khaled; Liu, Thomas T; Wierenga, Christina E; Jak, Amy J; Salmon, David P; Bondi, Mark W

2012-01-01

Functional magnetic resonance imaging (fMRI) of older adults at risk for Alzheimer's disease (AD) by virtue of their cognitive (i.e., mild cognitive impairment [MCI]) and/or genetic (i.e., apolipoprotein E [APOE] ε4 allele) status demonstrate divergent brain response patterns during memory encoding across studies. Using arterial spin labeling MRI, we examined the influence of AD risk on resting cerebral blood flow (CBF) as well as the CBF and blood oxygenation level dependent (BOLD) signal response to memory encoding in the medial temporal lobes (MTL) in 45 older adults (29 cognitively normal [14 APOE ε4 carriers and 15 noncarriers]; 16 MCI [8 APOE ε4 carriers, 8 noncarriers]). Risk groups were comparable in terms of mean age, years of education, gender distribution, and vascular risk burden. Individuals at genetic risk for AD by virtue of the APOE ε4 allele demonstrated increased MTL resting state CBF relative to ε4 noncarriers, whereas individuals characterized as MCI showed decreased MTL resting state CBF relative to their cognitively normal peers. For percent change CBF, there was a trend toward a cognitive status by genotype interaction. In the cognitively normal group, there was no difference in percent change CBF based on APOE genotype. In contrast, in the MCI group, APOE ε4 carriers demonstrated significantly greater percent change in CBF relative to ε4 noncarriers. No group differences were found for BOLD response. Findings suggest that abnormal resting state CBF and CBF response to memory encoding may be early indicators of brain dysfunction in individuals at risk for developing AD.

Psychometric Properties of the German Version of the Child Post-Traumatic Cognitions Inventory (CPTCI-GER).

PubMed

de Haan, Anke; Petermann, Franz; Meiser-Stedman, Richard; Goldbeck, Lutz

2016-02-01

Dysfunctional trauma-related cognitions are associated with posttraumatic stress disorder (PTSD). The psychometric properties of the German version of the Child Post-Traumatic Cognitions Inventory (CPTCI-GER) were assessed in a sample of 223 children and adolescents (7-16 years) with a history of different traumatic events. Confirmatory factor analyses supported the original two-factor structure--permanent and disturbing change (CPTCI-PC) and fragile person in a scary world (CPTCI-SW). The total scale and both subscales showed good internal consistency. Participants with PTSD had significantly more dysfunctional trauma-related cognitions than those without PTSD. Dysfunctional posttraumatic cognitions correlated significantly with posttraumatic stress symptoms (PTSS; r = .62), depression (r = .71), and anxiety (r = .67). The CPTCI-GER has good psychometric properties and may facilitate evaluation of treatments and further research on the function of trauma-related cognitions in children and adolescents. (Partial) correlations provide empirical support for the combined DSM-5 symptom cluster negative alterations in cognitions and mood.

Creativity on tap? Effects of alcohol intoxication on creative cognition.

PubMed

Benedek, Mathias; Panzierer, Lisa; Jauk, Emanuel; Neubauer, Aljoscha C

2017-11-01

Anecdotal reports link alcohol intoxication to creativity, while cognitive research highlights the crucial role of cognitive control for creative thought. This study examined the effects of mild alcohol intoxication on creative cognition in a placebo-controlled design. Participants completed executive and creative cognition tasks before and after consuming either alcoholic beer (BAC of 0.03) or non-alcoholic beer (placebo). Alcohol impaired executive control, but improved performance in the Remote Associates Test, and did not affect divergent thinking ability. The findings indicate that certain aspects of creative cognition benefit from mild attenuations of cognitive control, and contribute to the growing evidence that higher cognitive control is not always associated with better cognitive performance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Spatiotemporal Gait Characteristics Associated with Cognitive Impairment: A Multicenter Cross-Sectional Study, the Intercontinental "Gait, cOgnitiOn & Decline" Initiative.

PubMed

Beauchet, Olivier; Blumen, Helena M; Callisaya, Michele L; De Cock, Anne-Marie; Kressig, Reto W; Srikanth, Velandai; Steinmetz, Jean-Paul; Verghese, Joe; Allali, Gilles

2018-01-23

The study aims to determine the spatiotemporal gait parameters and/or their combination(s) that best differentiate between cognitively healthy individuals (CHI), patients with mild cognitive impairment (MCI) and those with mild and moderate dementia, regardless of the etiology of cognitive impairment. A total of 2099 participants (1015 CHI, 478 patients with MCI, 331 patients with mild dementia and 275 with moderate dementia) were selected from the intercontinental "Gait, cOgnitiOn & Decline" (GOOD) initiative, which merged different databases from seven cross-sectional studies. Mean values and coefficients of variation (CoV) of spatiotemporal gait parameters were recorded during usual walking with the GAITRite® system. The severity of cognitive impairment was associated with worse performance on all gait parameters. Stride velocity had the strongest association with cognitive impairment, regardless of cognitive status. High mean value and CoV of stride length characterized moderate dementia, whereas increased CoV of stride time was specific to MCI status. The findings support the existence of specific cognitive impairment-related gait disturbances with differences related to stages of cognitive impairment, which may be used to screen individuals with cognitive impairment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Piracetam improves mitochondrial dysfunction following oxidative stress

PubMed Central

Keil, Uta; Scherping, Isabel; Hauptmann, Susanne; Schuessel, Katin; Eckert, Anne; Müller, Walter E

2005-01-01

Mitochondrial dysfunction including decrease of mitochondrial membrane potential and reduced ATP production represents a common final pathway of many conditions associated with oxidative stress, for example, hypoxia, hypoglycemia, and aging. Since the cognition-improving effects of the standard nootropic piracetam are usually more pronounced under such pathological conditions and young healthy animals usually benefit little by piracetam, the effect of piracetam on mitochondrial dysfunction following oxidative stress was investigated using PC12 cells and dissociated brain cells of animals treated with piracetam. Piracetam treatment at concentrations between 100 and 1000 μM improved mitochondrial membrane potential and ATP production of PC12 cells following oxidative stress induced by sodium nitroprusside (SNP) and serum deprivation. Under conditions of mild serum deprivation, piracetam (500 μM) induced a nearly complete recovery of mitochondrial membrane potential and ATP levels. Piracetam also reduced caspase 9 activity after SNP treatment. Piracetam treatment (100–500 mg kg−1 daily) of mice was also associated with improved mitochondrial function in dissociated brain cells. Significant improvement was mainly seen in aged animals and only less in young animals. Moreover, the same treatment reduced antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and glutathione reductase) in aged mouse brain only, which are elevated as an adaptive response to the increased oxidative stress with aging. In conclusion, therapeutically relevant in vitro and in vivo concentrations of piracetam are able to improve mitochondrial dysfunction associated with oxidative stress and/or aging. Mitochondrial stabilization and protection might be an important mechanism to explain many of piracetam's beneficial effects in elderly patients. PMID:16284628

The influence of personality and dysfunctional sleep-related cognitions on the severity of insomnia.

PubMed

Park, Jang Ho; An, Hoyoung; Jang, Eun Sook; Chung, Seockhoon

2012-05-30

Previous findings suggest that personality traits and dysfunctional sleep-related cognitions may perpetuate insomnia, but findings concerning this have been scarce. Thus, we hypothesized that personality and sleep-related cognitions influence the severity of insomnia, and investigated the association personality and sleep-related cognitions had with various sleep-related parameters, including severity of insomnia. Forty-four patients with psychophysiological insomnia were assessed using The Temperament and Character Inventory, the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Dysfunctional Belief and Attitudes toward Sleep Scale, the Pre-Sleep Arousal Scale and the Hospital Anxiety and Depression Scale. Insomnia severity was significantly and positively correlated with harm avoidance, self-transcendence and sleep-related cognitions, and negatively correlated with novelty seeking, reward dependence, and cooperativeness. Dysfunctional sleep-related cognitions were positively correlated with insomnia severity and sleep quality. Stepwise multiple regression analysis showed that sleep-related cognitions, depression and reward dependence scores were significant determinants of insomnia severity, and that sleep-related cognitions and self-transcendence were significant positive determinants of sleep quality. Reward dependence, depression and sleep-related cognitions were associated with insomnia severity, and comparison with previous findings implied that 'internalizing behavior' and depression may be more plausible candidates for the link between personality and insomnia than anxiety. Considering the major role of cognitive-behavioral treatment (CBT) in the treatment of insomnia, assessment of these factors and management of sleep-related cognitions may help alleviate symptoms in patients with insomnia. Copyright © 2011 Elsevier Ltd. All rights reserved.

Age Effects on Cognitive and Physiological Parameters in Familial Caregivers of Alzheimer's Disease Patients

PubMed Central

Corrêa, Márcio Silveira; Giacobbo, Bruno Lima; Vedovelli, Kelem; de Lima, Daiane Borba; Ferrari, Pamela; Argimon, Irani Iracema de Lima; Walz, Julio Cesar

2016-01-01

Objectives Older familial caregivers of Alzheimer’s disease patients are subjected to stress-related cognitive and psychophysiological dysfunctions that may affect their quality of life and ability to provide care. Younger caregivers have never been properly evaluated. We hypothesized that they would show qualitatively similar cognitive and psychophysiological alterations to those of older caregivers. Method The cognitive measures of 17 young (31–58 years) and 18 old (63–84 years) caregivers and of 17 young (37–57 years) and 18 old (62–84 years) non-caregiver controls were evaluated together with their salivary cortisol and dehydroepiandrosterone (DHEA) levels, as measured by radioimmunoassays and ELISA assays of brain-derived neurotrophic factor (BDNF) in serum. Results Although younger caregivers had milder impairments in memory and executive functions than older caregivers, their performances fell to the same or lower levels as those of the healthy older controls. Decreases in DHEA and BDNF levels were correlated with the cognitive dysfunctions observed in the older and younger caregivers, respectively. Cortisol at 10PM increased in both caregiver groups. Discussion Younger caregivers were prone to cognitive impairments similar to older caregivers, although the degree and the neuropsychological correlates of the cognitive dysfunctions were somewhat different between the two groups. This work has implications for caregiver and care-recipient health and for research on the neurobiology of stress-related cognitive dysfunctions. PMID:27706235

A cognitive behavioural group therapy for patients diagnosed with mild cognitive impairment and their significant others: feasibility and preliminary results.

PubMed

Joosten-Weyn Banningh, Liesbeth W A; Kessels, Roy P C; Olde Rikkert, Marcel G M; Geleijns-Lanting, Caroline E; Kraaimaat, Floris W

2008-08-01

To evaluate the feasibility and present preliminary results of a cognitive behavioural group therapy for patients with mild cognitive impairment and their significant others. One group pretest-posttest design. Twenty-two patients with mild cognitive impairment and their significant others, running in four group programmes. The main goal of the cognitive behavioural group therapy was to strengthen adaptive behaviour in 10 weekly 2-hour sessions. Distress and mood: The RAND-36, Geriatric Depression Scale--short form; Acceptance and helplessness: Subscales Acceptance and Helplessness from the Illness Cognition Questionnaire; Marital satisfaction: Maudsley Marital Questionnaire; Alertness to memory failure and behaviour changes: Informant Questionnaire on Cognitive Decline in the Elderly and the Revised Memory and Behaviour Problems Checklist Burden. The burden of caregiving reported by the significant others: Sense of competence Questionnaire and Behaviour Problems Checklist Burden, Hindrance subscale. No changes were found on distress and mood measures in both patients and their significant others. Patients showed a significant increased level of acceptance (P<0.05) and a trend for an increased marital satisfaction (P<0.1). The significant others reported an increased awareness of memory and behavioural problems (P<0.05). Attendance was high, indicating a high motivation for this intervention. Preliminary results show evidence for positive changes after a cognitive behavioural group therapy for patients with mild cognitive impairment and their significant others. In addition, the developed programme is applicable and feasible. The programme's effectiveness should be studied further, with an estimated sample size of 70 couples in a controlled study design.

Primary Lateral Sclerosis.

PubMed

Statland, Jeffrey M; Barohn, Richard J; Dimachkie, Mazen M; Floeter, Mary Kay; Mitsumoto, Hiroshi

2015-11-01

Primary lateral sclerosis is characterized by insidious onset of progressive upper motor neuron dysfunction in the absence of clinical signs of lower motor neuron involvement. Patients experience stiffness; decreased balance and coordination; mild weakness; and, if the bulbar region is affected, difficulty speaking and swallowing, and emotional lability. The diagnosis is made based on clinical history, typical examination findings, and diagnostic testing negative for other causes of upper motor neuron dysfunction. Electromyogram is normal, or only shows mild neurogenic findings in a few muscles, not meeting El Escorial criteria. Treatment is largely supportive. Copyright © 2015 Elsevier Inc. All rights reserved.

Association Between Olfactory Dysfunction and Amnestic Mild Cognitive Impairment and Alzheimer Disease Dementia.

