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.

SGLT2-inhibitor and DPP-4 inhibitor improve brain function via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in HFD-induced obese rats.

PubMed

Sa-Nguanmoo, Piangkwan; Tanajak, Pongpan; Kerdphoo, Sasiwan; Jaiwongkam, Thidarat; Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-10-15

Dipeptidyl peptidase-4 inhibitor (vildagliptin) has been shown to exert beneficial effects on insulin sensitivity and neuroprotection in obese-insulin resistance. Recent studies demonstrated the neuroprotection of the sodium-glucose co-transporter 2 inhibitor (dapagliflozin) in diabetes. However, the comparative effects of both drugs and a combination of two drugs on metabolic dysfunction and brain dysfunction impaired by the obese-insulin resistance have never been investigated. Forty male Wistar rats were divided into two groups, and received either a normal-diet (ND, n=8) or a high-fat diet (HFD, n=32) for 16weeks. At week 13, the HFD-fed rats were divided into four subgroups (n=8/subgroup) to receive either a vehicle, vildagliptin (3mg/kg/day) dapagliflozin (1mg/kg/day) or combined drugs for four weeks. ND rats were given a vehicle for four weeks. Metabolic parameters and brain function were investigated. The results demonstrated that HFD rats developed obese-insulin resistance and cognitive decline. Dapagliflozin had greater efficacy on improved peripheral insulin sensitivity and reduced weight gain than vildagliptin. Single therapy resulted in equally improved brain mitochondrial function, insulin signaling, apoptosis and prevented cognitive decline. However, only dapagliflozin improved hippocampal synaptic plasticity. A combination of the drugs had greater efficacy in improving brain insulin sensitivity and reducing brain oxidative stress than the single drug therapy. These findings suggested that dapagliflozin and vildagliptin equally prevented cognitive decline in the obese-insulin resistance, possibly through some similar mechanisms. Dapagliflozin had greater efficacy than vildagliptin for preserving synaptic plasticity, thus combined drugs could be the best therapeutic approach for neuroprotection in the obese-insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

PARANOID INDIVIDUALS WITH SCHIZOPHRENIA SHOW GREATER SOCIAL COGNITIVE BIAS AND WORSE SOCIAL FUNCTIONING THAN NON-PARANOID INDIVIDUALS WITH SCHIZOPHRENIA.

PubMed

Pinkham, Amy E; Harvey, Philip D; Penn, David L

2016-03-01

Paranoia is a common symptom of schizophrenia that may be related to how individuals process and respond to social stimuli. Previous investigations support a link between increased paranoia and greater social cognitive impairments, but these studies have been limited to single domains of social cognition, and no studies have examined how paranoia may influence functional outcome. Data from 147 individuals with schizophrenia were used to examine whether actively paranoid and non-paranoid individuals with schizophrenia differ in social cognition and functional outcomes. On measures assessing social cognitive bias, paranoid individuals endorsed more hostile and blaming attributions and identified more faces as untrustworthy; however, paranoid and non-paranoid individuals did not differ on emotion recognition and theory of mind tasks assessing social cognitive ability. Likewise, paranoid individuals showed greater impairments in real-world interpersonal relationships and social acceptability as compared to non-paranoid patients, but these differences did not extend to performance based tasks assessing functional capacity and social competence. These findings isolate specific social cognitive disparities between paranoid and non-paranoid subgroups and suggest that paranoia may exacerbate the social dysfunction that is commonly experienced by individuals with schizophrenia.

A randomised controlled trial of adjunctive yoga and adjunctive physical exercise training for cognitive dysfunction in schizophrenia.

PubMed

Bhatia, Triptish; Mazumdar, Sati; Wood, Joel; He, Fanyin; Gur, Raquel E; Gur, Ruben C; Nimgaonkar, Vishwajit L; Deshpande, Smita N

2017-04-01

Yoga and physical exercise have been used as adjunctive intervention for cognitive dysfunction in schizophrenia (SZ), but controlled comparisons are lacking. Aims A single-blind randomised controlled trial was designed to evaluate whether yoga training or physical exercise training enhance cognitive functions in SZ, based on a prior pilot study. Consenting, clinically stable, adult outpatients with SZ (n=286) completed baseline assessments and were randomised to treatment as usual (TAU), supervised yoga training with TAU (YT) or supervised physical exercise training with TAU (PE). Based on the pilot study, the primary outcome measure was speed index for the cognitive domain of 'attention' in the Penn computerised neurocognitive battery. Using mixed models and contrasts, cognitive functions at baseline, 21 days (end of training), 3 and 6 months post-training were evaluated with intention-to-treat paradigm. Speed index of attention domain in the YT group showed greater improvement than PE at 6 months follow-up (p<0.036, effect size 0.51). In the PE group, 'accuracy index of attention domain showed greater improvement than TAU alone at 6-month follow-up (p<0.025, effect size 0.61). For several other cognitive domains, significant improvements were observed with YT or PE compared with TAU alone (p<0.05, effect sizes 0.30-1.97). Both YT and PE improved attention and additional cognitive domains well past the training period, supporting our prior reported beneficial effect of YT on speed index of attention domain. As adjuncts, YT or PE can benefit individuals with SZ.

Cognitive functioning in bilateral perisylvian polymicrogyria (BPP): clinical and radiological correlations.

PubMed

Jansen, An C; Leonard, Gabriel; Bastos, Alexandre C; Esposito-Festen, Josée E; Tampieri, Donatella; Watkins, Kate; Andermann, Frederick; Andermann, Eva

2005-05-01

Bilateral perisylvian polymicrogyria (BPP) is a malformation of cortical development, frequently associated with severe dysarthria or anarthria. BPP patients are therefore often labeled as severely retarded, but a detailed neuropsychological profile has not been reported to date. In a series of 14 patients, we demonstrated that only a minority had extremely low intelligence, and that some aspects of cognitive function correlated with the extent of the cortical disorganization. Early age at seizure onset correlated positively with Performance IQ scores (P<0.05) and negatively with the extent of the lesion (P<0.01), reflecting that patients with more severe BPP are more likely to have early seizure onset, resulting in greater interference with ongoing cognitive development. Receptive and expressive language skills were found to be equally poor. Frontal lobe function and memory abilities were relatively well preserved, suggesting that the observed cognitive profiles were related, at least in part, to specific areas of cortical dysfunction and not only to global dysfunction.

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

PubMed

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

2012-02-01

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

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.

A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy.

PubMed

Lawrence, J A; Griffin, L; Balcueva, E P; Groteluschen, D L; Samuel, T A; Lesser, G J; Naughton, M J; Case, L D; Shaw, E G; Rapp, S R

2016-02-01

Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. Women who received adjuvant chemotherapy 1-5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory-the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p = 0.033) and HVLT-R Discrimination (p = 0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results.

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.

Reduced Gray Matter Volume Is Associated With Poorer Instrumental Activities of Daily Living Performance in Heart Failure.

PubMed

Alosco, Michael L; Brickman, Adam M; Spitznagel, Mary Beth; Narkhede, Atul; Griffith, Erica Y; Cohen, Ronald; Sweet, Lawrence H; Josephson, Richard; Hughes, Joel; Gunstad, John

2016-01-01

Heart failure patients require assistance with instrumental activities of daily living in part because of the high rates of cognitive impairment in this population. Structural brain insult (eg, reduced gray matter volume) is theorized to underlie cognitive dysfunction in heart failure, although no study has examined the association among gray matter, cognition, and instrumental activities of daily living in heart failure. The aim of this study was to investigate the associations among gray matter volume, cognitive function, and functional ability in heart failure. A total of 81 heart failure patients completed a cognitive test battery and the Lawton-Brody self-report questionnaire to assess instrumental activities of daily living. Participants underwent magnetic resonance imaging to quantify total gray matter and subcortical gray matter volume. Impairments in instrumental activities of daily living were common in this sample of HF patients. Regression analyses controlling for demographic and medical confounders showed that smaller total gray matter volume predicted decreased scores on the instrumental activities of daily living composite, with specific associations noted for medication management and independence in driving. Interaction analyses showed that reduced total gray matter volume interacted with worse attention/executive function and memory to negatively impact instrumental activities of daily living. Smaller gray matter volume is associated with greater impairment in instrumental activities of daily living in persons with heart failure, possibly via cognitive dysfunction. Prospective studies are needed to clarify the utility of clinical correlates of gray matter volume (eg, cognitive dysfunction) in identifying heart failure patients at risk for functional decline and determine whether interventions that target improved brain and cognitive function can preserve functional independence in this high-risk population.

The prevalence of cognitive distortion in depressed adolescents.

PubMed

Marton, P; Kutcher, S

1995-01-01

This study examined the prevalence of cognitive distortion in depressed adolescents. Ninety-four consecutive depressed adolescent psychiatric outpatients were administered the Beck Depression Inventory, the Dysfunctional Attitude Scale, the Interpersonal Dependency Inventory and the Maudsley Personality Inventory. Depressed patients who scored above a threshold for cognitive distortion were compared to those who fell below the threshold. Of the depressed patients, 47.4% were found to meet the severity criteria for cognitive distortion, while the remaining 52.6% were found to be below the severity threshold. Cognitive distortion was associated with more severe symptoms of depression, lack of social self confidence and greater introversion. These results do not support the hypothesis that cognitive distortion is universal in clinical depression. However, they do suggest that cognitive distortion is associated with more severe depression.

The prevalence of cognitive distortion in depressed adolescents.

PubMed Central

Marton, P; Kutcher, S

1995-01-01

This study examined the prevalence of cognitive distortion in depressed adolescents. Ninety-four consecutive depressed adolescent psychiatric outpatients were administered the Beck Depression Inventory, the Dysfunctional Attitude Scale, the Interpersonal Dependency Inventory and the Maudsley Personality Inventory. Depressed patients who scored above a threshold for cognitive distortion were compared to those who fell below the threshold. Of the depressed patients, 47.4% were found to meet the severity criteria for cognitive distortion, while the remaining 52.6% were found to be below the severity threshold. Cognitive distortion was associated with more severe symptoms of depression, lack of social self confidence and greater introversion. These results do not support the hypothesis that cognitive distortion is universal in clinical depression. However, they do suggest that cognitive distortion is associated with more severe depression. PMID:7865499

An Examination of Executive Dysfunction Associated with Frontostriatal Circuitry in Parkinson’s Disease

PubMed Central

ZGALJARDIC, DENNIS J.; BOROD, JOAN C.; FOLDI, NANCY S.; MATTIS, PAUL J.; GORDON, MARK F.; FEIGIN, ANDREW; EIDELBERG, DAVID

2015-01-01

Parkinson’s disease (PD) is a neurodegenerative movement disorder presenting with subcortical pathology and characterized by motor deficits. However, as is frequently reported in the literature, patients with PD can also exhibit cognitive and behavioral (i.e., nonmotor) impairments, cognitive executive deficits and depression being the most prominent. Considerable attention has addressed the role that disruption to frontostriatal circuitry can play in mediating nonmotor dysfunction in PD. The three nonmotor frontostriatal circuits, which connect frontal cortical regions to the basal ganglia, originate from the dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). The objective of the current study was to use our understanding of frontostriatal circuit function (via literature review) to categorize neuropsychological measures of cognitive and behavioral executive functions by circuit. To our knowledge, such an approach has not been previously attempted in the study of executive dysfunction in PD. Neuropsychological measures of executive functions and self-report behavioral inventories, categorized by circuit function, were administered to 32 nondemented patients with Parkinson’s disease (NDPD) and to 29 demographically matched, healthy normal control participants (NC). Our findings revealed significant group differences for each circuit, with the PD group performing worse than the NC group. Among the patients with PD, indices of impairment were greater for tasks associated with DLPFC function than with OFC function. Further, only an index of DLPFC test performance was demonstrated to significantly discriminate individuals with and without PD. In conclusion, our findings suggest that nondemented patients with PD exhibit greater impairment on neuropsychological measures associated with DLPFC than with ACC or OFC circuit function. PMID:16840240

Adjustment and Other Factors Related to High School Aged Students Identified as Hearing Impaired

ERIC Educational Resources Information Center

Milano, Charlene; Upshire, Tara; Scarazzo, Sara; Schade, Benjamin P.; Larwin, Karen H.

2016-01-01

Healthy social, emotional and cognitive development of deaf children depends upon complex interactions between the many individual and environmental factors associated with deafness. Deaf children and adolescents have been reported to possess greater rates of mental health problems than hearing children and adolescents. Dysfunction in one or more…

Intraindividual variability as a marker of neurological dysfunction: a comparison of Alzheimer's disease and Parkinson's disease.

PubMed

Burton, Catherine L; Strauss, Esther; Hultsch, David F; Moll, Alex; Hunter, Michael A

2006-01-01

Individuals with certain neurological conditions may demonstrate greater inconsistency (i.e., intraindividual variability) on cognitive tasks compared to healthy controls. Several researchers have suggested that intraindividual variability may be a behavioral marker of compromised neurobiological mechanisms associated with aging, disease, or injury. The present study sought to investigate whether intraindividual variability is associated with general nervous system compromise, or rather, with certain types of neurological disturbances by comparing healthy adults, adults with Alzheimer's disease (AD), and Parkinson's disease (PD). Participants were assessed on four separate occasions using measures of reaction time and memory. Results indicated that inconsistency was correlated with indices of severity of impairment suggesting a dose-response relationship between cognitive disturbance and intraindividual variability: the more severe the cognitive disturbance, the greater the inconsistency. However, participants with AD were more inconsistent than those with PD, with both groups being more variable than the healthy group, even when controlling for group differences in overall severity of cognitive impairment or cognitive decline. Consequently, intraindividual variability may index both the severity of cognitive impairment and the nature of the neurological disturbance.

Mild Cognitive Dysfunction Does Not Affect Diabetes Mellitus Control in Minority Elderly Adults

PubMed Central

Palta, Priya; Golden, Sherita H.; Teresi, Jeanne; Palmas, Walter; Weinstock, Ruth S.; Shea, Steven; Manly, Jennifer J.; Luchsinger, Jose A.

2015-01-01

OBJECTIVES To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction. DESIGN Prospective cohort study. SETTING A minority cohort in New York City previously recruited for a trial of telemedicine. PARTICIPANTS Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black). MEASUREMENTS Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction. RESULTS Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction. CONCLUSION Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control. PMID:25439094

Mild cognitive dysfunction does not affect diabetes mellitus control in minority elderly adults.

PubMed

Palta, Priya; Golden, Sherita H; Teresi, Jeanne; Palmas, Walter; Weinstock, Ruth S; Shea, Steven; Manly, Jennifer J; Luchsinger, Jose A

2014-12-01

To determine whether older adults with type 2 diabetes mellitus and cognitive dysfunction have poorer metabolic control of glycosylated hemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than those without cognitive dysfunction. Prospective cohort study. A minority cohort in New York City previously recruited for a trial of telemedicine. Persons aged 73.0 ± 3.0 (N = 613; 69.5% female; 82.5% Hispanic, 15.5% non-Hispanic black). Participants were classified with executive or memory dysfunction based on standardized score cutoffs (<16th percentile) for the Color Trails Test and Selective Reminding Test. Linear mixed models were used to compare repeated measures of the metabolic measures and evaluate the rates of change in individuals with and without dysfunction. Of the 613 participants, 331 (54%) had executive dysfunction, 202 (33%) had memory dysfunction, and 96 (16%) had both. Over a median of 2 years, participants with executive or memory dysfunction did not exhibit significantly poorer metabolic control than those without executive function or memory type cognitive dysfunction. Cognitive dysfunction in the mild range did not seem to affect diabetes mellitus control parameters in this multiethnic cohort of older adults with diabetes mellitus, although it cannot be excluded that cognitive impairment was overcome through assistance from formal or informal caregivers. It is possible that more-severe cognitive dysfunction could affect control. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Dorsolateral prefrontal cortex activation during emotional anticipation and neuropsychological performance in posttraumatic stress disorder.

PubMed

Aupperle, Robin L; Allard, Carolyn B; Grimes, Erin M; Simmons, Alan N; Flagan, Taru; Behrooznia, Michelle; Cissell, Shadha H; Twamley, Elizabeth W; Thorp, Steven R; Norman, Sonya B; Paulus, Martin P; Stein, Murray B

2012-04-01

Posttraumatic stress disorder (PTSD) has been associated with executive or attentional dysfunction and problems in emotion processing. However, it is unclear whether these two domains of dysfunction are related to common or distinct neurophysiological substrates. To examine the hypothesis that greater neuropsychological impairment in PTSD relates to greater disruption in prefrontal-subcortical networks during emotional anticipation. Case-control, cross-sectional study. General community and hospital and community psychiatric clinics. Volunteer sample of 37 women with PTSD related to intimate partner violence and 34 age-comparable healthy control women. We used functional magnetic resonance imaging (fMRI) to examine neural responses during anticipation of negative and positive emotional images. The Clinician-Administered PTSD Scale was used to characterize PTSD symptom severity. The Wechsler Adult Intelligence Scale, Third Edition, Digit Symbol Test, Delis-Kaplan Executive Function System Color-Word Interference Test, and Wisconsin Card Sorting Test were used to characterize neuropsychological performance. Women with PTSD performed worse on complex visuomotor processing speed (Digit Symbol Test) and executive function (Color-Word Interference Inhibition/Switching subtest) measures compared with control subjects. Posttraumatic stress disorder was associated with greater anterior insula and attenuated lateral prefrontal cortex (PFC) activation during emotional anticipation. Greater dorsolateral PFC activation (anticipation of negative images minus anticipation of positive images) was associated with lower PTSD symptom severity and better visuomotor processing speed and executive functioning. Greater medial PFC and amygdala activation related to slower visuomotor processing speed. During emotional anticipation, women with PTSD show exaggerated activation in the anterior insula, a region important for monitoring internal bodily state. Greater dorsolateral PFC response in PTSD patients during emotional anticipation may reflect engagement of cognitive control networks that are beneficial for emotional and cognitive functioning. Novel treatments could be aimed at strengthening the balance between cognitive control (dorsolateral PFC) and affective processing (medial PFC and amygdala) networks to improve overall functioning for PTSD patients.

Subclinical hypothyroidism and cognitive dysfunction in the elderly.

PubMed

Resta, F; Triggiani, V; Barile, G; Benigno, M; Suppressa, P; Giagulli, V A; Guastamacchia, E; Sabbà, C

2012-09-01

While overt hypothyroidism is associated with reversible dementia in the elderly, the relationship of subclinical hypothyroidism with cognition remains a controversial issue. Our aim was to investigate the correlation between subclinical hypothyroidism and cognition in the elderly, with particular reference to long term memory and selective attention. We selected 337 outpatients (177 men and 160 women), mean age 74.3 years, excluding the subjects with thyroid dysfunction and those treated with drugs influencing thyroid function. The score of Mini Mental State Examination (MMSE) was significantly lower in the group of patients with subclinical hypothyroidism than in euthyroid subjects (p<0.03). It was observed that patients with subclinical hypothyroidism had a probability about 2 times greater (RR = 2.028, p<0.05) of developing cognitive impairment. Prose Memory Test (PMT) score resulted significantly lower in subjects with subclinical hypothyroidism (p<0.04). Considering the Matrix Test (MT) score, the performance was slightly reduced in subclinical hypothyroidism (NS). Furthermore, TSH was negatively correlated with MMSE (p<0.04), PMT (p<0.05) and MT score (NS). No correlation was found between FT4 and FT3 and MMSE, PMT and MT score. In the elderly, subclinical hypothyroidism is associated with cognitive impairment, and its impact on specific aspects of cognition (long term memory and selective attention) is less evident.

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

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

Differential effects of psychopathy and antisocial personality disorder symptoms on cognitive and fear processing in female offenders.

PubMed

Anton, Marja E; Baskin-Sommers, Arielle R; Vitale, Jennifer E; Curtin, John J; Newman, Joseph P

2012-12-01

Psychopathy and antisocial personality disorder (APD) have long been considered important risk factors for criminal behavior and incarceration. However, little is known about the psychobiological underpinnings that give rise to the disinhibited behavior of female offenders. Using an instructed fear-conditioning paradigm and a sample of incarcerated female offenders, we manipulated attentional focus and cognitive load to characterize and differentiate between the dysfunctional cognitive and affective processes associated with these syndromes. We used fear-potentiated startle (FPS) and event-related potentials as measures of affective and cognitive processing, respectively. After controlling for APD symptoms, psychopathic women displayed greater FPS while attending directly to threat-relevant stimuli and displayed less FPS while performing a demanding task that directed attention to threat-irrelevant information. Conversely, controlling for psychopathy, women with high APD symptoms displayed less overall FPS, especially when instructed to focus on threat-relevant stimuli. However, as the demands on cognitive resources increased, they displayed greater FPS. For both psychopathy and APD, analysis of the event-related potentials qualified these findings and further specified the abnormal cognitive processes associated with these two syndromes. Overall, simultaneous analysis of psychopathy and APD revealed distinct patterns of cognitive processing and fear reactivity.

Pituitary Dysfunction after Blast Traumatic Brain Injury: The UK BIOSAP Study

PubMed Central

Baxter, David; Sharp, David J; Feeney, Claire; Papadopoulou, Debbie; Ham, Timothy E; Jilka, Sagar; Hellyer, Peter J; Patel, Maneesh C; Bennett, Alexander N; Mistlin, Alan; McGilloway, Emer; Midwinter, Mark; Goldstone, Anthony P

2013-01-01

Objective Pituitary dysfunction is a recognized consequence of traumatic brain injury (TBI) that causes cognitive, psychological, and metabolic impairment. Hormone replacement offers a therapeutic opportunity. Blast TBI (bTBI) from improvised explosive devices is commonly seen in soldiers returning from recent conflicts. We investigated: (1) the prevalence and consequences of pituitary dysfunction following moderate to severe bTBI and (2) whether it is associated with particular patterns of brain injury. Methods Nineteen male soldiers with moderate to severe bTBI (median age = 28.3 years) and 39 male controls with moderate to severe nonblast TBI (nbTBI; median age = 32.3 years) underwent full dynamic endocrine assessment between 2 and 48 months after injury. In addition, soldiers had structural brain magnetic resonance imaging, including diffusion tensor imaging (DTI), and cognitive assessment. Results Six of 19 (32.0%) soldiers with bTBI, but only 1 of 39 (2.6%) nbTBI controls, had anterior pituitary dysfunction (p = 0.004). Two soldiers had hyperprolactinemia, 2 had growth hormone (GH) deficiency, 1 had adrenocorticotropic hormone (ACTH) deficiency, and 1 had combined GH/ACTH/gonadotrophin deficiency. DTI measures of white matter structure showed greater traumatic axonal injury in the cerebellum and corpus callosum in those soldiers with pituitary dysfunction than in those without. Soldiers with pituitary dysfunction after bTBI also had a higher prevalence of skull/facial fractures and worse cognitive function. Four soldiers (21.1%) commenced hormone replacement(s) for hypopituitarism. Interpretation We reveal a high prevalence of anterior pituitary dysfunction in soldiers suffering moderate to severe bTBI, which was more frequent than in a matched group of civilian moderate to severe nbTBI subjects. We recommend that all patients with moderate to severe bTBI should routinely have comprehensive assessment of endocrine function. Ann Neurol 2013;74:527–536 PMID:23794460

[Greater level of physical activity associated with better cognitive function in hemodialysis in end stage renal disease].

PubMed

Stringuetta-Belik, Fernanda; Shiraishi, Flávio Gobbis; Oliveira e Silva, Viviana Rugolo; Barretti, Pasqual; Caramori, Jacqueline Costa Teixeira; Bôas, Paulo José Fortes Villas; Martin, Luis Cuadrado; Franco, Roberto Jorge da Silva

2012-01-01

Patients with chronic kidney disease (CKD) have a lower exercise tolerance and poor functional capacity, carry on a sedentary lifestyle. Another important change found in patients with CKD is cognitive dysfunction. Physical inactivity has been associated with cognitive dysfunction in the general population, but few studies have evaluated this association in CKD. To assess the association between physical activity and cognitive function in patients with CKD on hemodialysis (HD). We evaluated 102 patients undergoing HD. The participants completed the International Physical Activity Questionnaire, which assesses the level of physical activity and the Mini Mental State Examination, used for cognitive screening. Patients were divided into three groups according to their level of physical activity (GI: active/GII: irregularly active/GIII: sedentary). It was applied logistic regression analysis and adopted as outcome variable the presence of cognitive impairment and preserving as independent variables those with a probability of statistical difference between groups of less than 0.1. It was considered statistically significant when p less than 0.05. The groups were similar in age, duration of HD, and smoking. Statistically significant difference regarding race, body mass index, diabetes mellitus, underlying disease and degree of cognitive impairment. Regarding laboratory data, the groups differed in terms of creatinine, glucose, hemoglobin and hematocrit. There was significant association with better physical activity and cognitive function, even adjusting for confounding variables. the highest level of physical activity was associated with better cognitive function in CKD patients undergoing HD.

Age as a Predictor of Cognitive Decline in Bipolar Disorder

PubMed Central

Lewandowski, Kathryn E.; Sperry, Sarah H.; Malloy, Mary C.; Forester, Brent P.

2013-01-01

Objective Cognitive dysfunction is a core feature of Bipolar Disorder (BD) in both adult and geriatric patients. However, little is known about whether cognitive functioning declines at a faster rate in patients with BD and there are conflicting reports regarding the relationship between age and cognitive functioning in this population. This cross-sectional study examined the relationship between age and cognitive functioning in patients with BD. Methods Patients with BD I (n=113) and healthy adults (n=64) ages 18–87 completed measures of processing speed, attention, executive functioning, verbal fluency, and clinical symptomatology. Groupwise comparisons were used to examine differences between patients and the comparison group and adult and geriatric BD cohorts. A series of linear regressions was conducted to examine the relationship of age and cognitive functioning, and clinical variables and cognition. Results Patients performed significantly worse than the comparison group on all neuropsychological measures. Age was a significant predictor of Trails A scores with older age associated with worse performance. Conclusions Older age was associated with poorer performance on Trails A in patients with BD but not healthy adults. These results are suggestive of greater dysfunction in processing speed with older age in patients with BD compared to a healthy comparison group. As cognitive functioning is associated with community outcomes, these findings suggest a need for treatments targeting cognitive symptoms across the lifespan. Future research exploring neurobiological evidence for neurodegenerative processes in bipolar disorder will pave the way for potential therapeutic interventions. PMID:24262287

Multi-Modal Hallucinations and Cognitive Function in Parkinson's Disease

PubMed Central

Katzen, Heather; Myerson, Connie; Papapetropoulos, Spiridon; Nahab, Fatta; Gallo, Bruno; Levin, Bonnie

2010-01-01

Background/Aims Hallucinations have been linked to a constellation of cognitive deficits in Parkinson's disease (PD), but it is not known whether multi-modal hallucinations are associated with greater neuropsychological dysfunction. Methods 152 idiopathic PD patients were categorized based on the presence or absence of hallucinations and then were further subdivided into visual-only (VHonly; n = 35) or multi-modal (VHplus; n = 12) hallucination groups. All participants underwent detailed neuropsychological assessment. Results Participants with hallucinations performed more poorly on select neuropsychological measures and exhibited more mood symptoms. There were no differences between VHonly and VHplus groups. Conclusions PD patients with multi-modal hallucinations are not at greater risk for neuropsychological impairment than those with single-modal hallucinations. PMID:20689283

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.

The development and initial validation of a sensitive bedside cognitive screening test.

PubMed

Faust, D; Fogel, B S

1989-01-01

Brief bedside cognitive examinations such as the Mini-Mental State Examination are designed to detect delirium and dementia but not more subtle or delineated cognitive deficits. Formal neuropsychological evaluation provides greater sensitivity and detects a wider range of cognitive deficits but is too lengthy for efficient use at the bedside or in epidemiological studies. The authors developed the High Sensitivity Cognitive Screen (HSCS), a 20-minute interview-based test, to identify patients who show disorder on formal neuropsychological evaluation. An initial study demonstrated satisfactory test-retest and interrater reliability. The HSCS was then administered to 60 psychiatric and neurological patients with suspected cognitive deficits but without gross impairment, who also completed formal neuropsychological testing. Results of both tests were independently classified as either normal, borderline, or abnormal. The HSCS correctly classified 93% of patients across the normal-abnormal dichotomy and showed promise for characterizing the extent and severity of cognitive dysfunction.

[Alcohol-related cognitive impairment and the DSM-5].

PubMed

Walvoort, S J W; Wester, A J; Doorakkers, M C; Kessels, R P C; Egger, J I M

2016-01-01

It is evident from the dsm-iv-tr that alcohol-related impairment is extremely difficult to classify accurately. As a result, cognitive deficits can easily be overlooked. The dsm-5, however, incorporates a new category, namely 'neurocognitive disorders', which may lead to significant improvements in clinical practice. To compare the classification of alcohol-related cognitive dysfunction in dsm-iv-tr and dsm-5 and to discuss the clinical relevance of the revised classification in the dsm-5. We compare the chapters of the dsm-iv-tr and the dsm-5 concerning alcohol-related cognitive impairment and describe the changes that have been made. The dsm-5 puts greater emphasis on alcohol-related neurocognitive impairment. Not only does dsm-5 distinguish between the degree of severity (major or minor neurocognitive disorder), it also distinguishes between the type of impairment (non-amnestic-type versus confabulating-amnestic type). It also makes a distinction between the durations of impairment (behavioural and/or persistent disorders). The dsm-5 gives a clearer description of alcohol-related neurocognitive dysfunction than does dsm-iv-tr and it stresses the essential role of neuropsychological assessment in the classification, diagnosis, and treatment of neurocognitive disorders.

Objective measurement of daytime napping, cognitive dysfunction and subjective sleepiness in Parkinson's disease.

PubMed

Bolitho, Samuel J; Naismith, Sharon L; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R; Lewis, Simon J G

2013-01-01

Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson's disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms.

Objective Measurement of Daytime Napping, Cognitive Dysfunction and Subjective Sleepiness in Parkinson’s Disease

PubMed Central

Bolitho, Samuel J.; Naismith, Sharon L.; Salahuddin, Pierre; Terpening, Zoe; Grunstein, Ron R.; Lewis, Simon J. G.

2013-01-01

Introduction Sleep-wake disturbances and concomitant cognitive dysfunction in Parkinson’s disease (PD) contribute significantly to morbidity in patients and their carers. Subjectively reported daytime sleep disturbance is observed in over half of all patients with PD and has been linked to executive cognitive dysfunction. The current study used daytime actigraphy, a novel objective measure of napping and related this to neuropsychological performance in a sample of PD patients and healthy, age and gender-matched controls. Furthermore this study aimed to identify patients with PD who may benefit from pharmacologic and behavioural intervention to improve these symptoms. Methods Eighty-five PD patients and 21 healthy, age-matched controls completed 14 days of wrist actigraphy within two weeks of neuropsychological testing. Objective napping measures were derived from actigraphy using a standardised protocol and subjective daytime sleepiness was recorded by the previously validated Epworth Sleepiness Scale. Results Patients with PD had a 225% increase in the mean nap time per day (minutes) as recorded by actigraphy compared to age matched controls (39.2 ± 35.2 vs. 11.5 ± 11.0 minutes respectively, p < 0.001). Significantly, differences in napping duration between patients, as recorded by actigraphy were not distinguished by their ratings on the subjective measurement of excessive daytime sleepiness. Finally, those patients with excessive daytime napping showed greater cognitive deficits in the domains of attention, semantic verbal fluency and processing speed. Conclusion This study confirms increased levels of napping in PD, a finding that is concordant with subjective reports. However, subjective self-report measures of excessive daytime sleepiness do not robustly identify excessive napping in PD. Fronto-subcortical cognitive dysfunction was observed in those patients who napped excessively. Furthermore, this study suggests that daytime actigraphy, a non-invasive and inexpensive objective measure of daytime sleep, can identify patients with PD who may benefit from pharmacologic and behavioural interventions to improve these symptoms. PMID:24278399

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 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.

Cognitive reserve and self-efficacy as moderators of the relationship between stress exposure and executive functioning among spousal dementia caregivers.

PubMed

Pertl, M M; Hannigan, C; Brennan, S; Robertson, I H; Lawlor, B A

2017-04-01

A substantial literature has reported that stress negatively impacts on cognitive processes. As dementia caregiving can be stressful, it has been hypothesized that the challenges of dementia care may increase caregivers' own vulnerability to cognitive decline. Prefrontal processes are thought to be most vulnerable to stress; however, few studies have examined whether greater caregiver stress predicts poorer executive dysfunction, and no previous research has considered potential moderators of this relationship. We examined (1) whether greater psychological stress mediated a relationship between caregiver stress exposure and executive functioning and (2) whether greater self-efficacy and cognitive reserve (CR) moderated this relationship. Spousal dementia caregivers (n = 253) completed the Neuropsychiatric Inventory Questionnaire (stress exposure), the Perceived Stress Scale, the National Adult Reading Test (CR), the Fortinsky dementia-specific caregiver self-efficacy scale, and the Color Trails Test (executive functioning). Moderated mediation was tested using the PROCESS macro. Age, gender, and dementia risk factors were included as covariates. Greater stress exposure indirectly predicted executive functioning through psychological stress. Stronger relationships between greater psychological stress and poorer executive functioning were observed among caregivers with lower CR; there was no evidence that self-efficacy moderated the relationship between stress exposure and psychological stress. Our findings are in line with the idea that greater psychological stress in response to challenges associated with dementia care predicts poorer caregiver executive functioning, particularly among caregivers with low CR. However, these findings are cross sectional; it is also possible that poorer executive functioning contributes to greater caregiver stress.

Cognitive and family therapies for adolescent depression: treatment specificity, mediation, and moderation.

PubMed

Kolko, D J; Brent, D A; Baugher, M; Bridge, J; Birmaher, B

2000-08-01

The specificity of cognitive and family therapies, and potential treatment mediators and moderators, was examined in a randomized clinical trial for adolescent depression. After acute treatment, cognitive-behavioral therapy (CBT) exerted specific effects on cognitive distortions relative to either systemic-behavioral family therapy (SBFT) or nondirective supportive therapy (NST). At 2-year follow-up, SBFT was found to impact family conflict and parent-child relationship problems more than CBT; NST and CBT tended to show a greater reduction in anxiety symptoms than SBFT. Nonspecific therapist variables qualified few outcome analyses. No measures of cognitive distortion or family dysfunction mediated or moderated treatment outcome. As in adult studies, relatively few areas of treatment specificity or mediation were identified. The implications of these findings for clinical treatment and research in adolescent depression are discussed.

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.

Intraindividual variability in cognitive performance in three groups of older adults: cross-domain links to physical status and self-perceived affect and beliefs.

PubMed

Strauss, Esther; MacDonald, Stuart W S; Hunter, Michael; Moll, Alex; Hultsch, David F

2002-11-01

Intraindividual variability of physical status and affect/beliefs as well as their relations with cognition were examined in 3 groups of older adults: healthy elderly, individuals with a nonneurological health-related disturbance (arthritis) and people with neurological compromise (dementia). The findings showed that greater inconsistency in physical performance was observed in groups characterized by central nervous system dysfunction. By contrast, fluctuations in affect appeared to reflect other more transient sources, such as pain. In general, increased inconsistency in non-cognitive domains was associated with poorer cognitive function. There were cross-domain links between inconsistency in physical functioning and fluctuations in cognitive performance, although the nature of the links depended largely upon the neurological status of the individuals. Considered together, the result indicated that measures of cognitive as well as physical variability are important behavioral markers of neurological integrity.

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 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.

Cognitive Remediation for the Treatment of Cognitive Dysfunction in the Early Course of Psychosis.

PubMed

Lewandowski, Kathryn E

2016-01-01

The development of cognitive remediation programs has been a key step toward the creation of a treatment approach to address the cognitive-symptom domain in psychosis. Studies support the efficacy of cognitive remediation in producing moderate effects on cognition at the group level in patients with schizophrenia. Cognitive remediation may harness neuroplasticity in relevant systems that underpin the cognitive functions being addressed. Since neuroplasticity may be greater in people who (1) are younger and (2) have not yet experienced the consequences of long-term psychosis, cognitive remediation may be particularly effective in people in the early course of illness or in the prodrome, prior to the onset of frank symptoms. The present article reviews the evidence for implementing cognitive remediation in patients with recent-onset psychosis and people identified as being at high risk for developing schizophrenia, and also the evidence for cognitive remediation to modify neural targets. Promising findings suggest that cognitive remediation may be useful in addressing cognitive deficits in early-course and prodromal participants. Additionally, a growing literature using neuroimaging techniques demonstrates the ability of cognitive remediation paradigms to engage neural targets.

Differential effects of psychopathy and antisocial personality disorder symptoms on cognitive and fear processing in female offenders

PubMed Central

Anton, Marja E.; Vitale, Jennifer E.; Curtin, John J.; Newman, Joseph P.

2012-01-01

Psychopathy and antisocial personality disorder (APD) have long been considered important risk factors for criminal behavior and incarceration. However, little is known about the psychobiological underpinnings that give rise to the disinhibited behavior of female offenders. Using an instructed fear-conditioning paradigm and a sample of incarcerated female offenders, we manipulated attentional focus and cognitive load to characterize and differentiate between the dysfunctional cognitive and affective processes associated with these syndromes. We used fear-potentiated startle (FPS) and event-related potentials as measures of affective and cognitive processing, respectively. After controlling for APD symptoms, psychopathic women displayed greater FPS while attending directly to threat-relevant stimuli and displayed less FPS while performing a demanding task that directed attention to threat-irrelevant information. Conversely, controlling for psychopathy, women with high APD symptoms displayed less overall FPS, especially when instructed to focus on threat-relevant stimuli. However, as the demands on cognitive resources increased, they displayed greater FPS. For both psychopathy and APD, analysis of the event-related potentials qualified these findings and further specified the abnormal cognitive processes associated with these two syndromes. Overall, simultaneous analysis of psychopathy and APD revealed distinct patterns of cognitive processing and fear reactivity. PMID:22886692

PATTERNS OF CLINICALLY SIGNIFICANT COGNITIVE IMPAIRMENT IN HOARDING DISORDER.

PubMed

Mackin, R Scott; Vigil, Ofilio; Insel, Philip; Kivowitz, Alana; Kupferman, Eve; Hough, Christina M; Fekri, Shiva; Crothers, Ross; Bickford, David; Delucchi, Kevin L; Mathews, Carol A

2016-03-01

The cognitive characteristics of individuals with hoarding disorder (HD) are not well understood. Existing studies are relatively few and somewhat inconsistent but suggest that individuals with HD may have specific dysfunction in the cognitive domains of categorization, speed of information processing, and decision making. However, there have been no studies evaluating the degree to which cognitive dysfunction in these domains reflects clinically significant cognitive impairment (CI). Participants included 78 individuals who met DSM-V criteria for HD and 70 age- and education-matched controls. Cognitive performance on measures of memory, attention, information processing speed, abstract reasoning, visuospatial processing, decision making, and categorization ability was evaluated for each participant. Rates of clinical impairment for each measure were compared, as were age- and education-corrected raw scores for each cognitive test. HD participants showed greater incidence of CI on measures of visual memory, visual detection, and visual categorization relative to controls. Raw-score comparisons between groups showed similar results with HD participants showing lower raw-score performance on each of these measures. In addition, in raw-score comparisons HD participants also demonstrated relative strengths compared to control participants on measures of verbal and visual abstract reasoning. These results suggest that HD is associated with a pattern of clinically significant CI in some visually mediated neurocognitive processes including visual memory, visual detection, and visual categorization. Additionally, these results suggest HD individuals may also exhibit relative strengths, perhaps compensatory, in abstract reasoning in both verbal and visual domains. © 2015 Wiley Periodicals, Inc.

Stroke injury, cognitive impairment and vascular dementia☆

PubMed Central

Kalaria, Raj N.; Akinyemi, Rufus; Ihara, Masafumi

2016-01-01

The global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25–30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood–brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26806700

Effects of brief mindful acceptance induction on implicit dysfunctional attitudes and concordance between implicit and explicit dysfunctional attitudes.

PubMed

Keng, Shian-Ling; Seah, Stanley T H; Tong, Eddie M W; Smoski, Moria

2016-08-01

Mindfulness-based interventions have been shown to be effective in alleviating depressive symptoms. While much work has examined the effects of mindfulness training on subjective symptoms and experiences, and less is known regarding whether mindfulness training may alter relatively uncontrollable cognitive processes associated with depressed mood, particularly implicit dysfunctional attitudes. The present study examined the effects of a brief mindful acceptance induction on implicit dysfunctional attitudes and degree of concordance between implicit and explicit dysfunctional attitudes in the context of sad mood. A total of 79 adult participants with elevated depressive symptoms underwent an autobiographical mood induction procedure before being randomly assigned to mindful acceptance or thought wandering inductions. Results showed that the effect of mindful acceptance on implicit dysfunctional attitude was significantly moderated by trait mindfulness. Participants high on trait mindfulness demonstrated significant improvements in implicit dysfunctional attitudes following the mindful acceptance induction. Those low on trait mindfulness demonstrated significantly worse implicit dysfunctional attitudes following the induction. Significantly greater levels of concordance between implicit and explicit dysfunctional attitudes were observed in the mindful acceptance condition versus the thought wandering condition. The findings highlight changes in implicit dysfunctional attitudes and improvements in self-concordance as two potential mechanisms underlying the effects of mindfulness-based interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

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

Linking the developmental and degenerative theories of schizophrenia: association between infant development and adult cognitive decline.

PubMed

Kobayashi, Hiroyuki; Isohanni, Matti; Jääskeläinen, Erika; Miettunen, Jouko; Veijola, Juha; Haapea, Marianne; Järvelin, Marjo-Riitta; Jones, Peter B; Murray, Graham K

2014-11-01

Neurodevelopmental and neurodegenerative theories may be viewed as incompatible accounts that compete to explain the pathogenesis of schizophrenia. However, it is possible that neurodevelopmental and neurodegenerative processes could both reflect common underlying causal mechanisms. We hypothesized that cognitive dysfunction would gradually deteriorate over time in schizophrenia and the degree of this deterioration in adulthood would be predicted by an infant measure of neurodevelopment. We aimed to examine the association between age of learning to stand in infancy and deterioration of cognitive function in adulthood. Participants were nonpsychotic control subjects (n = 76) and participants with schizophrenia (n = 36) drawn from the Northern Finland 1966 Birth Cohort study. The schizophrenia group showed greater deterioration in abstraction with memory than controls, but there were no differences between schizophrenia and controls in rate of change of other cognitive measures. Age of learning to stand in infancy significantly inversely predicted later deterioration of abstraction with memory in adult schizophrenia (later infant development linked to greater subsequent cognitive deterioration during adulthood), possibly suggesting a link between abnormal neurodevelopmental and neurodegenerative processes in schizophrenia. © The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.

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.

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 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.

Telerehabilitation for addressing executive dysfunction after traumatic brain injury.

PubMed

Ng, Edith M W; Polatajko, Helene J; Marziali, Elsa; Hunt, Anne; Dawson, Deirdre R

2013-01-01

To investigate the feasibility of implementing the Cognitive Orientation to daily Occupational Performance approach (CO-OP) in a telerehabilitation format and to examine its impact on community integration and executive dysfunction for adults with traumatic brain injury (TBI). A pilot series of three case studies with 3-month follow-up was conducted. Three adults (all males, >10 years post-TBI) and their significant others were recruited. The CO-OP intervention, a meta-cognitive approach, was delivered through videoconferencing via Internet to train three of five participant-identified goals. Two goals were not trained to allow examination of transfer. Outcome measures included the Canadian Occupational Performance Measure, the Mayo-Portland Adaptability Inventory-4 Participation Index, and the Dysexecutive Questionnaire. Descriptive statistical analysis was used. The CO-OP approach administered in a telerehabilitation format was found to be feasible. All participants indicated self-reported improvement in both trained and untrained goals. Trends toward fewer symptoms of executive dysfunction and greater community integration were demonstrated. All participants expressed satisfaction with the Internet delivery method. Telerehabilitation shows promise as a way to deliver the CO-OP approach and may help promote community integration of individuals living with TBI. Further study is warranted.

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

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.

Cognitive dysfunction in Body Dysmorphic Disorder: New implications for nosological systems & neurobiological models

PubMed Central

Jefferies-Sewell, K; Chamberlain, SR; Fineberg, NA; Laws, KR

2017-01-01

Background Body dysmorphic disorder (BDD) is a debilitating disorder, characterised by obsessions and compulsions relating specifically to perceived appearance, newly classified within the DSM-5 Obsessive-Compulsive and Related Disorders grouping. Until now, little research has been conducted into the cognitive profile of this disorder. Materials and Methods Participants with BDD (n=12) and healthy controls (n=16) were tested using a computerised neurocognitive battery investigating attentional set-shifting (Intra/Extra Dimensional Set Shift Task), decision-making (Cambridge Gamble Task), motor response-inhibition (Stop-Signal Reaction Time Task) and affective processing (Affective Go-No Go Task). The groups were matched for age, IQ and education. Results In comparison to controls, patients with BDD showed significantly impaired attentional set shifting, abnormal decision-making, impaired response inhibition and greater omission and commission errors on the emotional processing task. Conclusions Despite the modest sample size, our results showed that individuals with BDD performed poorly compared to healthy controls on tests of cognitive flexibility, reward and motor impulsivity and affective processing. Results from separate studies in OCD patients suggest similar cognitive dysfunction. Therefore, these findings are consistent with the re-classification of BDD alongside OCD. These data also hint at additional areas of decision-making abnormalities that might contribute specifically to the psychopathology of BDD. PMID:27899165

Functional Connectivity in Brain Networks Underlying Cognitive Control in Chronic Cannabis Users

PubMed Central

Harding, Ian H; Solowij, Nadia; Harrison, Ben J; Takagi, Michael; Lorenzetti, Valentina; Lubman, Dan I; Seal, Marc L; Pantelis, Christos; Yücel, Murat

2012-01-01

The long-term effect of regular cannabis use on brain function underlying cognitive control remains equivocal. Cognitive control abilities are thought to have a major role in everyday functioning, and their dysfunction has been implicated in the maintenance of maladaptive drug-taking patterns. In this study, the Multi-Source Interference Task was employed alongside functional magnetic resonance imaging and psychophysiological interaction methods to investigate functional interactions between brain regions underlying cognitive control. Current cannabis users with a history of greater than 10 years of daily or near-daily cannabis smoking (n=21) were compared with age, gender, and IQ-matched non-using controls (n=21). No differences in behavioral performance or magnitude of task-related brain activations were evident between the groups. However, greater connectivity between the prefrontal cortex and the occipitoparietal cortex was evident in cannabis users, as compared with controls, as cognitive control demands increased. The magnitude of this connectivity was positively associated with age of onset and lifetime exposure to cannabis. These findings suggest that brain regions responsible for coordinating behavioral control have an increased influence on the direction and switching of attention in cannabis users, and that these changes may have a compensatory role in mitigating cannabis-related impairments in cognitive control or perceptual processes. PMID:22534625

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.

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.

The Impact of Spirituality Before and After Treatment of Major Depressive Disorder

PubMed Central

Peselow, Eric; Pi, Sarah; Lopez, Enrique; Besada, André; IsHak, Waguih W.

2014-01-01

Objective: The authors sought to assess spirituality in depressed patients and evaluate whether the degree of initial depressive symptoms and response to pharmacotherapy treatment has a correlation with degree of spirituality and belief in God. Methods: Our participants included 84 patients who presented to a depression/anxiety clinic for naturalistic treatment of their depressive illness over the course of two years. All patients met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria for major depression, as confirmed by structured interviews using the Structured Clinical Interview for DSM-IV, and were treated with selective serotonin reuptake inhibitors for eight weeks. Measurements: Patients were evaluated at baseline and after treatment using the Montgomery Asberg Depression Rating Scale, the Beck Hopelessness Scale, the Dysfunctional Attitude Scale, and the Spiritual Orientation to Life scale. Results: At baseline, patients reporting greater spirituality had significantly lower measures of hopelessness, dysfunctional attitudes, and depressive symptoms. Those who believed in God had a greater mean change score than those who did not on the Montgomery Asberg Depression Rating Scale, the Beck Hopelessness Scale, and the Dysfunctional Attitude Scale, with the Montgomery Asberg Depression Rating Scale showing the greatest mean change score. Significant correlations were detected between the Spiritual Orientation to Life scale score and the Montgomery Asberg Depression Rating Scale, the Beck Hopelessness Scale, and the Dysfunctional Attitude Scale pre-scores, post-scores, and change scores. Conclusion: The findings suggest that greater spirituality is associated with less severe depression. Moreover, the degree to which the measures of depressive symptom severity, hopelessness, and cognitive distortions improved over the course of eight weeks was significantly greater for those patients who were more spiritual. PMID:24800129

Online insomnia treatment and the reduction of anxiety symptoms as a secondary outcome in a randomised controlled trial: The role of cognitive-behavioural factors.

PubMed

Gosling, John A; Batterham, Phil; Ritterband, Lee; Glozier, Nick; Thorndike, Frances; Griffiths, Kathleen M; Mackinnon, Andrew; Christensen, Helen M

2018-04-01

Insomnia and anxiety commonly co-occur, yet the mechanisms underlying this remain unclear. The current paper describes the impact of an Internet-based intervention for insomnia on anxiety, and explores the influence of two cognitive-behavioural constructs - dysfunctional beliefs about sleep and sleep-threat monitoring. A large-scale, 9-week, two-arm randomised controlled trial ( N = 1149) of community-dwelling Australian adults with insomnia and elevated yet subclinical depression symptoms was conducted, comparing a cognitive behavioural therapy-based online intervention for insomnia (Sleep Healthy Using The Internet) with an attention-matched online control intervention (HealthWatch). Symptoms of anxiety were assessed at pretest, posttest, and 6-month follow-up. Dysfunctional beliefs about sleep and sleep threat monitoring were assessed only at pretest. Sleep Healthy Using The Internet led to a greater reduction in anxiety symptoms at both posttest ( t 724.27  = -6.77, p < 0.001) and at 6-month follow-up ( t 700.67  = -4.27, p < 0.001) than HealthWatch. At posttest and follow-up, this effect was found to moderated by sleep-threat monitoring ( t 713.69  = -2.39, p < 0.05 and t 694.77  = -2.98, p < 0.01 respectively) but not by dysfunctional beliefs about sleep at either posttest or follow-up ( t 717.53  = -0.61, p = 0.55 and t 683.79  = 0.22, p = 0.83 respectively). Participants in the Sleep Healthy Using The Internet condition with higher levels of sleep-threat monitoring showed a greater reduction in anxiety than those with lower levels from pretest to posttest, ( t 724.27  = -6.77, p < 0.001) and through to 6-month follow-up ( t 700.67  = -4.27, p < 0.001). This result remained after controlling for baseline anxiety levels. The findings suggest that online cognitive behavioral therapy interventions for insomnia are beneficial for reducing anxiety regardless of people's beliefs about their sleep and insomnia, and this is particularly the case for those with high sleep-threat monitoring. This study also provides further evidence for cognitive models of insomnia.

Diabetes and Cognitive Decline in Older Adults: The Ginkgo Evaluation of Memory Study.

PubMed

Palta, Priya; Carlson, Michelle C; Crum, Rosa M; Colantuoni, Elizabeth; Sharrett, A Richey; Yasar, Sevil; Nahin, Richard L; DeKosky, Steven T; Snitz, Beth; Lopez, Oscar; Williamson, Jeff D; Furberg, Curt D; Rapp, Stephen R; Golden, Sherita Hill

2017-12-12

Previous studies have shown that individuals with diabetes exhibit accelerated cognitive decline. However, methodological limitations have limited the quality of this evidence. Heterogeneity in study design, cognitive test administration, and methods of analysis of cognitive data have made it difficult to synthesize and translate findings to practice. We analyzed longitudinal data from the Ginkgo Evaluation of Memory Study to test our hypothesis that older adults with diabetes have greater test-specific and domain-specific cognitive declines compared to older adults without diabetes. Tests of memory, visuo-spatial construction, language, psychomotor speed, and executive function were administered. Test scores were standardized to z-scores and averaged to yield domain scores. Linear random effects models were used to compare baseline differences and changes over time in test and domain scores among individuals with and without diabetes. Among the 3,069 adults, aged 72-96 years, 9.3% reported diabetes. Over a median follow-up of 6.1 years, participants with diabetes exhibited greater baseline differences in a test of executive function (trail making test, Part B) and greater declines in a test of language (phonemic verbal fluency). For the composite cognitive domain scores, participants with diabetes exhibited lower baseline executive function and global cognition domain scores, but no significant differences in the rate of decline. Identifying cognitive domains most affected by diabetes can lead to targeted risk modification, possibly in the form of lifestyle interventions such as diet and physical activity, which we know to be beneficial for improving vascular risk factors, such as diabetes, and therefore may reduce the risk of executive dysfunction and possible dementia. © 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.

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.

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

Childhood cognitive ability and its relationship with anxiety and depression in adolescence.

PubMed

Weeks, M; Wild, T C; Ploubidis, G B; Naicker, K; Cairney, J; North, C R; Colman, I

2014-01-01

Childhood cognitive ability may have protective effects against internalizing symptoms in adolescence, although this may depend on the time of symptom assessment and child gender. Also, the effects of childhood stressors on adolescent internalizing symptoms may be moderated by childhood cognitive ability. The sample included 4405 individuals from the Canadian National Longitudinal Study of Children and Youth (NLSCY). Between ages 4-5 and 10-11, children completed a test of verbal ability and scholastic aptitude and a series of mathematics computation tests. Internalizing symptoms were assessed via self-reports at ages 12-13 and 14-15. Greater cognitive ability was generally associated with decreased odds of internalizing symptoms at age 12-13. However, greater cognitive ability generally increased, or had no effect on, the odds of internalizing symptoms at age 14-15. Some of the effects of childhood cognitive ability varied with child gender. Also, childhood cognitive ability attenuated the effects of family dysfunction and chronic illness throughout childhood on subsequent internalizing symptoms. These data are largely subject to some degree of reporting bias, the tests of cognitive ability are limited and may not represent overall cognitive ability, and there may be intermediary variables that account for the relationship between childhood cognitive ability and adolescent internalizing symptoms. Results suggest that programs attempting to increase early cognitive skills may be particularly beneficial for girls. Also, an increased focus on cognitive skills may attenuate the negative effects of some stressors on subsequent anxious and depressive symptoms, regardless of child gender. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Cognitive impairment at diagnosis predicts 10-year multiple sclerosis progression.

PubMed

Moccia, Marcello; Lanzillo, Roberta; Palladino, Raffaele; Chang, Kiara Chu-Mei; Costabile, Teresa; Russo, Cinzia; De Rosa, Anna; Carotenuto, Antonio; Saccà, Francesco; Maniscalco, Giorgia Teresa; Brescia Morra, Vincenzo

2016-04-01

Cognitive impairment occurs from the early phases of multiple sclerosis (MS), and more frequently affects secondary progressive (SP) subjects than relapsing-remitting (RR). To investigate relationships between cognitive dysfunctions in newly diagnosed RRMS, and long-term MS-related outcomes. The present 10-year retrospective longitudinal study included 155 RRMS subjects, tested with the Rao Brief Repeatable Battery at MS diagnosis. The reaching of Expanded Disability Status Scale (EDSS) 4.0, and the SP conversion were recorded. 67 subjects (43.2%) reached EDSS 4.0, and 34 subjects (21.9%) converted to SP during a follow-up period of 10.0±1.8 years. Subjects with cognitive impairment at diagnosis had a rate of reaching EDSS 4.0 more than three times greater (p<0.001; HR=3.183), and a rate of SP conversion more than two times greater, as compared to cognitively preserved subjects (p=0.008; HR=2.535). In particular, better scores in the Selective Reminding Test-Delayed Recall and in the Symbol Digit Modalities Test at baseline were associated with lower SP conversion rates during the follow-up period (p=0.018; HR=0.835; and p=0.001; HR=0.941, respectively). Cognitive impairment, with particular involvement of processing speed and memory, predicts disability progression and SP conversion in newly diagnosed RRMS, highlighting the importance of cognitive assessment from the beginning of MS. © The Author(s), 2015.

Visuospatial and Mathematical Dysfunction in Major Depressive Disorder and/or Panic Disorder: A Study of Parietal Functioning

PubMed Central

Nelson, Brady D.; Shankman, Stewart A.

2015-01-01

The parietal cortex is critical for several different cognitive functions, including visuospatial processing and mathematical abilities. There is strong evidence indicating parietal dysfunction in depression. However, it is less clear whether anxiety is associated with parietal dysfunction, and whether comorbid depression and anxiety is associated with greater impairment. The present study compared participants with major depression (MDD), panic disorder (PD), comorbid MDD/PD, and controls on neuropsychological measures of visuospatial processing, Judgment of Line Orientation (JLO), and mathematical abilities, Wide Range Achievement Arithmetic (WRAT-Arithmetic). Only comorbid MDD/PD was associated with decreased performance on JLO, whereas all psychopathological groups exhibited comparably decreased performance on WRAT-Arithmetic. Furthermore, the results were not accounted for by other comorbid disorders, medication use, or psychopathology severity. The present study suggests comorbid depression and anxious arousal is associated with impairment in visuospatial processing and provides novel evidence indicating mathematical deficits across depression and/or anxiety. Implications for understanding parietal dysfunction in internalizing psychopathology are discussed. PMID:25707308

[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.

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.

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.

Determination of the relationship between cognitive function and hand dexterity in patients with chronic obstructive pulmonary disease (COPD): a cross-sectional study.

PubMed

Soysal Tomruk, Melda; Ozalevli, Sevgi; Dizdar, Gorkem; Narin, Selnur; Kilinc, Oguz

2015-07-01

Hand dexterity is important for daily living activities and can be related to cognitive functions in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the relationship between cognitive dysfunction and hand dexterity in patients with COPD. 35 COPD patients and 36 healthy individuals were assessed. The Minnesota Hand Dexterity Test and Mini Mental State Examination (MMSE) were used for assessment of cognitive function and hand dexterity. Hand dexterity test scores and cognitive function of COPD patients' were significantly lower than the healthy group (p < 0.01). The MMSE scores were negatively correlated with hand dexterity scores in the COPD group (p < 0.05). There was a relationship between cognitive function and hand dexterity in the patients with COPD; however, hand dexterity did not alter according to hypoxemia severity. Hand dexterity which is important in daily living activities should be evaluated in greater detail with further studies in COPD patients.

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.

Cognitive reactivity to sad mood provocation and the prediction of depressive relapse.

PubMed

Segal, Zindel V; Kennedy, Sidney; Gemar, Michael; Hood, Karyn; Pedersen, Rebecca; Buis, Tom

2006-07-01

Episode remission in unipolar major depression, while distinguished by minimal symptom burden, can also be a period of marked sensitivity to emotional stress as well as an increased risk of relapse. To examine whether mood-linked changes in dysfunctional thinking predict relapse in recovered patients who were depressed. In phase 1 of this study, patients with major depressive disorder were randomly assigned to receive either antidepressant medication or cognitive behavior therapy. In phase 2, patients who achieved clinical remission underwent sad mood provocation and were then observed with regular clinical assessments for 18 months. Outpatient psychiatric clinics at the Centre for Addiction and Mental Health, Toronto, Ontario. A total of 301 outpatients with major depressive disorder, aged 18 to 65 years, participated in phase 1 of this study and 99 outpatients with major depressive disorder in remission, aged 18 to 65 years, participated in phase 2. Occurrence of a relapse meeting DSM-IV criteria for a major depressive episode as assessed by the longitudinal interval follow-up evaluation and a Hamilton Depression Rating Scale score of 16 or greater. Patients who recovered through antidepressant medication showed greater cognitive reactivity following the mood provocation than those who received cognitive behavior therapy. Regardless of type of prior treatment, the magnitude of mood-linked cognitive reactivity was a significant predictor of relapse over the subsequent 18 months. Patients whose mood-linked endorsement of dysfunctional attitudes increased by a minimum of 8 points had a significantly shorter time to relapse than those whose scores were not as elevated. The vulnerability of remitted depressed patients for illness relapse may be related to the (re)activation of depressive thinking styles triggered by temporary dysphoric states. This is the first study to link such differences to prognosis following successful treatment for depression. Further understanding of factors predisposing to relapse/recurrence in recovered patients may help to shorten the potentially lifelong course of depression.

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).

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

PubMed

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

2012-01-01

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

Association between Metabolic Syndrome and Cognitive Impairment after Acute Ischemic Stroke: A Cross-Sectional Study in a Chinese Population.

PubMed

Li, Pan; Quan, Wei; Lu, Da; Wang, Yan; Zhang, Hui-Hong; Liu, Shuai; Jiang, Rong-Cai; Zhou, Yu-Ying

2016-01-01

Metabolic syndrome (MetS), a risk factor for many vascular conditions, is associated with vascular cognitive disorders. The objective of the present study was to explore the associations of MetS and its individual components with the risks of cognitive impairment and neurological dysfunction in patients after acute stroke. This cross-sectional study enrolled 840 patients ranging in age from 53 to 89 years from the Tianjin area of North China. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination. Neuropsychiatric behavior was assessed using the Neuropsychiatric Inventory Questionnaire. Emotional state was examined according to the Hamilton Depression Rating Scale, and neuromotor function was evaluated using the National Institutes of Health Stroke Scale, Barthel index, and the Activity of Daily Living test. After overnight fasting, blood samples were obtained to measure biochemistry indicators. MetS and its individual components were closely correlated with MoCA score. MetS patients had high levels of inflammation and a 3.542-fold increased odds ratio (OR) for cognitive impairment [95% confidence interval (CI): 1.972-6.361]. Of the individual MetS components, central obesity (OR 3.039; 95% CI: 1.839-5.023), high fasting plasma glucose (OR 1.915; 95% CI: 1.016-3.607), and type 2 diabetes (OR 2.241; 95% CI: 1.630-3.081) were associated with an increased incidence of cognitive impairment. Consistent and significant worsening in different neurological domains was observed with greater numbers of MetS components. MetS was associated with worse cognitive function, neuromotor dysfunction, and neuropsychological symptoms among Chinese acute stroke patients.

A cognitive vulnerability model on sleep and mood in adolescents under naturalistically restricted and extended sleep opportunities.

PubMed

Bei, Bei; Wiley, Joshua F; Allen, Nicholas B; Trinder, John

2015-03-01

School terms and vacations represent naturally occurring periods of restricted and extended sleep opportunities. A cognitive model of the relationships among objective sleep, subjective sleep, and negative mood was tested across these periods, with sleep-specific (i.e., dysfunctional beliefs and attitudes about sleep) and global (i.e., dysfunctional attitudes) cognitive vulnerabilities as moderators. Longitudinal study over the last week of a school term (Time-E), the following 2-w vacation (Time-V), and the first week of the next term (Time-S). General community. 146 adolescents, 47.3% male, mean age =16.2 years (standard deviation +/- 1 year). N/A. Objective sleep was measured continuously by actigraphy. Sociodemographics and cognitive vulnerabilities were assessed at Time-E; subjective sleep, negative mood (anxiety and depressive symptoms), and academic stress were measured at each time point. Controlling for academic stress and sex, subjective sleep quality mediated the relationship between objective sleep and negative mood at all time points. During extended (Time-V), but not restricted (Time-E and Time-S) sleep opportunity, this mediation was moderated by global cognitive vulnerability, with the indirect effects stronger with higher vulnerability. Further, at Time-E and Time-V, but not Time-S, greater sleep-specific and global cognitive vulnerabilities were associated with poorer subjective sleep quality and mood, respectively. Results highlighted the importance of subjective sleep perception in the development of sleep related mood problems, and supported the role of cognitive vulnerabilities as potential mechanisms in the relationships between objective sleep, subjective sleep, and negative mood. Adolescents with higher cognitive vulnerability are more susceptible to perceived poor sleep and sleep related mood problems. These findings have practical implications for interventions. © 2015 Associated Professional Sleep Societies, LLC.

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.

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…

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.

Mild Cognitive Dysfunction: An Epidemiological Perspective with an Emphasis on African Americans

PubMed Central

Unverzagt, Frederick W.; Gao, Sujuan; Lane, Kathleen A.; Callahan, Christopher; Ogunniyi, Adesola; Baiyewu, Olusegun; Gureje, Oye; Hall, Kathleen S.; Hendrie, Hugh C.

2009-01-01

In this review, we begin with a historical accounting of the evolution of the concept of mild cognitive dysfunction including nomenclature and criteria from Kral to Petersen. A critical analysis of the main elements relating to assessment and diagnosis of mild cognitive dysfunction are described. Methodological limitations in design, measurement, and characterization, especially as they relate to older African Americans, are identified. Data from a 15-year longitudinal study of community-dwelling, African Americans in Indianapolis indicate 23% prevalence of all-cause mild cognitive dysfunction with approximately 25% progressing to dementia in 2 years and another 25% reverting to normal in the same interval. Factors contributing to this longitudinal variability in outcome are reviewed including the role of medical health factors. We close with suggestions for next steps in the epidemiological research of mild cognitive impairment. PMID:18004008

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.

Metacognition moderates the relationship between dysfunctional self-appraisal and social functioning in prolonged schizophrenia independent of psychopathology.

PubMed

James, Alison V; Hasson-Ohayon, Ilanit; Vohs, Jenifer; Minor, Kyle S; Leonhardt, Bethany L; Buck, Kelly D; George, Sunita; Lysaker, Paul H

2016-08-01

Both dysfunctional self-appraisal and metacognitive deficits, or impairments in the ability to form complex and integrated ideas about oneself and others, may contribute to social deficits in schizophrenia. Little is known, however, about how they interact with each other. In this study, we examined the hypothesis that both higher metacognition and more positive self-appraisal are necessary for increased social functioning. Concurrent assessments of self-appraisal, metacognition, and social functioning were gathered from 66 adults with schizophrenia in a non-acute phase of disorder. Three forms of self-appraisal were used: self-esteem, hope and self-efficacy. Metacognition was assessed using the Metacognitive Assessment Scale-Abbreviated, and social functioning with the Quality of Life Scale. Measures of psychopathology, neurocognition and social cognition were also gathered for use as potential covariates. A single index of self-appraisal was generated from subjecting the assessments of self-appraisal to a principal components analysis. Linear regression analyses revealed that after controlling for severity of psychopathology, metacognition moderated the effect of the self-appraisal factor score upon social functioning. A median split of metacognition and the self-appraisal index yielded four groups. ANCOVA analyses revealed that participants with higher levels of metacognition and more positive self-appraisal had greater capacities for social relatedness than all other participants, regardless of levels of positive and negative symptoms. Correlational analyses revealed that metacognition but not self-appraisal was related to the frequencies of social contact independent of the effects of psychopathology. Assessments of social cognition and neurocognition were not significantly linked with social dysfunction. Greater social functioning is made possible by a combination of both more positive self-appraisals and greater metacognitive capacity. Individuals with schizophrenia who struggle to relate to others may benefit from interventions which address both their beliefs about themselves and their capacity for metacognition. Published by Elsevier Inc.

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

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.

Acute Modafinil Effects on Attention and Inhibitory Control in Methamphetamine-Dependent Humans*

PubMed Central

Dean, Andy C.; Sevak, Rajkumar J.; Monterosso, John R.; Hellemann, Gerhard; Sugar, Catherine A.; London, Edythe D.