PubMed

Roberts, Rosebud O; Christianson, Teresa J H; Kremers, Walter K; Mielke, Michelle M; Machulda, Mary M; Vassilaki, Maria; Alhurani, Rabe E; Geda, Yonas E; Knopman, David S; Petersen, Ronald C

2016-01-01

To increase the opportunity to delay or prevent mild cognitive impairment (MCI) or Alzheimer disease (AD) dementia, markers of early detection are essential. Olfactory impairment may be an important clinical marker and predictor of these conditions and may help identify persons at increased risk. To examine associations of impaired olfaction with incident MCI subtypes and progression from MCI subtypes to AD dementia. Participants enrolled in the population-based, prospective Mayo Clinic Study of Aging between 2004 and 2010 were clinically evaluated at baseline and every 15 months through 2014. Participants (N = 1630) were classified as having normal cognition, MCI (amnestic MCI [aMCI] and nonamnestic MCI [naMCI]), and dementia. We administered the Brief Smell Identification Test (B-SIT) to assess olfactory function. Mild cognitive impairment, AD dementia, and longitudinal change in cognitive performance measures. Of the 1630 participants who were cognitively normal at the time of the smell test, 33 died before follow-up and 167 were lost to follow-up. Among the 1430 cognitively normal participants included, the mean (SD) age was 79.5 (5.3) years, 49.4% were men, the mean duration of education was 14.3 years, and 25.4% were APOE ε4 carriers. Over a mean 3.5 years of follow-up, there were 250 incident cases of MCI among 1430 cognitively normal participants. We observed an association between decreasing olfactory identification, as measured by a decrease in the number of correct responses in B-SIT score, and an increased risk of aMCI. Compared with the upper B-SIT quartile (quartile [Q] 4, best scores), hazard ratios (HRs) (95% CI) were 1.12 (0.65-1.92) for Q3 (P = .68); 1.95 (1.25-3.03) for Q2 (P = .003); and 2.18 (1.36-3.51) for Q1 (P = .001) (worst scores; P for trend <.001) after adjustment for sex and education, with age as the time scale. There was no association with naMCI. There were 64 incident dementia cases among 221 prevalent MCI cases. The B-SIT score also predicted progression from aMCI to AD dementia, with a significant dose-response with worsening B-SIT quartiles. Compared with Q4, HR (95% CI) estimates were 3.02 (1.06-8.57) for Q3 (P = .04); 3.63 (1.19-11.10) for Q2 (P = .02); and 5.20 (1.90-14.20) for Q1 (P = .001). After adjusting for key predictors of MCI risk, B-SIT (as a continuous measure) remained a significant predictor of MCI (HR, 1.10 [95% CI, 1.04-1.16]; P < .001) and improved the model concordance. Olfactory impairment is associated with incident aMCI and progression from aMCI to AD dementia. These findings are consistent with previous studies that have reported associations of olfactory impairment with cognitive impairment in late life and suggest that olfactory tests have potential utility for screening for MCI and MCI that is likely to progress.

Three-Dimensional Gray Matter Atrophy Mapping in Mild Cognitive Impairment and Mild Alzheimer Disease

PubMed Central

Apostolova, Liana G.; Steiner, Calen A.; Akopyan, Gohar G.; Dutton, Rebecca A.; Hayashi, Kiralee M.; Toga, Arthur W.; Cummings, Jeffrey L.; Thompson, Paul M.

2011-01-01

Background Alzheimer disease (AD) is the most common form of dementia worldwide. Mild cognitive impairment (MCI) is the recent terminology for patients with cognitive deficiencies in the absence of functional decline. Most patients with MCI harbor the pathologic changes of AD and demonstrate transition to dementia at a rate of 10% to 15% per year. Patients with AD and MCI experience progressive brain atrophy. Objective To analyze the structural magnetic resonance imaging data for 24 patients with amnestic MCI and 25 patients with mild AD using an advanced 3-dimensional cortical mapping technique. Design Cross-sectional cohort design. Patients/Methods We analyzed the structural magnetic resonance imaging data of 24 amnestic MCI (mean MMSE, 28.1; SD, 1.7) and 25 mild AD patients (all MMSE scores, >18; mean MMSE, 23.7; SD, 2.9) using an advanced 3-dimensional cortical mapping technique. Results We observed significantly greater cortical atrophy in patients with mild AD. The entorhinal cortex, right more than left lateral temporal cortex, right parietal cortex, and bilateral precuneus showed 15% more atrophy and the remainder of the cortex primarily exhibited 10% to 15% more atrophy in patients with mild AD than in patients with amnestic MCI. Conclusion There are striking cortical differences between mild AD and the immediately preceding cognitive state of amnestic MCI. Cortical areas affected earlier in the disease process are more severely affected than those that are affected late. Our method may prove to be a reliable in vivo disease-tracking technique that can also be used for evaluating disease-modifying therapies in the future. PMID:17923632

Rational Pharmacological Approaches for Cognitive Dysfunction and Depression in Parkinson’s Disease

PubMed Central

Sandoval-Rincón, Maritza; Sáenz-Farret, Michel; Miguel-Puga, Adán; Micheli, Federico; Arias-Carrión, Oscar

2015-01-01

Parkinson’s disease (PD) is not a single entity but rather a heterogeneous neurodegenerative disorder. The present study aims to conduct a critical systematic review of the literature to describe the main pharmacological strategies to treat cognitive dysfunction and major depressive disorder in PD patients. We performed a search of articles cited in PubMed from 2004 to 2014 using the following MeSH terms (Medical subject headings) “Parkinson disease”; “Delirium,” “Dementia,” “Amnestic,” “Cognitive disorders,” and “Parkinson disease”; “depression,” “major depressive disorder,” “drug therapy.” We found a total of 71 studies related to pharmacological treatment in cognitive dysfunction and 279 studies for pharmacological treatment in major depressive disorder. After fulfillment of all the inclusion and exclusion criteria, 13 articles remained for cognitive dysfunction and 11 for major depressive disorder, which are presented and discussed in this study. Further research into non-motor symptoms of PD may provide insights into mechanisms of neurodegeneration, and provide better quality of life by using rational drugs. PMID:25873910

Right ventricular dysfunction after resuscitation predicts poor outcomes in cardiac arrest patients independent of left ventricular function.

PubMed

Ramjee, Vimal; Grossestreuer, Anne V; Yao, Yuan; Perman, Sarah M; Leary, Marion; Kirkpatrick, James N; Forfia, Paul R; Kolansky, Daniel M; Abella, Benjamin S; Gaieski, David F

2015-11-01

Determination of clinical outcomes following resuscitation from cardiac arrest remains elusive in the immediate post-arrest period. Echocardiographic assessment shortly after resuscitation has largely focused on left ventricular (LV) function. We aimed to determine whether post-arrest right ventricular (RV) dysfunction predicts worse survival and poor neurologic outcome in cardiac arrest patients, independent of LV dysfunction. A single-center, retrospective cohort study at a tertiary care university hospital participating in the Penn Alliance for Therapeutic Hypothermia (PATH) Registry between 2000 and 2012. 291 in- and out-of-hospital adult cardiac arrest patients at the University of Pennsylvania who had return of spontaneous circulation (ROSC) and post-arrest echocardiograms. Of the 291 patients, 57% were male, with a mean age of 59 ± 16 years. 179 (63%) patients had LV dysfunction, 173 (59%) had RV dysfunction, and 124 (44%) had biventricular dysfunction on the initial post-arrest echocardiogram. Independent of LV function, RV dysfunction was predictive of worse survival (mild or moderate: OR 0.51, CI 0.26-0.99, p<0.05; severe: OR 0.19, CI 0.06-0.65, p=0.008) and neurologic outcome (mild or moderate: OR 0.33, CI 0.17-0.65, p=0.001; severe: OR 0.11, CI 0.02-0.50, p=0.005) compared to patients with normal RV function after cardiac arrest. Echocardiographic findings of post-arrest RV dysfunction were equally prevalent as LV dysfunction. RV dysfunction was significantly predictive of worse outcomes in post-arrest patients after accounting for LV dysfunction. Post-arrest RV dysfunction may be useful for risk stratification and management in this high-mortality population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Executive functioning of complicated-mild to moderate traumatic brain injury patients with frontal contusions.

PubMed

Ghawami, Heshmatollah; Sadeghi, Sadegh; Raghibi, Mahvash; Rahimi-Movaghar, Vafa

2017-01-01

Executive dysfunctions are among the most prevalent neurobehavioral sequelae of traumatic brain injuries (TBIs). Using culturally validated tests from the Delis-Kaplan Executive Function System (D-KEFS: Trail Making, Verbal Fluency, Design Fluency, Sorting, Twenty Questions, and Tower) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS: Rule Shift Cards, Key Search, and Modified Six Elements), the current study was the first to examine executive functioning in a group of Iranian TBI patients with focal frontal contusions. Compared with a demographically matched normative sample, the frontal contusion patients showed substantial impairments, with very large effect sizes (p ≤ .003, 1.56 < d < 3.12), on all the executive measures. Controlling for respective lower-level/fundamental conditions, the differences on the highest-level executive (cognitive switching) conditions were still significant. The frontal patients also committed more errors. Patients with lateral prefrontal (LPFC) contusions were qualitatively worst. For example, only the LPFC patients committed perseverative repetition errors. Altogether, our results support the notion that the frontal lobes, specifically the lateral prefrontal regions, play a critical role in cognitive executive functioning, over and above the contributions of respective lower-level cognitive abilities. The results provide clinical evidence for validity of the cross-culturally adapted versions of the tests.

Hormonal treatment, mild cognitive impairment and Alzheimer's disease

PubMed Central

Ryan, Joanne; Scali, Jaqueline; Carriere, Isabelle; Ritchie, Karen; Ancelin, Marie-Laure

2008-01-01

A plethora of in vitro and in vivo studies have supported the neuroprotective role of estrogens and their impact on the neurotransmitter systems implicated in cognition. Recent hormonal replacement therapy trials in non-demented post-menopausal women suggest a temporary positive effect (notably on verbal memory), and four meta-analyses converge to suggest a possible protective effect in relation to Alzheimer’s disease (reducing risk by 29 to 44%). However, data from the only large randomized controlled trial published to date, the Women’s Health Initiative Memory Study, did not confirm these observations and have even suggested an increase in dementia risk for women using hormonal replacement therapy compared to controls. Apart from methodological differences, one key short-coming of this trial has probably been the focus on late-onset (postmenopausal) hormonal changes, i.e. at a time when the neurodegenerative process has already begun and without taking into account individual lifetime exposure to hormone variability. Multifactorial models based on an exhaustive view of all hormonal events throughout the reproductive life (rather than on a specific exposure to a given steroid) together with other risk factors (notably genetic risk factors related to estrogen receptor polymorphisms) should be explored to clarify the role of hormonal risk factors, or protective factors for cognitive dysfunction and dementia. PMID:18072983

The Relations of Cognitive, Behavioral, and Physical Activity Variables to Depression Severity in Traumatic Brain Injury: Reanalysis of Data From a Randomized Controlled Trial.

PubMed

Bombardier, Charles H; Fann, Jesse R; Ludman, Evette J; Vannoy, Steven D; Dyer, Joshua R; Barber, Jason K; Temkin, Nancy R

To explore the relations of cognitive, behavioral, and physical activity variables to depression severity among people with traumatic brain injury (TBI) undergoing a depression treatment trial. Community. Adults (N = 88) who sustained complicated mild to severe TBI within the past 10 years, met criteria for major depressive disorder, and completed study measures. Randomized controlled trial. Participants were randomized to cognitive-behavioral therapy (n = 58) or usual care (n = 42). Outcomes were measured at baseline and 16 weeks. We combined the groups and used regressions to explore the relations among theoretical variables and depression outcomes. Depression severity was measured with the Hamilton Depression Rating Scale and Symptom Checklist-20. Theory-based measures were the Dysfunctional Attitudes Scale (DAS), Automatic Thoughts Questionnaire (ATQ), Environmental Rewards Observation Scale (EROS), and the International Physical Activity Questionnaire (IPAQ). Compared with non-TBI norms, baseline DAS and ATQ scores were high and EROS and IPAQ scores were low. All outcomes improved from baseline to 16 weeks except the DAS. The ATQ was an independent predictor of baseline depression. An increase in EROS scores was correlated with decreased depression. Increasing participation in meaningful roles and pleasant activities may be a promising approach to treating depression after TBI.

Decreased microvascular cerebral blood flow assessed by diffuse correlation spectroscopy after repetitive concussions in mice.

PubMed

Buckley, Erin M; Miller, Benjamin F; Golinski, Julianne M; Sadeghian, Homa; McAllister, Lauren M; Vangel, Mark; Ayata, Cenk; Meehan, William P; Franceschini, Maria Angela; Whalen, Michael J

2015-12-01

Repetitive concussions are associated with long-term cognitive dysfunction that can be attenuated by increasing the time intervals between concussions; however, biomarkers of the safest rest interval between injuries remain undefined. We hypothesize that deranged cerebral blood flow (CBF) is a candidate biomarker for vulnerability to repetitive concussions. Using a mouse model of human concussion, we examined the effect of single and repetitive concussions on cognition and on an index of CBF (CBFi) measured with diffuse correlation spectroscopy. After a single mild concussion, CBFi was reduced by 35±4% at 4 hours (P<0.01 versus baseline) and returned to preinjury levels by 24 hours. After five concussions spaced 1 day apart, CBFi was also reduced from preinjury levels 4 hours after each concussion but had returned to preinjury levels by 72 hours after the final concussion. Interestingly, in this repetitive concussion model, lower CBFi values measured both preinjury and 4 hours after the third concussion were associated with worse performance on the Morris water maze assessed 72 hours after the final concussion. We conclude that low CBFi measured either before or early on in the evolution of injury caused by repetitive concussions could be a useful predictor of cognitive outcome.

Applying a cognitive neuroscience perspective to the disorder of psychopathy.

PubMed

Blair, R J R

2005-01-01

Four models of psychopathy (frontal lobe dysfunction, response set modulation, fear dysfunction, and violence inhibition mechanism hypotheses) are reviewed from the perspective of cognitive neuroscience. Each model is considered both with respect to the psychopathy data and, more importantly, for the present purposes, with respect to the broader cognitive neuroscience fields to which the model refers (e.g., models of attention with respect to the response set modulation account and models of emotion with respect to the fear dysfunction and violence inhibition mechanism models). The paper concludes with an articulation of the more recent integrated emotion systems model, an account inspired both by recent findings in affective cognitive neuroscience as well as in the study of psychopathy. Some directions for future work are considered.

Estrogen replacement therapy, Alzheimer's disease, and mild cognitive impairment.

PubMed

Mulnard, Ruth A; Corrada, Marìa M; Kawas, Claudia H

2004-09-01

This article highlights the latest findings regarding estrogen replacement therapy in the treatment and prevention of Alzheimer's disease (AD) and mild cognitive impairment in women. Despite considerable evidence from observational studies, recent randomized clinical trials of conjugated equine estrogens, alone and in combination with progestin, have shown no benefit for either the treatment of established AD or for the short-term prevention of AD, mild cognitive impairment, or cognitive decline. Based on the evidence, there is no role at present for estrogen replacement therapy in the treatment or prevention of AD or cognitive decline, despite intriguing results from the laboratory and from observational studies. However, numerous questions remain about the biologic effects of estrogens on brain structure and function. Additional basic and clinical investigations are necessary to examine different forms and dosages of estrogens, other populations, and the relevance of timing and duration of exposure.