2011-01-01

Objective: Individuals who are methamphetamine dependent exhibit higher rates of cognitive dysfunction than healthy people who do not use methamphetamine, and this dysfunction may have a negative effect on the success of behavioral treatments for the disorder. Therefore, a medication that improves cognition, such as modafinil (Provigil), may serve as a useful adjunct to behavioral treatments for methamphetamine dependence. Although cognitive-enhancing effects of modafinil have been reported in several populations, little is known about the effects of modafinil in methamphetamine-dependent individuals. We thus sought to evaluate the effects of modafinil on the cognitive performance of methamphetamine-dependent and healthy individuals. Method: Seventeen healthy subjects and 24 methamphetamine-dependent subjects participated in this randomized, double-blind, placebo-controlled, crossover study. Effects of modafinil (200 mg, single oral dose) were assessed on participants’ performance on tests of inhibitory control, working memory, and processing speed/attention. Results: Across subjects, modafinil improved performance on a test of sustained attention, with no significant improvement on any other cognitive tests. However, within the methamphetamine-dependent group only, participants with a high baseline frequency of methamphetamine use demonstrated a greater effect of modafinil on tests of inhibitory control and processing speed than those participants with low baseline use of methamphetamine. Conclusions: Although modafinil produced limited effects across all participants, methamphetamine-dependent participants with a high baseline use of methamphetamine demonstrated significant cognitive improvement on modafinil relative to those with low baseline methamphetamine use. These results add to the findings from a clinical trial that suggested that modafinil may be particularly useful in methamphetamine-dependent subjects who use the drug frequently. PMID:22051208

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…

Neuropsychological Impairments in Schizophrenia and Psychotic Bipolar Disorder: Findings from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) Study

PubMed Central

Hill, S. Kristian; Reilly, James L.; Keefe, Richard S.E.; Gold, James M.; Bishop, Jeffrey R.; Gershon, Elliot S.; Tamminga, Carol A.; Pearlson, Godfrey D.; Keshavan, Matcheri S.; Sweeney, John A.

2017-01-01

Objective Familial neuropsychological deficits are well established in schizophrenia but remain less well characterized in other psychotic disorders. This study from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP) consortium 1) compares cognitive impairment in schizophrenia and bipolar disorder with psychosis, 2) tests a continuum model of cognitive dysfunction in psychotic disorders, 3) reports familiality of cognitive impairments across psychotic disorders, and 4) evaluates cognitive impairment among nonpsychotic relatives with and without cluster A personality traits. Method Participants included probands with schizophrenia (N=293), psychotic bipolar disorder (N=227), schizoaffective disorder (manic, N=110; depressed, N=55), their first-degree relatives (N=316, N=259, N=133, and N=64, respectively), and healthy comparison subjects (N=295). All participants completed the Brief Assessment of Cognition in Schizophrenia (BACS) neuropsychological battery. Results Cognitive impairments among psychotic probands, compared to healthy comparison subjects, were progressively greater from bipolar disorder (z=−0.77) to schizoaffective disorder (manic z=−1.08; depressed z=−1.25) to schizophrenia (z=−1.42). Profiles across subtests of the BACS were similar across disorders. Familiality of deficits was significant and comparable in schizophrenia and bipolar disorder. Of particular interest were similar levels of neuropsychological deficits in relatives with elevated cluster A personality traits across proband diagnoses. Nonpsychotic relatives of schizophrenia probands without these personality traits exhibited significant cognitive impairments, while relatives of bipolar probands did not. Conclusions Robust cognitive deficits are present and familial in schizophrenia and psychotic bipolar disorder. Severity of cognitive impairments across psychotic disorders was consistent with a continuum model, in which more prominent affective features and less enduring psychosis were associated with less cognitive impairment. Cognitive dysfunction in first-degree relatives is more closely related to psychosis-spectrum personality disorder traits in psychotic bipolar disorder than in schizophrenia. PMID:23771174

Cognitive dysfunction and anxious-impulsive personality traits are endophenotypes for drug dependence.

PubMed

Ersche, Karen D; Turton, Abigail J; Chamberlain, Samuel R; Müller, Ulrich; Bullmore, Edward T; Robbins, Trevor W

2012-09-01

Not everyone who takes drugs becomes addicted, but the likelihood of developing drug addiction is greater in people with a family history of drug or alcohol dependence. Relatively little is known about how genetic risk mediates the development of drug dependence. By comparing the phenotypic profile of individuals with and without a family history of addiction, the authors sought to clarify the extent to which cognitive dysfunction and personality traits are shared by family members--and therefore likely to have predated drug dependence--and which aspects are specific to drug-dependent individuals. The authors assessed cognitive function and personality traits associated with drug dependence in stimulant-dependent individuals (N=50), their biological siblings without a history of drug dependence (N=50), and unrelated healthy volunteers (N=50). Cognitive function was significantly impaired in the stimulant-dependent individuals across a range of domains. Deficits in executive function and response control were identified in both the stimulant-dependent individuals and in their non-drug-dependent siblings. Drug-dependent individuals and their siblings also exhibited elevated anxious-impulsive personality traits relative to healthy comparison volunteers. Deficits in executive function and response regulation as well as anxious-impulsive personality traits may represent endophenotypes associated with the risk of developing cocaine or amphetamine dependence. The identification of addiction endophenotypes may be useful in facilitating the rational development of therapeutic and preventive strategies.

Effect of sugammadex versus neostigmine/atropine combination on postoperative cognitive dysfunction after elective surgery.

PubMed

Batistaki, C; Riga, M; Zafeiropoulou, F; Lyrakos, G; Kostopanagiotou, G; Matsota, P

2017-09-01

This study aimed to assess the effects of sugammadex and neostigmine/atropine on postoperative cognitive dysfunction (POCD) in adult patients after elective surgery. A randomised, double-blind controlled trial was carried out on 160 American Society of Anesthesiologists physical status I to III patients who were >40 years. The Mini-Mental State Evaluation, clock-drawing test and the Isaacs Set test were used to assess cognitive function at three timepoints: 1) preoperatively, 2) one hour postoperatively, and 3) at discharge. The anaesthetic protocol was the same for all patients, except for the neuromuscular block reversal, which was administered by random allocation using either sugammadex or neostigmine/atropine after the reappearance of T2 in the train-of-four sequence. POCD was defined as a decline ≥1 standard deviation in ≥2 cognitive tests. The incidence of POCD was similar in both groups at one hour postoperatively and at discharge (28% and 10%, in the neostigmine group, 23% and 5.4% in the sugammadex group, P =0.55 and 0.27 respectively). In relation to individual tests, a significant decline of clock-drawing test in the neostigmine group was observed at one hour postoperatively and at discharge. For the Isaacs Set test, a greater decline was found in the sugammadex group. These findings suggest that there are no clinically important differences in the incidence of POCD after neostigmine or sugammadex administration.

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

Profile of cognitive impairment and underlying pathology in multiple system atrophy.

PubMed

Koga, Shunsuke; Parks, Adam; Uitti, Ryan J; van Gerpen, Jay A; Cheshire, William P; Wszolek, Zbigniew K; Dickson, Dennis W

2017-03-01

The objectives of this study were to elucidate any potential association between α-synuclein pathology and cognitive impairment and to determine the profile of cognitive impairment in multiple system atrophy (MSA) patients. To do this, we analyzed the clinical and pathologic features in autopsy-confirmed MSA patients. We retrospectively reviewed medical records, including neuropsychological test data, in 102 patients with autopsy-confirmed MSA in the Mayo Clinic brain bank. The burden of glial cytoplasmic inclusions and neuronal cytoplasmic inclusions were semiquantitatively scored in the limbic regions and middle frontal gyrus. We also assessed concurrent pathologies potentially causing dementia including Alzheimer's disease, hippocampal sclerosis, and cerebrovascular pathology. Of 102 patients, 33 (32%) were documented to have cognitive impairment. Those that received objective testing, deficits primarily in processing speed and attention/executive functions were identified, which suggests a frontal-subcortical pattern of dysfunction. Of these 33 patients with cognitive impairment, 8 patients had concurrent pathologies of dementia. MSA patients with cognitive impairment had a greater burden of neuronal cytoplasmic inclusions in the dentate gyrus than patients without cognitive impairment, both including and excluding patients with concurrent pathologies of dementia. The cognitive deficits observed in this study were more evident on neuropsychological assessment than with cognitive screens. Based on these findings, we recommend that clinicians consider more in-depth neuropsychological assessments if patients with MSA present with cognitive complaints. Although we did not identify the correlation between cognitive deficits and responsible neuroanatomical regions, a greater burden of neuronal cytoplasmic inclusions in the limbic regions was associated with cognitive impairment in MSA. © 2016 International Parkinson and Movement Disorder Society. © 2016 International Parkinson and Movement Disorder Society.

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.

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…

Three screening methods for cognitive dysfunction using the Mini-Mental State Examination and Korean Dementia Screening Questionnaire.

PubMed

Choi, Seong Hye; Park, Moon Ho

2016-02-01

To screen for and determine cognitive dysfunction, cognitive tests and/or informant reports are commonly used. However, these cognitive tests and informant reports are not always available. The present study investigated three screening methods using the Mini-Mental State Examination (MMSE) as the cognitive test, and the Korean dementia screening questionnaire (KDSQ) as the informant report. Participants were recruited from the Korea Clinical Research Center for Dementia of South Korea, and included 2861 patients with Alzheimer's disease (dementia), 3519 patients with mild cognitive impairment and 1375 controls with no cognitive dysfunction. Three screening methods were tested: (i) MMSE alone (MMSE(cut-off) ); (ii) a conventional combination of MMSE and KDSQ (MMSE+KDSQ(cut-off) ); and (iii) a decision tree with MMSE and KDSQ (MMSE+KDSQ(decision tree) ). For discriminating any cognitive dysfunction from controls, MMSE+KDSQ(cut-off) had the highest area under the receiver operating characteristic curve (0.784). For discriminating dementia from controls, MMSE+KDSQ(cut-off) had the highest area under the receiver operating characteristic curve (0.899). For discriminating mild cognitive impairment from controls, MMSE(cut-off) had the highest area under the receiver operating characteristic curve (0.683). MMSE+KDSQ(decision tree) showed the highest sensitivity for all discriminations. For overall classification accuracy, MMSE+KDSQ(decision tree) had the highest value (70.0%). These three methods had different advantageous properties for screening and staging cognitive dysfunction. As there might be different availability across clinical settings, these three methods can be selected and used according to situational needs. © 2015 Japan Geriatrics Society.

Skin picking disorder with co-occurring body dysmorphic disorder.

PubMed

Grant, Jon E; Redden, Sarah A; Leppink, Eric W; Odlaug, Brian L

2015-09-01

There is clinical overlap between skin picking disorder (SPD) and body dysmorphic disorder (BDD), but little research has examined clinical and cognitive correlates of the two disorders when they co-occur. Of 55 participants with SPD recruited for a neurocognitive study and two pharmacological studies, 16 (29.1%) had co-occurring BDD. SPD participants with and without BDD were compared to each other and to 40 healthy volunteers on measures of symptom severity, social functioning, and cognitive assessments using the Stop-signal task (assessing response impulsivity) and the Intra-dimensional/Extra-dimensional Set Shift task (assessing cognitive flexibility). Individuals with SPD and BDD exhibited significantly worse picking, significantly worse overall psychosocial functioning, and significantly greater dysfunction on aspects of cognitive flexibility. These results indicate that when SPD co-occurs with BDD unique clinical and cognitive aspects of SPD may be more pronounced. Future work should explore possible subgroups in SPD and whether these predict different treatment outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Assessment of attention and inhibitory control in rodent developmental neurotoxicity studies.

PubMed

Driscoll, Lori L; Strupp, Barbara J

2015-01-01

In designing screens to assess potential neurotoxicants, the paramount goal is that the selected assessment tools detect dysfunction if it exists. This goal is particularly challenging in the case of cognitive assessments. Cognition is not a unitary phenomenon, and indeed there is growing evidence that different aspects of cognitive functioning are subserved by distinct neural systems. As a result, if a particular neurotoxicant selectively damages certain neural systems but not others, it can impair some cognitive, sensory, or affective functions, but leave many others intact. Accordingly, studies with human subjects use batteries of cognitive tests, cognizant of the fact that no one test is capable of detecting all forms of cognitive dysfunction. In contrast, assessment of cognitive functioning in non-human animal developmental neurotoxicity (DNT) studies typically consists of a single, presumably representative, "learning and memory" task that is expected to detect all potential effects on cognitive functioning. Streamlining the cognitive assessment in these studies saves time and money, but these shortcuts can have serious consequences if the aspect of cognitive functioning that is impaired is not tapped by the single selected task. In particular, executive functioning - a constellation of cognitive functions which enables the organism to focus on multiple streams of information simultaneously, and revise plans as necessary - is poorly assessed in most animal DNT studies. The failure to adequately assess these functions - which include attention, working memory, inhibitory control, and planning - is particularly worrisome in light of evidence that the neural systems that subserve these functions may be uniquely vulnerable to early developmental insults. We illustrate the importance of tapping these areas of functioning in DNT studies by describing the pattern of effects produced by early developmental Pb exposure. Rats exposed to lead (Pb) early in development were tested on a series of automated attention tasks, as well as on a radial arm maze task. The lead-exposed rats were not impaired in this demanding radial arm maze task, despite conditions which tapped the limits of both working and long-term memory. In contrast, the automated tests designed to assess rodent executive functioning revealed selective and functionally important deficits in attention and regulation of emotion or negative affect (produced by committing an error or not receiving an expected reward). This example underscores the importance of including tasks to specifically tap executive functioning in DNT batteries. Such tasks are not only sensitive but can also shed light on the specific nature of the dysfunction, and they can implicate dysfunction of specific neural systems, information which can be used to design therapeutic interventions. Although the use of such tasks increases the time and effort needed to complete the battery, the benefits outweigh the cost, in light of the greater sensitivity of the battery and the more complete characterization of effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Brain structure and verbal function across adulthood while controlling for cerebrovascular risks.

PubMed

Sanfratello, L; Lundy, S L; Qualls, C; Knoefel, J E; Adair, J C; Caprihan, A; Stephen, J M; Aine, C J

2017-04-08

The development and decline of brain structure and function throughout adulthood is a complex issue, with cognitive aging trajectories influenced by a host of factors including cerebrovascular risk. Neuroimaging studies of age-related cognitive decline typically reveal a linear decrease in gray matter (GM) volume/density in frontal regions across adulthood. However, white matter (WM) tracts mature later than GM, particularly in regions necessary for executive functions and memory. Therefore, it was predicted that a middle-aged group (MC: 35-45 years) would perform best on a verbal working memory task and reveal greater regional WM integrity, compared with both young (YC: 18-25 years) and elder groups (EC: 60+ years). Diffusion tensor imaging (DTI) and magnetoencephalography (MEG) were obtained from 80 healthy participants. Objective measures of cerebrovascular risk and cognition were also obtained. As predicted, MC revealed best verbal working memory accuracy overall indicating some maturation of brain function between YC and MC. However, contrary to the prediction fractional anisotropy values (FA), a measure of WM integrity, were not greater in MC (i.e., there were no significant differences in FA between YC and MC but both groups showed greater FA than EC). An overall multivariate model for MEG ROIs showed greater peak amplitudes for MC and YC, compared with EC. Subclinical cerebrovascular risk factors (systolic blood pressure and blood glucose) were negatively associated with FA in frontal callosal, limbic, and thalamic radiation regions which correlated with executive dysfunction and slower processing speed, suggesting their contribution to age-related cognitive decline. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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.

Brain volume and cognitive function in patients with revascularized coronary artery disease.

PubMed

Ottens, Thomas H; Hendrikse, Jeroen; Nathoe, Hendrik M; Biessels, Geert Jan; van Dijk, Diederik

2017-03-01

The pathogenesis of cognitive dysfunction in patients with CAD remains unclear. CAD is associated with brain atrophy and specific lesions. Detailed knowledge about the association of brain volume measured with MRI, and cognitive function in patients with CAD is lacking. We therefore investigated brain volume and cognitive function in patients with revascularized coronary artery disease (CAD), and controls without CAD. Brain MRI scans and cognitive tests from patients with CAD were compared with data from control subjects without CAD. Cognitive performance was assessed with the Rey Auditory Verbal Learning (short term memory) and Trailmaking (divided attention) tests. Multivariable regression analysis was used to study associations between CAD, brain volume and cognitive function. A total of 102 patients with CAD and 48 control subjects were included. Level of education and age were comparable between the groups. Compared with controls, patients with CAD had smaller total brain volume (expressed as fraction of intracranial volume) [%ICV, mean (SD), 0.78 (0.03) vs 0.80 (0.02), P=0.001] and larger volume of non-ventricular cerebrospinal fluid [%ICV, median (IQR) 0.19 (0.18 to 0.21) vs 0.18 (0.17 to 0.20), P=0.001]. Patients in the CAD group had poorer cognitive function [mean (SD) Z-score -0.16 (0.72) vs 0.41 (0.69), P<0.01]. Multivariable regression showed that CAD, higher age, lower level of education and greater cerebrospinal fluid volume were independent predictors of poorer cognitive function. CAD patients had a smaller total brain volume and poorer cognitive function than controls. Greater volume of cerebrospinal fluid was an independent predictor of poorer cognitive function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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.

Characterizing executive functioning in older special populations: from cognitively elite to cognitively impaired.

PubMed

de Frias, Cindy M; Dixon, Roger A; Strauss, Esther

2009-11-01

The authors examined the structure and invariance of executive functions (EF) across (a) a continuum of cognitive status in 3 groups of older adults (cognitively elite [CE], cognitively normal [CN], and cognitively impaired [CI]) and (b) a 3-year longitudinal interval. Using latent variable analyses (LISREL 8.80), the authors tested 3-factor models ("Inhibition": Hayling [Burgess & Shallice, 1997], Stroop [Regard, 1981]; "Shifting": Brixton [Burgess & Shallice, 1997], Color Trails [D'Elia et al., 1996]; and "Updating": Reading and Computational Span [Salthouse & Babcock, 1991]) and 1-factor models within each group. Participants (initial N = 570; 53-90 years) were from the Victoria Longitudinal Study (Sample 3, Waves 1 and 2). Cross-sectionally, the authors observed a 3-factor EF structure especially for the CE group and 1-factor solutions for all 3 groups. Longitudinally, temporal invariance was supported for the 3-factor model (CE and CN groups) and the 1-factor model (CI and CN groups). Subgroups with higher cognitive status and greater 3-year stability performed better on EF factors than corresponding groups with lower cognitive status and less stability. Studies of EF structure, performance, dedifferentiation, and dysfunction will benefit from considering initial cognitive status and longitudinal stability.

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.

Fibromyalgia Syndrome Module at OMERACT 9

PubMed Central

Mease, Philip; Arnold, Lesley M; Choy, Ernest H; Clauw, Daniel J.; Crofford, Leslie; Glass, Jennifer M; Martin, Susan A; Morea, Jessica; Simon, Lee; Strand, Vibeke; Williams, David A

2012-01-01

Objectives (1) Establish a core domain set for fibromyalgia (FM) assessment in clinical trials and practice, (2) review outcome measures’ performance characteristics, (3) discuss development of a responder index for the assessment of FM in clinical trials, (4) review objective markers, (5) review the domain of cognitive dysfunction, (6) establish a research agenda for work regarding outcomes research. Methods (1) Results of univariate and multivariate analysis of 10 different FM clinical trials of four different drugs, mapping key domains identified in previously presented patient focus group: Delphi exercises and a clinician/researcher Delphi exercise, breakout discussions to vote on possible essential domains and reliable measures. (2) Updates presented regarding outcome measures’ status. (3) Presented update on objective markers to measure FM disease state. 4) The issue of cognitive dysfunction (dyscognition) in FM was reviewed. Results (1) Greater than 70% of OMERACT participants agreed that pain, tenderness, fatigue, patient global, multidimensional function and sleep disturbance domains should be measured in all FM clinical trials, dyscognition and depression in some trial, and domains of research interest include stiffness, anxiety, functional imaging, and cerebrospinal fluid biomarkers. (2) FM domains’ outcome measures have generally proven to be reliable, discriminative, and feasible. More sophisticated and comprehensive measures are in development, as is a responder index for FM. (3) Increasing number of objective markers are being developed for FM assessment. (4) Cognitive dysfunction assessment by self-assessed and applied outcome measures is being developed. Conclusions A multidimensional symptom core set is proposed for the evaluation of FM in clinical trials. There is ongoing research on improved measures of single domains and composite measures. PMID:19820221

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 correlates of gray matter abnormalities in adolescent siblings of patients with childhood-onset schizophrenia

PubMed Central

Wagshal, Dana; Knowlton, Barbara Jean; Cohen, Jessica Rachel; Bookheimer, Susan Yost; Bilder, Robert Martin; Fernandez, Vindia Gisela; Asarnow, Robert Franklin

2015-01-01

Patients with childhood onset schizophrenia (COS) display widespread gray matter (GM) structural brain abnormalities. Healthy siblings of COS patients share some of these structural abnormalities, suggesting that GM abnormalities are endophenotypes for schizophrenia. Another possible endophenotype for schizophrenia that has been relatively unexplored is corticostriatal dysfunction. The corticostriatal system plays an important role in skill learning. Our previous studies have demonstrated corticostriatal dysfunction in COS siblings with a profound skill learning deficit and abnormal pattern of brain activation during skill learning. This study investigated whether structural abnormalities measured using volumetric brain morphometry (VBM) were present in siblings of COS patients and whether these were related to deficits in cognitive skill learning. Results revealed smaller GM volume in COS siblings relative to controls in a number of regions, including occipital, parietal, and subcortical regions including the striatum, and greater GM volume relative to controls in several subcortical regions. Volume in the right superior frontal gyrus and cerebellum were related to performance differences between groups on the weather prediction task, a measure of cognitive skill learning. Our results support the idea that corticostriatal and cerebellar impairment in unaffected siblings of COS patients are behaviorally relevant and may reflect genetic risk for schizophrenia. PMID:25541139

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.

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.

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…

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.

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…

Longitudinal assessment of psychopathological domains over late-stage schizophrenia in relation to duration of initially untreated psychosis: 3-year prospective study in a long-term inpatient population.

PubMed

Meagher, David J; Quinn, John F; Bourke, Stephanie; Linehan, Sally; Murphy, Patrice; Kinsella, Anthony; Mullaney, James; Waddington, John L

2004-05-30

There remains uncertainty regarding any progressive nature of psychopathology and cognitive dysfunction in late-stage schizophrenia, and whether duration of initially untreated psychosis (DUP) might be associated with such 'progression'. This study examines longitudinally, over 3 years, the psychopathology and neuropsychology in 82 inpatients with DSM-IV schizophrenia, many of whom were admitted in the pre-neuroleptic era. Increase in executive dysfunction exceeded that in general cognitive impairment. Positive but not negative symptom severity decreased modestly; the primary predictor of negative symptom severity was DUP. On index assessment, psychopathology evidenced a three-factor structure; at follow-up, psychomotor poverty evidenced greater prominence and cohesion, and was on both occasions predicted primarily by DUP, while reality distortion was altered and disorganisation disassembled into alternative elements. It would appear that as years of chronic, refractory illness accrue, psychomotor poverty becomes more sharply delineated and dominant within the overall structure of psychopathology, and its prominence is predicted enduringly by DUP. Copyright 2004 Elsevier Ireland Ltd.

A Cognitive Vulnerability Model of Sleep and Mood in Adolescents under Naturalistically Restricted and Extended Sleep Opportunities

PubMed Central

Bei, Bei; Wiley, Joshua F.; Allen, Nicholas B.; Trinder, John

2015-01-01

Study Objectives: School terms and vacations represent naturally occurring periods of restricted and extended sleep opportunities. A cognitive model of the relationships among objective sleep, subjective sleep, and negative mood was tested across these periods, with sleep-specific (i.e., dysfunctional beliefs and attitudes about sleep) and global (i.e., dysfunctional attitudes) cognitive vulnerabilities as moderators. Design: Longitudinal study over the last week of a school term (Time-E), the following 2-w vacation (Time-V), and the first week of the next term (Time-S). Setting: General community. Participants: 146 adolescents, 47.3% male, mean age = 16.2 years (standard deviation ± 1 year). Interventions: N/A. Measurements and Results: Objective sleep was measured continuously by actigraphy. Sociodemographics and cognitive vulnerabilities were assessed at Time-E; subjective sleep, negative mood (anxiety and depressive symptoms), and academic stress were measured at each time point. Controlling for academic stress and sex, subjective sleep quality mediated the relationship between objective sleep and negative mood at all time points. During extended (Time-V), but not restricted (Time-E and Time-S) sleep opportunity, this mediation was moderated by global cognitive vulnerability, with the indirect effects stronger with higher vulnerability. Further, at Time-E and Time-V, but not Time-S, greater sleep-specific and global cognitive vulnerabilities were associated with poorer subjective sleep quality and mood, respectively. Conclusions: Results highlighted the importance of subjective sleep perception in the development of sleep related mood problems, and supported the role of cognitive vulnerabilities as potential mechanisms in the relationships between objective sleep, subjective sleep, and negative mood. Adolescents with higher cognitive vulnerability are more susceptible to perceived poor sleep and sleep related mood problems. These findings have practical implications for interventions. Citation: Bei B, Wiley JF, Allen NB, Trinder J. A cognitive vulnerability model of sleep and mood in adolescents under naturalistically restricted and extended sleep opportunities. SLEEP 2015;38(3):453–461. PMID:25325471

What Changes in Cognitive Therapy for Depression? An Examination of Cognitive Therapy Skills and Maladaptive Beliefs

PubMed Central

Adler, Abby D.; Strunk, Daniel R.; Fazio, Russell H.

2015-01-01

This study examined effortful cognitive skills and underlying maladaptive beliefs among patients treated with Cognitive Therapy for depression (CT). Depressed patients (n = 44) completed cognitive measures before and after 16 weeks of CT. Measures included: an assessment of CT skills (Ways of Responding Scale, WOR), an implicit test of maladaptive beliefs (Implicit Association Test, IAT), and a self-report questionnaire of maladaptive beliefs (Dysfunctional Attitude Scale, DAS). A matched sample of never-depressed participants (n = 44) also completed study measures. Prior to treatment, depressed patients endorsed significantly more undesirable cognitions on the WOR, IAT, and DAS compared to never-depressed participants. Patients displayed improvement on the WOR and DAS over the course of treatment, but showed no change on the IAT. Additionally, improvements on the WOR and DAS were each related to greater reductions in depressive symptoms. Results suggest that the degree of symptom reduction among patients participating in CT is related to changes in patients’ acquisition of coping skills requiring deliberate efforts and reflective thought, but not related to reduced endorsement of implicitly-assessed maladaptive beliefs. PMID:25526838

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.

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.

Problem Solving Therapy and Supportive Therapy in Older Adults with Major Depression and Executive Dysfunction: Effect on Disability

PubMed Central

Alexopoulos, George S.; Raue, Patrick J.; Kiosses, Dimitris N.; Mackin, R. Scott; Kanellopoulos, Dora; McCulloch, Charles; Areán, Patricia A.

2010-01-01

Context Older patients with depression and executive dysfunction represent a population with significant disability and high likelihood of failing pharmacotherapy. Objective To examine whether Problem Solving Therapy (PST) reduces disability more than Supportive Therapy (ST) in older patients with depression and executive dysfunction, and whether this effect is mediated by improvement in depressive symptoms. Design Randomized controlled trail, with participant recruitment from 12/02-11/07 and follow-up for 36 weeks. Setting Weill Cornell and University of California, San Francisco. Participants Adults (>59 years) with major depression and executive dysfunction. Intervention 12 sessions of either PST modified for older depressed adults with executive impairment, or ST. Main Outcome Measure Disability as quantified by the World Health Organization Assessment Schedule II (WHODAS II)-12 item form. Results 653 individuals were referred to this study, 221 of whom met criteria and were randomized to PST or ST. PST and ST led to comparable improvement of disability in the first 6 weeks of treatment, but a more prominent reduction in PST participants at weeks 9 and 12. The difference between PST and ST was greater in patients with greater cognitive impairment and higher number of previous episodes. Reduction in disability paralleled reduction in depressive symptoms. The therapeutic advantage of PST over ST in reducing depression was in part due to greater reduction of disability by PST. While disability increased during the 24 weeks following the end of treatment, the advantage of PST over ST-treated patients was retained. Conclusions This study suggests that PST is more effective than ST in reducing disability in older patients with major depression and executive dysfunction, and its benefits were retained after the end of treatment. The clinical value of this finding is that PST may be a treatment alternative in an older patient population likely to be resistant to pharmacotherapy. PMID:21199963

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.

[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.

Vision science and schizophrenia research: toward a re-view of the disorder. Editors' introduction to special section.

PubMed

Silverstein, Steven M; Keane, Brian P

2011-07-01

This theme section on vision science and schizophrenia research demonstrates that our understanding of the disorder could be significantly accelerated by a greater adoption of the methods of vision science. In this introduction, we briefly describe what vision science is, how it has advanced our understanding of schizophrenia, and what challenges and opportunities lay ahead regarding schizophrenia research. We then summarize the articles that follow. These include reviews of abnormal form perception (perceptual organization and backward masking) and motion processing, and an article on reduced size contrast illusions experienced by hearing but not deaf persons with schizophrenia. These articles reveal that the methods of basic vision research can provide insights into a number of aspects of the disorder, including pathophysiology, development, cognition, social cognition, and phenomenology. Importantly, studies of visual processing in schizophrenia make it clear that there are impairments in the functioning of basic neural mechanisms (e.g., center-surround modulation, contextual modulation of feedforward processing, reentrant processing) that are found throughout the cortex and that are operative in multiple forms of cognitive dysfunction in the illness. Such evidence allows for an updated view of schizophrenia as a condition involving generalized failures in neural network formation and maintenance, as opposed to a primary failure in a higher level factor (e.g., cognitive control) that accounts for all other types of perceptual and cognitive dysfunction. Finally, studies of vision in schizophrenia can identify sensitive probes of neural functioning that can be used as biomarkers of treatment response.

Vision Science and Schizophrenia Research: Toward a Re-view of the Disorder Editors’ Introduction to Special Section

PubMed Central

Silverstein, Steven M.; Keane, Brian P.

2011-01-01

This theme section on vision science and schizophrenia research demonstrates that our understanding of the disorder could be significantly accelerated by a greater adoption of the methods of vision science. In this introduction, we briefly describe what vision science is, how it has advanced our understanding of schizophrenia, and what challenges and opportunities lay ahead regarding schizophrenia research. We then summarize the articles that follow. These include reviews of abnormal form perception (perceptual organization and backward masking) and motion processing, and an article on reduced size contrast illusions experienced by hearing but not deaf persons with schizophrenia. These articles reveal that the methods of basic vision research can provide insights into a number of aspects of the disorder, including pathophysiology, development, cognition, social cognition, and phenomenology. Importantly, studies of visual processing in schizophrenia make it clear that there are impairments in the functioning of basic neural mechanisms (eg, center-surround modulation, contextual modulation of feedforward processing, reentrant processing) that are found throughout the cortex and that are operative in multiple forms of cognitive dysfunction in the illness. Such evidence allows for an updated view of schizophrenia as a condition involving generalized failures in neural network formation and maintenance, as opposed to a primary failure in a higher level factor (eg, cognitive control) that accounts for all other types of perceptual and cognitive dysfunction. Finally, studies of vision in schizophrenia can identify sensitive probes of neural functioning that can be used as biomarkers of treatment response. PMID:21700588

Executive functions and basic symptoms in adolescent antisocial behavior: a cross-sectional study on an Italian sample of late-onset offenders.

PubMed

Muscatello, Maria Rosaria A; Scimeca, Giuseppe; Pandolfo, Gianluca; Micò, Umberto; Romeo, Vincenzo M; Mallamace, Domenico; Mento, Carmela; Zoccali, Rocco; Bruno, Antonio

2014-04-01

Executive cognitive functions (ECFs) and other cognitive impairments, such as lower IQ and verbal deficits, have been associated with the pattern of antisocial and delinquent behavior starting in childhood (early-onset), but not with late-onset antisocial behavior. Beyond objective measures of ECF, basic symptoms are prodromal, subjectively experienced cognitive, perceptual, affective, and social disturbances, associated with a range of psychiatric disorders, mainly with psychosis. The goal of the present study was to examine ECF and basic symptoms in a sample of late-onset juvenile delinquents. Two-hundred nine male adolescents (aged 15-20 years) characterized by a pattern of late-onset delinquent behavior with no antecedents of Conduct Disorder, were consecutively recruited from the Social Services of the Department of Juvenile Justice of the city of Messina (Italy), and compared with nonantisocial controls matched for age, educational level, and socio-demographic features on measures for ECF dysfunction and basic symptoms. Significant differences between late-onset offenders (completers=147) and control group (n=150) were found on ECF and basic symptoms measures. Chi-square analysis showed that a significantly greater number of late-onset offending participants scored in the clinical range on several ECF measures. Executive cognitive impairment, even subtle and subclinical, along with subjective symptoms of cognitive dysfunction (basic symptom), may be contributing factor in the development and persistence of antisocial behaviors displayed by late-onset adolescent delinquents. The findings also suggest the need for additional research aimed to assess a broader range of cognitive abilities and specific vulnerability and risk factors for late-onset adolescent offenders. Copyright © 2014 Elsevier Inc. All rights reserved.

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…

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.

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.

Neurobiological correlates of illness progression in the recurrent affective disorders.

PubMed

Post, Robert M; Fleming, Jaclyn; Kapczinski, Flavio

2012-05-01

Some clinical aspects of affective illness progression, such as episode-, stress-, and substance-induced sensitization, have been well documented in the literature, but others have received less attention. These include cognitive deficits, treatment-refractoriness, and neurobiological correlates of illness progression, which are the primary focus of this paper. We review the evidence that cognitive dysfunction, treatment resistance, medical comorbidities, and neurobiological abnormalities increase as a function of the number of prior episodes or duration of illness in the recurrent unipolar and bipolar disorders. Substantial evidence supports the view that cognitive dysfunction and vulnerability to a diagnosis of dementia in old age increases as a function of number of prior mood episodes as does non-response to many therapeutic interventions as well as naturalistic treatment. Neurobiological abnormalities that correlate with the number of mood episodes or duration of illness include: anatomical, functional, and biochemical deficits in the prefrontal cortex and hippocampus, as well as amygdala hyperactivity and cortisol hyper-secretion. Some neurotrophic factors and inflammatory markers may also change with greater illness burden. Causality cannot be inferred from these correlative relationships. Nonetheless, given the potentially grave consequences of episode recurrence and progression for morbidity and treatment non-responsiveness, it is clinically wise to assume episodes are causing some of the progressive cognitive and neurobiological abnormalities. As such, earlier and more sustained long-term prophylaxis to attempt to reduce these adverse outcomes is indicated. Copyright © 2012 Elsevier Ltd. All rights reserved.

Psychotic depression, posttraumatic stress disorder, and engagement in cognitive-behavioral therapy within an outpatient sample of adults with serious mental illness.

PubMed

Gottlieb, Jennifer D; Mueser, Kim T; Rosenberg, Stanley D; Xie, Haiyi; Wolfe, Rosemarie S

2011-01-01

Depression with psychotic features afflicts a substantial number of people and has been characterized by significantly greater impairment, higher levels of dysfunctional beliefs, and poorer response to psychopharmacologic and psychosocial interventions than nonpsychotic depression. Those with psychotic depression also experience a host of co-occurring disorders, including posttraumatic stress disorder (PTSD), which is not surprising given the established relationships between trauma exposure and increased rates of psychosis and between PTSD and major depression. To date, there has been very limited research on the psychosocial treatment of psychotic depression; and even less is known about those who also suffer from PTSD. The purpose of this study was to better understand the rates and clinical correlates of psychotic depression in those with PTSD. Clinical and symptom characteristics of 20 individuals with psychotic depression and 46 with nonpsychotic depression, all with PTSD, were compared before receiving cognitive-behavioral therapy for PTSD treatment or treatment as usual. Patients with psychotic depression exhibited significantly higher levels of depression and anxiety, a weaker perceived therapeutic alliance with their case managers, more exposure to traumatic events, and more negative beliefs related to their traumatic experiences, as well as increased levels of maladaptive cognitions about themselves and the world, compared with participants without psychosis. Implications for cognitive-behavioral therapy treatment aimed at dysfunctional thinking for this population are discussed. © 2011 Elsevier Inc. All rights reserved.

Apolipoprotein Eε4: A Biomarker for Executive Dysfunction among Parkinson's Disease Patients with Mild Cognitive Impairment.

PubMed

Samat, Nor A; Abdul Murad, Nor A; Mohamad, Khairiyah; Abdul Razak, Mohd R; Mohamed Ibrahim, Norlinah

2017-01-01

Background: Cognitive impairment is prevalent in Parkinson's disease (PD), affecting 15-20% of patients at diagnosis. α-synuclein expression and genetic polymorphisms of Apolipoprotein E ( ApoE ) have been associated with the presence of cognitive impairment in PD although data have been inconsistent. Objectives: To determine the prevalence of cognitive impairment in patients with PD using Montreal Cognitive Assessment (MoCA), Comprehensive Trail Making Test (CTMT) and Parkinson's disease-cognitive rating scale (PDCRS), and its association with plasma α-synuclein and ApoE genetic polymorphisms. Methods: This was across-sectional study involving 46 PD patients. Patients were evaluated using Montreal cognitive assessment test (MoCA), and detailed neuropsychological tests. The Parkinson's disease cognitive rating scale (PDCRS) was used for cognitive function and comprehensive trail making test (CTMT) for executive function. Blood was drawn for plasma α-synuclein measurements and ApoE genetic analysis. ApoE polymorphism was detected using MutaGEL APoE from ImmunDiagnostik. Plasma α-synuclein was detected using the ELISA Technique (USCN Life Science Inc.) according to the standard protocol. Results: Based on MoCA, 26 (56.5%) patients had mild cognitive impairment (PD-MCI) and 20 (43.5%) had normal cognition (PD-NC). Based on the PDCRS, 18 (39.1%) had normal cognition (PDCRS-NC), 17 (37%) had mild cognitive impairment (PDCRS-MCI), and 11 (23.9%) had dementia (PDCRS-PDD). In the PDCRS-MCI group, 5 (25%) patients were from PD-NC group and all PDCRS-PDD patients were from PD-MCI group. CTMT scores were significantly different between patients with MCI and normal cognition on MoCA ( p = 0.003). Twenty one patients (72.4%) with executive dysfunction were from the PD-MCI group; 17 (77.3%) with severe executive dysfunction and 4 (57.1%) had mild to moderate executive dysfunction. There were no differences in the plasma α-synuclein concentration between the presence or types of cognitive impairment based on MoCA, PDCRS, and CTMT. The ApoEe4 allele carrier frequency was significantly higher in patients with executive dysfunction ( p = 0.014). Conclusion: MCI was prevalent in our PD population. PDCRS appeared to be more discriminatory in detecting MCI and PDD than MoCA. Plasma α-synuclein level was not associated with presence nor type of cognitive impairment, but the ApoEe4 allele carrier status was significantly associated with executive dysfunction in PD.

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.

Genetic epileptic encephalopathies: is all written into the DNA?

PubMed

Striano, Pasquale; de Jonghe, Peter; Zara, Federico

2013-11-01

Epileptic encephalopathy is a condition in which epileptic activity, clinical or subclinical, is thought to be responsible for any disturbance of cognition, behavior, or motor control. However, experimental evidence supporting this clinical observation are still poor and the causal relationship between pharmacoresistant seizures and cognitive outcome is controversial. In the past two decades, genetic studies shed new light onto complex mechanisms underlying different severe epileptic conditions associated with intellectual disability and behavioral abnormalities, thereby providing important clues on the relationship between seizures and cognitive outcome. Dravet syndrome is a childhood disorder associated with loss-of-function mutations in SCN1A and is characterized by frequent seizures and severe cognitive impairment, thus well illustrating the concept of epileptic encephalopathy. However, it is difficult to determine the causative role of the underlying sodium channel dysfunction and that of the consequent seizures in influencing cognitive outcome in these children. It is also difficult to demonstrate whether a recognizable profile of cognitive impairment or a definite behavioral phenotype exists. Data from the laboratory and the clinics may provide greater insight into the degree to which epileptic activity may contribute to cognitive impairment in individual syndromes. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Enhancement of Cognitive Processing by Multiple Sclerosis Patients Using Liquid Cooling Technology: A Case Study

NASA Technical Reports Server (NTRS)

Montgomery, Leslie D.; Montgomery, Richard W.; Ku, Yu-Tsuan; Luna, Bernadette (Technical Monitor)

1997-01-01

Cognitive dysfunction is a common symptom in patients with multiple sclerosis (MS). This can have a significant impact on the quality of life of both the patient and of their primary care giver. This case study explores the possibility that liquid cooling therapy may be used to enhance the cognitive processing of MS patients in the same way that it provides temporary relief of some physical impairment. Two MS patients were presented a series of pattern discrimination tasks before and after being cooled with a liquid cooling garment for a one hour period. The subject whose ear temperature was reduced during cooling showed greater electroencephalographic (EEG) activity and scored much better on the task after cooling. The patient whose ear temperature was unaffected by cooling showed less EEG activity and degraded performance after the one hour cooling period.

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.

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

Fibromyalgia syndrome module at OMERACT 9: domain construct.

PubMed

Mease, Philip; Arnold, Lesley M; Choy, Ernest H; Clauw, Daniel J; Crofford, Leslie J; Glass, Jennifer M; Martin, Susan A; Morea, Jessica; Simon, Lee; Strand, C Vibeke; Williams, David A

2009-10-01

The objective of the module was to (1) establish a core domain set for fibromyalgia (FM) assessment in clinical trials and practice, (2) review outcome measure performance characteristics, (3) discuss development of a responder index for assessment of FM in clinical trials, (4) review objective markers, (5) review the domain of cognitive dysfunction, and (6) establish a research agenda for outcomes research. Presentations at the module included: (1) Results of univariate and multivariate analysis of 10 FM clinical trials of 4 drugs, mapping key domains identified in previous patient focus group: Delphi exercises and a clinician/researcher Delphi exercise, and breakout discussions to vote on possible essential domains and reliable measures; (2) Updates regarding outcome measure status; (3) Update on objective markers to measure FM disease state; and (4) Review of the issue of cognitive dysfunction (dyscognition) in FM. Consensus was reached as follows: (1) Greater than 70% of OMERACT participants agreed that pain, tenderness, fatigue, patient global, multidimensional function and sleep disturbance domains should be measured in all FM clinical trials; dyscognition and depression should be measured in some trials; and stiffness, anxiety, functional imaging, and cerebrospinal fluid biomarkers were identified as domains of research interest. (2) FM domain outcome measures have generally proven to be reliable, discriminative, and feasible. More sophisticated and comprehensive measures are in development, as is a responder index for FM. (3) Increasing numbers of objective markers are being developed for FM assessment. (4) Cognitive dysfunction assessment by self-assessed and applied outcome measures is being developed. In conclusion, a multidimensional symptom core set is proposed for evaluation of FM in clinical trials. Research on improved measures of single domains and composite measures is ongoing.

Increased Resting-State Functional Connectivity in the Cingulo-Opercular Cognitive-Control Network after Intervention in Children with Reading Difficulties

PubMed Central

Horowitz-Kraus, Tzipi; Toro-Serey, Claudio; DiFrancesco, Mark

2015-01-01

Dyslexia, or reading difficulty, is characterized by slow, inaccurate reading accompanied by executive dysfunction. Reading training using the Reading Acceleration Program improves reading and executive functions in both children with dyslexia and typical readers. This improvement is associated with increased activation in and functional connectivity between the anterior cingulate cortex, part of the cingulo-opercular cognitive-control network, and the fusiform gyrus during a reading task after training. The objective of the current study was to determine whether the training also has an effect on functional connectivity of the cingulo-opercular and fronto-parietal cognitive-control networks during rest in children with dyslexia and typical readers. Fifteen children with reading difficulty and 17 typical readers (8-12 years old) were included in the study. Reading and executive functions behavioral measures and resting-state functional magnetic resonance imaging data were collected before and after reading training. Imaging data were analyzed using a graphical network-modeling tool. Both reading groups had increased reading and executive-functions scores after training, with greater gains among the dyslexia group. Training may have less effect on cognitive control in typical readers and a more direct effect on the visual area, as previously reported. Statistical analysis revealed that compared to typical readers, children with reading difficulty had significantly greater functional connectivity in the cingulo-opercular network after training, which may demonstrate the importance of cognitive control during reading in this population. These results support previous findings of increased error-monitoring activation after reading training in children with dyslexia and confirm greater gains with training in this group. PMID:26197049

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

Cognitive Emotion Regulation Strategies Associated With the DSM-5 Posttraumatic Stress Disorder Criteria.

PubMed

Kaczkurkin, Antonia N; Zang, Yinyin; Gay, Natalie G; Peterson, Alan L; Yarvis, Jeffrey S; Borah, Elisa V; Dondanville, Katherine A; Hembree, Elizabeth A; Litz, Brett T; Mintz, Jim; Young-McCaughan, Stacey; Foa, Edna B

2017-08-01

Maladaptive cognitive emotion regulation strategies have been proposed to contribute to the maintenance of posttraumatic stress disorder (PTSD). Prior work has focused on the relationship between these strategies and PTSD as a whole, rather than on how they are related to each PTSD symptom cluster. The purpose of the current study was to determine whether cognitive emotion regulation strategies are predictive of certain PTSD symptom clusters under the Diagnostic and Statistical Manual of Mental Disorders 5th ed. (DSM-5; American Psychiatric Association, 2013) criteria (intrusive thoughts, avoidance, negative alterations in cognitions and mood, and hyperarousal). Participants included 365 treatment-seeking, active-duty military personnel with PTSD. The negative alterations in cognitions and mood cluster were associated with dysfunctional cognitions: greater negative cognitions about the self, negative cognitions about the world, and self-blame, as well as catastrophizing (Rc2 = .519). The negative alterations in cognitions and mood cluster did not show a strong relationship with blaming others, possibly due to the complex nature of self- and other-blame in this primarily deployment-related PTSD sample. Finally, the intrusive thoughts cluster was associated with catastrophizing (Rc2 = .211), suggesting an association between frequent intrusive memories and excessively negative interpretation of those memories. Copyright © 2017 International Society for Traumatic Stress Studies.

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.

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.

Dependent, but not Perfectionistic, Dysfunctional Attitudes Predict Worsened Mood and Appraisals after Emotional Support from a Romantic Partner

PubMed Central

Felix, Steven A. M.; Hooker, Christine I.

2016-01-01

Background: Receiving emotional support from a romantic partner often leads to emotional costs via negative appraisals about the self and one's relationship, but it is unclear whether certain individuals are more susceptible to these costs. We evaluate whether the presence of perfectionistic and dependent dysfunctional attitudes leads to more negative effects of receiving emotional support from a romantic partner. Methods: Twenty-nine couples (27 men, 31 women; mean age 24.5) completed the Dysfunctional Attitudes Scale and then a daily online questionnaire by recording their mood, appraisals, and received emotional support. Mixed-effects regressions were used to evaluate whether perfectionistic and dependent dysfunctional attitudes moderated the relationship between emotional support receipt and subsequent mood and appraisals. Results: Perfectionism did not interact with emotional support but exerted a main effect of increasing negative moods and appraisals. Dependency interacted with emotional support such that those with more dependent attitudes reported greater negative next-day moods and appraisals as a function of emotional support. Conclusions: Individuals with dependent, but not perfectionistic, dysfunctional attitudes are more likely to experience emotional and cognitive costs after receiving emotional support. These costs may stem from activation or exacerbation of the attitudes specific to dependency, including need for acceptance, support, and approval of others. PMID:27790161

Web-based cognitive rehabilitation for survivors of adult cancer: A randomised controlled trial.

PubMed

Mihuta, Mary E; Green, Heather J; Shum, David H K

2018-04-01

Cognitive dysfunction associated with cancer is frequently reported and can reduce quality of life. This study evaluated a Web-based cognitive rehabilitation therapy program (eReCog) in cancer survivors compared with a waitlist control group. Adult cancer survivors with self-reported cognitive symptoms who had completed primary treatment at least 6 months prior were recruited. Participants completed telephone screening and were randomly allocated to the 4-week online intervention or waitlist. Primary outcome was perceived cognitive impairment assessed with the Functional Assessment of Cancer Therapy-Cognitive Function version 3. Secondary outcomes were additional measures of subjective cognitive functioning, objective cognitive functioning, and psychosocial variables. Seventy-six women were allocated to the intervention (n = 40) or waitlist (n = 36). A significant interaction was found on the instrumental activities of daily living measure of self-reported prospective memory whereby the intervention group reported a greater reduction in prospective memory failures than the waitlist group. Interaction trends were noted on perceived cognitive impairments (P = .089) and executive functioning (P = .074). No significant interactions were observed on other measures of objective cognitive functioning or psychosocial variables. The Web-based intervention shows promise for improving self-reported cognitive functioning in adult cancer survivors. Further research is warranted to better understand the mechanisms by which the intervention might contribute to improved self-reported cognition. Copyright © 2017 John Wiley & Sons, Ltd.

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

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.

Combined Blockade of Interleukin-1α and -1β Signaling Protects Mice from Cognitive Dysfunction after Traumatic Brain Injury

PubMed Central

Newell, Elizabeth A.; Todd, Brittany P.; Mahoney, Jolonda; Pieper, Andrew A.; Ferguson, Polly J.

2018-01-01

Abstract Diffuse activation of interleukin-1 inflammatory cytokine signaling after traumatic brain injury (TBI) elicits progressive neurodegeneration and neuropsychiatric dysfunction, and thus represents a potential opportunity for therapeutic intervention. Although interleukin (IL)-1α and IL-1β both activate the common type 1 IL-1 receptor (IL-1RI), they manifest distinct injury-specific roles in some models of neurodegeneration. Despite its potential relevance to treating patients with TBI, however, the individual contributions of IL-1α and IL-1β to TBI-pathology have not been previously investigated. To address this need, we applied genetic and pharmacologic approaches in mice to dissect the individual contributions of IL-1α, IL-β, and IL-1RI signaling to the pathophysiology of fluid percussion–mediated TBI, a model of mixed focal and diffuse TBI. IL-1RI ablation conferred a greater protective effect on brain cytokine expression and cognitive function after TBI than did individual IL-1α or IL-1β ablation. This protective effect was recapitulated by treatment with the drug anakinra, a recombinant naturally occurring IL-1RI antagonist. Our data thus suggest that broad targeting of IL-1RI signaling is more likely to reduce neuroinflammation and preserve cognitive function after TBI than are approaches that individually target IL-1α or IL-1β signaling. PMID:29662944

Combined Blockade of Interleukin-1α and -1β Signaling Protects Mice from Cognitive Dysfunction after Traumatic Brain Injury.

PubMed

Newell, Elizabeth A; Todd, Brittany P; Mahoney, Jolonda; Pieper, Andrew A; Ferguson, Polly J; Bassuk, Alexander G

2018-01-01

Diffuse activation of interleukin-1 inflammatory cytokine signaling after traumatic brain injury (TBI) elicits progressive neurodegeneration and neuropsychiatric dysfunction, and thus represents a potential opportunity for therapeutic intervention. Although interleukin (IL)-1α and IL-1β both activate the common type 1 IL-1 receptor (IL-1RI), they manifest distinct injury-specific roles in some models of neurodegeneration. Despite its potential relevance to treating patients with TBI, however, the individual contributions of IL-1α and IL-1β to TBI-pathology have not been previously investigated. To address this need, we applied genetic and pharmacologic approaches in mice to dissect the individual contributions of IL-1α, IL-β, and IL-1RI signaling to the pathophysiology of fluid percussion-mediated TBI, a model of mixed focal and diffuse TBI. IL-1RI ablation conferred a greater protective effect on brain cytokine expression and cognitive function after TBI than did individual IL-1α or IL-1β ablation. This protective effect was recapitulated by treatment with the drug anakinra, a recombinant naturally occurring IL-1RI antagonist. Our data thus suggest that broad targeting of IL-1RI signaling is more likely to reduce neuroinflammation and preserve cognitive function after TBI than are approaches that individually target IL-1α or IL-1β signaling.

Assessment of Cognitive Processing by Multiple Sclerosis Patients Using Electroencephalographic Energy Density Analysis

NASA Technical Reports Server (NTRS)

Montgomery, Leslie D.; Ku, Yu-Tsuan E.; Luna, Bernadette; Montgomery, Richard W.; Kliss, Mark (Technical Monitor)

1997-01-01

Recent neuropsychological studies demonstrate that cognitive dysfunction is a common symptom in patients with multiple sclerosis. In many cases the presence of cognitive impairment affects the patient's daily activities to a greater extent than would be found due to their physical disability alone. Cognitive dysfunction can have a significant impact on the quality of life of both the patient and that of their primary caregiver. Two cognitively impaired male MS patients were given a visual discrimination task before and after a one hour cooling period. The subjects were presented a series of either red or blue circles or triangles. One of these combinations, or one fourth of the stimuli, was designated as the "target" presentation. EEG was recorded from 20 scalp electrodes using a Tracor Northern 7500 EEG/ERP system. Oral and ear temperatures were obtained and recorded manually every five minutes during the one hour cooling period. The EEG ERP signatures from each series of stimuli were analyzed in the energy density domain to determine the locus of neural activity at each EEG sampling time. The first subject's ear temperature did not decrease during the cooling period. It was actually elevated approximately 0.05C by the end of the cooling period compared to his mean of control period value. In turn, Subject One's discrimination performance and cortical energy remained essentially the same after body cooling. In contrast, Subject Two's ear temperature decreased approx. 0.8C during his cooling period. Subject Two's ERROR score decreased from 12 during the precooling control period to 2 after cooling. His ENERGY value increased approximately 300%, from a precooling value of approximately 200 to a postcooling value of nearly 600.

Corpus callosum damage predicts disability progression and cognitive dysfunction in primary-progressive MS after five years.

PubMed

Bodini, Benedetta; Cercignani, Mara; Khaleeli, Zhaleh; Miller, David H; Ron, Maria; Penny, Sophie; Thompson, Alan J; Ciccarelli, Olga

2013-05-01

We aim to identify specific areas of white matter (WM) and grey matter (GM), which predict disability progression and cognitive dysfunction after five years in patients with primary-progressive multiple sclerosis (PPMS). Thirty-two patients with early PPMS were assessed at baseline and after five years on the Expanded Disability Status Scale (EDSS), and EDSS step-changes were calculated. At year five, a subgroup of 25 patients and 31 healthy controls underwent a neuropsychological assessment. Baseline imaging consisted of dual-echo (proton density and T2-weighted), T1-weighted volumetric, and diffusion tensor imaging. Fractional anisotropy (FA) maps were created, and fed into tract-based spatial statistics. To compensate for the potential bias introduced by WM lesions, the T1 volumes underwent a lesion-filling procedure before entering a voxel-based morphometry protocol. To investigate whether FA and GM volume predicted EDSS step-changes over five years and neuropsychological tests scores at five years, voxelwise linear regression analyses were performed. Lower FA in the splenium of the corpus callosum (CC) predicted a greater progression of disability over the follow-up. Lower FA along the entire CC predicted worse verbal memory, attention and speed of information processing, and executive function at five years. GM baseline volume did not predict any clinical variable. Our findings highlight the importance of damage to the interhemispheric callosal pathways in determining physical and cognitive disability in PPMS. Disruption of these pathways, which interconnect motor and cognitive networks between the two hemispheres, may result in a disconnection syndrome that contributes to long-term physical and cognitive disability. Copyright © 2011 Wiley Periodicals, Inc.

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

Neural, Hormonal, and Cognitive Correlates of Metabolic Dysfunction and Emotional Reactivity.

PubMed

Wolf, Tovah; Tsenkova, Vera; Ryff, Carol D; Davidson, Richard J; Willette, Auriel A

2018-06-01

Prediabetes and type 2 diabetes (i.e., hyperglycemia) are characterized by insulin resistance. These problems with energy metabolism may exacerbate emotional reactivity to negatively valenced stimuli and related phenomena such as predisposition toward negative affect, as well as cognitive deficits. Higher emotional reactivity is seen with hyperglycemia and insulin resistance. However, it is largely unknown how metabolic dysfunction correlates with related neural, hormonal, and cognitive outcomes. Among 331 adults from the Midlife in the United States study, eye-blink response (EBR) we cross sectionally examined to gauge reactivity to negative, positive, or neutrally valenced pictures from international affect picture system stimuli proximal to an acoustic startle probe. Increased EBR to negative stimuli was considered an index of stress reactivity. Frontal alpha asymmetry, a biomarker of negative affect predisposition, was determined using resting electroencephalography. Baseline urinary cortisol output was collected. Cognitive performance was gauged using the Brief Test of Adult Cognition by telephone. Fasting glucose and insulin characterized hyperglycemia or the homeostatic model assessment of insulin resistance. Higher homeostatic model assessment of insulin resistance corresponded to an increased startle response, measured by EBR magnitude, for negative versus positive stimuli (R = 0.218, F(1,457) = 5.48, p = .020, euglycemia: M(SD) = .092(.776), hyperglycemia: M(SD) = .120(.881)). Participants with hyperglycemia versus euglycemia showed greater right frontal alpha asymmetry (F(1,307) = 6.62, p = .011, euglycemia: M(SD) = .018(.167), hyperglycemia: M(SD) = -.029(.160)), and worse Brief Test of Adult Cognition by telephone arithmetic performance (F(1,284) = 4.25, p = .040, euglycemia: M(SD) = 2.390(1.526), hyperglycemia: M(SD) = 1.920(1.462)). Baseline urinary cortisol (log10 μg/12 hours) was also dysregulated in individuals with hyperglycemia (F(1,324) = 5.09, p = .025, euglycemia: M(SD) = 1.052 ± .332, hyperglycemia: M(SD) = .961 (.362)). These results suggest that dysmetabolism is associated with increased emotional reactivity, predisposition toward negative affect, and specific cognitive deficits.

Evidence of Cognitive Dysfunction after Soccer Playing with Ball Heading Using a Novel Tablet-Based Approach

PubMed Central

Lin, Angela H.; Patel, Saumil S.; Sereno, Anne B.

2013-01-01

Does frequent head-to-ball contact cause cognitive dysfunctions and brain injury to soccer players? An iPad-based experiment was designed to examine the impact of ball-heading among high school female soccer players. We examined both direct, stimulus-driven, or reflexive point responses (Pro-Point) as well as indirect, goal-driven, or voluntary point responses (Anti-Point), thought to require cognitive functions in the frontal lobe. The results show that soccer players were significantly slower than controls in the Anti-Point task but displayed no difference in Pro-Point latencies, indicating a disruption specific to voluntary responses. These findings suggest that even subconcussive blows in soccer can result in cognitive function changes that are consistent with mild traumatic brain injury of the frontal lobes. There is great clinical and practical potential of a tablet-based application for quick detection and monitoring of cognitive dysfunction. PMID:23460843

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.

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.

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

What changes in cognitive therapy for depression? An examination of cognitive therapy skills and maladaptive beliefs.

PubMed

Adler, Abby D; Strunk, Daniel R; Fazio, Russell H

2015-01-01

This study examined effortful cognitive skills and underlying maladaptive beliefs among patients treated with cognitive therapy (CT) for depression. Depressed patients (n=44) completed cognitive measures before and after 16 weeks of CT. Measures included an assessment of CT skills (Ways of Responding Scale; WOR), an implicit test of maladaptive beliefs (Implicit Association Test; IAT), and a self-report questionnaire of maladaptive beliefs (Dysfunctional Attitude Scale; DAS). A matched sample of never-depressed participants (n=44) also completed study measures. Prior to treatment, depressed patients endorsed significantly more undesirable cognitions on the WOR, IAT, and DAS compared with never-depressed participants. Patients displayed improvement on the WOR and DAS over the course of treatment, but showed no change on the IAT. Additionally, improvements on the WOR and DAS were each related to greater reductions in depressive symptoms. Results suggest that the degree of symptom reduction among patients participating in CT is related to changes in patients' acquisition of coping skills requiring deliberate efforts and reflective thought, but not related to reduced endorsement of implicitly assessed maladaptive beliefs. Copyright © 2014. Published by Elsevier Ltd.

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

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

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.

Multi-level comparison of empathy in schizophrenia: an fMRI study of a cartoon task.

PubMed

Lee, Seung Jae; Kang, Do Hyung; Kim, Chi-Won; Gu, Bon Mi; Park, Ji-Young; Choi, Chi-Hoon; Shin, Na Young; Lee, Jong-Min; Kwon, Jun Soo

2010-02-28

Empathy deficits might play a role in social dysfunction in schizophrenia. However, few studies have investigated the neuroanatomical underpinnings of the subcomponents of empathy in schizophrenia. This study investigated the hemodynamic responses to three subcomponents of empathy in patients with schizophrenia (N=15) and healthy volunteers (N=18), performing an empathy cartoon task during functional magnetic resonance imaging. The experiment used a block design with four conditions: cognitive, emotional, and inhibitory empathy, and physical causality control. Data were analyzed by comparing the blood-oxygen-level-dependent (BOLD) signal activation between the two groups. The cognitive empathy condition activated the right temporal pole to a lesser extent in the patient group than in comparison subjects. In the emotional and inhibitory conditions, the patients showed greater activation in the left insula and in the right middle/inferior frontal cortex, respectively. These findings add to our understanding of the impaired empathy in patients with schizophrenia by identifying a multi-level cortical dysfunction that underlies a deficit in each subcomponent of empathy and highlighting the importance of the fronto-temporal cortical network in ability to empathize. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Neural mechanisms of response inhibition and impulsivity in 22q11.2 deletion carriers and idiopathic attention deficit hyperactivity disorder.

PubMed

Montojo, C A; Congdon, E; Hwang, L; Jalbrzikowski, M; Kushan, L; Vesagas, T K; Jonas, R K; Ventura, J; Bilder, R M; Bearden, C E

2015-01-01

•22q11DS offers a compelling model to understand the neural substrates of attentional dysfunction.•First study directly comparing neural function in 22q11DS vs. ADHD patients•22q11DS and ADHD patients show a shared deficit in RI-related activation.•ADHD patients showed greater activity in the middle frontal gyrus than 22q11DS during RI.•Neural activity is inversely correlated with self-reported Cognitive Impulsivity in 22q11DS.

[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.

Attention-deficit/hyperactivity disorder dimensions and sluggish cognitive tempo symptoms in relation to college students' sleep functioning.

PubMed

Becker, Stephen P; Luebbe, Aaron M; Langberg, Joshua M

2014-12-01

This study examined separate inattentive, hyperactive, and impulsive dimensions of attention-deficit/hyperactivity disorder (ADHD), as well as sluggish cognitive tempo (SCT) symptoms, in relation to college students' sleep functioning. Participants were 288 college students (ages 17-24; 65 % female; 90 % non-Hispanic White; 12 % self-reported having an ADHD diagnoses) who completed measures of ADHD/SCT symptoms and sleep functioning. Participants reported obtaining an average of 6.8 h of sleep per night (only 26 % reported obtaining ≥8 h of sleep) and having a sleep onset latency of 25 min. 63 % were classified as "poor sleepers," and poor sleepers had higher rates of ADHD and SCT symptoms than "good sleepers". Path analysis controlling for ADHD status and psychiatric medication use was used to determine associations between psychopathology and sleep functioning domains. Above and beyond covariates and other psychopathologies, hyperactivity (but not impulsivity) was significantly associated with poorer sleep quality, longer sleep latency, shorter sleep duration, and more use of sleep medications. SCT symptoms (but not inattention) were significantly associated with poorer sleep quality and increased nighttime sleep disturbance (e.g., having bad dreams, waking up in the middle of the night, feeling too cold or too hot). Both inattention and SCT were associated with greater daytime dysfunction. Regression analyses demonstrated that hyperactivity predicted sleep quality above and beyond the influence of daytime dysfunction, and inattention and SCT predicted daytime dysfunction above and beyond sleep quality. Further studies are needed to examine the interrelations of nighttime sleep functioning, ADHD/SCT, and daytime dysfunction, as well to elucidate mechanisms contributing to related functional impairments.

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.

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.

Executive dysfunction, brain aging, and political leadership.

PubMed

Fisher, Mark; Franklin, David L; Post, Jerrold M

2014-01-01

Decision-making is an essential component of executive function, and a critical skill of political leadership. Neuroanatomic localization studies have established the prefrontal cortex as the critical brain site for executive function. In addition to the prefrontal cortex, white matter tracts as well as subcortical brain structures are crucial for optimal executive function. Executive function shows a significant decline beginning at age 60, and this is associated with age-related atrophy of prefrontal cortex, cerebral white matter disease, and cerebral microbleeds. Notably, age-related decline in executive function appears to be a relatively selective cognitive deterioration, generally sparing language and memory function. While an individual may appear to be functioning normally with regard to relatively obvious cognitive functions such as language and memory, that same individual may lack the capacity to integrate these cognitive functions to achieve normal decision-making. From a historical perspective, global decline in cognitive function of political leaders has been alternatively described as a catastrophic event, a slowly progressive deterioration, or a relatively episodic phenomenon. Selective loss of executive function in political leaders is less appreciated, but increased utilization of highly sensitive brain imaging techniques will likely bring greater appreciation to this phenomenon. Former Israeli Prime Minister Ariel Sharon was an example of a political leader with a well-described neurodegenerative condition (cerebral amyloid angiopathy) that creates a neuropathological substrate for executive dysfunction. Based on the known neuroanatomical and neuropathological changes that occur with aging, we should probably assume that a significant proportion of political leaders over the age of 65 have impairment of executive function.

Reduced Cardiac Vagal Modulation Impacts on Cognitive Performance in Chronic Fatigue Syndrome

PubMed Central

Beaumont, Alison; Burton, Alexander R.; Lemon, Jim; Bennett, Barbara K.; Lloyd, Andrew; Vollmer-Conna, Uté

2012-01-01

Background Cognitive difficulties and autonomic dysfunction have been reported separately in patients with chronic fatigue syndrome (CFS). A role for heart rate variability (HRV) in cognitive flexibility has been demonstrated in healthy individuals, but this relationship has not as yet been examined in CFS. The objective of this study was to examine the relationship between HRV and cognitive performance in patients with CFS. Methods Participants were 30 patients with CFS and 40 healthy controls; the groups were matched for age, sex, education, body mass index, and hours of moderate exercise/week. Questionnaires were used to obtain relevant medical and demographic information, and assess current symptoms and functional impairment. Electrocardiograms, perceived fatigue/effort and performance data were recorded during cognitive tasks. Between–group differences in autonomic reactivity and associations with cognitive performance were analysed. Results Patients with CFS showed no deficits in performance accuracy, but were significantly slower than healthy controls. CFS was further characterized by low and unresponsive HRV; greater heart rate (HR) reactivity and prolonged HR-recovery after cognitive challenge. Fatigue levels, perceived effort and distress did not affect cognitive performance. HRV was consistently associated with performance indices and significantly predicted variance in cognitive outcomes. Conclusions These findings reveal for the first time an association between reduced cardiac vagal tone and cognitive impairment in CFS and confirm previous reports of diminished vagal activity. PMID:23166694

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…

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.

Developing a Cognitive Training Strategy for First-Episode Schizophrenia: Integrating Bottom-Up and Top-Down Approaches

PubMed Central

Nuechterlein, Keith H.; Ventura, Joseph; Subotnik, Kenneth L.; Hayata, Jacqueline N.; Medalia, Alice; Bell, Morris D.

2014-01-01

It is clear that people with schizophrenia typically have cognitive problems in multiple domains as part of their illness. The cognitive deficits are among the main contributors to limitations in their everyday functioning, including their work recovery. Cognitive remediation has been applied successfully to help people with long-term, persistent schizophrenia to improve their cognitive functioning, but it is only beginning to be applied with individuals who have recently had a first episode of psychosis. Several different approaches to cognitive training have been developed. Some approaches emphasize extensive systematic practice with lower-level cognitive processes and building toward higher-level processes (“bottom-up”), while others emphasize greater focus on high-level cognitive processes that normally integrate and organize lower-level processes (“top-down”). Each approach has advantages and disadvantages for a disorder like schizophrenia, with its multiple levels of cognitive dysfunction. In addition, approaches to cognitive remediation differ in the extent to which they systematically facilitate transfer of learning to everyday functioning. We describe in this article the cognitive training approach that was developed for a UCLA study of people with a recent first episode of schizophrenia, a group that may benefit greatly from early intervention that focuses on cognition and recovery of work functioning. This approach integrated bottom-up and top-down computerized cognitive training and incorporated an additional weekly group session to bridge between computerized training and application to everyday work and school functioning. PMID:25489275

Social disinterest attitudes and group cognitive-behavioral social skills training for functional disability in schizophrenia.