Cognitive Dysfunction in Major Depressive Disorder. A Translational Review in Animal Models of the Disease

PubMed Central

Darcet, Flavie; Gardier, Alain M.; Gaillard, Raphael; David, Denis J.; Guilloux, Jean-Philippe

2016-01-01

Major Depressive Disorder (MDD) is the most common psychiatric disease, affecting millions of people worldwide. In addition to the well-defined depressive symptoms, patients suffering from MDD consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Among cognitive symptoms, impairments in attention, working memory, learning and memory or executive functions are often reported. However, available data about the heterogeneity of MDD patients and magnitude of cognitive symptoms through the different phases of MDD remain difficult to summarize. Thus, the first part of this review briefly overviewed clinical studies, focusing on the cognitive dysfunctions depending on the MDD type. As animal models are essential translational tools for underpinning the mechanisms of cognitive deficits in MDD, the second part of this review synthetized preclinical studies observing cognitive deficits in different rodent models of anxiety/depression. For each cognitive domain, we determined whether deficits could be shared across models. Particularly, we established whether specific stress-related procedures or unspecific criteria (such as species, sex or age) could segregate common cognitive alteration across models. Finally, the role of adult hippocampal neurogenesis in rodents in cognitive dysfunctions during MDD state was also discussed. PMID:26901205

Cognitive performance of people with traumatic spinal cord injury: a cross-sectional study comparing people with subacute and chronic injuries.

PubMed

Molina, B; Segura, A; Serrano, J P; Alonso, F J; Molina, L; Pérez-Borrego, Y A; Ugarte, M I; Oliviero, A

2018-02-22

Cross-sectional study. To assess the impact of spinal cord injury (SCI) on cognitive function in individuals with subacute and chronic SCI. National Hospital for SCI patients (Spain). The present investigation was designed to determine the nature, pattern, and extent of cognitive deficits in a group of participants with subacute (n = 32) and chronic (n = 34) SCI, using a comprehensive battery of reliable and validated neuropsychological assessments to study a broad range of cognitive functions. Twenty-seven able-bodied subjects matched to the groups with SCI for age and educational level formed the control group. The neuropsychological assessment showed alterations in the domain of attention, processing speed, memory and learning, executive functions, and in recognition in participants with SCI. The prevalence of cognitive dysfunction in the chronic stage was also confirmed at the individual level. The comparison of the neuropsychological assessment between the groups with subacute and chronic SCI showed a worsening of cognitive functions in those with chronic SCI compared to the group with subacute SCI. In participants with SCI, cognitive dysfunctions are present in the subacute stage and worsen over time. From a clinical point of view, we confirmed the presence of cognitive dysfunction that may interfere with the first stage of rehabilitation which is the most intense and important. Moreover, cognitive dysfunction may be important beyond the end of the first stage of rehabilitation as it can affect an individual's quality of life and possible integration to society.

Motivational processes in mild cognitive impairment and Alzheimer's disease: results from the Motivational Reserve in Alzheimer's (MoReA) study.

PubMed

Forstmeier, Simon; Maercker, Andreas

2015-11-17

Brain reserve, i.e., the ability of the brain to tolerate age- and disease-related changes in a way that cognitive function is still maintained, is assumed to be based on the lifelong training of various abilities. The Motivational Reserve in Alzheimer's (MoReA) is a longitudinal study that aims to examine motivational processes as a protective factor in mild Alzheimer's dementia (AD) and mild cognitive impairment (MCI). This paper presents the results of motivational variables, frequency of diagnoses, and prediction of global cognition as well as depression in a one-year longitudinal study. The sample consists of 64 subjects with MCI and 47 subjects with mild AD at baseline. At baseline, the physical/neurological examinations, standard clinical assessment, neuropsychological testing, and assessment of motivational variables were performed. At follow-up (FU) one year later, neuropsychological testing including cognition, functional abilities, behavioral and affective symptoms, and global clinical assessments of severity have been repeated. AD cases have lower motivational capacities as measured with a midlife motivation-related occupational score and informant-reported present motivational processes, but do not differ with regard to delay of gratification (DoG) and self-reported motivational processes. DoG and delay discounting (DD) were relatively stable during the measurement interval. However, 20 % of the MCI cases converted to mild AD at FU, and 17 % of the mild AD cases converted to moderate AD. The rate of depression of Alzheimer's disease was 9 at baseline and 21 % at FU, and the rate of apathy was 7 and 14 %, respectively. Global cognition at FU was mainly predicted by baseline global cognition but also by one of the motivational variables (scenario test). Depression at FU was predicted mainly by two motivational variables (self-reported and informant-reported motivational processes). This research might inform motivation-related strategies for prevention and early intervention with older people or people at risk for AD.

Older people with mild cognitive impairment -- their views about assessing driving safety.

PubMed

Johnson, David A; Frank, Oliver; Pond, Dimity; Stocks, Nigel

2013-05-01

Driving is important for older people to maintain agency, independence and social connectedness. Little research has been conducted into the views of older people with mild cognitive impairment about who decides if they are safe to drive. This qualitative study investigates the views of older people with mild cognitive impairment about decision making on driving cessation. Participants value their agency; they wanted to decide when they should stop driving themselves. However, they were also prepared to accept their general practitioner's advice when they became unfit to drive. In the interim, they self regulated the timing and distance of their driving to reduce accident risk.

Association Between Gait and Dual Task With Cognitive Domains in Older People With Cognitive Impairment.

PubMed

Ansai, Juliana Hotta; Andrade, Larissa Pires de; Rossi, Paulo Giusti; Almeida, Mariana Luciano; Carvalho Vale, Francisco Assis; Rebelatto, José Rubens

2017-09-13

The authors investigated whether impaired gait and dual-task performances are associated with specific cognitive domains among older people with preserved cognition (PC), mild cognitive impairment (MCI), and mild Alzheimer's disease (AD). The sample comprised 40 older adults with PC, 40 with MCI, and 38 with mild AD. The assessment consisted of gait (measured by 10-m walk test and Timed Up and Go Test [TUGT]), dual task (measured by TUGT associated with a cognitive-motor task of calling a phone number), and cognition (domains of the Addenbrooke Cognitive Examination-Revised and Frontal Assessment Battery [FAB]). For data analysis, the Pearson product-moment correlation and the backward stepwise linear regression were conducted. Language, fluency, and visuospatial domains predicted the 10-m walk test measure specifically in PC, MCI, and AD groups. Only the visuospatial domain was independently associated with the TUGT measure in the MCI and AD groups. FAB score, language domain, and FAB score and fluency domain were the strongest predictors for the isolated cognitive-motor task measure in the PC, MCI, and AD groups, respectively. The visuospatial domain was independently associated with the dual-task test measure in all 3 groups. The study findings demonstrate the influence of specific cognitive domains in daily mobility tasks in people with different cognitive profiles.

Long-Term Cognitive Impairment after Hospitalization for Community-Acquired Pneumonia: a Prospective Cohort Study.

PubMed

Girard, Timothy D; Self, Wesley H; Edwards, Kathryn M; Grijalva, Carlos G; Zhu, Yuwei; Williams, Derek J; Jain, Seema; Jackson, James C

2018-06-01

Recent studies suggest older patients hospitalized for community-acquired pneumonia are at risk for new-onset cognitive impairment. The characteristics of long-term cognitive impairment after pneumonia, however, have not been elucidated. To characterize long-term cognitive impairment among adults of all ages hospitalized for community-acquired pneumonia. Prospective cohort study. Adults without severe preexisting cognitive impairment who were hospitalized with community-acquired pneumonia. At enrollment, we estimated baseline cognitive function with the Short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). At 2- and 12-month follow-up, we assessed cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and tests of executive function, diagnosing cognitive impairment when results were ≥ 1.5 standard deviations below published age-adjusted means for the general population. We also identified subtypes of mild cognitive impairment using standard definitions. We assessed 58 (73%) of 80 patients who survived to 2-month follow-up and 57 (77%) of 74 who survived to 12-month follow-up. The median [range] age of survivors tested was 57 [19-97] years. Only 8 (12%) had evidence of mild cognitive impairment at baseline according to the Short IQCODE, but 21 (38%) at 2 months and 17 (30%) at 12 months had mild cognitive impairment per the RBANS. Moderate-to-severe cognitive impairment was common among adults ≥ 65 years [4/13 (31%) and 5/13 (38%) at 2 and 12 months, respectively] but also affected many of those < 65 years [10/43 (23%) and 8/43 (19%) at 2 and 12 months, respectively]. Deficits were most often noted in visuospatial function, attention, and memory. A year after hospitalization for community-acquired pneumonia, moderate-to-severe impairment in multiple cognitive domains affected one-third of patients ≥ 65 years old and 20% of younger patients, and another third of survivors had mild cognitive impairment.

Recent neuroimaging techniques in mild traumatic brain injury.

PubMed

Belanger, Heather G; Vanderploeg, Rodney D; Curtiss, Glenn; Warden, Deborah L

2007-01-01

Mild traumatic brain injury (TBI) is characterized by acute physiological changes that result in at least some acute cognitive difficulties and typically resolve by 3 months postinjury. Because the majority of mild TBI patients have normal structural magnetic resonance imaging (MRI)/computed tomography (CT) scans, there is increasing attention directed at finding objective physiological correlates of persistent cognitive and neuropsychiatric symptoms through experimental neuroimaging techniques. The authors review studies utilizing these techniques in patients with mild TBI; these techniques may provide more sensitive assessment of structural and functional abnormalities following mild TBI. Particular promise is evident with fMRI, PET, and SPECT scanning, as demonstrated by associations between brain activation and clinical outcomes.

Butyrylcholinesterase inhibitors ameliorate cognitive dysfunction induced by amyloid-β peptide in mice

PubMed Central

Furukawa-Hibi, Yoko; Alkam, Tursun; Nitta, Atsumi; Matsuyama, Akihiro; Mizoguchi, Hiroyuki; Suzuki, Kazuhiko; Moussaoui, Saliha; Yu, Qian-Sheng; Greig, Nigel H.; Nagai, Taku; Yamada, Kiyofumi

2016-01-01

The cholinesterase inhibitor, rivastigmine, ameliorates cognitive dysfunction and is approved for the treatment of Alzheimer's disease (AD). Rivastigmine is a dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE); however, the impact of BuChE inhibition on cognitive dysfunction remains to be determined. We compared the effects of a selective BuChE inhibitor, N1-phenethylnorcymserine (PEC), rivastigmine and donepezil (an AChE-selective inhibitor) on cognitive dysfunction induced by amyloid-β peptide (Aβ1–40) in mice. Five-week-old imprinting control region (ICR) mice were injected intracerebroventricularly (i.c.v.) with either Aβ1–40 or the control peptide Aβ40–1 on Day 0, and their recognition memory was analyzed by a novel object recognition test. Treatment with donepezil (1.0 mg/kg), rivastigmine (0.03, 0.1, 0.3 mg/kg) or PEC (1.0, 3.0 mg/kg) 20 min prior to, or immediately after the acquisition session (Day 4) ameliorated the Aβ1–40 induced memory impairment, indicating a beneficial effect on memory acquisition and consolidation. In contrast, none of the investigated drugs proved effective when administrated before the retention session (Day 5). Repeated daily administration of donepezil, rivastigmine or PEC, on Days 0–3 inclusively, ameliorated the cognitive dysfunction in Aβ1–40 challenged mice. Consistent with the reversal of memory impairments, donepezil, rivastigmine or PEC treatment significantly reduced Aβ1–40 induced tyrosine nitration of hippocampal proteins, a marker of oxidative damage. These results indicate that BuChE inhibition, as well as AChE inhibition, is a viable therapeutic strategy for cognitive dysfunction in AD. PMID:21820013

An early and late peak in microglial activation in Alzheimer's disease trajectory.

PubMed

Fan, Zhen; Brooks, David J; Okello, Aren; Edison, Paul

2017-03-01

Amyloid-β deposition, neuroinflammation and tau tangle formation all play a significant role in Alzheimer's disease. We hypothesized that there is microglial activation early on in Alzheimer's disease trajectory, where in the initial phase, microglia may be trying to repair the damage, while later on in the disease these microglia could be ineffective and produce proinflammatory cytokines leading to progressive neuronal damage. In this longitudinal study, we have evaluated the temporal profile of microglial activation and its relationship between fibrillar amyloid load at baseline and follow-up in subjects with mild cognitive impairment, and this was compared with subjects with Alzheimer's disease. Thirty subjects (eight mild cognitive impairment, eight Alzheimer's disease and 14 controls) aged between 54 and 77 years underwent 11C-(R)PK11195, 11C-PIB positron emission tomography and magnetic resonance imaging scans. Patients were followed-up after 14 ± 4 months. Region of interest and Statistical Parametric Mapping analysis were used to determine longitudinal alterations. Single subject analysis was performed to evaluate the individualized pathological changes over time. Correlations between levels of microglial activation and amyloid deposition at a voxel level were assessed using Biological Parametric Mapping. We demonstrated that both baseline and follow-up microglial activation in the mild cognitive impairment cohort compared to controls were increased by 41% and 21%, respectively. There was a longitudinal reduction of 18% in microglial activation in mild cognitive impairment cohort over 14 months, which was associated with a mild elevation in fibrillar amyloid load. Cortical clusters of microglial activation and amyloid deposition spatially overlapped in the subjects with mild cognitive impairment. Baseline microglial activation was increased by 36% in Alzheimer's disease subjects compared with controls. Longitudinally, Alzheimer's disease subjects showed an increase in microglial activation. In conclusion, this is one of the first longitudinal positron emission tomography studies evaluating longitudinal changes in microglial activation in mild cognitive impairment and Alzheimer's disease subjects. We found there is an initial longitudinal reduction in microglial activation in subjects with mild cognitive impairment, while subjects with Alzheimer's disease showed an increase in microglial activation. This could reflect that activated microglia in mild cognitive impairment initially may adopt a protective activation phenotype, which later change to a cidal pro-inflammatory phenotype as disease progresses and amyloid clearance fails. Thus, we speculate that there might be two peaks of microglial activation in the Alzheimer's disease trajectory; an early protective peak and a later pro-inflammatory peak. If so, anti-microglial agents targeting the pro-inflammatory phenotype would be most beneficial in the later stages of the disease. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Impact of first-ever mild stroke on participation at 3 and 6 month post-event: the TABASCO study.