PubMed

Granholm, Eric; Ben-Zeev, Dror; Link, Peter C

2009-09-01

The majority of clinical trials of cognitive-behavioral therapy (CBT) for schizophrenia have used individual therapy to target positive symptoms. Promising results have been found, however, for group CBT interventions and other treatment targets like psychosocial functioning. CBT for functioning in schizophrenia is based on a cognitive model of functional outcome in schizophrenia that incorporates dysfunctional attitudes (eg, social disinterest, defeatist performance beliefs) as mediators between neurocognitive impairment and functional outcome. In this report, 18 clinical trials of CBT for schizophrenia that included measures of psychosocial functioning were reviewed, and two-thirds showed improvements in functioning in CBT. The cognitive model of functional outcome was also tested by examining the relationship between social disinterest attitudes and functional outcome in 79 people with schizophrenia randomized to either group cognitive-behavioral social skills training or a goal-focused supportive contact intervention. Consistent with the cognitive model, lower social disinterest attitudes at baseline and greater reduction in social disinterest during group therapy predicted better functional outcome at end of treatment for both groups. However, the groups did not differ significantly with regard to overall change in social disinterest attitudes during treatment, suggesting that nonspecific social interactions during group therapy can lead to changes in social disinterest, regardless of whether these attitudes are directly targeted by cognitive therapy interventions.

The Activation of Incompetence Schemas in Response to Negative Sexual Events in Heterosexual and Lesbian Women: The Moderator Role of Personality Traits and Dysfunctional Sexual Beliefs.

PubMed

Peixoto, Maria Manuela; Nobre, Pedro

2017-01-01

Personality traits and dysfunctional sexual beliefs have been described as vulnerability factors for sexual dysfunction in women, and have also been proposed as dispositional variables for the activation of incompetence schemas in response to negative sexual events. However, no study has tested the role of personality traits and dysfunctional sexual beliefs in the activation of incompetence schemas. The current study aimed to assess the moderator role of neuroticism, extraversion, and dysfunctional sexual beliefs in the association between frequency of unsuccessful sexual episodes and activation of incompetence schemas in heterosexual and lesbian women. An online survey was completed by 1,121 women (831 heterosexual; 290 lesbian). Participants completed the NEO Five-Factor Inventory (NEO-FFI), the Sexual Dysfunctional Beliefs Questionnaire-Female Version (SDBQ), and the Questionnaire of Cognitive Schemas Activated in Sexual Context (QCSASC). Findings indicate that neuroticism moderates the association between frequency of negative sexual events and activation of incompetence schemas in heterosexual women. Moreover, several sexual beliefs also act as moderators of the relationship between negative sexual episodes and the activation of cognitive schemas in both heterosexual and lesbian women. Overall, findings support the cognitive-emotional model of sexual dysfunctions, emphasizing the role of personality traits and dysfunctional sexual beliefs as facilitators of the activation of incompetence schemas in response to negative events in women.

Cognitive dysfunction in antiphospholipid antibody (aPL)-negative systemic lupus erythematosus (SLE) versus aPL-positive non-SLE patients.

PubMed

Kozora, Elizabeth; Erkan, Doruk; Zhang, Lening; Zimmerman, Robert; Ramon, Glendalee; Ulug, Aziz M; Lockshin, Michael D

2014-01-01

The aim of this study was to compare the cognitive function of antiphospholipid antibody (aPL)-negative systemic lupus erythematosus (SLE) and aPL-positive non-SLE patients. Twenty aPL-negative SLE and 20 aPL-positive non-SLE female patients with no history of overt neuropsychiatric manifestations took standardised cognitive tests of learning and memory, attention and working memory, executive functions, verbal fluency, visuoconstruction, and motor function. The primary outcome measure was an established global cognitive impairment index (CII). Cranial magnetic resonance imaging (MRI) was also obtained on all patients. Twelve of 20 (60%) of the SLE and 8/20 (40%) of the aPL-positive patients had global cognitive impairment on CII; there were no group differences on CII or on individual measures. Cognitive impairment was not associated with duration of disease, level of disease activity, or prednisone use. No correlations were found between clinical disease factors and cognitive impairment, and neither group showed an association between incidental or major MRI abnormalities and cognitive dysfunction. Both aPL-negative SLE and aPL-positive non-SLE patients, without other overt neuropsychiatric disease, demonstrated high levels of cognitive impairment. No clinical, serologic, or radiologic characteristics were associated with cognitive impairment. Cognitive dysfunction is common in APS and in SLE, but its mechanisms remain unknown.

Chronic methamphetamine self-administration disrupts cortical control of cognition.

PubMed

Bernheim, Aurelien; See, Ronald E; Reichel, Carmela M

2016-10-01

Methamphetamine (meth) is one of the most abused substances worldwide. Chronic use has been associated with repeated relapse episodes that may be exacerbated by cognitive impairments during drug abstinence. Growing evidence demonstrates that meth compromises prefrontal cortex activity, resulting in persisting attentional and memory impairments. After summarizing recent studies of meth-induced cognitive dysfunction using a translationally relevant model of self-administered meth, this review emphasizes the cortical brain changes contributing to cognitive dysregulation during abstinence. Finally, we propose the use of cognitive enhancers during abstinence that may promote a drug-free state by reversing cortical dysfunction linked with prolonged meth abuse. Copyright © 2016 Elsevier Ltd. All rights reserved.

Thinking through postoperative cognitive dysfunction: How to bridge the gap between clinical and pre-clinical perspectives.

PubMed

Hovens, Iris B; Schoemaker, Regien G; van der Zee, Eddy A; Heineman, Erik; Izaks, Gerbrand J; van Leeuwen, Barbara L

2012-10-01

Following surgery, patients may experience cognitive decline, which can seriously reduce quality of life. This postoperative cognitive dysfunction (POCD) is mainly seen in the elderly and is thought to be mediated by surgery-induced inflammatory reactions. Clinical studies tend to define POCD as a persisting, generalised decline in cognition, without specifying which cognitive functions are impaired. Pre-clinical research mainly describes early hippocampal dysfunction as a consequence of surgery-induced neuroinflammation. These different approaches to study POCD impede translation between clinical and pre-clinical research outcomes and may hamper the development of appropriate interventions. This article analyses which cognitive domains deteriorate after surgery and which brain areas might be involved. The most important outcomes are: (1) POCD encompasses a wide range of cognitive impairments; (2) POCD affects larger areas of the brain; and (3) individual variation in the vulnerability of neuronal networks to neuroinflammatory mechanisms may determine if and how POCD manifests itself. We argue that, for pre-clinical and clinical research of POCD to advance, the effects of surgery on various cognitive functions and brain areas should be studied. Moreover, in addition to general characteristics, research should take inter-relationships between cognitive complaints and physical and mental characteristics into account. Copyright © 2012 Elsevier Inc. All rights reserved.

Cognitive Visual Dysfunctions in Preterm Children with Periventricular Leukomalacia

ERIC Educational Resources Information Center

Fazzi, Elisa; Bova, Stefania; Giovenzana, Alessia; Signorini, Sabrina; Uggetti, Carla; Bianchi, Paolo

2009-01-01

Aim: Cognitive visual dysfunctions (CVDs) reflect an impairment of the capacity to process visual information. The question of whether CVDs might be classifiable according to the nature and distribution of the underlying brain damage is an intriguing one in child neuropsychology. Method: We studied 22 children born preterm (12 males, 10 females;…

Cerebellar Dysfunction, Cognitive Flexibility and Autistic Traits in a Non-Clinical Sample

ERIC Educational Resources Information Center

Ridley, Nicole J.; Homewood, Judi; Walters, Jenny

2011-01-01

Cerebellar dysfunction and impaired cognitive flexibility are key features of autism spectrum disorders (ASD). However, despite the increasing interest in subclinical autism, no research has yet examined the relationship between these signs and autistic traits in the wider population. This study used the Autism-Spectrum Quotient (AQ) questionnaire…

Specificity of spontaneous EEG associated with different levels of cognitive and communicative dysfunctions in children.

PubMed

Kozhushko, Nadezhda Ju; Nagornova, Zhanna V; Evdokimov, Sergey A; Shemyakina, Natalia V; Ponomarev, Valery A; Tereshchenko, Ekaterina P; Kropotov, Jury D

2018-06-01

This study aimed to reveal electrophysiological markers of communicative and cognitive dysfunctions of different severity in children with autism spectrum disorder (ASD). Eyes-opened electroencephalograms (EEGs) of 42 children with ASD, divided into two groups according to the severity of their communicative and cognitive dysfunctions (24 with severe and 18 children with less severe ASD), and 70 age-matched controls aged 4-9 years were examined by means of spectral and group independent component (gIC) analyses. A predominance of theta and beta EEG activity in both groups of children with ASD compared to the activity in the control group was found in the global gIC together with a predominance of beta EEG activity in the right occipital region. The quantity of local gICs with enhanced slow and high-frequency EEG activity (within the frontal, temporal, and parietal cortex areas) in children 4-9 years of age might be considered a marker of cognitive and communicative dysfunction severity. Copyright © 2018 Elsevier B.V. All rights reserved.

Neuroprotective effects of voluntary running on cognitive dysfunction in an α-synuclein rat model of Parkinson's disease.

PubMed

Crowley, Erin K; Nolan, Yvonne M; Sullivan, Aideen M

2018-05-01

Parkinson's disease (PD) is no longer primarily classified as a motor disorder due to increasing recognition of the impact on patients of several nonmotor PD symptoms, including cognitive dysfunction. These nonmotor symptoms are highly prevalent and greatly affect the quality of life of patients with PD, and so, therapeutic interventions to alleviate these symptoms are urgently needed. The aim of this study was to investigate the potential neuroprotective effects of voluntary running on cognitive dysfunction in an adeno-associated virus-α-synuclein rat model of PD. Bilateral intranigral administration of adeno-associated virus-α-synuclein was found to induce motor dysfunction and a significant loss of nigral dopaminergic neurons, neither of which were rescued by voluntary running. Overexpression of α-synuclein also resulted in significant impairment on hippocampal neurogenesis-dependent pattern separation, a cognitive task; this was rescued by voluntary running. This was substantiated by an effect of running on neurogenesis levels in the dorsal dentate gyrus, suggesting that the functional effects of running on pattern separation were mediated via increased neurogenesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Neuroprotective effects of oleuropein against cognitive dysfunction induced by colchicine in hippocampal CA1 area in rats.

PubMed

Pourkhodadad, Soheila; Alirezaei, Masoud; Moghaddasi, Mehrnoush; Ahmadvand, Hassan; Karami, Manizheh; Delfan, Bahram; Khanipour, Zahra

2016-09-01

Alzheimer's disease is a progressive neurodegenerative disorder with decline in memory. The role of oxidative stress is well known in the pathogenesis of the disease. The purpose of this study was to evaluate pretreatment effects of oleuropein on oxidative status and cognitive dysfunction induced by colchicine in the hippocampal CA1 area. Male Wistar rats were pretreated orally once daily for 10 days with oleuropein at doses of 10, 15 and 20 mg/kg. Thereafter, colchicine (15 μg/rat) was administered into the CA1 area of the hippocampus to induce cognitive dysfunction. The Morris water maze was used to assess learning and memory. Biochemical parameters such as glutathione peroxidase and catalase activities, nitric oxide and malondialdehyde concentrations were measured to evaluate the antioxidant status in the rat hippocampus. Our results indicated that colchicine significantly impaired spatial memory and induced oxidative stress; in contrast, oleuropein pretreatment significantly improved learning and memory retention, and attenuated the oxidative damage. The results clearly indicate that oleuropein has neuroprotective effects against colchicine-induced cognitive dysfunction and oxidative damage in rats.

The effects of desvenlafaxine on neurocognitive and work functioning in employed outpatients with major depressive disorder.

PubMed

Lam, Raymond W; Iverson, Grant L; Evans, Vanessa C; Yatham, Lakshmi N; Stewart, Kurtis; Tam, Edwin M; Axler, Auby; Woo, Cindy

2016-10-01

Major depressive disorder (MDD) is associated with staggering personal and economic costs, a major proportion of which stem from impaired psychosocial and occupational functioning. Few studies have examined the impact of depression-related cognitive dysfunction on work functioning. We examined the association between neurocognitive and work functioning in employed patients with MDD. Employed adult outpatients (n=36) with MDD of at least moderate severity (≥23 on the Montgomery Asberg Depression Rating Scale, MADRS) and subjective cognitive complaints completed neurocognitive tests (CNS Vital Signs computerized battery) and validated self-reports of their work functioning (LEAPS, HPQ) before and after 8 weeks of open-label treatment with flexibly-dosed desvenlafaxine 50-100mg/day. Relationships between neurocognitive tests and functional measures were examined using bivariate correlational and multiple regression analyses, as appropriate. An ANCOVA model examined whether significant change in neurocognitive performance, defined as improvement of ≥1SD in the Neurocognition Index (NCI) from baseline to post-treatment, was associated with improved outcomes. Patients showed significant improvements in depressive symptom, neurocognitive, and work functioning measures following treatment with desvenlafaxine (e.g., MADRS response=77% and MADRS remission=49%). There were no significant correlations between changes in NCI or cognitive domain subscales and changes in MADRS, LEAPS, or HPQ scores. However, patients demonstrating significant improvement in NCI scores (n=11, 29%) had significantly greater improvement in clinical and work functioning outcomes compared to those without NCI improvement. The limitations of this study include small sample size, lack of a placebo control group, and lack of a healthy comparison group. Our sample also had more years of education and higher premorbid intelligence than the general population. There were no significant correlations between changes in neurocognitive and work functioning measures in this study. However, meaningful improvement in neurocognitive functioning with desvenlafaxine was associated with greater improvement in both mood and occupational outcomes. This suggests that addressing cognitive dysfunction may improve clinical and occupational outcomes in employed patients with MDD. However, the relationship between neurocognitive and work functioning in MDD is complex and requires further study. Copyright © 2016 Elsevier B.V. All rights reserved.

Modification of dysfunctional thoughts about caregiving in dementia family caregivers: description and outcomes of an intervention programme.

PubMed

Márquez-González, M; Losada, A; Izal, M; Pérez-Rojo, G; Montorio, I

2007-11-01

Among the diverse group of interventions developed to help dementia family caregivers cognitive-behavioural approaches show especially promising results. This study describes a cognitive-behavioural group intervention aimed principally at the modification of dysfunctional thoughts associated with caregiving (MDTC). The efficacy of the MDTC intervention in reducing caregivers' depressive symptomatology, together with the frequency and appraisal of problem behaviours, is compared to that of a waiting-list control group (WL). Furthermore, the potential mediating role of the dysfunctional thoughts in the relationship between this intervention and caregivers' depressive symptomatology is analyzed. Of the 74 dementia caregivers who were randomized to one of two conditions (MDTC and WL), 39 completed the post-intervention assessment. Statistical analyses were performed on an intention-to-treat basis, using last observation carried forward. The results reveal that the MDTC intervention is successful in reducing caregivers' level of depressive symptomatology and dysfunctional thoughts about caregiving, as well as in modifying their appraisal of their relative's problem behaviours. Furthermore, a mediating role for dysfunctional thoughts was found in the relationship between the MDTC intervention and levels of depressive symptomatology. The relevance of addressing dysfunctional thoughts and cognitive distortions in group interventions with caregivers is highlighted.

A Brief Dietary Assessment Predicts Executive Dysfunction in an Elderly Cohort: Results from the Einstein Aging Study.

PubMed

Sundermann, Erin E; Katz, Mindy J; Lipton, Richard B; Lichtenstein, Alice H; Derby, Carol A

2016-11-01

To examine the association between diet and executive function, episodic memory and global verbal cognition in the Einstein Aging Study (EAS) cohort and determine whether race modifies this relationship. Cross-sectional. Community. EAS participants without dementia who completed the Rapid Eating and Activity Assessment for Patients (REAP) (N = 492). The previously validated REAP is based on the 2000 U.S. dietary guidelines. REAP scores were dichotomized as less-healthy (

Diagnosing Contributions of Sensory and Cognitive Deficits to Hearing Dysfunction in Blast Exposed/TBI Service Members

DTIC Science & Technology

2016-10-01

1 AWARD NUMBER: W81XWH-15-1-0490 TITLE: Diagnosing Contributions of Sensory and Cognitive Deficits to Hearing Dysfunction in Blast-Exposed/ TBI...3. DATES COVERED 15 Sep 2015 - 14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Diagnosing Contributions of Sensory and Cognitive Deficits to...installed at WRNMMC, and is running finalized versions of both the auditory and visual selective attention tasks. Subject recruitment has started, and

mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling atherosclerosis and vascular cognitive impairment.

PubMed

Jahrling, Jordan B; Lin, Ai-Ling; DeRosa, Nicholas; Hussong, Stacy A; Van Skike, Candice E; Girotti, Milena; Javors, Martin; Zhao, Qingwei; Maslin, Leigh Ann; Asmis, Reto; Galvan, Veronica

2018-01-01

We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis. We measured CBF, BVD, cognitive function, markers of inflammation, and parameters of cardiovascular disease in LDLR -/- mice fed maintenance or high-fat diet ± rapamycin. Cardiovascular pathologies were proportional to severity of brain vascular dysfunction. Aortic atheromas were reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated potentially through reduction in systemic and brain inflammation following chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular integrity and function and that mTOR attenuation may restore neurovascular function and cardiovascular health. Together with our previous studies in AD models, our data suggest mTOR-driven vascular damage may be a mechanism shared by age-associated neurological diseases. Therefore, mTOR attenuation may have promise for treatment of cognitive impairment in atherosclerosis.

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.

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy.

PubMed

Packer, Rowena M A; McGreevy, Paul D; Salvin, Hannah E; Valenzuela, Michael J; Chaplin, Chloe M; Volk, Holger A

2018-01-01

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments.

Cognitive dysfunction in naturally occurring canine idiopathic epilepsy

PubMed Central

McGreevy, Paul D.; Salvin, Hannah E.; Valenzuela, Michael J.; Chaplin, Chloe M.; Volk, Holger A.

2018-01-01

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments. PMID:29420639

White matter structural network abnormalities underlie executive dysfunction in amyotrophic lateral sclerosis.

PubMed

Dimond, Dennis; Ishaque, Abdullah; Chenji, Sneha; Mah, Dennell; Chen, Zhang; Seres, Peter; Beaulieu, Christian; Kalra, Sanjay

2017-03-01

Research in amyotrophic lateral sclerosis (ALS) suggests that executive dysfunction, a prevalent cognitive feature of the disease, is associated with abnormal structural connectivity and white matter integrity. In this exploratory study, we investigated the white matter constructs of executive dysfunction, and attempted to detect structural abnormalities specific to cognitively impaired ALS patients. Eighteen ALS patients and 22 age and education matched healthy controls underwent magnetic resonance imaging on a 4.7 Tesla scanner and completed neuropsychometric testing. ALS patients were categorized into ALS cognitively impaired (ALSci, n = 9) and ALS cognitively competent (ALScc, n = 5) groups. Tract-based spatial statistics and connectomics were used to compare white matter integrity and structural connectivity of ALSci and ALScc patients. Executive function performance was correlated with white matter FA and network metrics within the ALS group. Executive function performance in the ALS group correlated with global and local network properties, as well as FA, in regions throughout the brain, with a high predilection for the frontal lobe. ALSci patients displayed altered local connectivity and structural integrity in these same frontal regions that correlated with executive dysfunction. Our results suggest that executive dysfunction in ALS is related to frontal network disconnectivity, which potentially mediates domain-specific, or generalized cognitive impairment, depending on the degree of global network disruption. Furthermore, reported co-localization of decreased network connectivity and diminished white matter integrity suggests white matter pathology underlies this topological disruption. We conclude that executive dysfunction in ALSci is associated with frontal and global network disconnectivity, underlined by diminished white matter integrity. Hum Brain Mapp 38:1249-1268, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Comparing the effects of treatment with sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women: a randomized controlled clinical trial

PubMed Central

Omidi, Abdollah; Ahmadvand, Afshin; Najarzadegan, Mohammad Reza; Mehrzad, Fateme

2016-01-01

Background Sexual dysfunction in women is prevalent and common in women after menopause. Many attempts to treat patients with sexual dysfunction by cognitive-behavioral therapy (CBT) methods. But to the best of our knowledge, there has been no study that compared these two methods. Objective The aim of this study was to assess and compare the effects of sildenafil and cognitive-behavioral therapy on treatment of sexual dysfunction in women. Methods In this randomized, controlled, clinical trial, 86 women with arousal and orgasm dysfunction were surveyed. The patients were divided into two groups, i.e., sildenafil and CBT groups. The patients in the sildenafil group were treated by 50 mg of oral sildenafil one hour before intercourse, and the other group had weekly sessions of CBT for eight weeks. Sexual dysfunctions were evaluated by the Female Sexual Function Index (FSFI), a sexual satisfaction questionnaire, and the Enrich marital satisfaction scale. Results The mean age of the participants was 33.14 ± 7.34 years. The mean scores for female sexual function index, sexual satisfaction, and the Enrich marital satisfaction scale were increased in both groups during treatment (p < 0.001). It was found that cognitive-behavioral therapy compared to treatment with sildenafil increased all subscales, except arousal, orgasm, and lubrication. Conclusion Cognitive-behavioral therapy is more effective than treatment with sildenafil for improving female sexual function. Clinical trial registration The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the IRCT ID: IRCT2014070318338N1. Funding The authors received no financial support for the research, authorship, and/or publication of this article. PMID:27382439

Cognitive structures in women with sexual dysfunction: the role of early maladaptive schemas.

PubMed

Oliveira, Cátia; Nobre, Pedro J

2013-07-01

Cognitive schemas are often related to psychological problems. However, the role of these structures within sexual problems is not yet well established. The aim of this study was to evaluate the presence and importance of early maladaptive schemas on women's sexual functioning and cognitive schemas activated in response to negative sexual events. A total of 228 women participated in the study: a control sample of 167 women without sexual problems, a subclinical sample of 37 women with low sexual functioning, and a clinical sample of 24 women with sexual dysfunction. Participants completed several self-reported measures: the Schema Questionnaire, the Questionnaire of Cognitive Schema Activation in Sexual Context, the Brief Symptom Inventory, the Beck Depression Inventory, and the Female Sexual Function Index. Findings indicated that women with sexual dysfunction presented significantly more early maladaptive schemas from the Impaired Autonomy and Performance domain, particularly failure (P < 0.001, η(2) = 0.08), dependence/incompetence (P < 0.05, η(2) = 0.03), and vulnerability to danger (P < 0.05, η(2) = 0.04). Additionally, in response to negative sexual events, women with sexual dysfunction presented significantly higher scores on incompetence (P < 0.001, η(2) = 0.16), self-depreciation (P < 0.01, η(2) = 0.05), and difference/loneliness (P < 0.01, η(2) = 0.05) schemas. Results supported differences between women with and without sexual problems regarding cognitive factors. This may have implications for the knowledge, assessment, and treatment of sexual dysfunction in women. © 2012 International Society for Sexual Medicine.

Thyroid function abnormalities and cognitive impairment in elderly people: results of the Invecchiare in Chianti study.

PubMed

Ceresini, Graziano; Lauretani, Fulvio; Maggio, Marcello; Ceda, Gian Paolo; Morganti, Simonetta; Usberti, Elisa; Chezzi, Carlo; Valcavi, Rita; Bandinelli, Stefania; Guralnik, Jack M; Cappola, Anne R; Valenti, Giorgio; Ferrucci, Luigi

2009-01-01

To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition. Cross-sectional. Community-based. One thousand one hundred seventy-one men and women aged 23 to 102. Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated using the Mini-Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 vs > or =65). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association between thyroid dysfunction and MMSE score was evaluated adjusting for confounders. Subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (subclinical hypothyroidism, 3.5% vs 0.4%, P<.03; subclinical hyperthyroidism, 7.8% vs 1.9%, P<.002). In euthyroid participants, TSH and FT3 declined with age, whereas FT4 increased. Older participants with subclinical hyperthyroidism had lower MMSE scores than euthyroid subjects (22.61+/-6.88 vs 24.72+/-4.52, P<.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (hazard rate=2.26, P=.003). Subtle age-related changes in FT3, FT4, and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment.

No strong evidence for abnormal levels of dysfunctional attitudes, automatic thoughts, and emotional information-processing biases in remitted bipolar I affective disorder.

PubMed

Lex, Claudia; Meyer, Thomas D; Marquart, Barbara; Thau, Kenneth

2008-03-01

Beck extended his original cognitive theory of depression by suggesting that mania was a mirror image of depression characterized by extreme positive cognition about the self, the world, and the future. However, there were no suggestions what might be special regarding cognitive features in bipolar patients (Mansell & Scott, 2006). We therefore used different indicators to evaluate cognitive processes in bipolar patients and healthy controls. We compared 19 remitted bipolar I patients (BPs) without any Axis I comorbidity with 19 healthy individuals (CG). All participants completed the Beck Depression Inventory, the Dysfunctional Attitude Scale, the Automatic Thoughts Questionnaire, the Emotional Stroop Test, and an incidental recall task. No significant group differences were found in automatic thinking and the information-processing styles (Emotional Stroop Test, incidental recall task). Regarding dysfunctional attitudes, we obtained ambiguous results. It appears that individuals with remitted bipolar affective disorder do not show cognitive vulnerability as proposed in Beck's theory of depression if they only report subthreshold levels of depressive symptoms. Perhaps, the cognitive vulnerability might only be observable if mood induction procedures are used.

Cognitive Dysfunction in Patients with Renal Failure Requiring Hemodialysis

PubMed Central

Thimmaiah, Rohini; Murthy, K. Krishna; Pinto, Denzil

2012-01-01

Background and Objectives: Renal failure patients show significant impairment on measures of attention and memory, and consistently perform significantly better on neuropsychological measures of memory and attention, approximately 24 hours after hemodialysis treatment. The objectives are to determine the cognitive dysfunction in patients with renal failure requiring hemodialysis. Materials and Methods: A total of 60 subjects comprising of 30 renal failure patients and 30 controls were recruited. The sample was matched for age, sex, and socioeconomic status. The tools used were the Standardized Mini-Mental State Examination and the Brief Cognitive Rating Scale. Results: The patients showed high cognitive dysfunction in the pre-dialysis group, in all the five dimensions (concentration, recent memory, past memory, orientation and functioning, and self-care), and the least in the 24-hour post dialysis group. This difference was found to be statistically significant (P=0.001). Conclusion: Patients with renal failure exhibited pronounced cognitive impairment and these functions significantly improved after the introduction of hemodialysis. PMID:23439613

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.

Vascular cognitive impairment, a cardiovascular complication.

PubMed

Frances, Adiukwu; Sandra, Ofori; Lucy, Ugbomah

2016-06-22

Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension.

Vascular cognitive impairment, a cardiovascular complication

PubMed Central

Frances, Adiukwu; Sandra, Ofori; Lucy, Ugbomah

2016-01-01

Over the past two decades, the term vascular cognitive impairment (VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from PubMed, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension. PMID:27354961

COGNITION AS A THERAPEUTIC TARGET IN LATE-LIFE DEPRESSION: POTENTIAL FOR NICOTINIC THERAPEUTICS

PubMed Central

Zurkovsky, Lilia; Taylor, Warren D.; Newhouse, Paul A.

2013-01-01

Depression is associated with impairments to cognition and brain function at any age, but such impairments in the elderly are particularly problematic because of the additional burden of normal cognitive aging and in some cases, structural brain pathology. Individuals with late-life depression exhibit impairments in cognition and brain structural integrity, alongside mood dysfunction. Antidepressant treatment improves symptoms in some but not all patients, and those who benefit may not return to the cognitive and functional level of nondepressed elderly. Thus, for comprehensive treatment of late-life depression, it may be necessary to address both the affective and cognitive deficits. In this review, we propose a model for the treatment of late-life depression in which nicotinic stimulation is used to improve cognitive performance and improve the efficacy of an antidepressant treatment of the syndrome of late-life depression. The cholinergic system is well-established as important to cognition. Although muscarinic stimulation may exacerbate depressive symptoms, nicotinic stimulation may improve cognition and neural functioning without a detriment to mood. While some studies of nicotinic subtype specific receptor agonists have shown promise in improving cognitive performance, less is known regarding how nicotinic receptor stimulation affects cognition in depressed elderly patients. Late-life depression thus represents a new therapeutic target for the development of nicotinic agonist drugs and parallel treatment of cognitive dysfunction along with medical and psychological approaches to treating mood dysfunction may be necessary to ensure full resolution of depressive illness in aging. PMID:23933385

Obesity Reduces Cognitive and Motor Functions across the Lifespan

PubMed Central

Wang, Chuanming; Chan, John S. Y.; Ren, Lijie; Yan, Jin H.

2016-01-01

Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised. PMID:26881095

Obesity Reduces Cognitive and Motor Functions across the Lifespan.

PubMed

Wang, Chuanming; Chan, John S Y; Ren, Lijie; Yan, Jin H

2016-01-01

Due to a sedentary lifestyle, more and more people are becoming obese nowadays. In addition to health-related problems, obesity can also impair cognition and motor performance. Previous results have shown that obesity mainly affects cognition and motor behaviors through altering brain functions and musculoskeletal system, respectively. Many factors, such as insulin/leptin dysregulation and inflammation, mediate the effect of obesity and cognition and motor behaviors. Substantial evidence has suggested exercise to be an effective way to improve obesity and related cognitive and motor dysfunctions. This paper aims to discuss the association of obesity with cognition and motor behaviors and its underlying mechanisms. Following this, mechanisms of exercise to improve obesity-related dysfunctions are described. Finally, implications and future research direction are raised.

Load-dependent dysfunction of the putamen during attentional processing in patients with clinically isolated syndrome suggestive of multiple sclerosis.

PubMed

Tortorella, C; Romano, R; Direnzo, V; Taurisano, P; Zoccolella, S; Iaffaldano, P; Fazio, L; Viterbo, R; Popolizio, T; Blasi, G; Bertolino, A; Trojano, M

2013-08-01

Load-related functional magnetic resonance imaging (fMRI) abnormalities of brain activity during performance of attention tasks have been described in definite multiple sclerosis (MS). No data are available in clinically isolated syndrome (CIS) suggestive of MS. The objective of this research is to evaluate in CIS patients the fMRI pattern of brain activation during an attention task and to explore the effect of increasing task load demand on neurofunctional modifications. Twenty-seven untreated CIS patients and 32 age- and sex-matched healthy controls (HCs) underwent fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. Random-effects models were used for statistical analyses of fMRI data. CIS patients had reduced accuracy and greater reaction time at the VAC task compared with HCs (p=0.007). On blood oxygenation level-dependent (BOLD)-fMRI, CIS patients had greater activity in the right parietal cortex (p=0.0004) compared with HCs. Furthermore, CIS patients had greater activity at the lower (p=0.05) and reduced activity at the greater (p=0.04) level of attentional control demand in the left putamen, compared with HCs. This study demonstrates the failure of attentional control processing in CIS. The load-related fMRI dysfunction of the putamen supports the role of basal ganglia in the failure of attention observed at the earliest stage of MS.

Non-erotic thoughts, attentional focus, and sexual problems in a community sample.

PubMed

Nelson, Andrea L; Purdon, Christine

2011-04-01

According to Barlow's model of sexual dysfunction, anxiety in sexual situations leads to attentional focus on sexual performance at the expense of erotic cues, which compromises sexual arousal. This negative experience will enhance anxiety in future sexual situations, and non-erotic thoughts (NETs) relevant to performance will receive attentional priority. Previous research with student samples (Purdon & Holdaway, 2006; Purdon & Watson, 2010) has found that people experience many types of NETs in addition to performance-relevant thoughts, and that, consistent with Barlow's model, the frequency of and anxiety evoked by these thoughts is positively associated with sexual problems. Extending this previous work, the current study found that, in a community sample of women (N = 81) and men (N = 72) in long-term relationships, women were more likely to report body image concerns and external consequences of the sexual activity, while men were more likely to report performance-related concerns. Equally likely among men and women were thoughts about emotional consequences of the sexual activity. Regardless of thought content, experiencing more frequent NETs was associated with more sexual problems in both women and men. Moreover, as per Barlow's model, greater negative affect in anticipation of and during sexual activity predicted greater frequency of NETs and greater anxiety in response to NETs was associated with greater difficulty dismissing the thoughts. However, greater difficulty in refocusing on erotic thoughts during sexual activity uniquely predicted more sexual problems above the frequency and dismissability of NETs. Together, these data support the cognitive interference mechanism implicated by Barlow's causal model of sexual dysfunction and have implications for the treatment of sexual problems.

Spatial Working Memory Impairment in Patients with Non-neuropsychiatric Systemic Lupus Erythematosus: A Blood-oxygen-level Dependent Functional Magnetic Resonance Imaging Study.

PubMed

Zhu, Chun-Min; Ma, Ye; Xie, Lei; Huang, Jin-Zhuang; Sun, Zong-Bo; Duan, Shou-Xing; Lin, Zhi-Rong; Yin, Jing-Jing; Le, Hong-Bo; Sun, Dan-Miao; Xu, Wen-Can; Ma, Shu-Hua

2017-02-01

Using ethology and functional magnetic resonance imaging (fMRI) to explore mild cognitive dysfunction and spatial working memory (WM) impairment in patients with systemic lupus erythematosus (SLE) without overt neuropsychiatric symptoms (non-NPSLE) and to study whether any clinical biomarkers could serve as predictors of brain dysfunction in this disease. Eighteen non-NPSLE patients and 18 matched subjects were all tested using the Montreal cognitive assessment scale test and scanned using blood-oxygen-level dependent fMRI while performing the n-back task to investigate the activation intensity of some cognition-related areas. Ethology results showed that non-NPSLE patients had mild cognitive dysfunction and memory dysfunction (p < 0.05). The fMRI scan confirmed a neural network consisting of bilateral dorsolateral prefrontal cortex (DLPFC), premotor area, parietal lobe, and supplementary motor area (SMA)/anterior cingulate cortex (ACC) that was activated during the n-back task, with right hemisphere dominance. However, only the right SMA/ACC showed a load effect in the non-NPSLE group; the activation intensity of most WM-related brain areas for the non-NPSLE group was lower than for the control group under 3 memory loads. Further, we found that the activation intensity of some cognition-related areas, including the bilateral caudate nucleus/insula and hippocampus/parahippocampal gyrus were lower than the control group under the memory loads. An inverse correlation existed between individual activation intensity and disease duration. Non-NPSLE-related brain damage with right DLPFC-posterior parietal lobe and parahippocampal gyrus default network causes impairment of spatial WM and mild cognitive dysfunction. Patients with longer disease duration would be expected to exhibit increased central nervous system damage.

Suicidal Ideation and Schizophrenia: Contribution of Appraisal, Stigmatization, and Cognition.

PubMed

Stip, Emmanuel; Caron, Jean; Tousignant, Michel; Lecomte, Yves

2017-10-01

To predict suicidal ideation in people with schizophrenia, certain studies have measured its relationship with the variables of defeat and entrapment. The relationships are positive, but their interactions remain undefined. To further their understanding, this research sought to measure the relationship between suicidal ideation with the variables of loss, entrapment, and humiliation. The convenience sample included 30 patients with schizophrenia spectrum disorders. The study was prospective (3 measurement times) during a 6-month period. Results were analyzed by stepwise multiple regression. The contribution of the 3 variables to the variance of suicidal ideation was not significant at any of the 3 times (T1: 16.2%, P = 0.056; T2: 19.9%, P = 0.117; T3: 11.2%, P = 0.109). Further analyses measured the relationship between the variables of stigmatization, perceived cognitive dysfunction, symptoms, depression, self-esteem, reason to live, spirituality, social provision, and suicidal ideation. Stepwise multiple regression demonstrated that the contribution of the variables of stigmatization and perceived cognitive dysfunction to the variance of suicidal ideation was significant at all 3 times (T1: 41.7.5%, P = 0.000; T2: 35.2%, P = 0.001; T3: 21.5%, P = 0.012). Yet, over time, the individual contribution of the variables changed: T1, stigmatization (β = 0.518; P = 0.002); T2, stigmatization (β = 0.394; P = 0.025) and perceived cognitive dysfunction (β = 0.349; P = 0.046). Then, at T3, only perceived cognitive dysfunction contributed significantly to suicidal ideation (β = 0.438; P = 0.016). The results highlight the importance of the contribution of the variables of perceived cognitive dysfunction and stigmatization in the onset of suicidal ideation in people with schizophrenia spectrum disorders.

Ursolic acid improves domoic acid-induced cognitive deficits in mice

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

Wu, Dong-mei; Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Xuzhou Normal University, Xuzhou 221116, Jiangsu Province; Lu, Jun, E-mail: lu-jun75@163.com

Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitivemore » deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders. - Highlights: • Ursolic acid (UA) is a naturally triterpenoid compound. • UA attenuated the mitochondrial dysfunction and cognitive deficits. • Mechanistically, UA activates PI3K/Akt signaling and suppresses FoxO1 activity. • UA could be recommended as a possible candidate for anti-excitotoxic brain disorders.« less

Suicidal Ideation and Schizophrenia: Contribution of Appraisal, Stigmatization, and Cognition

PubMed Central

Stip, Emmanuel; Caron, Jean; Tousignant, Michel

2017-01-01

Objective: To predict suicidal ideation in people with schizophrenia, certain studies have measured its relationship with the variables of defeat and entrapment. The relationships are positive, but their interactions remain undefined. To further their understanding, this research sought to measure the relationship between suicidal ideation with the variables of loss, entrapment, and humiliation. Method: The convenience sample included 30 patients with schizophrenia spectrum disorders. The study was prospective (3 measurement times) during a 6-month period. Results were analyzed by stepwise multiple regression. Results: The contribution of the 3 variables to the variance of suicidal ideation was not significant at any of the 3 times (T1: 16.2%, P = 0.056; T2: 19.9%, P = 0.117; T3: 11.2%, P = 0.109). Further analyses measured the relationship between the variables of stigmatization, perceived cognitive dysfunction, symptoms, depression, self-esteem, reason to live, spirituality, social provision, and suicidal ideation. Stepwise multiple regression demonstrated that the contribution of the variables of stigmatization and perceived cognitive dysfunction to the variance of suicidal ideation was significant at all 3 times (T1: 41.7.5%, P = 0.000; T2: 35.2%, P = 0.001; T3: 21.5%, P = 0.012). Yet, over time, the individual contribution of the variables changed: T1, stigmatization (β = 0.518; P = 0.002); T2, stigmatization (β = 0.394; P = 0.025) and perceived cognitive dysfunction (β = 0.349; P = 0.046). Then, at T3, only perceived cognitive dysfunction contributed significantly to suicidal ideation (β = 0.438; P = 0.016). Conclusion: The results highlight the importance of the contribution of the variables of perceived cognitive dysfunction and stigmatization in the onset of suicidal ideation in people with schizophrenia spectrum disorders. PMID:28673099

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

Working memory deficits in high-functioning adolescents with autism spectrum disorders: neuropsychological and neuroimaging correlates.

PubMed

Barendse, Evelien M; Hendriks, Marc Ph; Jansen, Jacobus Fa; Backes, Walter H; Hofman, Paul Am; Thoonen, Geert; Kessels, Roy Pc; Aldenkamp, Albert P

2013-06-04

Working memory is a temporary storage system under attentional control. It is believed to play a central role in online processing of complex cognitive information and may also play a role in social cognition and interpersonal interactions. Adolescents with a disorder on the autism spectrum display problems in precisely these domains. Social impairments, communication difficulties, and repetitive interests and activities are core domains of autism spectrum disorders (ASD), and executive function problems are often seen throughout the spectrum. As the main cognitive theories of ASD, including the theory of mind deficit hypotheses, weak central coherence account, and the executive dysfunction theory, still fail to explain the broad spectrum of symptoms, a new perspective on the etiology of ASD is needed. Deficits in working memory are central to many theories of psychopathology, and are generally linked to frontal-lobe dysfunction. This article will review neuropsychological and (functional) brain imaging studies on working memory in adolescents with ASD. Although still disputed, it is concluded that within the working memory system specific problems of spatial working memory are often seen in adolescents with ASD. These problems increase when information is more complex and greater demands on working memory are made. Neuroimaging studies indicate a more global working memory processing or connectivity deficiency, rather than a focused deficit in the prefrontal cortex. More research is needed to relate these working memory difficulties and neuroimaging results in ASD to the behavioral difficulties as seen in individuals with a disorder on the autism spectrum.

Chronic Tobacco-Smoking on Psychopathological Symptoms, Impulsivity and Cognitive Deficits in HIV-Infected Individuals.

PubMed

Chang, Linda; Lim, Ahnate; Lau, Eric; Alicata, Daniel

2017-09-01

HIV-infected individuals (HIV+) has 2-3 times the rate of tobacco smoking than the general population, and whether smoking may lead to greater psychiatric symptoms or cognitive deficits remains unclear. We evaluated the independent and combined effects of being HIV+ and chronic tobacco-smoking on impulsivity, psychopathological symptoms and cognition. 104 participants [27 seronegative (SN)-non-Smokers, 26 SN-Smokers, 29 HIV+ non-Smokers, 22 HIV+ Smokers] were assessed for psychopathology symptoms (Symptom Checklist-90, SCL-90), depressive symptoms (Center for Epidemiologic Studies-Depression Scale, CES-D), impulsivity (Barratt Impulsiveness Scale, BIS), decision-making (The Iowa Gambling Task, IGT, and Wisconsin Card Sorting Test, WCST), and cognition (seven neurocognitive domains). Both HIV+ and Smoker groups had higher SCL-90 and CES-D scores, with highest scores in HIV+ Smokers. On BIS, both HIV+ and Smokers had higher Total Impulsiveness scores, with higher behavioral impulsivity in Smokers, highest in HIV+ Smokers. Furthermore, across the four groups, HIV+ Smokers lost most money and made fewest advantageous choices on the IGT, and had highest percent errors on WCST. Lastly, HIV+ had lower z-scores on all cognitive domains, with the lowest scores in HIV+ Smokers. These findings suggest that HIV-infection and chronic tobacco smoking may lead to additive deleterious effects on impulsivity, psychopathological (especially depressive) symptoms and cognitive dysfunction. Although greater impulsivity may be premorbid in HIV+ and Smokers, the lack of benefits of nicotine in chronic Smokers on attention and psychopathology, especially those with HIV-infection, may be due to the negative effects of chronic smoking on dopaminergic and cardio-neurovascular systems. Tobacco smoking may contribute to psychopathology and neurocognitive disorders in HIV+ individuals.

The contribution of cognition and spasticity to driving performance in multiple sclerosis.

PubMed

Marcotte, Thomas D; Rosenthal, Theodore J; Roberts, Erica; Lampinen, Sara; Scott, J Cobb; Allen, R Wade; Corey-Bloom, Jody

2008-09-01

To examine the independent and combined impact of cognitive dysfunction and spasticity on driving tasks involving high cognitive workload and lower-limb mobility in persons with multiple sclerosis (MS). Single-visit cohort study. Clinical research center. Participants included 17 drivers with MS and 14 referent controls. The group with MS exhibited a broad range of cognitive functioning and disability. Of the 17 patients with MS, 8 had significant spasticity in the knee used to manipulate the accelerator and brake pedals (based on the Modified Ashworth Scale). Not applicable. A brief neuropsychologic test battery and 2 driving simulations. Simulation 1 required participants to maintain a constant speed and lane position while attending to a secondary task. Simulation 2 required participants to adjust their speed to accelerations and decelerations of a lead car in front of them. Patients with MS showed greater variability in lane position (effect size, g=1.30), greater difficulty in maintaining a constant speed (g=1.25), and less ability to respond to lead car speed changes (g=1.85) compared with controls. Within the MS group, in a multivariate model that included neuropsychologic and spasticity measures, cognitive functioning was the strongest predictor of difficulty in maintaining lane position during the divided attention task and poor response time to lead car speed changes, whereas spasticity was associated with reductions in accuracy of tracking the lead car movements and speed maintenance. In this preliminary study, cognitive and physical impairments associated with MS were related to deficits in specific components of simulated driving. Assessment of these factors may help guide the clinician regarding the types of driving behaviors that would put patients with MS at an increased risk for an automobile crash.

The Contribution of Cognition and Spasticity to Driving Performance in Multiple Sclerosis

PubMed Central

Marcotte, Thomas D.; Rosenthal, Theodore J.; Roberts, Erica; Lampinen, Sara; Scott, J. Cobb; Allen, R. Wade; Corey-Bloom, Jody

2014-01-01

Objective To examine the independent and combined impact of cognitive dysfunction and spasticity on driving tasks involving high cognitive workload and lower-limb mobility in individuals with multiple sclerosis (MS). Design Single-visit cohort study. Setting Clinical research center. Participants Seventeen drivers with MS and 14 normal controls. The MS group exhibited a broad range of cognitive functioning and disability. Eight MS patients had significant spasticity in the knee proximal to the pedals (based on the Modified Ashworth Scale). Interventions Not applicable. Main Outcome Measures A brief neuropsychologic test battery and 2 driving simulations. Simulation 1 required participants to maintain a constant speed and lane position while attending to a secondary task. Simulation 2 required participants to adjust their speed to accelerations and decelerations of a lead car in front of them. Results MS patients demonstrated greater variability in lane position (effect size g=1.30), greater difficulty in maintaining a constant speed (g=1.25), and less ability to respond to lead car speed changes (g=1.85) compared with controls. Within the MS group, in a multivariate model that included neuropsychologic and spasticity measures, cognitive functioning was the strongest predictor of difficulty in maintaining lane position during the divided attention task and poor response time to lead car speed changes, whereas spasticity was associated with reductions in accuracy of tracking the lead car movements and speed maintenance. Conclusions In this preliminary study, cognitive and physical impairments associated with MS were related to deficits in specific components of simulated driving, and assessment of these factors may help guide the clinician regarding the types of driving behaviors that would put MS patients at increased risk for a crash. PMID:18760160

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.

A multilevel analysis of cognitive dysfunction and psychopathology associated with chromosome 22q11.2 deletion syndrome in children

PubMed Central

SIMON, TONY J.; BISH, JOEL P.; BEARDEN, CARRIE E.; DING, LIJUN; FERRANTE, SAMANTHA; NGUYEN, VY; GEE, JAMES C.; McDONALD–McGINN, DONNA M.; ZACKAI, ELAINE H.; EMANUEL, BEVERLY S.

2006-01-01

We present a multilevel approach to developing potential explanations of cognitive impairments and psychopathologies common to individuals with chromosome 22q11.2 deletion syndrome. Results presented support our hypothesis of posterior parietal dysfunction as a central determinant of characteristic visuospatial and numerical cognitive impairments. Converging data suggest that brain development anomalies, primarily tissue reductions in the posterior brain and changes to the corpus callosum, may affect parietal connectivity. Further findings indicate that dysfunction in “frontal” attention systems may explain some executive cognition impairments observed in affected children, and that there may be links between these domains of cognitive function and some of the serious psychiatric conditions, such as attention-deficit/hyperactivity disorder, autism, and schizophrenia, that have elevated incidence rates in the syndrome. Linking the neural structure and the cognitive processing levels in this way enabled us to develop an elaborate structure/function mapping hypothesis for the impairments that are observed. We show also, that in the case of the catechol-O-methyltransferase gene, a fairly direct relationship between gene expression, cognitive function, and psychopathology exists in the affected population. Beyond that, we introduce the idea that variation in other genes may further explain the phenotypic variation in cognitive function and possibly the anomalies in brain development. PMID:16262991

Cognitive Dysfunction, Locus of Control and Treatment Outcome among Chronic Alcoholics.

ERIC Educational Resources Information Center

Abbott, Max W.

While alcoholism is no longer regarded as a unitary disorder, conventional measures of congition and personality have yet to be shown capable of consistently predicting clinical outcomes. To investigate cognitive dysfunction and locus of control as predictors of post treatment outcome in a large sample of alcoholics, 106 alcoholics (74 men, 32…

[Social dysfunction in schizotypy].

PubMed

de Wachter, O; De La Asuncion, J; Sabbe, B; Morrens, M

2016-01-01

Schizotypy is a personality organisation that is closely related to schizotypal personality disorder and schizophrenia and is characterised by deficits in social functioning. Although the dimensions of social dysfunction have not yet been fully explored certain aspects of social dysfunction are promising predictive markers for schizophrenia. To describe schizotypy and its influence on social functioning. We reviewed the literature systematically using the online databases PubMed and PsycINFO. The disorder known as schizotypy lies at the basis of schizotypal personality disorder. Both disorders are characterised by an increased risk for schizophrenia. The social dysfunctioning seen in schizotypy corresponds to the social dysfunction seen in schizophrenia. Impairments in social cognition are causal factors of this social dysfunction. Both the negative and the positive dimension of schizotypy influence social cognition. More focused, objective and interactive research to the various aspects of social functioning in schizotypy is needed in order to discover potential premorbid markers for schizophrenia.

Temporal Cerebral Microbleeds Are Associated With Radiation Necrosis and Cognitive Dysfunction in Patients Treated for Nasopharyngeal Carcinoma

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

Shen, Qingyu; Department of Neurology, Zengcheng People's Hospital, Guangzhou; Lin, Focai

Purpose: Radiation therapy for patients with nasopharyngeal carcinoma (NPC) may be complicated with radiation-induced brain necrosis (RN), resulting in deteriorated cognitive function. However, the underlying mechanism of this phenomenon remains unclear. This study attempts to elucidate the association between cerebral microbleeds (CMBs) and radiation necrosis and cognitive dysfunction in NPC patients treated with radiation therapy. Methods and Materials: This cross-sectional study included 106 NPC patients who were exposed to radiation therapy (78 patients with RN and 28 without RN). Sixty-six patients without discernable intracranial pathology were included as the control group. CMBs were confirmed using susceptibility-weighted magnetic resonance imaging. Cognitivemore » function was accessed using Montreal Cognitive Assessment. Patients with a total score below 26 were defined as cognitively dysfunction. Results: Seventy-seven patients (98.7%) in the RN group and 12 patients (42.9%) in the non-RN group had at least 1 CMB. In contrast, only 14 patients (21.2%) in the control group had CMBs. In patients with a history of radiation therapy, CMBs most commonly presented in temporal lobes (76.4%) followed by cerebellum (23.7%). Patients with RN had more temporal CMBs than those in the non-RN group (37.7 ± 51.9 vs 3.8 ± 12.6, respectively; P<.001). The number of temporal lobe CMBs was predictive for larger volume of brain necrosis (P<.001) in multivariate linear regression analysis. Although cognitive impairment was diagnosed in 55.1% of RN patients, only 7.1% of non-RN patients sustained cognitive impairment (P<.001). After adjusting for age, sex, education, period after radiation therapy, CMBs in other lobes, and RN volume, the number of temporal CMBs remained an independent risk factor for cognitive dysfunction (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.04; P=.003). Conclusions: CMBs is a common radiological manifestation in NPC patients with RN. The number of temporal CMBs is independently associated with increased likelihood of cognitive dysfunction in patients with RN.« less

Beyond Emotional and Spatial Processes: Cognitive Dysfunction in a Depressive Phenotype Produced by Long Photoperiod Exposure.

PubMed

Barnes, Abigail K; Smith, Summer B; Datta, Subimal

2017-01-01

Cognitive dysfunction in depression has recently been given more attention and legitimacy as a core symptom of the disorder. However, animal investigations of depression-related cognitive deficits have generally focused on emotional or spatial memory processing. Additionally, the relationship between the cognitive and affective disturbances that are present in depression remains obscure. Interestingly, sleep disruption is one aspect of depression that can be related both to cognition and affect, and may serve as a link between the two. Previous studies have correlated sleep disruption with negative mood and impaired cognition. The present study investigated whether a long photoperiod-induced depressive phenotype showed cognitive deficits, as measured by novel object recognition, and displayed a cognitive vulnerability to an acute period of total sleep deprivation. Adult male Wistar rats were subjected to a long photoperiod (21L:3D) or a normal photoperiod (12L:12D) condition. Our results indicate that our long photoperiod exposed animals showed behaviors in the forced swim test consistent with a depressive phenotype, and showed significant deficits in novel object recognition. Three hours of total sleep deprivation, however, did not significantly change novel object recognition in either group, but the trends suggest that the long photoperiod and normal photoperiod groups had different cognitive responses to total sleep deprivation. Collectively, these results underline the extent of cognitive dysfunction present in depression, and suggest that altered sleep plays a role in generating both the affective and cognitive symptoms of depression.

Blunted brain activation in patients with schizophrenia in response to emotional cognitive inhibition: a functional near-infrared spectroscopy study.

PubMed

Egashira, Kazuteru; Matsuo, Koji; Nakashima, Mami; Watanuki, Toshio; Harada, Kenichiro; Nakano, Masayuki; Matsubara, Toshio; Takahashi, Kanji; Watanabe, Yoshifumi

2015-03-01

Patients with schizophrenia (SZ) have deficits of facial emotion processing and cognitive inhibition, but the brain pathophysiology underlying these deficits and their interaction are not clearly understood. We tested brain activity during an emotional face go/no-go task that requires rapid executive control affected by emotional stimuli in patients with SZ using functional near-infrared spectroscopy (fNIRS). Twenty-five patients with SZ and 28 healthy control subjects were studied. We evaluated behavioral performance and used fNIRS to measure oxygenated hemoglobin concentration changes in fronto-temporal areas during the emotional go/no-go task with emotional and non-emotional blocks. Patients with SZ made more errors and had longer reaction times in both test blocks compared with healthy subjects. Significantly greater activation in the inferior, superior, middle, and orbital frontal regions were observed in healthy subjects during the emotional go/no-go block compared to the non-emotional go/no-go block, but this difference was not observed in patients with SZ. Relative to healthy subjects, patients with SZ showed less activation in the superior and orbital frontal and middle temporal regions during the emotional go/no-go block. Our results suggest that fronto-temporal dysfunction in patients with SZ is due to an interaction between abnormal processing of emotional facial expressions with negative valence and cognitive inhibition, especially during the rapid selection of rule-based associations that override automatic emotional response tendencies. They indicate that fronto-temporal dysfunction is involved in the pathophysiology of emotional-cognitive deficits in patients with SZ. Copyright © 2015 Elsevier B.V. All rights reserved.

Brain imaging and cognitive dysfunctions in Huntington's disease

PubMed Central

Montoya, Alonso; Price, Bruce H.; Menear, Matthew; Lepage, Martin

2006-01-01

Recent decades have seen tremendous growth in our understanding of the cognitive dysfunctions observed in Huntington's disease (HD). Advances in neuroimaging have contributed greatly to this growth. We reviewed the role that structural and functional neuroimaging techniques have played in elucidating the cerebral bases of the cognitive deficits associated with HD. We conducted a computer-based search using PubMed and PsycINFO databases to retrieve studies of patients with HD published between 1965 and December 2004 that reported measures on cognitive tasks and used neuroimaging techniques. Structural neuroimaging has provided important evidence of morphological brain changes in HD. Striatal and cortical atrophy are the most common findings, and they correlate with cognitive deficits in attention, working memory and executive functions. Functional studies have also demonstrated correlations between striatal dysfunction and cognitive performance. Striatal hypoperfusion and decreased glucose utilization correlate with executive dysfunction. Hypometabolism also occurs throughout the cerebral cortex and correlates with performance on recognition memory, language and perceptual tests. Measures of presynaptic and postsynaptic dopamine biochemistry have also correlated with measurements of episodic memory, speed of processing and executive functioning. Aided by the results of numerous neuroimaging studies, it is becoming increasingly clear that cognitive deficits in HD involve abnormal connectivity between the basal ganglia and cortical areas. In the future, neuroimaging techniques may shed the most light on the pathophysiology of HD by defining neurodegenerative disease phenotypes as a valuable tool for knowing when patients become “symptomatic,” having been in a gene-positive presymptomatic state, and as a biomarker in following the disease, thereby providing a prospect for improved patient care. PMID:16496032

Can Valeriana officinalis root extract prevent early postoperative cognitive dysfunction after CABG surgery? A randomized, double-blind, placebo-controlled trial.

PubMed

Hassani, Soghra; Alipour, Abbas; Darvishi Khezri, Hadi; Firouzian, Abolfazl; Emami Zeydi, Amir; Gholipour Baradari, Afshin; Ghafari, Rahman; Habibi, Wali-Allah; Tahmasebi, Homeyra; Alipour, Fatemeh; Ebrahim Zadeh, Pooneh

2015-03-01

We hypothesized that valerian root might prevent cognitive dysfunction in coronary artery bypass graft (CABG) surgery patients through stimulating serotonin receptors and anti-inflammatory activity. The aim of this study was to evaluate the effect of Valeriana officinalis root extract on prevention of early postoperative cognitive dysfunction after on-pump CABG surgery. In a randomized, double-blind, placebo-controlled trial, 61 patients, aged between 30 and 70 years, scheduled for elective CABG surgery using cardiopulmonary bypass (CPB), were recruited into the study. Patients were randomly divided into two groups who received either one valerian capsule containing 530 mg of valerian root extract (1,060 mg/daily) or placebo capsule each 12 h for 8 weeks, respectively. For all patients, cognitive brain function was evaluated before the surgery and at 10-day and 2-month follow-up by Mini Mental State Examination (MMSE) test. Mean MMSE score decreased from 27.03 ± 2.02 in the preoperative period to 26.52 ± 1.82 at the 10th day and then increased to 27.45 ± 1.36 at the 60th day in the valerian group. Conversely, its variation was reduced significantly after 60 days in the placebo group, 27.37 ± 1.87 at the baseline to 24 ± 1.91 at the 10th day, and consequently slightly increased to 24.83 ± 1.66 at the 60th day. Valerian prophylaxis reduced odds of cognitive dysfunction compared to placebo group (OR = 0.108, 95 % CI 0.022-0.545). We concluded that, based on this study, the cognitive state of patients in the valerian group was better than that in the placebo group after CABG; therefore, it seems that the use of V. officinalis root extract may prevent early postoperative cognitive dysfunction after on-pump CABG surgery.

Thyroid Function Abnormalities and Cognitive Impairment in the Elderly. Results of the InCHIANTI Study

PubMed Central

Ceresini, Graziano; Lauretani, Fulvio; Maggio, Marcello; Ceda, Gian Paolo; Morganti, Simonetta; Usberti, Elisa; Chezzi, Carlo; Valcavi, Rita; Bandinelli, Stefania; Guralnik, Jack M.; Cappola, Anne R.; Valenti, Giorgio; Ferrucci, Luigi

2008-01-01

Objectives To investigate thyroid function testing abnormalities in older persons and to explore the relationship between thyroid dysfunction and cognition. Design Cross-sectional study Setting Community-based Participants 1171 men and women aged 23-102 yrs Measurements Thyroid function was evaluated by measuring plasma concentrations of thyrotropin (TSH), free thyroxine (FT4), and free triiodothyronine (FT3). Cognition was evaluated by the Mini Mental State Examination (MMSE). Prevalence of overt and subclinical thyroid dysfunction was evaluated in different age groups (<65 versus ≥65 years). Age trends in TSH, FT4, and FT3 were examined in euthyroid participants. The cross-sectional association of thyroid dysfunction with MMSE score was evaluated adjusting for confounders. Results Both subclinical hypothyroidism and subclinical hyperthyroidism were more prevalent in older than in younger participants (Subclinical hypothyroidism, 0.4 % vs 3.5 % in younger vs older participants, respectively, P<.03 Subclinical hyperthyroidism, 1.9 % vs 7.8 % in younger vs older participants, respectively, P<.002). In euthyroid participants TSH and FT3 declined with age while FT4 increased. Old participants with subclinical hyperthyroidism had a lower MMSE score than euthyroid subjects (22.61 ± 6.88 vs 24.72 ± 4.52, P<.03). In adjusted analyses, participants with subclinical hyperthyroidism were significantly more likely to have cognitive dysfunction (HR: 2.26, P= .003). Conclusion Subtle age-related changes in FT3, FT4 and TSH occur in individuals who remain euthyroid. Subclinical hyperthyroidism is the most prevalent thyroid dysfunction in Italian older persons and is associated with cognitive impairment. PMID:19054181

Histone Deacetylase Inhibitor Trichostatin A Ameliorated Endotoxin-Induced Neuroinflammation and Cognitive Dysfunction

PubMed Central

Chen, Yeong-Chang; Wei, Tsui-Shan; Sun, Ding-Ping; Wang, Jhi-Joung; Yeh, Ching-Hua

2015-01-01

Excessive production of cytokines by microglia may cause cognitive dysfunction and long-lasting behavioral changes. Activating the peripheral innate immune system stimulates cytokine secretion in the central nervous system, which modulates cognitive function. Histone deacetylases (HDACs) modulate cytokine synthesis and release. Trichostatin A (TSA), an HDAC inhibitor, is documented to be anti-inflammatory and neuroprotective. We investigated whether TSA reduces lipopolysaccharide- (LPS-) induced neuroinflammation and cognitive dysfunction. ICR mice were first intraperitoneally (i.p.) injected with vehicle or TSA (0.3 mg/kg). One hour later, they were injected (i.p.) with saline or Escherichia coli LPS (1 mg/kg). We analyzed the food and water intake, body weight loss, and sucrose preference of the injected mice and then determined the microglia activation and inflammatory cytokine expression in the brains of LPS-treated mice and LPS-treated BV-2 microglial cells. In the TSA-pretreated mice, microglial activation was lower, anhedonia did not occur, and LPS-induced cognitive dysfunction (anorexia, weight loss, and social withdrawal) was attenuated. Moreover, mRNA expression of HDAC2, HDAC5, indoleamine 2,3-dioxygenase (IDO), TNF-α, MCP-1, and IL-1β in the brain of LPS-challenged mice and in the LPS-treated BV-2 microglial cells was lower. TSA diminished LPS-induced inflammatory responses in the mouse brain and modulated the cytokine-associated changes in cognitive function, which might be specifically related to reducing HDAC2 and HDAC5 expression. PMID:26273133

Hemodynamic Profiles of Functional and Dysfunctional Forms of Repetitive Thinking.

PubMed

Ottaviani, Cristina; Brosschot, Jos F; Lonigro, Antonia; Medea, Barbara; Van Diest, Ilse; Thayer, Julian F

2017-04-01

The ability of the human brain to escape the here and now (mind wandering) can take functional (problem solving) and dysfunctional (perseverative cognition) routes. Although it has been proposed that only the latter may act as a mediator of the relationship between stress and cardiovascular disease, both functional and dysfunctional forms of repetitive thinking have been associated with blood pressure (BP) reactivity of the same magnitude. However, a similar BP reactivity may be caused by different physiological determinants, which may differ in their risk for cardiovascular pathology. To examine the way (hemodynamic profile) and the extent (compensation deficit) to which total peripheral resistance and cardiac output compensate for each other in determining BP reactivity during functional and dysfunctional types of repetitive thinking. Fifty-six healthy participants randomly underwent a perseverative cognition, a mind wandering, and a problem solving induction, each followed by a 5-min recovery period while their cardiovascular parameters were continuously monitored. Perseverative cognition and problem solving (but not mind wandering) elicited BP increases of similar magnitude. However, perseverative cognition was characterized by a more vascular (versus myocardial) profile compared to mind wandering and problem solving. As a consequence, BP recovery was impaired after perseverative cognition compared to the other two conditions. Given that high vascular resistance and delayed recovery are the hallmarks of hypertension the results suggest a potential mechanism through which perseverative cognition may act as a mediator in the relationship between stress and risk for developing precursors to cardiovascular disease.

A Network Meta-Analysis Comparing Effects of Various Antidepressant Classes on the Digit Symbol Substitution Test (DSST) as a Measure of Cognitive Dysfunction in Patients with Major Depressive Disorder.

PubMed

Baune, Bernhard T; Brignone, Mélanie; Larsen, Klaus Groes

2018-02-01

Major depressive disorder is a common condition that often includes cognitive dysfunction. A systematic literature review of studies and a network meta-analysis were carried out to assess the relative effect of antidepressants on cognitive dysfunction in major depressive disorder. MEDLINE, Embase, Cochrane, CDSR, and PsychINFO databases; clinical trial registries; and relevant conference abstracts were searched for randomized controlled trials assessing the effects of antidepressants/placebo on cognition. A network meta-analysis comparing antidepressants was conducted using a random effects model. The database search retrieved 11337 citations, of which 72 randomized controlled trials from 103 publications met the inclusion criteria. The review identified 86 cognitive tests assessing the effect of antidepressants on cognitive functioning. However, the Digit Symbol Substitution Test, which targets multiple domains of cognition and is recognized as being sensitive to change, was the only test that was used across 12 of the included randomized controlled trials and that allowed the construction of a stable network suitable for the network meta-analysis. The interventions assessed included selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other non-selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors. The network meta-analysis using the Digit Symbol Substitution Test showed that vortioxetine was the only antidepressant that improved cognitive dysfunction on the Digit Symbol Substitution Test vs placebo {standardized mean difference: 0.325 (95% CI = 0.120; 0.529, P=.009}. Compared with other antidepressants, vortioxetine was statistically more efficacious on the Digit Symbol Substitution Test vs escitalopram, nortriptyline, and the selective serotonin reuptake inhibitor and tricyclic antidepressant classes. This study highlighted the large variability in measures used to assess cognitive functioning. The findings on the Digit Symbol Substitution Test indicate differential effects of various antidepressants on improving cognitive function in patients with major depressive disorder. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Role of fruits, nuts, and vegetables in maintaining cognitive health.

PubMed

Miller, Marshall G; Thangthaeng, Nopporn; Poulose, Shibu M; Shukitt-Hale, Barbara

2017-08-01

Population aging is leading to an increase in the incidence of age-related cognitive dysfunction and, with it, the health care burden of caring for older adults. Epidemiological studies have shown that consumption of fruits, nuts, and vegetables is positively associated with cognitive ability; however, these foods, which contain a variety of neuroprotective phytochemicals, are widely under-consumed. Surprisingly few studies have investigated the effects of individual plant foods on cognitive health but recent clinical trials have shown that dietary supplementation with individual foods, or switching to a diet rich in several of these foods, can improve cognitive ability. While additional research is needed, increasing fruit, nut, and vegetable intake may be an effective strategy to prevent or delay the onset of cognitive dysfunction during aging. Published by Elsevier Inc.

Awareness of financial skills in dementia.

PubMed

Van Wielingen, L E; Tuokko, H A; Cramer, K; Mateer, C A; Hultsch, D F

2004-07-01

The present study examined the relations among levels of cognitive functioning, executive dysfunction, and awareness of financial management capabilities among a sample of 42 community-dwelling persons with dementia. Financial tasks on the Measure of Awareness of Financial Skills (MAFS) were dichotomized as simple or complex based on Piaget's operational levels of childhood cognitive development. Severity of global cognitive impairment and executive dysfunction were significantly related to awareness of financial abilities as measured by informant-participant discrepancy scores on the MAFS. For persons with mild and moderate/severe dementia, and persons with and without executive dysfunction, proportions of awareness within simple and complex financial task categories were tabulated. Significantly less awareness of financial abilities occurred on complex compared with simple tasks. Individuals with mild dementia were significantly less aware of abilities on complex items, whereas persons with moderate/severe dementia were less aware of abilities, regardless of task complexity. Similar patterns of awareness were observed for individuals with and without executive dysfunction. These findings support literature suggesting that deficits associated with dementia first occur for complex cognitive tasks involving inductive reasoning or decision-making in novel situations, and identify where loss of function in the financial domain may first be expected. Copyright Taylor & Francis Ltd

Dopamine and the Development of Executive Dysfunction in Autism Spectrum Disorders

PubMed Central

Kriete, Trenton; Noelle, David C.