PubMed

Adamit, Tal; Maeir, Adina; Ben Assayag, Einor; Bornstein, Natan M; Korczyn, Amos D; Katz, Noomi

2015-01-01

This study focused on the relationships between cognition, participation and quality of life (QoL) among first-ever mild ischemic stroke patients 3 months post-event. We hypothesized that significant correlations exist between cognition, executive functions (EF), QoL and participation; and that EF and QoL will significantly contribute to participation beyond demographics and stroke severity at 3 and from 3 to 6 months post-stroke. A prospective cohort study, recruiting consecutive first-ever stroke patients from a large tertiary hospital. The inclusion criteria were first event, mild stroke (NIHSS ≤ 5), and no previous significant neurological or cognitive impairment. In addition to assessment every 6 month at the hospital, an assessment battery was administered at home 3 months post-stroke. Participants showed mild to moderate difficulties in cognition and participation (n = 249). Low to moderate correlations were found between cognition and EF with participation (-0.380, p < 0.05; r = 0.460, p < 0.001, respectively); and cognition with QoL (r = 0.421, p < 0.001). EF and QoL contributed significantly to participation at 3 months (R(2) = 0.961) and in addition education at 6 months (R(2) = 0.701). Participants after mild ischemic stroke experienced cognitive and EF difficulties that affect their participation and QoL. Further studies are needed of mild stroke survivors to enhance our understanding of the variables that affect participation. The findings of the current study have significant implications for the participation of people after mild stroke in the community. Health care systems in general and rehabilitation programs, in particular, do not consider that these clients need rehabilitation as most of them perform basic daily functions independently. Thus, although cognitive and EF deficits are found in people following even mild stroke, but are not externally apparent, these impairments are mostly neglected by the health care system. Mild stroke has long-term effects in most cases and effect family members as well. The implications of the study's results, as well as those of other studies, emphasize the necessity of follow-up and rehabilitation efforts at home and in the community. These efforts should focus on re-enabling the individual to participate in previous activities as much as possible and on providing support for family members. The strength of this study lies in the large number of participants who were evaluated at home in their natural environments. Studies of this kind are rarely performed in the participants' real-life settings, thus the current study provides an important perspective on the participation of this population in the community.

Methodological improvements in quantifying cognitive change in clinical trials: an example with single-dose administration of donepezil.

PubMed

Pietrzak, R H; Maruff, P; Snyder, P J

2009-03-01

Change in cognitive function in response to a pharmacologic challenge can be observed with greater sensitivity by employing cognitive tests with optimal psychometric properties and a statistical approach that more accurately accounts for individual variability in performance. To demonstrate this approach we examined the cognitive effects of a single acute dose administration of an acetylcholinesterase inhibitor, donepezil, in healthy older adults and in older adults with mild Alzheimer's disease (AD). Placebo-controlled crossover study with three separate testing days: baseline, placebo, and donepezil, with assessments at baseline, and 1-, 2-, 3-, 6-, and 8-hrs post-dosing on each day. Early phase I clinical trial. 15 healthy older adults; 14 older adults with mild Alzheimer's disease. Single acute dose of 5mg donepezil. Performance on the Groton Maze Learning Test (GMLT), a computerized neuropsychological measure of spatial working memory and error monitoring. A single acute dose of donepezil improved GMLT performance in healthy older adults (effect size: 0.83 at 6 hrs post-dosing) and older adults with mild AD (effect size: 0.58 at 3 hrs post-dosing). The GMLT detected cognitive improvement following a single, acute dose administration of donepezil in healthy older adults and older adults with mild AD. The choice of cognitive tests designed for repeated administration, as well as an analytic approach that emphasizes individual-level change in cognitive function, provides a sensitive approach to detecting central nervous system drug penetration and activity of cognitive-enhancing agents.

[Clinicopathologic findings of argyrophilic-grain dementia in a case of mild cognitive impairment converting to dementia].

PubMed

Iwasaki, Yasushi; Mori, Keiko; Ito, Masumi; Tatsumi, Shinsui; Mimuro, Maya; Yoshida, Mari

2012-01-01

An 84-year-old Japanese woman with no family history of dementia visited our memory clinic complaining of memory disturbance. Neurological examination revealed no apparent motor abnormalities, focal cerebral signs, parkinsonism, or cerebellar dysfunction. Hasegawa's Dementia Scale-Revised (HDS-R) and Mini mental state examination (MMSE) scores were 24 and 23 points, respectively. MRI revealed left-side-dominant dilatation of the inferior horn of the lateral ventricle. Although egocentric behavior was remarkable, no disturbance of intelligence was apparent at the first examination, and she was diagnosed as having mild cognitive impairment. Her memory disturbance and disorientation gradually worsened. Atrophy of the cerebrum and dilatation of the lateral ventricle advanced gradually on MRI. Two years later, she required care to perform activities of daily living. HDS-R and MMSE scores had dropped to 13 and 18 points, respectively, and conversion to dementia was diagnosed. Ability to perform 3D cube-copying was well preserved. The patient died due to acute myocardial infarction at the age of 87. The clinical diagnosis was Alzheimer disease. At autopsy, the brain weighed 1,250g, and argyrophilic grains were widely observed in the limbic system, corresponding to Saito's stage III. Neuron loss, gliosis, spongiform change, and tissue rarefaction were recognized in the superficial layer of the parahippocampal gyrus. Ballooned neurons, pretangles, oligodendroglial coiled bodies, and neuropil threads were also observed. Neurofibrillary tangles and senile plaques, mainly consisting of diffuse plaque, were recognized as corresponding to Braak stage III and CERAD stage B, respectively. Neither Lewy nor Pick bodies were observed. Although mild phosphorylated TDP-43 immunoreactivity was observed, it was suspected to be due to secondary degeneration of tau deposition. The patient was diagnosed pathologically as having argyrophilic grain dementia. The clinical findings of the present patient reveal important observations that help to clinically discriminate between various dementias such as Alzheimer disease and argyrophilic grain dementia.

Time-dependent effects of CX3CR1 in a mouse model of mild traumatic brain injury.

PubMed

Febinger, Heidi Y; Thomasy, Hannah E; Pavlova, Maria N; Ringgold, Kristyn M; Barf, Paulien R; George, Amrita M; Grillo, Jenna N; Bachstetter, Adam D; Garcia, Jenny A; Cardona, Astrid E; Opp, Mark R; Gemma, Carmelina

2015-09-02

Neuroinflammation is an important secondary mechanism that is a key mediator of the long-term consequences of neuronal injury that occur in traumatic brain injury (TBI). Microglia are highly plastic cells with dual roles in neuronal injury and recovery. Recent studies suggest that the chemokine fractalkine (CX3CL1, FKN) mediates neural/microglial interactions via its sole receptor CX3CR1. CX3CL1/CX3CR1 signaling modulates microglia activation, and depending upon the type and time of injury, either protects or exacerbates neurological diseases. In this study, mice deficient in CX3CR1 were subjected to mild controlled cortical impact injury (CCI), a model of TBI. We evaluated the effects of genetic deletion of CX3CR1 on histopathology, cell death/survival, microglia activation, and cognitive function for 30 days post-injury. During the acute post-injury period (24 h-15 days), motor deficits, cell death, and neuronal cell loss were more profound in injured wild-type than in CX3CR1(-/-) mice. In contrast, during the chronic period of 30 days post-TBI, injured CX3CR1(-/-) mice exhibited greater cognitive dysfunction and increased neuronal death than wild-type mice. The protective and deleterious effects of CX3CR1 were associated with changes in microglia phenotypes; during the acute phase CX3CR1(-/-) mice showed a predominant anti-inflammatory M2 microglial response, with increased expression of Ym1, CD206, and TGFβ. In contrast, increased M1 phenotypic microglia markers, Marco, and CD68 were predominant at 30 days post-TBI. Collectively, these novel data demonstrate a time-dependent role for CX3CL1/CX3CR1 signaling after TBI and suggest that the acute and chronic responses to mild TBI are modulated in part by distinct microglia phenotypes.

Development and initial validation of a brief self-report measure of cognitive dysfunction in fibromyalgia.

PubMed

Kratz, Anna L; Schilling, Stephen G; Goesling, Jenna; Williams, David A

2015-06-01

Pain is often the focus of research and clinical care in fibromyalgia (FM); however, cognitive dysfunction is also a common, distressing, and disabling symptom in FM. Current efforts to address this problem are limited by the lack of a comprehensive, valid measure of subjective cognitive dysfunction in FM that is easily interpretable, accessible, and brief. The purpose of this study was to leverage cognitive functioning item banks that were developed as part of the Patient Reported Outcomes Measurement Information System (PROMIS) to devise a 10-item short form measure of cognitive functioning for use in FM. In study 1, a nationwide (U.S.) sample of 1,035 adults with FM (age range = 18-82, 95.2% female) completed 2 cognitive item pools. Factor analyses and item response theory analyses were used to identify dimensionality and optimally performing items. A recommended 10-item measure, called the Multidimensional Inventory of Subjective Cognitive Impairment (MISCI) was created. In study 2, 232 adults with FM completed the MISCI and a legacy measure of cognitive functioning that is used in FM clinical trials, the Multiple Ability Self-Report Questionnaire (MASQ). The MISCI showed excellent internal reliability, low ceiling/floor effects, and good convergent validity with the MASQ (r = -.82). This paper presents the MISCI, a 10-item measure of cognitive dysfunction in FM, developed through classical test theory and item response theory. This brief but comprehensive measure shows evidence of excellent construct validity through large correlations with a lengthy legacy measure of cognitive functioning. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

The role of nonverbal cognitive ability in the association of adverse life events with dysfunctional attitudes and hopelessness in adolescence.

PubMed

Flouri, Eirini; Panourgia, Constantina

2012-10-01

The aim of this study was to test whether nonverbal cognitive ability buffers the effect of life stress (number of adverse life events in the last year) on diatheses for depression. It was expected that, as problem-solving aptitude, nonverbal cognitive ability would moderate the effect of life stress on those diatheses (such as dysfunctional attitudes) that are depressogenic because they represent deficits in information-processing or problem-solving skills, but not on diatheses (such as hopelessness) that are depressogenic because they represent deficits in motivation or effort to apply problem-solving skills. The sample included 558 10- to 19-year-olds from a state secondary school in London. Nonverbal cognitive ability was negatively associated with both dysfunctional attitudes and hopelessness. As expected, nonverbal cognitive ability moderated the association between life adversity and dysfunctional attitudes. However, hopelessness was not related to life stress, and therefore, there was no life stress effect for nonverbal cognitive ability to moderate. This study adds to knowledge about the association between problem-solving ability and depressogenic diatheses. By identifying life stress as a risk factor for dysfunctional attitudes but not hopelessness, it highlights the importance of considering outcome specificity in models predicting adolescent outcomes from adverse life events. Importantly for practice, it suggests that an emphasis on recent life adversity will likely underestimate the true level of hopelessness among adolescents. Copyright © 2012 Elsevier Inc. All rights reserved.

Multiple sclerosis masquerading as Alzheimer-type dementia: Clinical, radiological and pathological findings.

PubMed

Tobin, W O; Popescu, B F; Lowe, V; Pirko, I; Parisi, J E; Kantarci, K; Fields, J A; Bruns, M B; Boeve, B F; Lucchinetti, C F

2016-04-01

We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry. © The Author(s), 2015.

Executive Dysfunction and Depressive Symptoms Associated With Reduced Participation of People With Severe Congestive Heart Failure

PubMed Central

Foster, Erin R.; Cunnane, Kathleen B.; Edwards, Dorothy F.; Morrison, M. Tracy; Ewald, Gregory A.; Geltman, Edward M.; Zazulia, Allyson R.

2011-01-01

OBJECTIVE We investigated participation levels and relationships among cognition, depression, and participation for people with severe congestive heart failure (CHF). METHOD People with severe CHF (New York Heart Association Class III or IV) awaiting heart transplantation (N = 27) completed standardized tests of cognition and self-report measures of executive dysfunction, depressive symptoms, and participation. RESULTS Possible depression (64%) and cognitive impairment (15%–59%) were prevalent. Participants reported significant reductions in participation across all activity domains since CHF diagnosis (ps < .001). Worse executive dysfunction and depressive symptoms were associated with reduced participation and together accounted for 35%–46% of the variance in participation (ps < .01). CONCLUSION Participation restrictions associated with CHF are not limited to physically demanding activities and are significantly associated with executive dysfunction and depression. Cardiac rehabilitation should address cognitive and psychological functioning in the context of all life situations instead of focusing solely on physical function and disability. PMID:21675336

Effectiveness of the second-stage rehabilitation in stroke patients with cognitive impairment.

PubMed

Milinavičienė, Eglė; Rastenytė, Daiva; Kriščiūnas, Aleksandras

2011-01-01

The aim of this study was to evaluate the recovery of functional status and effectiveness of the second-stage rehabilitation depending on the degree of cognitive impairment in stroke patients. The study sample comprised 226 stroke patients at the Viršužiglis Hospital of rehabilitation, Hospital of Lithuanian University of Health Sciences. Functional status was evaluated with the Functional Independence Measure, cognitive function with the Mini-Mental Status Examination scale, and severity of neurologic condition with the National Institutes of Health Stroke Scale. The patients were divided into 4 study groups based on cognitive impairment: severe, moderate, mild, or no impairment. More than half (53%) of all cases were found to have cognitive impairment, while patients with different degree of cognitive impairment were equally distributed: mild impairment (18%), moderate impairment (17%), and severe impairment (18%). Improvement of functional status was observed in all study groups (P<0.001). In the patients with moderate and severe cognitive impairment, cognitive recovery was significantly more expressed than in other study groups (P<0.001). Insufficient recovery of functional status was significantly associated with hemiplegia (OR, 11.15; P=0.015), urinary incontinence (OR, 14.91; P<0.001), joint diseases (OR, 5.52; P=0.022), heart diseases (OR, 4.10; P=0.041), and severe cognitive impairment (OR, 15.18; P<0.001), while moderate and mild cognitive impairment was not associated with the recovery of functional status. During the second-stage rehabilitation of stroke patients, functional status as well as cognitive and motor skills were improved both in patients with and without cognitive impairment; however, the patients who were diagnosed with severe or moderate cognitive impairment at the beginning of second-stage rehabilitation showed worse neurological and functional status during the whole second-stage rehabilitation than the patients with mild or no cognitive impairment.

Cognitive Load in Mild Traumatic Brain Injury: A Pupillometric Assessment of Multiple Attentional Processes

DTIC Science & Technology

2016-05-20

such as Schizophrenia and ADHD (27; 77). Another such condition is mild traumatic brain injury. Mild TBI is caused by a closed head injury (e.g., car...cognitive load on semantic priming in patients with schizophrenia . Journal of Abnormal Psychology 104:576 26. Hogan MJ, Carolan L, Roche RAP...performance and cerebral functional response during working memory in schizophrenia . Schizophrenia research 53:45-56 28. Iverson G, Lange R. 2011

Cannabis and cognitive dysfunction: parallels with endophenotypes of schizophrenia?

PubMed

Solowij, Nadia; Michie, Patricia T

2007-01-01

Currently, there is a lot of interest in cannabis use as a risk factor for the development of schizophrenia. Cognitive dysfunction associated with long-term or heavy cannabis use is similar in many respects to the cognitive endophenotypes that have been proposed as vulnerability markers of schizophrenia. In this overview, we examine the similarities between these in the context of the neurobiology underlying cognitive dysfunction, particularly implicating the endogenous cannabinoid system, which plays a significant role in attention, learning and memory, and in general, inhibitory regulatory mechanisms in the brain. Closer examination of the cognitive deficits associated with specific parameters of cannabis use and interactions with neurodevelopmental stages and neural substrates will better inform our understanding of the nature of the association between cannabis use and psychosis. The theoretical and clinical significance of further research in this field is in enhancing our understanding of underlying pathophysiology and improving the provision of treatments for substance use and mental illness.

The Association between Mild Traumatic Brain Injury History and Cognitive Control

ERIC Educational Resources Information Center

Pontifex, Matthew B.; O'Connor, Phillip M.; Broglio, Steven P.; Hillman, Charles H.

2009-01-01

The influence of multiple mild traumatic brain injuries (mTBIs) on neuroelectric and task performance indices of the cognitive control of action monitoring was assessed in individuals with and without a history of concussion. Participants completed a standard clinical neurocognitive assessment and the error-related negativity of the…

The Prevalence and Severity of Autonomic Dysfunction in Chronic Inflammatory Demyelinating Polyneuropathy

PubMed Central

Pasangulapati, Suresh Babu; Murthy, T. V.; Sivadasan, Ajith; Gideon, L. Rynjah; Prabhakar, A. T.; Sanjith, Aaron; Mathew, Vivek; Alexander, Mathew

2017-01-01

Introduction: In chronic inflammatory demyelinating polyneuropathy (CIDP), emphasis has been on motor disabilities, and autonomic dysfunction in these patients has not been addressed systematically. Materials and Methods: Autonomic function was prospectively analyzed in 38 patients with CIDP. Quantitative autonomic function testing was done using Finometer® PRO and severity of adrenergic and cardiovagal dysfunction graded according to composite autonomic severity score and sudomotor dysfunction assessed using sympathetic skin response. Results: Thirty-four (89%) patients had features of autonomic dysfunction. Thirty-three (86%) patients had cardiovagal dysfunction, 21 (55%) had adrenergic dysfunction, and 24 (63%) had sudomotor dysfunction. Autonomic dysfunction was mild to moderate in the majority (86%). Conclusions: Autonomic dysfunction in CIDP is underreported and potentially amenable to therapy. Our cohort had a high proportion of adrenergic dysfunction compared to previous studies. PMID:28904461

The ROSAS Cohort: A Prospective, Longitudinal Study of Biomarkers for Alzheimer's Disease. Strategy, Methods and Initial Results.

PubMed

de Mauléon, A; Soto, M; Kiyasova, V; Delrieu, J; Guignot, I; Galtier, S; Lilamand, M; Cantet, C; Lala, F; Sastre, N; Andrieu, S; Pueyo, M; Ousset, P J; Vellas, B

2017-01-01

The aims of the Research Of biomarkers in Alzheimer's diseaSe (ROSAS) study were to determine the biofluid and imaging biomarkers permitting an early diagnosis of Alzheimer's disease and better characterisation of cognitive and behavioural course of the pathology. This paper outlines the overall strategy, methodology of the study, baseline characteristics of the population and first longitudinal results from the ROSAS cohort. Longitudinal prospective monocentric observational study performed at the Alzheimer's disease Research centre in Toulouse. A total of 387 patients were studied and analyzed in 3 groups: 184 patients with dementia of Alzheimer's type, 96 patients with memory disorders without dementia (Mild Cognitive Impairment) and 107 patients without abnormal memory tests (control group), and were followed up during 4 years. Patient's sociodemographic characteristics, risk factors, medical conditions, previous and current medications, neuropsychological assessment and overall cognitive status were recorded. Blood and urine samples were collected at every year, Magnetic Resonance Imaging were performed at inclusion, after one year of follow-up and at the end of the study. At baseline, three different groups of the cohort differed interestingly in age, level of education, and in percentage of ApoEε4 carriers whereas the history of cardiovascular and endocrine pathologies were similar among the groups. During the follow-up period (3-4 years) 42 mild cognitive impairment patients (43.8%) progressed to dementia, 7 controls progressed into mild cognitive impairment and 1 patient in the control group converted from mild cognitive impairment group to dementia of Alzheimer's type group. During the first year of follow up, the incidence of progression from mild cognitive impairment to dementia of Alzheimer's type was 12.7 per 100, during the second year 33.9 per 100 and 46.7 per 100 for the third year. This paper presents the baseline characteristics of the unique French prospective monocenter study in which the natural course of dementia of Alzheimer's type was evaluated. Future analysis of blood and urine samples collection from the ROSAS study will permit to identify possible biofluid biomarkers predicting the early stages of the dementia of Alzheimer's type and risk of progression from Mild Cognitive Impairment to Alzheimer's disease.

Benefits of cognitive-motor intervention in MCI and mild to moderate Alzheimer disease.

PubMed

Olazarán, J; Muñiz, R; Reisberg, B; Peña-Casanova, J; del Ser, T; Cruz-Jentoft, A J; Serrano, P; Navarro, E; García de la Rocha, M L; Frank, A; Galiano, M; Fernández-Bullido, Y; Serra, J A; González-Salvador, M T; Sevilla, C

2004-12-28

To evaluate the efficacy of a cognitive-motor program in patients with early Alzheimer disease (AD) who are treated with a cholinesterase inhibitor (ChEI). Patients with mild cognitive impairment (MCI) (12), mild AD (48), and moderate AD (24) (Global Deterioration Scale stages 3, 4, and 5) were randomized to receive psychosocial support plus cognitive-motor intervention (experimental group) or psychosocial support alone (control group). Cognitive-motor intervention (CMI) consisted of a 1-year structured program of 103 sessions of cognitive exercises, plus social and psychomotor activities. The primary efficacy measure was the cognitive subscale of the AD Assessment Scale (ADAS-cog). Secondary efficacy measures were the Mini-Mental State Examination, the Functional Activities Questionnaire, and the Geriatric Depression Scale. Evaluations were conducted at 1, 3, 6, and 12 months by blinded evaluators. Patients in the CMI group maintained cognitive status at month 6, whereas patients in the control group had significantly declined at that time. Cognitive response was higher in the patients with fewer years of formal education. In addition, more patients in the experimental group maintained or improved their affective status at month 12 (experimental group, 75%; control group, 47%; p = 0.017). A long-term CMI in ChEI-treated early Alzheimer disease patients produced additional mood and cognitive benefits.

Executive dysfunction predicts social cognition impairment in amyotrophic lateral sclerosis.

PubMed

Watermeyer, Tamlyn J; Brown, Richard G; Sidle, Katie C L; Oliver, David J; Allen, Christopher; Karlsson, Joanna; Ellis, Catherine M; Shaw, Christopher E; Al-Chalabi, Ammar; Goldstein, Laura H

2015-07-01

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the motor system with recognised extra-motor and cognitive involvement. This cross-sectional study examined ALS patients' performance on measures requiring social inference, and determined the relationship between such changes and variations in mood, behaviour, personality, empathy and executive function. Fifty-five ALS patients and 49 healthy controls were compared on tasks measuring social cognition and executive function. ALS patients also completed measures examining mood, behaviour and personality. Regression analyses explored the contribution of executive function, mood, behaviour and personality to social cognition scores within the ALS sample. A between-group MANOVA revealed that, the ALS group was impaired relative to controls on two composite scores for social cognition and executive function. Patients also performed worse on individual tests of executive function measuring cognitive flexibility, response inhibition and concept formation, and on individual aspects of social cognition assessing the attribution of emotional and mental states. Regression analyses indicated that ALS-related executive dysfunction was the main predictor of social cognition performance, above and beyond demographic variables, behaviour, mood and personality. On at least some aspects of social cognition, impaired performance in ALS appears to be secondary to executive dysfunction. The profile of cognitive impairment in ALS supports a cognitive continuum between ALS and frontotemporal dementia.

Unirhinal Olfactory Testing for the Diagnostic Workup of Mild Cognitive Impairment.

PubMed

Huart, Caroline; Rombaux, Philippe; Gérard, Thomas; Hanseeuw, Bernard; Lhommel, Renaud; Quenon, Lisa; Ivanoiu, Adrian; Mouraux, André

2015-01-01

Olfactory dysfunction is associated with Alzheimer's disease (AD), and already present at pre-dementia stage. Based on the assumption that early neurodegeneration in AD is asymmetrical and that olfactory input is primarily processed in the ipsilateral hemisphere, we assessed whether unirhinal psychophysical and electrophysiological assessment of olfactory function can contribute to the diagnostic workup of mild cognitive impairment (MCI). Olfactory function of 13 MCI patients with positive amyloid PET, 13 aged-matched controls (AC) with negative amyloid PET and 13 patients with post-infectious olfactory loss (OD) was assessed unirhinally using (1) psychophysical testing of olfactory detection, discrimination and identification performance and (2) the recording of olfactory event-related brain potentials. Time-frequency analysis was used to enhance the signal-to-noise ratio of the electrophysiological responses. Psychophysical and electrophysiological assessment of auditory and trigeminal chemosensory function served as controls. As compared to AC and OD, MCI patients exhibited a significant asymmetry of olfactory performance. This asymmetry efficiently discriminated between MCI and AC (sensitivity: 85% , specificity: 77% ), as well as MCI and OD (sensitivity: 85% , specificity: 70% ). There was also an asymmetry of the electrophysiological responses, but not specific for MCI. In both MCI and OD, olfactory stimulation of the best nostril elicited significantly more activity than stimulation of the worse nostril, between 3-7.5 Hz and 1.2-2.0 s after stimulus onset. Trigeminal and auditory psychophysical testing did not show any difference between groups. MCI patients exhibit a marked asymmetry of behavioral olfactory function, which could be useful for the diagnostic workup of MCI.

[Usefulness of the 10 pictures reminding test for memory assessment for the diagnosis of Alzheimer's disease, mild cognitive impairment and anxiety/depression].

PubMed

Federico, D; Thomas-Anterion, C; Borg, C; Foyatier Michel, N; Dirson, S; Laurent, B

2008-10-01

Episodic memory is often considered to be essential in the neuropsychological examination of elderly people consulting in the memory clinics. Therefore, the performance of three different episodic memory tests were compared in Alzheimer's disease (AD), mild cognitive impairment (MCI) and anxiety/depression. Seventy-six patients with AD, 46 with MCI, and 36 with anxiety/depression performed three memory tests: (1) three-words immediate and delayed recall of the MMSE test; (2) 10-pictures reminding test; (3) 16-items free and cued reminding test. Patients with AD and MCI differed from the depressed/anxious participants on all subcomponents of the memory tests. Only the three-words immediate and delayed recall in the MMSE test as well as the immediate recall (encoding) of the free and cued reminding test (16-items) did not differ between AD and MCI. Significant correlations were also evidenced between the free and cued recall of the 10 pictures and the score of the 16-items for all patients. Scores of total and free recalls distinguished the three group of patients; also, a trend was observed for the free recall between the patients with AD and MCI. The three-words immediate and delayed recall of the MMSE test is linked with hippocampic dysfunction. Also, the present study suggests that the 10-pictures reminding test, is a simple and reliable test for investigating memory, in addition to other evaluation tests. Finally, further studies would be necessary to assess the sensitivity and specificity of the tests.

Extent and neural basis of semantic memory impairment in mild cognitive impairment.

PubMed

Barbeau, Emmanuel J; Didic, Mira; Joubert, Sven; Guedj, Eric; Koric, Lejla; Felician, Olivier; Ranjeva, Jean-Philippe; Cozzone, Patrick; Ceccaldi, Mathieu

2012-01-01

An increasing number of studies indicate that semantic memory is impaired in mild cognitive impairment (MCI). However, the extent and the neural basis of this impairment remain unknown. The aim of the present study was: 1) to evaluate whether all or only a subset of semantic domains are impaired in MCI patients; and 2) to assess the neural substrate of the semantic impairment in MCI patients using voxel-based analysis of MR grey matter density and SPECT perfusion. 29 predominantly amnestic MCI patients and 29 matched control subjects participated in this study. All subjects underwent a full neuropsychological assessment, along with a battery of five tests evaluating different domains of semantic memory. A semantic memory composite Z-score was established on the basis of this battery and was correlated with MRI grey matter density and SPECT perfusion measures. MCI patients were found to have significantly impaired performance across all semantic tasks, in addition to their anterograde memory deficit. Moreover, no temporal gradient was found for famous faces or famous public events and knowledge for the most remote decades was also impaired. Neuroimaging analyses revealed correlations between semantic knowledge and perirhinal/entorhinal areas as well as the anterior hippocampus. Therefore, the deficits in the realm of semantic memory in patients with MCI is more widespread than previously thought and related to dysfunction of brain areas beyond the limbic-diencephalic system involved in episodic memory. The severity of the semantic impairment may indicate a decline of semantic memory that began many years before the patients first consulted.