2015-01-01

Persons with autism regularly exhibit executive dysfunction (ED), including problems with deliberate goal-directed behavior, planning, and flexible responding in changing environments. Indeed, this array of deficits is sufficiently prominent to have prompted a theory that executive dysfunction is at the heart of these disorders. A more detailed examination of these behaviors reveals, however, that some aspects of executive function remain developmentaly appropriate. In particular, while people with autism often have difficulty with tasks requiring cognitive flexibility, their fundamental cognitive control capabilities, such as those involved in inhibiting an inappropriate but relatively automatic response, show no significant impairment on many tasks. In this article, an existing computational model of the prefrontal cortex and its role in executive control is shown to explain this dichotomous pattern of behavior by positing abnormalities in the dopamine-based modulation of frontal systems in individuals with autism. This model offers excellent qualitative and quantitative fits to performance on standard tests of cognitive control and cognitive flexibility in this clinical population. By simulating the development of the prefrontal cortex, the computational model also offers a potential explanation for an observed lack of executive dysfunction early in life. PMID:25811610

Dopamine and the development of executive dysfunction in autism spectrum disorders.

PubMed

Kriete, Trenton; Noelle, David C

2015-01-01

Persons with autism regularly exhibit executive dysfunction (ED), including problems with deliberate goal-directed behavior, planning, and flexible responding in changing environments. Indeed, this array of deficits is sufficiently prominent to have prompted a theory that executive dysfunction is at the heart of these disorders. A more detailed examination of these behaviors reveals, however, that some aspects of executive function remain developmentaly appropriate. In particular, while people with autism often have difficulty with tasks requiring cognitive flexibility, their fundamental cognitive control capabilities, such as those involved in inhibiting an inappropriate but relatively automatic response, show no significant impairment on many tasks. In this article, an existing computational model of the prefrontal cortex and its role in executive control is shown to explain this dichotomous pattern of behavior by positing abnormalities in the dopamine-based modulation of frontal systems in individuals with autism. This model offers excellent qualitative and quantitative fits to performance on standard tests of cognitive control and cognitive flexibility in this clinical population. By simulating the development of the prefrontal cortex, the computational model also offers a potential explanation for an observed lack of executive dysfunction early in life.

The effect of a negative mood priming challenge on dysfunctional attitudes, explanatory style, and explanatory flexibility.

PubMed

Fresco, David M; Heimberg, Richard G; Abramowitz, Adrienne; Bertram, Tara L

2006-06-01

Ninety-seven undergraduates, 48 of whom had a history of self-reported major depression, completed measures of mood and cognitive style (e.g. explanatory style, explanatory flexibility, dysfunctional attitudes) prior to and directly after a negative mood priming challenge that consisted of listening to sad music and thinking about an upsetting past event. Eighteen of the previously depressed participants endorsed baseline levels of depression, explanatory style for negative events, and dysfunctional attitudes higher than levels reported by never depressed participants or euthymic participants with a history of depression. All three groups (never depressed participants, dysphoric participants with a history of depression, euthymic participants with a history of depression) demonstrated increases in dysphoria and dysfunctional attitudes in response to the negative mood priming challenge. Dysphoric participants with a history of depression, but not the other two groups, evidenced modest increases in explanatory style following the negative mood priming challenge. Finally, euthymic participants with a history of depression, but not the other two groups, evidenced drops in explanatory flexibility. Findings from the present study suggest that the cognitive theories of depression may benefit from examining both cognitive content and cognitive flexibility when assessing risk for depression.

Memory and executive functioning in obsessive-compulsive disorder: a selective review.

PubMed

Olley, Amanda; Malhi, Gin; Sachdev, Perminder

2007-12-01

The neurocognitive deficits that underlie the unique features of obsessive-compulsive disorder (OCD) are not yet completely understood. This paper reviews the main neuropsychological findings in memory and executive functioning in this disorder, and examines a number of challenges facing this area of research. A selective review of the neuropsychological literature on OCD was conducted using MEDLINE and drawing on literature known to the authors. The neuropsychological profile of OCD appears to be one of primary executive dysfunction. Although memory functioning may be affected, these deficits appear secondary to an executive failure of organizational strategies during encoding. On tasks of executive functioning patients with OCD demonstrate increased response latencies, perseveration of responses, and difficulties utilizing feedback to adapt to change. A statistical meta-analysis was not performed and only the cognitive domains of memory and executive functioning were examined. Given the prominence of chronic doubt and indecision in clinical settings, it is surprising that decision making as a cognitive construct as related to OCD has not received greater attention in the neuropsychological literature. On the basis of emerging literature we suggest that it is a potential area of dysfunction and one that warrants further investigation as it may assist in enhancing our understanding of the pathophysiology of OCD.

Negative mood increases selective attention to food cues and subjective appetite.

PubMed

Hepworth, Rebecca; Mogg, Karin; Brignell, Catherine; Bradley, Brendan P

2010-02-01

Following negative reinforcement and affect-regulation models of dysfunctional appetitive motivation, this study examined the effect of negative mood on objective and subjective cognitive indices of motivation for food; i.e., attentional bias for food cues and self-reported hunger/urge to eat, respectively. The study extended previous research on the effect of mood on food motivation by using (i) an experimental mood manipulation, (ii) an established index of attentional bias from the visual-probe task and (iii) pictorial food cues, which have greater ecological validity than word stimuli. Young female adults (n=80) were randomly allocated to a neutral or negative mood induction procedure. Attentional biases were assessed at two cue exposure durations (500 and 2000ms). Results showed that negative mood increased both attentional bias for food cues and subjective appetite. Attentional bias and subjective appetite were positively inter-correlated, suggesting a common mechanism, i.e. activation of the food-reward system. Attentional bias was also associated with trait eating style, such as external and restrained eating. Thus, current mood and trait eating style each influenced motivation for food (as reflected by subjective appetite and attentional bias). Findings relate to models of cognitive mechanisms underlying normal and dysfunctional appetitive motivation and eating behaviour. 2009 Elsevier Ltd. All rights reserved.

Auditory top-down control and affective theory of mind in schizophrenia with and without hallucinations.

PubMed

Rominger, Christian; Bleier, Angelika; Fitz, Werner; Marksteiner, Josef; Fink, Andreas; Papousek, Ilona; Weiss, Elisabeth M

2016-07-01

Social cognitive impairments may represent a core feature of schizophrenia and above all are a strong predictor of positive psychotic symptoms. Previous studies could show that reduced inhibitory top-down control contributes to deficits in theory of mind abilities and is involved in the genesis of hallucinations. The current study aimed to investigate the relationship between auditory inhibition, affective theory of mind and the experience of hallucinations in patients with schizophrenia. In the present study, 20 in-patients with schizophrenia and 20 healthy controls completed a social cognition task (the Reading the Mind in the Eyes Test) and an inhibitory top-down Dichotic Listening Test. Schizophrenia patients with greater severity of hallucinations showed impaired affective theory of mind as well as impaired inhibitory top-down control. More dysfunctional top-down inhibition was associated with poorer affective theory of mind performance, and seemed to mediate the association between impairment to affective theory of mind and severity of hallucinations. The findings support the idea of impaired theory of mind as a trait marker of schizophrenia. In addition, dysfunctional top-down inhibition may give rise to hallucinations and may further impair affective theory of mind skills in schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Safety behaviors and sleep effort predict sleep disturbance and fatigue in an outpatient sample with anxiety and depressive disorders.

PubMed

Fairholme, Christopher P; Manber, Rachel

2014-03-01

Theoretical and empirical support for the role of dysfunctional beliefs, safety behaviors, and increased sleep effort in the maintenance of insomnia has begun to accumulate. It is not yet known how these factors predict sleep disturbance and fatigue occurring in the context of anxiety and mood disorders. It was hypothesized that these three insomnia-specific cognitive-behavioral factors would be uniquely associated with insomnia and fatigue among patients with emotional disorders after adjusting for current symptoms of anxiety and depression and trait levels of neuroticism and extraversion. Outpatients with a current anxiety or mood disorder (N = 63) completed self-report measures including the Dysfunctional Beliefs About Sleep Scale (DBAS), Sleep-Related Safety Behaviors Questionnaire (SRBQ), Glasgow Sleep Effort Scale (GSES), Pittsburgh Sleep Quality Index (PSQI), NEO Five-Factor Inventory (FFI), and the 21-item Depression Anxiety and Stress Scale (DASS). Multivariate path analysis was used to evaluate study hypotheses. SRBQ (B = .60, p < .001, 95% CI [.34, .86]) and GSES (B = .31, p < .01, 95% CI [.07, .55]) were both significantly associated with PSQI. There was a significant interaction between SRBQ and DBAS (B = .25, p < .05, 95% CI [.04, .47]) such that the relationship between safety behaviors and fatigue was strongest among individuals with greater levels of dysfunctional beliefs. Findings are consistent with cognitive behavioral models of insomnia and suggest that sleep-specific factors might be important treatment targets among patients with anxiety and depressive disorders with disturbed sleep. Copyright © 2013 Elsevier Inc. All rights reserved.

The relationship between cognitive dysfunction and coping abilities in schizophrenia.

PubMed

Wilder-Willis, Kelly E; Shear, Paula K; Steffen, John J; Borkin, Joyce

2002-06-01

Cognitive dysfunction is a core feature of schizophrenia [Psychiatr. Clin. North Am., 16 (1993) 295; Psychopharmacology: The fourth generation of progress, Raven Press, New York (1995) 1171; Clinical Neuropsychology, Oxford University Press, New York (1993) 449] and is related to psychosocial functioning in this population [Am. J. Psychiatry, 153 (1996) 321]. It is unclear whether cognitive dysfunction is related to specific areas of functioning in schizophrenia, such as coping abilities. Individuals with schizophrenia have deficient coping skills, which may contribute to their difficulties dealing with stressors [Am. J. Orthopsychiatry, 62 (1992) 117; J. Abnorm. Psychol., 82 (1986) 189]. The current study examined the relationship between coping abilities and cognitive dysfunction in a community sample of individuals with schizophrenia. It was hypothesized that executive dysfunction and mnemonic impairments would be positively related to deficiencies in active coping efforts involving problem solving and self-initiation (e.g. advocating for oneself and others with mental illness and becoming involved in meaningful activities, such as work), independent of the contributions of the general intellectual deficits associated with the disorder and psychiatric symptoms. The results indicated that both executive dysfunction and mnemonic impairments were related to decreased usage of active coping mechanisms after controlling for general intellectual deficits. Further, recognition memory made independent contributions to the prediction of coping involving action and help seeking after controlling for the effects of negative symptoms. These findings suggest that individuals with schizophrenia may be less flexible in their use of coping strategies, which may in turn contribute to their difficulties in coping with mental illness and its consequences.

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.

Applying a Cognitive Neuroscience Perspective to Disruptive Behavior Disorders: Implications for Schools.

PubMed

Tyler, Patrick M; White, Stuart F; Thompson, Ronald W; Blair, R J R

2018-02-12

A cognitive neuroscience perspective seeks to understand behavior, in this case disruptive behavior disorders (DBD), in terms of dysfunction in cognitive processes underpinned by neural processes. While this type of approach has clear implications for clinical mental health practice, it also has implications for school-based assessment and intervention with children and adolescents who have disruptive behavior and aggression. This review articulates a cognitive neuroscience account of DBD by discussing the neurocognitive dysfunction related to emotional empathy, threat sensitivity, reinforcement-based decision-making, and response inhibition. The potential implications for current and future classroom-based assessments and interventions for students with these deficits are discussed.

Oral aniracetam treatment in C57BL/6J mice without pre-existing cognitive dysfunction reveals no changes in learning, memory, anxiety or stereotypy

PubMed Central

Reynolds, Conner D.; Jefferson, Taylor S.; Volquardsen, Meagan; Pandian, Ashvini; Smith, Gregory D.; Holley, Andrew J.; Lugo, Joaquin N.

2017-01-01

Background: The piracetam analog, aniracetam, has recently received attention for its cognition enhancing potential, with minimal reported side effects.  Previous studies report the drug to be effective in both human and non-human models with pre-existing cognitive dysfunction, but few studies have evaluated its efficacy in healthy subjects. A previous study performed in our laboratory found no cognitive enhancing effects of oral aniracetam administration 1-hour prior to behavioral testing in naïve C57BL/6J mice. Methods: The current study aims to further evaluate this drug by administration of aniracetam 30 minutes prior to testing in order to optimize any cognitive enhancing effects. In this study, all naïve C57BL/6J mice were tested in tasks of delayed fear conditioning, novel object recognition, rotarod, open field, elevated plus maze, and marble burying. Results: Across all tasks, animals in the treatment group failed to show enhanced learning when compared to controls. Conclusions: These results provide further evidence suggesting that aniracetam conveys no therapeutic benefit to subjects without pre-existing cognitive dysfunction. PMID:29946420

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.

Latent Cognitive Phenotypes in De Novo Parkinson's Disease: A Person-Centered Approach.

PubMed

LaBelle, Denise R; Walsh, Ryan R; Banks, Sarah J

2017-08-01

Cognitive impairment is an important aspect of Parkinson's disease (PD), but there is considerable heterogeneity in its presentation. This investigation aims to identify and characterize latent cognitive phenotypes in early PD. Latent class analysis, a data-driven, person-centered, cluster analysis was performed on cognitive data from the Parkinson's Progressive Markers Initiative baseline visit. This analytic method facilitates identification of naturally occurring endophenotypes. Resulting classes were compared across biomarker, symptom, and demographic data. Six cognitive phenotypes were identified. Three demonstrated consistent performance across indicators, representing poor ("Weak-Overall"), average ("Typical-Overall"), and strong ("Strong-Overall") cognition. The remaining classes demonstrated unique patterns of cognition, characterized by "Strong-Memory," "Weak-Visuospatial," and "Amnestic" profiles. The Amnestic class evidenced greater tremor severity and anosmia, but was unassociated with biomarkers linked with Alzheimer's disease. The Weak-Overall class was older and reported more non-motor features associated with cognitive decline, including anxiety, depression, autonomic dysfunction, anosmia, and REM sleep behaviors. The Strong-Overall class was younger, more female, and reported less dysautonomia and anosmia. Classes were unrelated to disease duration, functional independence, or available biomarkers. Latent cognitive phenotypes with focal patterns of impairment were observed in recently diagnosed individuals with PD. Cognitive profiles were found to be independent of traditional biomarkers and motoric indices of disease progression. Only globally impaired class was associated with previously reported indicators of cognitive decline, suggesting this group may drive the effects reported in studies using variable-based analysis. Longitudinal and neuroanatomical characterization of classes will yield further insight into the evolution of cognitive change in the disease. (JINS, 2017, 23, 551-563).

[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 Attentional Syndrome and Metacognitive Beliefs in Male Sexual Dysfunction: An Exploratory Study.

PubMed

Giuri, Simona; Caselli, Gabriele; Manfredi, Chiara; Rebecchi, Daniela; Granata, Antonio; Ruggiero, Giovanni Maria; Veronese, Guido

2017-05-01

Erectile dysfunction (ED) and premature ejaculation (PE) are two forms of male sexual disorder with both psychological and physical features. While their cognitive, attentional, and affective components have been investigated separately, there is a lack of knowledge about the role played by cognitive attentional syndrome in their onset and maintenance. The aim of the present study was to investigate the possible contribution of perseverative thinking styles and thought control strategies to the development and maintenance of ED and PE. The authors hypothesized that such modes of processing might constitute a cognitive attentional syndrome specific to these disorders and sustained by particular metacognitive beliefs. A semistructured interview was administered to 11 participants with ED and 10 with PE in order to assess their metacognitive beliefs and cognitive attentional processes. The results suggest that individuals with ED and PE adopt a range of cognitive attentional strategies aimed at improving their sexual performance, and endorse both positive and negative metacognitive beliefs about these thinking responses. Overall, their cognitive and attentional patterns worsened negative internal states, reduced sexual excitement, detached them from their bodily sensations, and hindered sexual functioning. These preliminary findings suggest that perseverative thinking, thought control strategies, and metacognitive beliefs may play a key role in the onset and maintenance of male sexual dysfunction.

Association between unsafe driving performance and cognitive-perceptual dysfunction in older drivers.

PubMed

Park, Si-Woon; Choi, Eun Seok; Lim, Mun Hee; Kim, Eun Joo; Hwang, Sung Il; Choi, Kyung-In; Yoo, Hyun-Chul; Lee, Kuem Ju; Jung, Hi-Eun

2011-03-01

To find an association between cognitive-perceptual problems of older drivers and unsafe driving performance during simulated automobile driving in a virtual environment. Cross-sectional study. A driver evaluation clinic in a rehabilitation hospital. Fifty-five drivers aged 65 years or older and 48 drivers in their late twenties to early forties. All participants underwent evaluation of cognitive-perceptual function and driving performance, and the results were compared between older and younger drivers. The association between cognitive-perceptual function and driving performance was analyzed. Cognitive-perceptual function was evaluated with the Cognitive Perceptual Assessment for Driving (CPAD), a computer-based assessment tool consisting of depth perception, sustained attention, divided attention, the Stroop test, the digit span test, field dependency, and trail-making test A and B. Driving performance was evaluated with use of a virtual reality-based driving simulator. During simulated driving, car crashes were recorded, and an occupational therapist observed unsafe performances in controlling speed, braking, steering, vehicle positioning, making lane changes, and making turns. Thirty-five older drivers did not pass the CPAD test, whereas all of the younger drivers passed the test. When using the driving simulator, a significantly greater number of older drivers experienced car crashes and demonstrated unsafe performance in controlling speed, steering, and making lane changes. CPAD results were associated with car crashes, steering, vehicle positioning, and making lane changes. Older drivers who did not pass the CPAD test are 4 times more likely to experience a car crash, 3.5 times more likely to make errors in steering, 2.8 times more likely to make errors in vehicle positioning, and 6.5 times more likely to make errors in lane changes than are drivers who passed the CPAD test. Unsafe driving performance and car crashes during simulated driving were more prevalent in older drivers than in younger drivers. Unsafe performance in steering, vehicle positioning, making lane changes, and car crashes were associated with cognitive-perceptual dysfunction. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Role of brain iron accumulation in cognitive dysfunction: evidence from animal models and human studies.

PubMed

Schröder, Nadja; Figueiredo, Luciana Silva; de Lima, Maria Noêmia Martins

2013-01-01

Over the last decades, studies from our laboratory and other groups using animal models have shown that iron overload, resulting in iron accumulation in the brain, produces significant cognitive deficits. Iron accumulation in the hippocampus and the basal ganglia has been related to impairments in spatial memory, aversive memory, and recognition memory in rodents. These results are corroborated by studies showing that the administration of iron chelators attenuates cognitive deficits in a variety of animal models of cognitive dysfunction, including aging and Alzheimer's disease models. Remarkably, recent human studies using magnetic resonance image techniques have also shown a consistent correlation between cognitive dysfunction and iron deposition, mostly in the hippocampus, cortical areas, and basal ganglia. These findings may have relevant implications in the light of the knowledge that iron accumulates in brain regions of patients suffering from neurodegenerative diseases. A better understanding of the functional consequences of iron dysregulation in aging and neurological diseases may help to identify novel targets for treating memory problems that afflict a growing aging population.

Early Developmental Disturbances of Cortical Inhibitory Neurons: Contribution to Cognitive Deficits in Schizophrenia

PubMed Central

Volk, David W.; Lewis, David A.

2014-01-01

Cognitive dysfunction is a disabling and core feature of schizophrenia. Cognitive impairments have been linked to disturbances in inhibitory (gamma-aminobutyric acid [GABA]) neurons in the prefrontal cortex. Cognitive deficits are present well before the onset of psychotic symptoms and have been detected in early childhood with developmental delays reported during the first year of life. These data suggest that the pathogenetic process that produces dysfunction of prefrontal GABA neurons in schizophrenia may be related to altered prenatal development. Interestingly, adult postmortem schizophrenia brain tissue studies have provided evidence consistent with a disease process that affects different stages of prenatal development of specific subpopulations of prefrontal GABA neurons. Prenatal ontogeny (ie, birth, proliferation, migration, and phenotypic specification) of distinct subpopulations of cortical GABA neurons is differentially regulated by a host of transcription factors, chemokine receptors, and other molecular markers. In this review article, we propose a strategy to investigate how alterations in the expression of these developmental regulators of subpopulations of cortical GABA neurons may contribute to the pathogenesis of cortical GABA neuron dysfunction and consequently cognitive impairments in schizophrenia. PMID:25053651

Effectiveness of group cognitive-behavioral therapy in reducing self-stigma in Japanese psychiatric patients.

PubMed

Shimotsu, Sakie; Horikawa, Naoshi; Emura, Rina; Ishikawa, Shin-Ichi; Nagao, Ayako; Ogata, Akiko; Hiejima, Shigeto; Hosomi, Jun

2014-08-01

There is evidence that the stigma surrounding mental illness may be greater in Japan than elsewhere. However, few Japanese studies have focused on self-stigma (the internalization of social stigma), and few interventions to reduce self-stigma exist. To remedy this deficiency, we evaluated the efficacy of group cognitive-behavioral therapy (CBT) in reducing self-stigma and examined the relationship between cognitive restructuring and self-stigma. We administered a 10-session group CBT program to 46 Japanese outpatients with anxiety and depressive symptoms (36 men, 10 women; mean age=38.57 years, SD=8.33; 20 diagnosed with mood disorders; 24 with neurotic, stress-related, or somatoform disorders; and 2 with other disorders). A pretest-posttest design was used to examine the relationship between cognitive restructuring and self-stigma. Outcomes were measured using the Japanese versions of the Devaluation-Discrimination Scale, Dysfunctional Attitude Scale, Beck Depression Inventory-II, State-Trait Anxiety Inventory State-Form, and Rosenberg's Self Esteem Scale. Participants exhibited significant improvements in depression, anxiety, and maladjusted cognitive bias and reductions in self-stigma. Cognitive bias was significantly correlated with self-stigma. Group CBT is effective in improving both emotional symptoms and self-stigma in outpatients with anxiety and depressive symptoms. Reduction in self-stigma plays a mediating role in alleviating emotional symptoms and improving cognition. Copyright © 2014 Elsevier B.V. All rights reserved.

Cognitive function in women with HIV

PubMed Central

Rubin, Leah H.; Valcour, Victor; Martin, Eileen; Crystal, Howard; Young, Mary; Weber, Kathleen M.; Manly, Jennifer; Richardson, Jean; Alden, Christine; Anastos, Kathryn

2015-01-01

Objective: In the largest cohort study of neuropsychological outcomes among HIV-infected women to date, we examined the association between HIV status and cognition in relation to other determinants of cognitive function (aim 1) and the pattern and magnitude of impairment across cognitive outcomes (aim 2). Methods: From 2009 to 2011, 1,521 (1,019 HIV-infected) participants from the Women's Interagency HIV Study (WIHS) completed a comprehensive neuropsychological test battery. We used multivariable regression on raw test scores for the first aim and normative regression-based analyses (t scores) for the second aim. The design was cross-sectional. Results: The effect sizes for HIV status on cognition were very small, accounting for only 0.05 to 0.09 SD units. The effect of HIV status was smaller than that of years of education, age, race, income, and reading level. In adjusted analyses, HIV-infected women performed worse than uninfected women on verbal learning, delayed recall and recognition, and psychomotor speed and attention. The largest deficit was observed in delayed memory. The association of low reading level with cognition was greater in HIV-infected compared to HIV-uninfected women. HIV biomarkers (CD4 count, history of AIDS-defining illness, viral load) were associated with cognitive dysfunction. Conclusions: The effect of HIV on cognition in women is very small except among women with low reading level or HIV-related comorbidities. Direct comparisons of rates of impairment in well-matched groups of HIV-infected men and women are needed to evaluate possible sex differences in cognition. PMID:25540304

Correlates of Real World Executive Dysfunction in Bipolar I Disorder

PubMed Central

Peters, Amy T.; Peckham, Andrew D.; Stange, Jonathan P.; Sylvia, Louisa G.; Hansen, Natasha S.; Salcedo, Stephanie; Rauch, Scott L.; Nierenberg, Andrew A.; Dougherty, Darin D.; Deckersbach, Thilo

2014-01-01

Background Bipolar disorder is characterized by impairments in cognitive functioning, both during acute mood episodes and periods of euthymia, which interfere with functioning. Cognitive functioning is typically assessed using laboratory-based tests, which may not capture how cognitive dysfunction is experienced in real-life settings. Little is known about the specific illness characteristics of bipolar disorder that contribute to cognitive dysfunction in everyday life. Methods Participants met DSM-IV criteria for bipolar I disorder (n = 68) in a depressed or euthymic state. Everyday executive functioning was evaluated using the Behavior Rating Inventory of Executive Functioning (BRIEF) and the Frontal Systems Behavior Rating Scale (FrSBe). Participants completed clinician rated measures of mood state (Hamilton Depression Rating Scale, Young Mania Rating Scale), prior illness course and co-morbidities (Mini International Neuropsychiatric Interview), as well as self-report measures of psychotropic medication use and medical co-morbidity. Results Individuals in this study reported significant impairment in every domain of executive functioning. These deficits were associated with a multitude of illness factors, some directly impacted by mood symptoms and others shaped by illness chronicity, psychiatric comorbidity, medical co-morbidity, and medication use. Discussion Executive functioning problems observed in everyday functioning in bipolar disorder are not entirely mood-state dependent. Cognitive rehabilitation for executive dysfunction should be considered an important adjunctive treatment for many individuals with bipolar disorder. PMID:24655587

Selective Cognitive Dysfunction Is Related to a Specific Pattern of Cerebral Damage in Persons With Severe Traumatic Brain Injury.

PubMed

Di Paola, Margherita; Phillips, Owen; Costa, Alberto; Ciurli, Paola; Bivona, Umberto; Catani, Sheila; Formisano, Rita; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

2015-01-01

Cognitive dysfunction is a common sequela of traumatic brain injury (TBI); indeed, patients show a heterogeneous pattern of cognitive deficits. This study was aimed at investigating whether patients who show selective cognitive dysfunction after TBI present a selective pattern of cerebral damage. Post-Coma Unit, IRCCS Santa Lucia Foundation, Rome, Italy. We collected data from 8 TBI patients with episodic memory disorder and without executive deficits, 7 patients with executive function impairment and preserved episodic memory capacities, and 16 healthy controls. We used 2 complementary analyses: (1) an exploratory and qualitative approach in which we investigated the distribution of lesions in the TBI groups, and (2) a hypothesis-driven and quantitative approach in which we calculated the volume of hippocampi of individuals in the TBI and control groups. Neuropsychological scores and hippocampal volumes. We found that patients with TBI and executive functions impairment presented focal lesions involving the frontal lobes, whereas patients with TBI and episodic memory disorders showed atrophic changes of the mesial temporal structure (hippocampus). The complexity of TBI is due to several heterogeneous factors. Indeed, studying patients with TBI and selective cognitive dysfunction should lead to a better understanding of correlations with specific brain impairment and damage, better follow-up of long-term outcome scenarios, and better planning of selective and focused rehabilitation programs.

The Role of Sexual Abuse and Dysfunctional Attitudes in Perceived Stress and Negative Mood in Pregnant Adolescents: An Ecological Momentary Assessment Study

PubMed Central

Walsh, Kate; Basu, Archana; Monk, Catherine

2014-01-01

Study Objective Latinas have the highest rates of adolescent pregnancy in the US. Identifying means to improve the well-being among these young women is critical. The current study examined whether a history of child sexual abuse — itself a risk factor for adolescent pregnancy — was associated with more perceived stress and negative mood over the course of pregnancy and whether dysfunctional attitudes explained these associations. Design and Setting This mixed methods study involved lab-based assessments of perceived stress, sexual abuse history, and dysfunctional attitudes as well as Ecological Momentary Assessments (EMA) of mood states every 30 minutes during a 24-hour period once during each trimester of pregnancy. Participants Pregnant adolescents (n = 204, 85% Latina). Main Outcome Measures EMA mood states and lab-based retrospective self–reports of perceived stress. Results One in four pregnant adolescents had a history of sexual abuse. Sexually abused adolescents reported greater perceived stress during the first trimester relative to those without, though the groups did not differ on EMA negative mood ratings. Dysfunctional attitudes explained associations between sexual abuse and perceived stress. Sexual abuse was indirectly associated with the intercept and slope of negative mood through dysfunctional attitudes. Findings were circumscribed to sexual abuse and not other types of child abuse. Conclusions Identifying sexually abused pregnant adolescents and providing support and cognitive therapy to target dysfunctional beliefs may decrease stress during the first trimester as well as negative affect throughout pregnancy. PMID:26130137

Post-Operative Cognitive Dysfunction: An exploration of the inflammatory hypothesis and novel therapies.

PubMed

Skvarc, David R; Berk, Michael; Byrne, Linda K; Dean, Olivia M; Dodd, Seetal; Lewis, Matthew; Marriott, Andrew; Moore, Eileen M; Morris, Gerwyn; Page, Richard S; Gray, Laura

2018-01-01

Post-Operative Cognitive Dysfunction (POCD) is a highly prevalent condition with significant clinical, social and financial impacts for patients and their communities. The underlying pathophysiology is becoming increasingly understood, with the role of neuroinflammation and oxidative stress secondary to surgery and anaesthesia strongly implicated. This review aims to describe the putative mechanisms by which surgery-induced inflammation produces cognitive sequelae, with a focus on identifying potential novel therapies based upon their ability to modify these pathways. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

The effect of non-invasive positive pressure ventilation (NIPPV) on cognitive function in amyotrophic lateral sclerosis (ALS): a prospective study

PubMed Central

Newsom-Davis, I; Lyall, R; Leigh, P; Moxham, J; Goldstein, L

2001-01-01

OBJECTIVES—Neuropsychological investigations have shown a degree of cognitive dysfunction in a proportion of non-demented patients with ALS. Respiratory muscle weakness in ALS can lead to nocturnal hypoventilation, resulting in sleep disturbance and daytime somnolence. Sleep deprivation of this type may cause impairments in cognitive function, but this has not been formally evaluated in ALS.
METHODS—Cognitive functioning was evaluated in nine patients with ALS with sleep disturbance caused by nocturnal hypoventilation (NIPPV group), and in a comparison group of 10 similar patients without ventilation problems (control group). The NIPPV group then started non-invasive positive pressure ventilation (NIPPV) at night. After about 6 weeks, change in cognitive function was evaluated.
RESULTS—Statistically significant improvement in scores on two of the seven cognitive tests was demonstrated in the NIPPV group postventilation, and a trend towards significant improvement was found for two further tests. Scores in the control group did not improve significantly for these four tests, although an improvement was found on one other test.
CONCLUSIONS—Nocturnal hypoventilation and sleep disturbance may cause cognitive dysfunction in ALS. These deficits may be partially improved by NIPPV over a 6 week period. This has important implications for investigations of both cognitive dysfunction in non-demented patients with ALS, and the effect of ventilation on quality of life.

 PMID:11561031

A Competing Neurobehavioral Decision Systems Model of SES-Related Health and Behavioral Disparities

PubMed Central

Bickel, W. K.; Moody, L.; Quisenberry, A. J.; Ramey, C. T.; Sheffer, C. E.

2014-01-01

We propose that executive dysfunction is an important component relating the socioeconomic status gradient of select health behaviors. We review and find evidence supporting an SES gradient associated with (1) negative health behaviors (e.g., obesity, excessive use of alcohol, tobacco and other substances), and (2) executive dysfunction. Moreover, the evidence supports that stress and insufficient cognitive resources contribute to executive dysfunction and that executive dysfunction is evident among individuals who smoke cigarettes, are obese, abuse alcohol, and use illicit drugs. Collectively these data supports the dual system model of cognitive control, referred to here as the Competing Neurobehavioral Decision Systems hypothesis. The implications of these relationships for intervention and social justice considerations are discussed. PMID:25008219

Executive function in fibromyalgia: Comparing subjective and objective measures.

PubMed

Gelonch, Olga; Garolera, Maite; Valls, Joan; Rosselló, Lluís; Pifarré, Josep

2016-04-01

There is evidence to suggest the existence of an executive dysfunction in people diagnosed with fibromyalgia, although there are certain inconsistencies between studies. Here, we aim to compare executive performance between patients with fibromyalgia and a control group by using subjective and objective cognitive tests, analyzing the influence of patient mood on the results obtained, and studying associations between the two measures. 82 patients diagnosed with fibromyalgia and 42 healthy controls, matched by age and years of education, were assessed using the Behavioral Rating Inventory of Executive Function - Adult Version (BRIEF-A) as a subjective measure of executive functioning. A selection of objective cognitive tests were also used to measure a series of executive functions and to identify symptoms of depression and anxiety. Patients with fibromyalgia perceived greater difficulties than the control group on all of the BRIEF-A scales. However, after adjustments were made for depression and anxiety the only differences that remained were those associated with the working memory scale and the Metacognition and Global Executive Composite index. In the case of the objective cognitive tests, a significantly worse overall performance was evidenced for the fibromyalgia patients. However, this also disappeared when adjustments were made for depression and anxiety. After this adjustment, fibromyalgia patients only performed significantly worse for the interference effect in the Stroop Test. Although there were no significant associations between most of the objective cognitive tests and the BRIEF-A scales, depression and anxiety exhibited strong associations with almost all of the BRIEF-A scales and with several of the objective cognitive tests. Patients with fibromyalgia showed executive dysfunction in subjective and objective measures, although most of this impairment was associated with mood disturbances. Exceptions to this general rule were observed in the impairment of working memory evidenced on the BRIEF-A scale and the inhibition impairment exhibited by the interference effect from the Stroop Test. The two types of measurement provide different yet complementary information. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationships between self-reported sleep quality components and cognitive functioning in breast cancer survivors up to 10 years following chemotherapy.