Functional changes in the cortical semantic network in amnestic mild cognitive impairment.

PubMed

Pineault, Jessica; Jolicoeur, Pierre; Grimault, Stephan; Bermudez, Patrick; Brambati, Simona Maria; Lacombe, Jacinthe; Villalpando, Juan Manuel; Kergoat, Marie-Jeanne; Joubert, Sven

2018-05-01

Semantic memory impairment has been documented in individuals with amnestic Mild cognitive impairment (aMCI), who are at risk of developing Alzheimer's disease (AD), yet little is known about the neural basis of this breakdown. The aim of this study was to investigate the brain mechanisms associated with semantic performance in aMCI patients. A group of aMCI patients and a group of healthy controls carried out a semantic categorization task while their brain activity was recorded using magnetoencephalography (MEG). During the task, participants were shown famous faces and had to determine whether each famous person matched a given occupation. The main hypotheses were that (a) semantic processing should be compromised for aMCI patients, and (b) these deficits should be associated with cortical dysfunctions within specific areas of the semantic network. Behavioral results showed that aMCI participants were significantly slower and less accurate than controls at the semantic task. Additionally, relative to controls, a significant pattern of hyperactivation was found in the aMCI group within specific regions of the extended semantic network, including the right anterior temporal lobe (ATL) and fusiform gyrus. Abnormal functional activation within key areas of the semantic network suggests that it is compromised early in the disease process. Moreover, this pattern of right ATL and fusiform gyrus hyperactivation was positively associated with gray matter integrity in specific areas, but was not associated with any pattern of atrophy, suggesting that this pattern of hyperactivation may precede structural alteration of the semantic network in aMCI. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Alpha-7 nicotinic agonists for cognitive deficits in neuropsychiatric disorders: A translational meta-analysis of rodent and human studies

PubMed Central

Lewis, Alan S.; van Schalkwyk, Gerrit I.; Bloch, Michael H.

2017-01-01

Cognitive dysfunction in schizophrenia (SCZ) and Alzheimer’s disease (AD) is a major driver of functional disability but is largely unresponsive to current therapeutics. Animal models of cognitive dysfunction relevant to both disorders suggest the α7 nicotinic acetylcholine receptor (nAChR) may be a promising drug development target, with multiple clinical trials subsequently testing this hypothesis in individuals with SCZ and AD. However, the translational value of rodent cognitive tasks for predicting the overall efficacy of this therapeutic target in clinical trials is unknown. To compare effect sizes between rodent and human studies, we searched PubMed and the Cochrane Library for all randomized, placebo-controlled trials of compounds with pharmacological activity at the α7 nAChR for treatment of cognitive dysfunction in SCZ and AD and identified 18 studies comprising 2670 subjects treated with eight different compounds acting as full or partial agonists. Cognitive outcomes were standardized, and random-effects meta-analyses revealed no statistically significant effects of α7 nAChR agonists on overall cognition or any of eight cognitive subdomains when all doses were included (Range of all cognitive outcomes: Cohen’s d = −0.077 to 0.12, negative favoring drug). In contrast, analysis of 29 rodent studies testing the same α7 agonists revealed large effect sizes in multiple commonly used preclinical behavioral tests of cognition (Range: d = −1.18 to −0.73). Our results suggest that targeting the α7 nAChR with agonists is not a robust treatment for cognitive dysfunction in SCZ or AD and necessitate a better understanding of the translational gap for therapeutics targeting the α7 nAChR. PMID:28065843

Comparison of a gratitude-based and cognitive restructuring intervention for body dissatisfaction and dysfunctional eating behavior in college women.

PubMed

Wolfe, Wendy L; Patterson, Kaitlyn

2017-01-01

Researchers have investigated the efficacy of a gratitude intervention for decreasing body dissatisfaction (BD) in an internet treatment-seeking sample and demonstrated it worked equally well to decrease BD as cognitive restructuring. We extend this research by testing the efficacy of a gratitude intervention on BD, along with common sequelae of BD: dysfunctional eating, negative mood, and depressive symptoms. Females were randomly assigned to Gratitude, Cognitive Restructuring, or Control conditions. Pre- to post-intervention period comparisons found the gratitude intervention to perform better than the other conditions at increasing body esteem, decreasing BD, reducing dysfunctional eating, and reducing depressive symptoms.

Adolescent Executive Dysfunction in Daily Life: Relationships to Risks, Brain Structure and Substance Use

PubMed Central

Clark, Duncan B.; Chung, Tammy; Martin, Christopher S.; Hasler, Brant P.; Fitzgerald, Douglas H.; Luna, Beatriz; Brown, Sandra A.; Tapert, Susan F.; Brumback, Ty; Cummins, Kevin; Pfefferbaum, Adolf; Sullivan, Edith V.; Pohl, Kilian M.; Colrain, Ian M.; Baker, Fiona C.; De Bellis, Michael D.; Nooner, Kate B.; Nagel, Bonnie J.

2017-01-01

During adolescence, problems reflecting cognitive, behavioral and affective dysregulation, such as inattention and emotional dyscontrol, have been observed to be associated with substance use disorder (SUD) risks and outcomes. Prior studies have typically been with small samples, and have typically not included comprehensive measurement of executive dysfunction domains. The relationships of executive dysfunction in daily life with performance based testing of cognitive skills and structural brain characteristics, thought to be the basis for executive functioning, have not been definitively determined. The aims of this study were to determine the relationships between executive dysfunction in daily life, measured by the Behavior Rating Inventory of Executive Function (BRIEF), cognitive skills and structural brain characteristics, and SUD risks, including a global SUD risk indicator, sleep quality, and risky alcohol and cannabis use. In addition to bivariate relationships, multivariate models were tested. The subjects (n = 817; ages 12 through 21) were participants in the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) study. The results indicated that executive dysfunction was significantly related to SUD risks, poor sleep quality, risky alcohol use and cannabis use, and was not significantly related to cognitive skills or structural brain characteristics. In multivariate models, the relationship between poor sleep quality and risky substance use was mediated by executive dysfunction. While these cross-sectional relationships need to be further examined in longitudinal analyses, the results suggest that poor sleep quality and executive dysfunction may be viable preventive intervention targets to reduce adolescent substance use. PMID:29180956

Rasagiline for mild cognitive impairment in Parkinson's disease: A placebo-controlled trial.

PubMed

Weintraub, Daniel; Hauser, Robert A; Elm, Jordan J; Pagan, Fernando; Davis, Matthew D; Choudhry, Azhar

2016-05-01

This study's aims were to determine the efficacy and tolerability of rasagiline, a selective monoamine oxidase inhibitor B, for PD patients with mild cognitive impairment. Patients on stable dopaminergic therapy were randomized to adjunct rasagiline 1 mg/day or placebo in this 24-week, double-blind, placebo-controlled, multisite study. The primary endpoint was mean change from baseline to week 24 on the Scales for Outcomes of Parkinson's Disease-Cognition total score. Key secondary measures included changes in cognition, activities of daily living, motor scores, and Clinical Global Impression of Change, as well as safety and tolerability measures. Of the 170 patients randomized, 151 (88.2%) completed the study. Change in Scales for Outcomes of Parkinson's Disease-Cognition scores were not significantly different in the rasagiline and placebo groups (adjusted mean: 1.6 [standard error {SE} = 0.5] vs. 0.8 [SE = 0.5] points; LS means difference = 0.8; 95% confidence interval: -0.48, 2.05; P = 0.22). There were no between-group differences in change in the MoCA (p=0.84) or Penn Daily Activities Questionnaire (P = 0.48) scores or in the distribution of Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change modified for mild cognitive impairment (P = 0.1). Changes in motor (UPDRS part III; P = 0.02) and activities of daily living (UPDRS part II; P < 0.001) scores favored rasagiline. Rasagiline was well tolerated; the most common adverse events in both groups were falls and dizziness. Rasagiline treatment in PD patients with mild cognitive impairment was not associated with cognitive improvement. Rasagiline did not worsen cognition, improved motor symptoms and activities of daily living, and was well tolerated in elderly cognitively impaired patients. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

Alzheimer's neurofibrillary pathology and the spectrum of cognitive function: findings from the Nun Study.

PubMed

Riley, Kathryn P; Snowdon, David A; Markesbery, William R

2002-05-01

The development of interventions designed to delay the onset of dementia highlights the need to determine the neuropathologic characteristics of individuals whose cognitive function ranges from intact to demented, including those with mild cognitive impairments. We used the Braak method of staging Alzheimer's disease pathology in 130 women ages 76-102 years who were participants in the Nun Study, a longitudinal study of aging and Alzheimer's disease. All participants had complete autopsy data and were free from neuropathologic conditions other than Alzheimer's disease lesions that could affect cognitive function. Findings showed a strong relationship between Braak stage and cognitive state. The presence of memory impairment was associated with more severe Alzheimer's disease pathology and higher incidence of conversion to dementia in the groups classified as having mild or global cognitive impairments. In addition to Braak stage, atrophy of the neocortex was significantly related to the presence of dementia. Our data indicate that Alzheimer's neurofibrillary pathology is one of the neuropathologic substrates of mild cognitive impairments. Additional studies are needed to help explain the variability in neuropathologic findings seen in individuals whose cognitive performance falls between intact function and dementia.

Predictors of patient dependence in mild-to-moderate Alzheimer's disease.

PubMed

Benke, Thomas; Sanin, Günter; Lechner, Anita; Dal-Bianco, Peter; Ransmayr, Gerhard; Uranüs, Margarete; Marksteiner, Josef; Gaudig, Maren; Schmidt, Reinhold

2015-01-01

Patient dependence has rarely been studied in mild-to-moderate Alzheimer's disease (AD). To identify factors which predict patient dependence in mild-to-moderate AD. We studied 398 non-institutionalized AD patients (234 females) of the ongoing Prospective Registry on Dementia (PRODEM) in Austria. The Dependence Scale (DS) was used to assess patient dependence. Patient assessment comprised functional abilities, neuropsychiatric symptoms and cognitive functions. A multiple linear regression analysis was performed to identify predictors of patient dependence. AD patients were mildly-to-moderately impaired (mean scores and SDs were: CDR 0.84 ± 0.43; DAD 74.4 ± 23.3, MMSE = 22.5 ± 3.6). Psychopathology and caregiver burden were in the low range (mean NPI score 13.2, range 0 to 98; mean ZBI score 18, range 0-64). Seventy five percent of patients were classified as having a mild level of patient dependence (DS sum score 0 to 6). Patient dependence correlated significantly and positively with age, functional measures, psychopathology and depression, disease duration, and caregiver burden. Significant negative, but low correlations were found between patient dependence, cognitive variables, and global cognition. Activities of daily living, patient age, and disease severity accounted for 63% of variance in patient dependence, whereas cognitive variables accounted for only 11%. Dependence in this cohort was mainly related to age and functional impairment, and less so to cognitive and neuropsychiatric variables. This differs from studies investigating patients in more advanced disease stages which found abnormal behavior and impairments of cognition as main predictors of patient dependence.

The Test Your Memory for Mild Cognitive Impairment (TYM-MCI).

PubMed

Brown, Jeremy M; Lansdall, Claire J; Wiggins, Julie; Dawson, Kate E; Hunter, Kristina; Rowe, James B; Parker, Richard A

2017-12-01

To validate a short cognitive test: the Test Your Memory for Mild Cognitive Impairment (TYM-MCI) in the diagnosis of patients with amnestic mild cognitive impairment or mild Alzheimer's disease (aMCI/AD). Two hundred and two patients with mild memory problems were recruited. All had 'passed' the Mini-Mental State Examination (MMSE). Patients completed the TYM-MCI, the Test Your Memory test (TYM), MMSE and revised Addenbrooke's Cognitive Examination (ACE-R), had a neurological examination, clinical diagnostics and multidisciplinary team review. As a single test, the TYM-MCI performed as well as the ACE-R in the distinction of patients with aMCI/AD from patients with subjective memory impairment with a sensitivity of 0.79 and specificity of 0.91. Used in combination with the ACE-R, it provided additional value and identified almost all cases of aMCI/AD. The TYM-MCI correctly classified most patients who had equivocal ACE-R scores. Integrated discriminant improvement analysis showed that the TYM-MCI added value to the conventional memory assessment. Patients initially diagnosed as unknown or with subjective memory impairment who were later rediagnosed with aMCI/AD scored poorly on their original TYM-MCI. The TYM-MCI is a powerful short cognitive test that examines verbal and visual recall and is a valuable addition to the assessment of patients with aMCI/AD. It is simple and cheap to administer and requires minimal staff time and training. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice.

PubMed

Zhan, Gaofeng; Yang, Ning; Li, Shan; Huang, Niannian; Fang, Xi; Zhang, Jie; Zhu, Bin; Yang, Ling; Yang, Chun; Luo, Ailin

2018-06-10

Alzheimer's disease is characterized by cognitive dysfunction and aging is an important predisposing factor; however, the pathological and therapeutic mechanisms are not fully understood. Recently, the role of gut microbiota in Alzheimer's disease has received increasing attention. The cognitive function in senescence-accelerated mouse prone 8 (SAMP8) mice was significantly decreased and the Chao 1 and Shannon indices, principal coordinates analysis, and principal component analysis results were notably abnormal compared with that of those in senescence-accelerated mouse resistant 1 (SAMR1) mice. Moreover, 27 gut bacteria at six phylogenetic levels differed between SAMP8 and SAMR1 mice. In a separate study, we transplanted fecal bacteria from SAMP8 or SAMR1 mice into pseudo germ-free mice. Interestingly, the pseudo germ-free mice had significantly lower cognitive function prior to transplant. Pseudo germ-free mice that received fecal bacteria transplants from SAMR1 mice but not from SAMP8 mice showed improvements in behavior and in α-diversity and β-diversity indices. In total, 14 bacteria at six phylogenetic levels were significantly altered by the gut microbiota transplant. These results suggest that cognitive dysfunction in SAMP8 mice is associated with abnormal composition of the gut microbiota. Thus, improving abnormal gut microbiota may provide an alternative treatment for cognitive dysfunction and Alzheimer's disease.

Persistent activation of microglia and NADPH drive hippocampal dysfunction in experimental multiple sclerosis

PubMed Central

Di Filippo, Massimiliano; de Iure, Antonio; Giampà, Carmela; Chiasserini, Davide; Tozzi, Alessandro; Orvietani, Pier Luigi; Ghiglieri, Veronica; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Mancini, Andrea; Costa, Cinzia; Sarchielli, Paola; Fusco, Francesca Romana; Calabresi, Paolo

2016-01-01

Cognitive impairment is common in multiple sclerosis (MS). Unfortunately, the synaptic and molecular mechanisms underlying MS-associated cognitive dysfunction are largely unknown. We explored the presence and the underlying mechanism of cognitive and synaptic hippocampal dysfunction during the remission phase of experimental MS. Experiments were performed in a chronic-relapsing experimental autoimmune encephalomyelitis (EAE) model of MS, after the resolution of motor deficits. Immunohistochemistry and patch-clamp recordings were performed in the CA1 hippocampal area. The hole-board was utilized as cognitive/behavioural test. In the remission phase of experimental MS, hippocampal microglial cells showed signs of activation, CA1 hippocampal synapses presented an impaired long-term potentiation (LTP) and an alteration of spatial tests became evident. The activation of hippocampal microglia mediated synaptic and cognitive/behavioural alterations during EAE. Specifically, LTP blockade was found to be caused by the reactive oxygen species (ROS)-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We suggest that in the remission phase of experimental MS microglia remains activated, causing synaptic dysfunctions mediated by NADPH oxidase. Inhibition of microglial activation and NADPH oxidase may represent a promising strategy to prevent neuroplasticity impairment associated with active neuro-inflammation, with the aim to improve cognition and counteract MS disease progression. PMID:26887636

Relationship between maladaptive cognitions about sleep and recovery in patients with borderline personality disorder

PubMed Central

Plante, David T.; Frankenburg, Frances R.; Fitzmaurice, Garrett M.; Zanarini, Mary C.

2013-01-01

Borderline personality disorder (BPD) has been associated with maladaptive cognitive processes including dysfunctional attitudes and a negative attribution style. Comorbid insomnia affects the course of multiple psychiatric disorders, and has been associated with absence of recovery from BPD. Because dysfunctional beliefs and attitudes are common among patients with insomnia, the purpose of this study was to evaluate the association between maladaptive sleep-related cognitions and recovery status (symptomatic remission plus good concurrent psychosocial functioning) in patients with BPD. 223 BPD patients participating in the McLean Study of Adult Development (MSAD) were administered the Dysfunctional Beliefs and Attitudes about Sleep questionnaire (DBAS-16) as part of the 16-year follow-up wave. Maladaptive sleep cognitions were compared between recovered (n=105) and non-recovered (n=118) BPD participants, in analyses that adjusted for age, sex, depression, anxiety, and primary sleep disorders. Results demonstrated non-recovered BPD patients had significantly more severe maladaptive sleep-related cognitions as measured by the overall DBAS-16 score. These results demonstrate an association between dysfunctional beliefs and attitudes about sleep and recovery status among BPD patients. Further research is warranted to evaluate treatments targeted towards maladaptive sleep-related cognitions, and their subsequent effects on the course of BPD. PMID:23972789

Chronic Hypopituitarism Associated with Increased Postconcussive Symptoms Is Prevalent after Blast-Induced Mild Traumatic Brain Injury

PubMed Central

Undurti, Arundhati; Colasurdo, Elizabeth A.; Sikkema, Carl L.; Schultz, Jaclyn S.; Peskind, Elaine R.; Pagulayan, Kathleen F.; Wilkinson, Charles W.

2018-01-01

The most frequent injury sustained by US service members deployed to Iraq or Afghanistan is mild traumatic brain injuries (mTBI), or concussion, by far most often caused by blast waves from improvised explosive devices or other explosive ordnance. TBI from all causes gives rise to chronic neuroendocrine disorders with an estimated prevalence of 25–50%. The current study expands upon our earlier finding that chronic pituitary gland dysfunction occurs with a similarly high frequency after blast-related concussions. We measured circulating hormone levels and accessed demographic and testing data from two groups of male veterans with hazardous duty experience in Iraq or Afghanistan. Veterans in the mTBI group had experienced one or more blast-related concussion. Members of the deployment control (DC) group encountered similar deployment conditions but had no history of blast-related mTBI. 12 of 39 (31%) of the mTBI participants and 3 of 20 (15%) veterans in the DC group screened positive for one or more neuroendocrine disorders. Positive screens for growth hormone deficiency occurred most often. Analysis of responses on self-report questionnaires revealed main effects of both mTBI and hypopituitarism on postconcussive and posttraumatic stress disorder (PTSD) symptoms. Symptoms associated with pituitary dysfunction overlap considerably with those of PTSD. They include cognitive deficiencies, mood and anxiety disorders, sleep problems, diminished quality of life, deleterious changes in metabolism and body composition, and increased cardiovascular mortality. When such symptoms are due to hypopituitarism, they may be alleviated by hormone replacement. These findings suggest consideration of routine post-deployment neuroendocrine screening of service members and veterans who have experienced blast-related mTBI and are reporting postconcussive symptoms. PMID:29515515

Cognitive predictors and moderators of winter depression treatment outcomes in cognitive-behavioral therapy vs. light therapy.

PubMed

Sitnikov, Lilya; Rohan, Kelly J; Evans, Maggie; Mahon, Jennifer N; Nillni, Yael I

2013-12-01

There is no empirical basis for determining which seasonal affective disorder (SAD) patients are best suited for what type of treatment. Using data from a parent clinical trial comparing light therapy (LT), cognitive-behavioral therapy (CBT), and their combination (CBT + LT) for SAD, we constructed hierarchical linear regression models to explore baseline cognitive vulnerability constructs (i.e., dysfunctional attitudes, negative automatic thoughts, response styles) as prognostic and prescriptive factors of acute and next winter depression outcomes. Cognitive constructs did not predict or moderate acute treatment outcomes. Baseline dysfunctional attitudes and negative automatic thoughts were prescriptive of next winter treatment outcomes. Participants with higher baseline levels of dysfunctional attitudes and negative automatic thoughts had less severe depression the next winter if treated with CBT than if treated with LT. In addition, participants randomized to solo LT who scored at or above the sample mean on these cognitive measures at baseline had more severe depressive symptoms the next winter relative to those who scored below the mean. Baseline dysfunctional attitudes and negative automatic thoughts did not predict treatment outcomes in participants assigned to solo CBT or CBT + LT. Therefore, SAD patients with extremely rigid cognitions did not fare as well in the subsequent winter if treated initially with solo LT. Such patients may be better suited for initial treatment with CBT, which directly targets cognitive vulnerability processes. Copyright © 2013 Elsevier Ltd. All rights reserved.

Category and design fluency in mild cognitive impairment: Performance, strategy use, and neural correlates.

PubMed

Peter, Jessica; Kaiser, Jannis; Landerer, Verena; Köstering, Lena; Kaller, Christoph P; Heimbach, Bernhard; Hüll, Michael; Bormann, Tobias; Klöppel, Stefan

2016-12-01

The exploration and retrieval of words during category fluency involves different strategies to improve or maintain performance. Deficits in that task, which are common in patients with amnestic mild cognitive impairment (aMCI), mirror either impaired semantic memory or dysfunctional executive control mechanisms. Relating category fluency to tasks that place greater demands on either semantic knowledge or executive functions might help to determine the underlying cognitive process. The aims of this study were to compare performance and strategy use of 20 patients with aMCI to 30 healthy elderly controls (HC) and to identify the dominant component (either executive or semantic) for better task performance in category fluency. Thus, the relationship between category fluency, design fluency and naming was examined. As fluency tasks have been associated with the superior frontal gyrus (SFG), the inferior frontal gyrus (IFG), and the temporal pole, we further explored the relationship between gray matter volume in these areas and both performance and strategy use. Patients with aMCI showed significantly lower performance and significantly less strategy use during fluency tasks compared to HC. However, both groups equally improved their performance when repeatedly confronted with the same task. In aMCI, performance during category fluency was significantly predicted by design fluency performance, while in HC, it was significantly predicted by naming performance. In HC, volume of the SFG significantly predicted both category and design fluency performance, and strategy use during design fluency. In aMCI, the SFG and the IFG predicted performance during both category and design fluency. The IFG significantly predicted strategy use during category fluency in both groups. The reduced category fluency performance in aMCI seems to be primarily due to dysfunctional executive control mechanisms rather than impaired semantic knowledge. This finding is directly relevant to patients in the different stages of Alzheimer's disease as it links the known semantic fluency deficit in this population to executive functions. Although patients with aMCI are impaired in both performance and strategy use compared to HC, they are able to increase performance over time. However, only HC were able to significantly improve the utilization of fluency strategies in both category and design fluency over time. HC seem to rely more heavily on the SFG during fluency tasks, while in patients with aMCI additional frontal brain areas are involved, possibly reflecting compensational processes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Quantifying cognition at the bedside: a novel approach combining cognitive symptoms and signs in HIV.

PubMed

Brouillette, Marie-Josée; Fellows, Lesley K; Palladini, Lisa; Finch, Lois; Thomas, Réjean; Mayo, Nancy E

2015-11-13

Up to half of all people with HIV infection have some degree of cognitive impairment. This impairment is typically mild, but nonetheless often disabling. Although early detection of cognitive impairment offers the greatest hope of effective intervention, there are important barriers to this goal in most clinical settings. These include uncertainty about how self-reported cognitive symptoms relate to objective impairments, and the paucity of bedside measurement tools suitable for mild deficits. Clinicians need guidance in interpreting cognitive symptoms in this population, and a brief cognitive measurement tool targeted to mild impairment. We addressed these two problems together here. The objective of this study was to determine the extent to which performance on cognitive tests and self-reported cognitive symptoms form a unidimensional construct. Two hundred three HIV+ individuals completed the Montreal Cognitive Assessment, computerized cognitive tasks and a questionnaire eliciting cognitive symptoms. Rasch measurement theory was applied to determine whether patient-reported and performance items could be combined to measure cognition as a unidimensional latent construct. Performance-based items and cognitive symptoms are arranged hierarchically along the same continuum of cognitive ability, forming a measure with thresholds covering a broad spectrum of ability that has good internal reliability. The cognitive symptoms that fit the measurement model relate to important aspects of everyday life, providing evidence that the identified construct is meaningful. This finding lays the foundation for a rapid measure of cognitive ability in people with HIV infection that is feasible for routine clinical use, and shows that some cognitive symptoms are systematically related to performance in this population.

[Postoperative cognitive deficits].

PubMed

Kalezić, Nevena; Dimitrijević, Ivan; Leposavić, Ljubica; Kocica, Mladen; Bumbasirević, Vesna; Vucetić, Cedomir; Paunović, Ivan; Slavković, Nemanja; Filimonović, Jelena

2006-01-01

Cognitive dysfunctions are relatively common in postoperative and critically ill patients. This complication not only compromises recovery after surgery, but, if persistent, it minimizes and compromises surgery itself. Risk factors of postoperative cognitive disorders can be divided into age and comorbidity dependent, and those related to anesthesia and surgery. Cardiovascular, orthopedic and urologic surgery carries high risk of postoperative cognitive dysfunction. It can also occur in other types of surgical treatment, especially in elderly. Among risk factors of cognitive disorders, associated with comorbidity, underlying psychiatric and neurological disorders, substance abuse and conditions with elevation of intracranial pressure are in the first place in postoperative patients. Preoperative and perioperative predisposing conditions for cognitive dysfunction and their incidence were described in our paper. These are: geriatric patients, patients with substance abuse, preexisting psychiatric or cognitive disorders, neurologic disease with high intracranial pressure, cerebrovascular insufficiency, epilepsia, preeclampsia, acute intermittent porphyria, operation type, brain hypoxia, changes in blood glucose level, electrolyte imbalance, anesthetic agents, adjuvant medication and intraoperative awareness. For each of these factors, evaluation, prevention and treatment strategies were suggested, with special regard on anesthetic technique.

Neurocognitive function in obstructive sleep apnoea: a meta-review.

PubMed

Bucks, Romola S; Olaithe, Michelle; Eastwood, Peter

2013-01-01

Adult obstructive sleep apnoea (OSA) is associated with cognitive dysfunction. While many review articles have attempted to summarize the evidence for this association, it remains difficult to determine which domains of cognition are affected by OSA. This is because of marked differences in the nature of these reviews (e.g. many are unsystematic) and the many different tasks and domains assessed. This paper addresses this issue by comparing the results of only systematic reviews or meta-analyses assessing the effects of OSA on cognition, the relationship between OSA severity and cognition, and/or the effects of treatment on cognition in OSA. Electronic databases and hand-searching were undertaken to select reviews that reported on these areas. We found 33 reviews; five reviews met predetermined, stringent selection criteria. The majority of reviews supported deficits in attention/vigilance, delayed long-term visual and verbal memory, visuospatial/constructional abilities, and executive function in individuals with OSA. There is also general agreement that language ability and psychomotor function are unaffected by OSA. Data are equivocal for the effects of OSA on working memory, short-term memory and global cognitive functioning. Attention/vigilance dysfunction appears to be associated with sleep fragmentation and global cognitive function with hypoxaemia. Continuous positive airway pressure treatment of OSA appears to improve executive dysfunction, delayed long-term verbal and visual memory, attention/vigilance and global cognitive functioning. In order to improve our understanding of cognitive dysfunction in OSA, future research should pay particular attention to participant characteristics, measures of disease severity and choice of neuropsychological tests. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

Awareness of memory failures and motivation for cognitive training in mild cognitive impairment.

PubMed

Werheid, Katja; Ziegler, Matthias; Klapper, Annina; Kühl, Klaus-Peter

2010-01-01

Awareness of cognitive deficits is considered to be decisive for the effectiveness of cognitive training in mild cognitive impairment (MCI). However, it is unclear in what way awareness influences motivation to participate in cognitive training. Thirty-two elderly adults with MCI and 72 controls completed the 5-scale Memory Functioning Questionnaire (MFQ) and a motivation questionnaire. The predictive value of the MFQ scales on motivation was analyzed using regression analysis. In the MCI group, but not in controls, higher perceived frequency of memory failures was associated with a lower motivation score. Our findings indicate that, in MCI, greater awareness of cognitive deficits does not necessarily increase motivation to participate in cognitive trainings, and suggest that success expectancy may be a moderating factor. Copyright © 2010 S. Karger AG, Basel.

Marital quality in the context of mild cognitive impairment.

PubMed

Garand, Linda; Dew, Mary Amanda; Urda, Bridget; Lingler, Jennifer Hagerty; Dekosky, Steven T; Reynolds, Charles F

2007-12-01

Profound behavioral changes in persons with dementia often negatively affect the quality of marital relationships. Yet, little is known about the extent to which the marital relationship may be affected when the care recipient has milder degrees of cognitive impairment. This study characterizes marital quality among 27 adults who live with a spouse with mild cognitive impairment (MCI). This study demonstrates that at mild levels of cognitive impairment, specific behaviors in the affected person are distressing and may degrade the quality of the marital relationship. These results have implications for clinical practice and the delivery of health care and social services to these families. It is important to develop interventions to address the needs of these individuals and their caregivers. Results of this study suggest the need for mental health interventions designed to preserve the quality of these marital relationships.

Wechsler Memory Scale-III Faces test performance in patients with mild cognitive impairment and mild Alzheimer's disease.

PubMed

Seelye, Adriana M; Howieson, Diane B; Wild, Katherine V; Moore, Mindy Milar; Kaye, Jeffrey A

2009-08-01

Little is known about the sensitivity of the Wechsler Memory Scale-Third Edition (WMS-III) Faces subtest to memory impairment associated with mild cognitive impairment (MCI). In this study, Faces performance was examined in 24 MCI patients, 46 mild Alzheimer's disease (AD) patients, and 98 elderly controls. We hypothesized that participants with diagnoses of MCI or AD would be impaired relative to controls on Faces. Analyses showed that AD participants performed significantly worse than MCI and intact participants, although there were no significant differences between MCI and intact participants. Data suggest that brain areas specialized for face recognition memory may be less affected by MCI and mild AD than regions specialized for verbal memory.

Risk Factors for Falls in Older Adults With Mild Cognitive Impairment and Mild Alzheimer Disease.

PubMed

Ansai, Juliana Hotta; de Andrade, Larissa Pires; Masse, Fernando Arturo Arriagada; Gonçalves, Jessica; de Medeiros Takahashi, Anielle Cristhine; Vale, Francisco Assis Carvalho; Rebelatto, José Rubens

2017-03-03

Understanding fall risk factors in people with mild cognitive impairment (MCI) and Alzheimer disease (AD) can help to establish specific plans for prevention of falls. The purpose of this study was to identify fall risk factors in older adults with MCI and mild AD. A prospective study was conducted with community-dwelling older adults (40 MCI; 38 mild AD). The assessments consisted of sociodemographic and health variables, caloric expenditure, functional status, functional mobility (10-m walk test, dual-task test, and transition Timed Up and Go phases), cognitive domains, and depressive symptoms. Falls were recorded for 6 months by a falls calendar and monthly telephone calls. Falls were reported in 52.6% and 51.4% of people with MCI and mild AD, respectively. Among people with MCI, lower functional status, higher time spent on walk and dual task tests, and higher depressive symptom scores were associated with falls. Higher time spent on the dual-task test was independently associated with falls. Among people with mild AD, falls were associated with lower time spent on the walk test and turn-to-sit phase, and a higher visuospatial domain score. Lower time spent on the turn-to-sit phase was identified as an independent predictor of falls. Careful attention should be given to dual-task and turn-to-sit activities when detecting risk of falls among older people with MCI and mild AD.

Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease.

PubMed

Hayashi, Atsuko; Nomura, Hiroshi; Mochizuki, Ruriko; Ohnuma, Ayumu; Kimpara, Teiko; Suzuki, Kyoko; Mori, Etsuro

2015-01-01

We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji). A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients.

Nrf2 Deficiency Exacerbates Obesity-Induced Oxidative Stress, Neurovascular Dysfunction, Blood-Brain Barrier Disruption, Neuroinflammation, Amyloidogenic Gene Expression, and Cognitive Decline in Mice, Mimicking the Aging Phenotype.

PubMed

Tarantini, Stefano; Valcarcel-Ares, M Noa; Yabluchanskiy, Andriy; Tucsek, Zsuzsanna; Hertelendy, Peter; Kiss, Tamas; Gautam, Tripti; Zhang, Xin A; Sonntag, William E; de Cabo, Rafael; Farkas, Eszter; Elliott, Michael H; Kinter, Michael T; Deak, Ferenc; Ungvari, Zoltan; Csiszar, Anna

2018-06-14

Obesity has deleterious effects on cognitive function in the elderly adults. In mice, aging exacerbates obesity-induced oxidative stress, microvascular dysfunction, blood-brain barrier (BBB) disruption, and neuroinflammation, which compromise cognitive health. However, the specific mechanisms through which aging and obesity interact to remain elusive. Previously, we have shown that Nrf2 signaling plays a critical role in microvascular resilience to obesity and that aging is associated with progressive Nrf2 dysfunction, promoting microvascular impairment. To test the hypothesis that Nrf2 deficiency exacerbates cerebromicrovascular dysfunction induced by obesity Nrf2+/+ and Nrf2-/-, mice were fed an adipogenic high-fat diet (HFD). Nrf2 deficiency significantly exacerbated HFD-induced oxidative stress and cellular senescence, impairment of neurovascular coupling responses, BBB disruption, and microglia activation, mimicking the aging phenotype. Obesity in Nrf2-/- mice elicited complex alterations in the amyloidogenic gene expression profile, including upregulation of amyloid precursor protein. Nrf2 deficiency and obesity additively reduced long-term potentiation in the CA1 area of the hippocampus. Collectively, Nrf2 dysfunction exacerbates the deleterious effects of obesity, compromising cerebromicrovascular and brain health by impairing neurovascular coupling mechanisms, BBB integrity and synaptic function and promoting neuroinflammation. These results support a possible role for age-related Nrf2 dysfunction in the pathogenesis of vascular cognitive impairment and Alzheimer's disease.

BEHAVIORAL AND LEARNING DISABILITIES ASSOCIATED WITH COGNITIVE-MOTOR DYSFUNCTION. INTERIM REPORT.

ERIC Educational Resources Information Center

BRAUN, JEAN S.; RUBIN, ELI Z.

THIS REPORT EXAMINES THE RELATIONSHIP BETWEEN BEHAVIORAL AND ACADEMIC DISABILITIES AND COGNITIVE-MOTOR DYSFUNCTION AS REVEALED BY DATA ON 400 ELEMENTARY SCHOOL CHILDREN. THE BEHAVIOR CHECKLIST WAS USED AS A BASIS FOR SAMPLE SELECTION. BEHAVIOR CLUSTERS REFLECTING BOTH ANTI-SOCIAL TENDENCIES AND UNASSERTIVE, WITHDRAWN BEHAVIOR WERE IDENTIFIED. A…

Falls, Cognitive Impairment, and Gait Performance: Results From the GOOD Initiative

PubMed Central

Allali, Gilles; Launay, Cyrille P.; Blumen, Helena M.; Callisaya, Michele L.; De Cock, Anne-Marie; Kressig, Reto W.; Srikanth, Velandai; Steinmetz, Jean-Paul; Verghese, Joe; Beauchet, Olivier

2017-01-01

Objectives Falls are highly prevalent in individuals with cognitive decline. The complex relationship between falls and cognitive decline (including both subtype and severity of dementia) and the influence of gait disorders have not been studied. This study aimed to examine the association between the subtype (Alzheimer disease [AD] versus non-AD) and the severity (from preclinical to moderate dementia) of cognitive impairment and falls, and to establish an association between falls and gait parameters during the course of dementia. Design Multicenter cross-sectional study. Setting “Gait, cOgnitiOn & Decline” (GOOD) initiative. Participants A total of 2496 older adults (76.6 ± 7.6 years; 55.0% women) were included in this study (1161 cognitively healthy individuals [CHI], 529 patients with mild cognitive impairment [MCI], 456 patients with mild dementia, and 350 with moderate dementia) from 7 countries. Measurements Falls history was collected retrospectively at baseline in each study. Gait speed and stride time variability were recorded at usual walking pace with the GAITRite system. Results The prevalence of individuals who fall was 50% in AD and 64% in non-AD; whereas it was 25% in CHIs. Only mild and moderate non-AD dementia were associated with an increased risk for falls in comparison with CHI. Higher stride time variability was associated with falls in older adults without dementia (CHI and each MCI subgroup) and mild non-AD dementia, whereas lower gait speed was associated with falls in all participant groups, except in mild AD dementia. When gait speed was adjusted for, higher stride time variability was associated with falls only in CHIs (odds ratio 1.14; P = .012), but not in MCI or in patients with dementia. Conclusions These findings suggest that non-AD, but not AD dementia, is associated with increased falls in comparison with CHIs. The association between gait parameters and falls also differs across cognitive status, suggesting different mechanisms leading to falls in older individuals with dementia in comparison with CHIs who fall. PMID:27914848

Acetylcholinesterase inhibitor treatment alleviated cognitive impairment caused by delayed encephalopathy due to carbon monoxide poisoning: Two case reports and a review of the literature.

PubMed

Yanagiha, Kumi; Ishii, Kazuhiro; Tamaoka, Akira

2017-02-01

Delayed encephalopathy due to carbon monoxide (CO) poisoning can even occur in patients with mild symptoms of acute CO poisoning. Some cases taking conventional hyperbaric oxygen (HBO) therapy or steroid-pulse therapy may be insufficient, and AchEI may be effective. We report two cases of delayed encephalopathy after acute CO poisoning involving two women aged 69 (Case 1) and 60 years (Case 2) whose cognitive function improved with acetylcholinesterase inhibitor (AchEI) treatment. Delayed encephalopathy occurred 25 and 35 days after acute CO poisoning in Case 1 and Case 2, respectively. Both patients demonstrated cognitive impairment, apathy, and hypokinesia on admission. Although hyperbaric oxygen therapy did not yield any significant improvements, cognitive dysfunction improved substantially. This was evidenced by an improved Mini-Mental State Examination score ffom 9 to 28 points in Case 1 and an improved Hasegawa's dementia rating scale score from 4 to 25 points in Case 2 after administration of an AchEI. In Case 1, we administered galantamine hydrobromide, which was related with improved white matter lesions initially detected on brain magnetic resonance imaging. However, in Case 2 white matter lesions persisted despite AchEI treatment. AchEI treatment may result in improved cognitive and frontal lobe function by increasing low acetylcholine concentrations in the hippocampus and frontal lobe caused by decreased nicotinic acetylcholine receptor levels in delayed encephalopathy after CO poisoning. Physicians should consider AchEIs for patients demonstrating delayed encephalopathy due to CO poisoning.

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.

The evolution of the cognitive model of depression and its neurobiological correlates.

PubMed

Beck, Aaron T

2008-08-01

Although the cognitive model of depression has evolved appreciably since its first formulation over 40 years ago, the potential interaction of genetic, neurochemical, and cognitive factors has only recently been demonstrated. Combining findings from behavioral genetics and cognitive neuroscience with the accumulated research on the cognitive model opens new opportunities for integrated research. Drawing on advances in cognitive, personality, and social psychology as well as clinical observations, expansions of the original cognitive model have incorporated in successive stages automatic thoughts, cognitive distortions, dysfunctional beliefs, and information-processing biases. The developmental model identified early traumatic experiences and the formation of dysfunctional beliefs as predisposing events and congruent stressors in later life as precipitating factors. It is now possible to sketch out possible genetic and neurochemical pathways that interact with or are parallel to cognitive variables. A hypersensitive amygdala is associated with both a genetic polymorphism and a pattern of negative cognitive biases and dysfunctional beliefs, all of which constitute risk factors for depression. Further, the combination of a hyperactive amygdala and hypoactive prefrontal regions is associated with diminished cognitive appraisal and the occurrence of depression. Genetic polymorphisms also are involved in the overreaction to the stress and the hypercortisolemia in the development of depression--probably mediated by cognitive distortions. I suggest that comprehensive study of the psychological as well as biological correlates of depression can provide a new understanding of this debilitating disorder.

(Social) Cognitive Skills and Social Information Processing in Children with Mild to Borderline Intellectual Disabilities

ERIC Educational Resources Information Center

van Nieuwenhuijzen, M.; Vriens, A.

2012-01-01

The purpose of this study was to examine the unique contributions of (social) cognitive skills such as inhibition, working memory, perspective taking, facial emotion recognition, and interpretation of situations to the variance in social information processing in children with mild to borderline intellectual disabilities. Respondents were 79…

Cognitive Deficits in Problematic Drinkers with and without Mild to Borderline Intellectual Disability

ERIC Educational Resources Information Center

van Duijvenbode, Neomi; Didden, Robert; VanDerNagel, Joanne E. L.; Korzilius, Hubert P. L. M.; Engels, Rutger C. M. E.

2018-01-01

We examined cognitive deficits in problematic drinkers with and without mild to borderline intellectual disability (MBID). Problematic drinkers were expected to show a significantly lower estimated performance IQ (PIQ), but not a lower estimated verbal IQ (VIQ), compared to light drinkers. Participants (N = 474) were divided into four groups based…

Fruits, vegetables and their components and mild cognitive impairment and dementia: A review

USDA-ARS?s Scientific Manuscript database

The aim of this review is to evaluate the current literature on the role of fruit and vegetable (F&V) consumption and their components in the prevention of mild cognitive impairment (MCI) and dementia. The components investigated include vitamins C and E, carotenoids, polyphenols, and B-vitamins. Th...