PubMed

Henneghan, Ashley M; Carter, Patricia; Stuifbergan, Alexa; Parmelee, Brennan; Kesler, Shelli

2018-04-23

Links have been made between aspects of sleep quality and cognitive function in breast cancer survivors (BCS), but findings are heterogeneous. The objective of this study is to examine relationships between specific sleep quality components (latency, duration, efficiency, daytime sleepiness, sleep disturbance, use of sleep aids) and cognitive impairment (performance and perceived), and determine which sleep quality components are the most significant contributors to cognitive impairments in BCS 6 months to 10 years post chemotherapy. Women 21 to 65 years old with a history of non-metastatic breast cancer following chemotherapy completion were recruited. Data collection included surveys to evaluate sleep quality and perceived cognitive impairments, and neuropsychological testing to evaluate verbal fluency and memory. Descriptive statistics, bivariate correlations, and hierarchical multiple regression were calculated. 90 women (mean age 49) completed data collection. Moderate significant correlations were found between daytime dysfunction, sleep efficiency, sleep latency, and sleep disturbance and perceived cognitive impairment (Rs = -0.37 to -0.49, Ps<.00049), but not objective cognitive performance of verbal fluency, memory or attention. After accounting for individual and clinical characteristics, the strongest predictors of perceived cognitive impairments were daytime dysfunction, sleep efficiency, and sleep disturbance. Findings support links between sleep quality and perceived cognitive impairments in BCS and suggest specific components of sleep quality (daytime dysfunction, sleep efficiency, and sleep disturbance) are associated with perceived cognitive functioning in this population. Findings can assist clinicians in guiding survivors to manage sleep and cognitive problems and aid in the design of interventional research. This article is protected by copyright. All rights reserved.

The Effects of a Cognitive Information Processing Career Intervention on the Dysfunctional Career Thoughts, Locus of Control, and Career Decision Self-Efficacy of Underprepared College Students

ERIC Educational Resources Information Center

Henderson, Kristina M.

2009-01-01

This study investigated the impact of a seven-session career intervention in a First Year Experience course on the dysfunctional career thoughts, locus of control, and career decision self-efficacy of underprepared college students. The career intervention was based on the cognitive information processing approach to career decision making…

Personality and cognitive vulnerability in remitted recurrently depressed patients.

PubMed

van Rijsbergen, Gerard D; Kok, Gemma D; Elgersma, Hermien J; Hollon, Steven D; Bockting, Claudi L H

2015-03-01

Personality disorders (PDs) have been associated with a poor prognosis of Major Depressive Disorder (MDD). The aim of the current study was to examine cognitive vulnerability (i.e., dysfunctional beliefs, extremity of beliefs, cognitive reactivity, and rumination) that might contribute to this poor prognosis of patients with PD comorbidity. 309 outpatients with remitted recurrent MDD (SCID-I; HAM-D17 ≤ 10) were included within two comparable RCTs and were assessed at baseline with the Personality Diagnostic Questionnaire-4(+) (PDQ-4(+)), the Dysfunctional Attitude Scale Version-A (DAS-A), the Leiden Index of Depression Sensitivity (LEIDS), the Ruminative Response Scale (RRS), and the Inventory of Depressive Symptomatology-Self Report (IDS-SR). We found an indication that the PD prevalence was 49.5% in this remitted recurrently depressed sample. Having a PD (and higher levels of personality pathology) was associated with dysfunctional beliefs, cognitive reactivity, and rumination. Extreme 'black and white thinking' on the DAS was not associated with personality pathology. Brooding was only associated with a Cluster C classification (t(308) = 4.03, p < .001) and with avoidant PD specifically (t(308) = 4.82, p < .001), while surprisingly not with obsessive-compulsive PD. PDs were assessed by questionnaire and the analyses were cross-sectional in nature. Being the first study to examine cognitive reactivity and rumination in patients with PD and remitted MDD, we demonstrated that even after controlling for depressive symptomatology, dysfunctional beliefs, cognitive reactivity, and rumination were associated with personality pathology. Rumination might be a pathway to relapse for patients with avoidant PD. Replication of our findings concerning cognitive vulnerability and specific PDs is necessary. Copyright © 2014 Elsevier B.V. All rights reserved.

Insula Demonstrates a Non-Linear Response to Varying Demand for Cognitive Control and Weaker Resting Connectivity With the Executive Control Network in Smokers.

PubMed

Fedota, John R; Matous, Allison L; Salmeron, Betty Jo; Gu, Hong; Ross, Thomas J; Stein, Elliot A

2016-09-01

Deficits in cognitive control processes are a primary characteristic of nicotine addiction. However, while network-based connectivity measures of dysfunction have frequently been observed, empirical evidence of task-based dysfunction in these processes has been inconsistent. Here, in a sample of smokers (n=35) and non-smokers (n=21), a previously validated parametric flanker task is employed to characterize addiction-related alterations in responses to varying (ie, high, intermediate, and low) demands for cognitive control. This approach yields a demand-response curve that aims to characterize potential non-linear responses to increased demand for control, including insensitivities or lags in fully activating the cognitive control network. We further used task-based differences in activation between groups as seeds for resting-state analysis of network dysfunction in an effort to more closely link prior inconsistencies in task-related activation with evidence of impaired network connectivity in smokers. For both smokers and non-smokers, neuroimaging results showed similar increases in activation in brain areas associated with cognitive control. However, reduced activation in right insula was seen only in smokers and only when processing intermediate demand for cognitive control. Further, in smokers, this task-modulated right insula showed weaker functional connectivity with the superior frontal gyrus, a component of the task-positive executive control network. These results demonstrate that the neural instantiation of salience attribution in smokers is both more effortful to fully activate and has more difficulty communicating with the exogenous, task-positive, executive control network. Together, these findings further articulate the cognitive control dysfunction associated with smoking and illustrate a specific brain circuit potentially responsible.

Parsing trait and state effects of depression severity on neurocognition: Evidence from a 26-year longitudinal study.

PubMed

Sarapas, Casey; Shankman, Stewart A; Harrow, Martin; Goldberg, Joseph F

2012-11-01

Cognitive dysfunction in mood disorders falls along a continuum, such that more severe current depression is associated with greater cognitive impairment. It is not clear whether this association reflects transient state effects of current symptoms on cognitive performance, or persistent, trait-like differences in cognition that are related to overall disorder severity. We addressed this question in 42 unipolar and 47 bipolar participants drawn from a 26-year longitudinal study of psychopathology, using measures of attention/psychomotor processing speed, cognitive flexibility, verbal fluency, and verbal memory. We assessed (a) the extent to which current symptom severity and past average disorder severity predicted unique variance in cognitive performance; (b) whether cognitive performance covaried with within-individual changes in symptom severity; and (c) the stability of neurocognitive measures over six years. We also tested for differences among unipolar and bipolar groups and published norms. Past average depression severity predicted performance on attention/psychomotor processing speed in both groups, and in cognitive flexibility among unipolar participants, even after controlling for current symptom severity, which did not independently predict cognition. Within-participant state changes in depressive symptoms did not predict change in any cognitive domain. All domains were stable over the course of six years. Both groups showed generalized impairment relative to published norms, and bipolar participants performed more poorly than unipolar participants on attention/psychomotor processing speed. The results suggest a stable relationship between mood disorder severity and cognitive deficits. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Memory deficits in amyotrophic lateral sclerosis are not exclusively caused by executive dysfunction: a comparative neuropsychological study of amnestic mild cognitive impairment.

PubMed

Machts, Judith; Bittner, Verena; Kasper, Elisabeth; Schuster, Christina; Prudlo, Johannes; Abdulla, Susanne; Kollewe, Katja; Petri, Susanne; Dengler, Reinhard; Heinze, Hans-Jochen; Vielhaber, Stefan; Schoenfeld, Mircea A; Bittner, Daniel M

2014-06-30

Recent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impairment (aMCI) patients and 40 healthy controls (HC). The neuropsychological battery tested for impairment in executive functions, as well as memory and visuo-spatial skills, the results of which were compared across study groups. In addition, we calculated composite scores for memory (learning, recall, recognition) and executive functions (verbal fluency, cognitive flexibility, working memory). We hypothesized that the nature of memory impairment in ALS will be different from those exhibited by aMCI patients. Patient groups exhibited significant differences in their type of memory deficit, with the ALS group showing impairment only in recognition, whereas aMCI patients showed short and delayed recall performance deficits as well as reduced short-term capacity. Regression analysis revealed a significant impact of executive function on memory performance exclusively for the ALS group, accounting for one fifth of their memory performance. Interestingly, merging all sub scores into a single memory and an executive function score obscured these differences. The presented results indicate that the interpretation of neuropsychological scores needs to take the distinct cognitive profiles in ALS and aMCI into consideration. Importantly, the observed memory deficits in ALS were distinctly different from those observed in aMCI and can be explained only to some extent in the context of comorbid (coexisting) executive dysfunction. These findings highlight the qualitative differences in temporal lobe dysfunction between ALS and aMCI patients, and support temporal lobe dysfunction as a mechanism underlying the distinct cognitive impairments observed in ALS.

Rumination, distraction and mindful self-focus: effects on mood, dysfunctional attitudes and cortisol stress response.

PubMed

Kuehner, C; Huffziger, S; Liebsch, K

2009-02-01

Although aggravating effects of rumination on dysfunctional cognitions and endocrine stress responses have been proposed, experimental studies testing these assumptions are lacking. In parallel, mindfulness theory suggests beneficial effects of mindfulness on dysfunctional cognitions. This study aimed to investigate the effects of induced rumination, distraction and mindful self-focus on mood and dysfunctional attitudes and to assess the possible impact of induced rumination on participants' cortisol responses. Sixty university students were subjected to negative mood induction and subsequently randomly assigned to a rumination, distraction or mindful self-focus condition. The latter included statements focusing on self-acceptance and awareness of the breath. Four saliva cortisol samples were selected during the session. Compared to induced rumination, distraction showed a clear beneficial effect on the course of dysphoric mood, whereas a mindful self-focus did not. In contrast to distraction and mindful self-focus, participants induced to ruminate showed significant increases in dysfunctional attitudes from baseline to post-induction. Although rumination was not itself linked to higher cortisol responses, participants scoring high on the Beck Depression Inventory (BDI)-II who were induced to ruminate showed a smaller decrease in cortisol levels than those scoring low on the BDI-II. This study indicates that rumination as a dysfunctional mode of cognitive processing is able to maintain depression-linked dysfunctional thought content. Furthermore, our study revealed preliminary indications for a link between induced rumination and the cortisol stress response in vulnerable individuals.

BDNF pathway is involved in the protective effects of SS-31 on isoflurane-induced cognitive deficits in aging mice.

PubMed

Wu, Jing; Zhang, Mingqiang; Li, Huihui; Sun, Xiaoru; Hao, Shuangying; Ji, Muhuo; Yang, Jianjun; Li, Kuanyu

2016-05-15

Mitochondrial dysfunction has been linked to the earliest pathogenesis of isoflurane-induced cognitive impairments in developing or aging mammalian brain. However, its molecular mechanism is poorly understood and a pharmacologic treatment to rapidly reverse mitochondrial dysfunction is lacking. Fifteen-month-old male C57BL/6 mice were exposed to isoflurane for two hours following intraperitoneal administration of mitochondrion-targeted peptide SS-31 or vehicle with 30min interval. The hippocampus was immediately removed for biochemical assays and mitochondria isolation after inhalation. Behavioral tests were evaluated by the open field test and fear conditioning test 24h after the experiment. We showed that cognitive deficits induced by exposure of the aging mice to isoflurane were accompanied by mitochondrial dysfunction in hippocampus due to loss of the enzymatic activity of complex I. This loss resulted in the increase of reactive oxygen species production, decrease of ATP production and mitochondrial membrane potential, and opening of mitochondrial permeability transition pore. Further, we provided evidence that the BDNF signaling pathway was involved in this process to regulate synaptic plasticity-related proteins, for instance, downregulation of synapsin 1, PSD-95 and p-CREB, and upregulation of NR2A, NR2B, CaMKIIα and CaMKIIβ. Of note, the isoflurane-induced cognitive deficits were rescued by SS-31 through reversal of mitochondrial dysfunction, which facilitated the regulation of BDNF signaling including the expression reversal of aforementioned important synaptic-signaling proteins in aging mice. Our data demonstrate that reversing mitochondrial dysfunction by SS-31 enhances BDNF signaling pathway and synaptic plasticity, and provides protective effects on cognitive function, thereby support the notion that SS-31 may have therapeutic benefits for elderly humans undertaking anesthesia. Copyright © 2016 Elsevier B.V. All rights reserved.

Roles of vascular and metabolic components in cognitive dysfunction of Alzheimer disease: short- and long-term modification by non-genetic risk factors.

PubMed

Sato, Naoyuki; Morishita, Ryuichi

2013-11-05

It is well known that a specific set of genetic and non-genetic risk factors contributes to the onset of Alzheimer disease (AD). Non-genetic risk factors include diabetes, hypertension in mid-life, and probably dyslipidemia in mid-life. This review focuses on the vascular and metabolic components of non-genetic risk factors. The mechanisms whereby non-genetic risk factors modify cognitive dysfunction are divided into four components, short- and long-term effects of vascular and metabolic factors. These consist of (1) compromised vascular reactivity, (2) vascular lesions, (3) hypo/hyperglycemia, and (4) exacerbated AD histopathological features, respectively. Vascular factors compromise cerebrovascular reactivity in response to neuronal activity and also cause irreversible vascular lesions. On the other hand, representative short-term effects of metabolic factors on cognitive dysfunction occur due to hypoglycemia or hyperglycemia. Non-genetic risk factors also modify the pathological manifestations of AD in the long-term. Therefore, vascular and metabolic factors contribute to aggravation of cognitive dysfunction in AD through short-term and long-term effects. β-amyloid could be involved in both vascular and metabolic components. It might be beneficial to support treatment in AD patients by appropriate therapeutic management of non-genetic risk factors, considering the contributions of these four elements to the manifestation of cognitive dysfunction in individual patients, though all components are not always present. It should be clarified how these four components interact with each other. To answer this question, a clinical prospective study that follows up clinical features with respect to these four components: (1) functional MRI or SPECT for cerebrovascular reactivity, (2) MRI for ischemic lesions and atrophy, (3) clinical episodes of hypoglycemia and hyperglycemia, (4) amyloid-PET and tau-PET for pathological features of AD, would be required.

CBT for the treatment of depression in Parkinson's disease: a promising nonpharmacological approach.

PubMed

Dobkin, Roseanne DeFronzo; Menza, Matthew; Bienfait, Karina L

2008-01-01

Depression is very common in Parkinson's disease (PD) and linked with a faster progression of physical symptoms, greater cognitive decline and poorer quality of life. Nonpharmacological approaches, such as cognitive-behavioral therapy (CBT), for the treatment of depression in PD (dPD) have received little experimental attention despite strong demonstrated efficacy in other geriatric and medical populations. Depressed PD patients often differ from the depressed non-PD elderly in that they present with increased rates of both executive dysfunction and comorbid psychiatric diagnoses, may differ in their depressive symptom presentation and typically have caregivers who are highly involved in their treatment. Therefore, it is not possible to conclude that empirically validated treatments in the depressed aged will generalize to those with PD. In order to be most effective for PD patients, CBT should be tailored to their unique needs. Additional controlled research is needed to further explore the efficacy of CBT for dPD.

Evaluating the Effect of Cognitive Dysfunction on Mental Imagery in Patients with Stroke Using Temporal Congruence and the Imagined ‘Timed Up and Go’ Test (iTUG)

PubMed Central

Bonnyaud, Céline; Fery, Yves-André; Bussel, Bernard; Roche, Nicolas

2017-01-01

Background Motor imagery (MI) capacity may be altered following stroke. MI is evaluated by measuring temporal congruence between the timed performance of an imagined and an executed task. Temporal congruence between imagined and physical gait-related activities has not been evaluated following stroke. Moreover, the effect of cognitive dysfunction on temporal congruence is not known. Objective To assess temporal congruence between the Timed Up and Go test (TUG) and the imagined TUG (iTUG) tests in patients with stroke and to investigate the role played by cognitive dysfunctions in changes in temporal congruence. Methods TUG and iTUG performance were recorded and compared in twenty patients with chronic stroke and 20 controls. Cognitive function was measured using the Montreal Cognitive Assessment (MOCA), the Frontal Assessment Battery at Bedside (FAB) and the Bells Test. Results The temporal congruence of the patients with stroke was significantly altered compared to the controls, indicating a loss of MI capacity (respectively 45.11 ±35.11 vs 24.36 ±17.91, p = 0.02). Furthermore, iTUG test results were positively correlated with pathological scores on the Bells Test (r = 0.085, p = 0.013), likely suggesting that impairment of attention was a contributing factor. Conclusion These results highlight the importance of evaluating potential attention disorder in patients with stroke to optimise the use of MI for rehabilitation and recovery. However further study is needed to determine how MI should be used in the case of cognitive dysfunction. PMID:28125616

Evaluating the Effect of Cognitive Dysfunction on Mental Imagery in Patients with Stroke Using Temporal Congruence and the Imagined 'Timed Up and Go' Test (iTUG).

PubMed

Geiger, Maxime; Bonnyaud, Céline; Fery, Yves-André; Bussel, Bernard; Roche, Nicolas

2017-01-01

Motor imagery (MI) capacity may be altered following stroke. MI is evaluated by measuring temporal congruence between the timed performance of an imagined and an executed task. Temporal congruence between imagined and physical gait-related activities has not been evaluated following stroke. Moreover, the effect of cognitive dysfunction on temporal congruence is not known. To assess temporal congruence between the Timed Up and Go test (TUG) and the imagined TUG (iTUG) tests in patients with stroke and to investigate the role played by cognitive dysfunctions in changes in temporal congruence. TUG and iTUG performance were recorded and compared in twenty patients with chronic stroke and 20 controls. Cognitive function was measured using the Montreal Cognitive Assessment (MOCA), the Frontal Assessment Battery at Bedside (FAB) and the Bells Test. The temporal congruence of the patients with stroke was significantly altered compared to the controls, indicating a loss of MI capacity (respectively 45.11 ±35.11 vs 24.36 ±17.91, p = 0.02). Furthermore, iTUG test results were positively correlated with pathological scores on the Bells Test (r = 0.085, p = 0.013), likely suggesting that impairment of attention was a contributing factor. These results highlight the importance of evaluating potential attention disorder in patients with stroke to optimise the use of MI for rehabilitation and recovery. However further study is needed to determine how MI should be used in the case of cognitive dysfunction.

Interleukin-6 and C-Reactive Protein Levels and 9-Year Cognitive Decline in Community-Dwelling Older Women: The Women's Health and Aging Study II.

PubMed

Palta, Priya; Xue, Qian-Li; Deal, Jennifer A; Fried, Linda P; Walston, Jeremy D; Carlson, Michelle C

2015-07-01

Elevated inflammation is a proposed mechanism relating chronic diseases to cognitive dysfunction. The objective of this study was to test the hypothesis that greater levels of inflammation, as measured by the proinflammatory cytokine interleukin-6 (IL-6) and C-reactive protein, are associated with faster rates of cognitive decline among cognitively intact community-dwelling older women. We analyzed 336 women from the Women's Health and Aging Study II. Cognitive assessments were performed at baseline and every 18-36 months, and included the following domains: immediate and delayed memory (Hopkins Verbal Learning Test), psychomotor speed (Trail Making Test, Part A), and executive function (Trail Making Test, Part B). Aggregate measures of IL-6 and C-reactive protein, based on the average from visits one and two, were analyzed categorically. Random effects models were employed to test the relationship between tertiles of each inflammatory marker and changes in cognitive domain scores over 9 years. Moderate and high levels of IL-6 predicted early declines in psychomotor speed by 1.0 connection/min per year. There were no differences in baseline scores or rates of change across tertiles of IL-6 in memory or executive function. No differences were observed across tertiles of C-reactive protein for all cognitive domains. Higher levels of serum IL-6 were associated with greater declines in psychomotor speed over 9 years. This finding could suggest that elevated IL-6 may result in microvascular changes that may lead to damage of myelin sheaths that line neuronal axons, leading to decreased neuron propagation and impaired processing speed; however, mechanistic studies are needed to evaluate these hypotheses. © The Author 2014. 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.

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.

The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview.

PubMed

Liu, Jiankang

2008-01-01

We have identified a group of nutrients that can directly or indirectly protect mitochondria from oxidative damage and improve mitochondrial function and named them "mitochondrial nutrients". The direct protection includes preventing the generation of oxidants, scavenging free radicals or inhibiting oxidant reactivity, and elevating cofactors of defective mitochondrial enzymes with increased Michaelis-Menten constant to stimulate enzyme activity, and also protect enzymes from further oxidation, and the indirect protection includes repairing oxidative damage by enhancing antioxidant defense systems either through activation of phase 2 enzymes or through increase in mitochondrial biogenesis. In this review, we take alpha-lipoic acid (LA) as an example of mitochondrial nutrients by summarizing the protective effects and possible mechanisms of LA and its derivatives on age-associated cognitive and mitochondrial dysfunction of the brain. LA and its derivatives improve the age-associated decline of memory, improve mitochondrial structure and function, inhibit the age-associated increase of oxidative damage, elevate the levels of antioxidants, and restore the activity of key enzymes. In addition, co-administration of LA with other mitochondrial nutrients, such as acetyl-L: -carnitine and coenzyme Q10, appears more effective in improving cognitive dysfunction and reducing oxidative mitochondrial dysfunction. Therefore, administrating mitochondrial nutrients, such as LA and its derivatives in combination with other mitochondrial nutrients to aged people and patients suffering from neurodegenerative diseases, may be an effective strategy for improving mitochondrial and cognitive dysfunction.

Myopia and cognitive dysfunction among elderly Chinese adults: a propensity score matching analysis.

PubMed

Sun, Hong-Peng; Liu, Hu; Xu, Yong; Pan, Chen-Wei

2016-03-01

The association between myopia and cognitive dysfunction among elderly adults was assessed by applying a Propensity Score Matching (PSM) approach. This is a statistical method which allows investigators to estimate causal treatment effects using observational or nonrandomised data. The study was designed as a community-based cross-sectional study based on a Chinese cohort aged 60 years or older in China. Objective refraction was measured using an autorefractor and subjective refraction was used to refine vision, using the results of the objective refraction as the starting point. Myopia was defined as a spherical equivalent value of less than -0.50 dioptre (D) in the right eye. The Abbreviated Mental Test (AMT) was used for cognitive assessment. The propensity scores for myopia were formulated using 13 potential confounders. We matched the propensity scores for subjects with and without myopia within a caliper of 0.01 of logit function of propensity scores. About 4123 elderly adults who successfully completed the AMT were included in this analysis. The odds ratio (OR) of cognitive dysfunction for myopia before matching was 1.98 (95% confidence interval [CI] 1.61, 2.44; p < 0.001). There were significant covariate imbalances between comparison groups and after propensity score matching, covariate imbalance was significantly reduced. After propensity score matching, the OR of cognitive dysfunction was marginally significant and the magnitude of association was reduced (OR: 1.31 95% CI 1.00, 1.71; p = 0.05). Traditional multivariate logistic regression modelling found an OR of 1.52 (95% CI 1.23, 2.06; p < 0.001) after adjusting for the 13 potential confounders. Myopia was associated with a higher prevalence of cognitive dysfunction among elderly Chinese aged 60 years or older in China. The PSM approach may be a useful method to address selection bias in observational studies when randomised trials cannot ethically be conducted. © 2015 The Authors Ophthalmic & Physiological Optics © 2015 The College of Optometrists.

Vascular Factors and Cognitive Dysfunction in Alzheimer Disease.

PubMed

Pąchalska, Maria; Bidzan, Leszek; Bidzan, Mariola; Góral-Półrola, Jolanta

2015-11-12

The purpose of the present study was to assess the influence of vascular factors on the degree of intensity and rate of progression of cognitive disorders in the course of Alzheimer Disease (AD). The research group consisted of 39 persons, all of whom were diagnosed with AD according to the NINCDS/ADRDA criteria. We divided these patients into 2 subgroups, based on the vascular factors measured by the modified Hachinski Ischemic Scale (Ha-mod): group A, without the vascular component (HA-mod score of 0-1 point), and group B, with the vascular component (a score over 1 point). Cognitive functions were evaluated at baseline and again 2 years later, using the Cognitive Part of the Alzheimer Disease Assessment Scale (ADAS-cog). We found that the patients from subgroup B, with the stronger vascular component, demonstrated the highest intensity of cognitive disorders at baseline, both in terms of the overall ADAS-cog score, and in the subscores for ideational praxis, orientation, spoken language ability, comprehension of spoken language, and word-finding difficulty in spontaneous speech. Another variable which was connected with the intensity of dementia was age. After 2 years, however, the rate of progression of cognitive disorders was not significantly different between the 2 groups. The severity of vascular factors correlates directly with the intensity of cognitive disturbances. At the 2-year follow-up examination, however, no correlation was observed in the research group between greater vascular involvement and more rapid progression of cognitive disorders, as measured by the ADAS-cog scale.

Hyper-modulation of brain networks by the amygdala among women with Borderline Personality Disorder: Network signatures of affective interference during cognitive processing.

PubMed

Soloff, Paul H; Abraham, Kristy; Ramaseshan, Karthik; Burgess, Ashley; Diwadkar, Vaibhav A

2017-05-01

Emotion dysregulation is a core characteristic of patients with Borderline Personality Disorder (BPD), and is often attributed to an imbalance in fronto-limbic network function. Hyperarousal of amygdala, especially in response to negative affective stimuli, results in affective interference with cognitive processing of executive functions. Clinical consequences include the impulsive-aggression, suicidal and self-injurious behaviors which characterize BPD. Dysfunctional interactions between amygdala and its network targets have not been well characterized during cognitive task performance. Using psychophysiological interaction analysis (PPI), we mapped network profiles of amygdala interaction with key regulatory regions during a Go No-Go task, modified to use negative, positive and neutral Ekman faces as targets. Fifty-six female subjects, 31 BPD and 25 healthy controls (HC), completed the affectively valenced Go No-Go task during fMRI scanning. In the negative affective condition, the amygdala exerted greater modulation of its targets in BPD compared to HC subjects in Rt. OFC, Rt. dACC, Rt. Parietal cortex, Rt. Basal Ganglia, and Rt. dlPFC. Across the spectrum of affective contrasts, hypermodulation in BPD subjects observed the following ordering: Negative > Neutral > Positive contrast. The amygdala seed exerted modulatory effects on specific target regions important in processing response inhibition and motor impulsiveness. The vulnerability of BPD subjects to affective interference with impulse control may be due to specific network dysfunction related to amygdala hyper-arousal and its effects on prefrontal regulatory regions such as the OFC and dACC. Copyright © 2017 Elsevier Ltd. All rights reserved.

Negative Mood States or Dysfunctional Cognitions: Their Independent and Interactional Effects in Influencing Severity of Gambling Among Chinese Problem Gamblers in Hong Kong.

PubMed

Wong, Daniel Fu Keung; Zhuang, Xiao Yu; Jackson, Alun; Dowling, Nicki; Lo, Herman Hay Ming

2017-09-04

Gambling-related cognitions and negative psychological states have been proposed as major factors in the initiation and maintenance of problem gambling (PG). While there are a substantial number of studies supporting the role of cognitive dysfunctions in the initiation and maintenance of PG, very few empirical studies have explored the specific role of negative psychological states in influencing PG behaviours. In addition, very few studies have examined the interaction effects of cognitive dysfunctions and negative psychological states in exerting influence on PG behaviours. Therefore, the present study aims to examine the main and interaction effects of gambling-related cognitions and psychological states on the gambling severity among a group of problem gamblers in Hong Kong. A cross-sectional research design was adopted. A purposive sample of 177 problem gamblers who sought treatment from a social service organization in Hong Kong completed a battery of standardised questionnaires. While gambling-related cognitions were found to exert significant effects on gambling severity, negative psychological states (i.e. stress) significantly moderated the relationship between gambling cognitions and gambling severity. In essence, those participants who reported a higher level of stress had more stable and serious gambling problems than those who reported a lower level of stress irrespective of the level of gambling-related cognitions. The findings of the moderating role of negative emotions in the relationship between cognitive distortions and severity of gambling provide insight towards developing an integrated intervention model which includes both cognitive-behavioural and emotion regulation strategies in helping people with PG.

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

PubMed Central

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

2016-01-01

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

Peripheral DNA methylation, cognitive decline and brain aging: pilot findings from the Whitehall II imaging study.

PubMed

Chouliaras, Leonidas; Pishva, Ehsan; Haapakoski, Rita; Zsoldos, Eniko; Mahmood, Abda; Filippini, Nicola; Burrage, Joe; Mill, Jonathan; Kivimäki, Mika; Lunnon, Katie; Ebmeier, Klaus P

2018-05-01

The present study investigated the link between peripheral DNA methylation (DNAm), cognitive impairment and brain aging. We tested the association between blood genome-wide DNAm profiles using the Illumina 450K arrays, cognitive dysfunction and brain MRI measures in selected participants of the Whitehall II imaging sub-study. Eight differentially methylated regions were associated with cognitive impairment. Accelerated aging based on the Hannum epigenetic clock was associated with mean diffusivity and global fractional anisotropy. We also identified modules of co-methylated loci associated with white matter hyperintensities. These co-methylation modules were enriched among pathways relevant to β-amyloid processing and glutamatergic signaling. Our data support the notion that blood DNAm changes may have utility as a biomarker for cognitive dysfunction and brain aging.

Olfactory Function is Associated with Cognitive Performance: Results of the Heinz Nixdorf Recall Study.

PubMed

Tebrügge, Sarah; Winkler, Angela; Gerards, Diana; Weimar, Christian; Moebus, Susanne; Jöckel, Karl-Heinz; Erbel, Raimund; Jokisch, Martha

2018-01-01

There is strong evidence for an association of olfactory dysfunction and neurodegenerative diseases. Studies on the association of olfaction and cognition in the general population are rare. To evaluate gender- and age-specific associations of olfactory function and cognitive performance in a well characterized population-based study sample. At the third examination of the Heinz Nixdorf Recall study (n = 3,087), 2,640 participants (48% men; 68.2±7.2 years) underwent Sniffin' Sticks Screening Test measuring olfactory function on a scale of 0-12 points. Olfactory function was rated as anosmic, hyposmic, or normosmic (≤6, 7-10 or ≥11 points, respectively). All participants performed eight validated cognitive subtests. Age- (55-64 years, 65-74 years, 75-86 years) and gender-stratified multivariate analysis of covariance was used to evaluate group differences in cognitive performance. Women showed better olfactory function than men (p < 0.001). For middle-aged participants, olfactory groups differed in almost all cognitive subtests. The analyses revealed no gender effects, although associations were slightly greater for women than for men. Anosmics showed the worst cognitive performance and normosmics showed the best cognitive performance. In the young- and old-aged groups, a quantitative association was found for anosmics in all subtests and for normosmics and hyposmics in almost all subtests. This is the first study reporting on age-specific associations of olfactory function and cognitive performance in the general population. The association found in middle-aged participants (65-74 years) may serve as a marker to improve identification of persons at high risk for cognitive decline and dementia.

The anatomy of cognitive impairment in amyotrophic lateral sclerosis: more than frontal lobe dysfunction.

PubMed

Tsermentseli, Stella; Leigh, P Nigel; Goldstein, Laura H

2012-02-01

Cognitive and behavioural impairments accompanying amyotrophic lateral sclerosis (ALS) have been reported since the early 20th century. Typically, these changes can be associated with a dysexecutive syndrome or manifest as a frontotemporal dementia (FTD). Although the nature of specific frontotemporal dysfunction in ALS remains to be refined, as with the clinical presentation, there is likely to be significant heterogeneity. This article will review the current state of knowledge regarding the neuropathological and neuroanatomical basis for cognitive dysfunction in ALS. Neuropathological findings suggest that ALS does not selectively affect the frontotemporal network but rather is part of a broad clinico-pathological spectrum now known as TAR-DNA binding protein (TDP)-43 proteinopathies. Functional neuroimaging has supported neuropsychological findings of frontotemporal dysfunction but has also implied the involvement of somatosensory areas. Structural neuroimaging has not been able to establish a specific hypothesis of extra-motor cortical atrophy beyond the combination of various frontal, temporal and limbic areas. The finding of reduction in the integrity of white matter in the frontal, temporal and parietal lobes including long association fibers suggests that subcortical involvement may underlie both cognitive and functional changes in ALS. Future perspectives for further investigations are highlighted. Copyright © 2011 Elsevier Srl. All rights reserved.

The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer’s Disease of humans and mice

PubMed Central

Cacciottolo, Mafalda; Christensen, Amy; Moser, Alexandra; Liu, Jiahui; Pike, Christian J.; Sullivan, Patrick M.; Morgan, Todd E.; Dolzhenko, Egor; Charidimou, Andreas; Wahlund, Lars-Olaf; Wiberg, Maria Kristofferson; Shams, Sara; Chiang, Gloria Chia-Yi; Finch, Caleb E.

2015-01-01

The APOE4 allele confers greater risk of Alzheimer’s Disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment (MCI) and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in two clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes. At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy (CAA), plaques, and soluble Aβ also showed female excess. Both the cerebral microbleeds and CAA increased in proportion to individual Aβ load. In humans, the opposite sex bias of APOE4 allele for microbleeds vs the plaques and tangles is the first example of organ-specific, sex-linked APOE allele effects, and further shows AD as a uniquely human condition. PMID:26686669

The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice.

PubMed

Cacciottolo, Mafalda; Christensen, Amy; Moser, Alexandra; Liu, Jiahui; Pike, Christian J; Smith, Conor; LaDu, Mary Jo; Sullivan, Patrick M; Morgan, Todd E; Dolzhenko, Egor; Charidimou, Andreas; Wahlund, Lars-Olof; Wiberg, Maria Kristofferson; Shams, Sara; Chiang, Gloria Chia-Yi; Finch, Caleb E

2016-01-01

The apolipoprotein APOE4 allele confers greater risk of Alzheimer's disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in 2 clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes (5XFAD (+/-) /human APOE(+/+)). At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy, plaques, and soluble Aβ also showed female excess. Both the cerebral microbleeds and cerebral amyloid angiopathy increased in proportion to individual Aβ load. In humans, the opposite sex bias of APOE4 allele for microbleeds versus the plaques and tangles is the first example of organ-specific, sex-linked APOE allele effects, and further shows AD as a uniquely human condition. Copyright © 2016 Elsevier Inc. All rights reserved.

Diagnosis and treatment of vascular damage in dementia.

PubMed

Biessels, Geert Jan

2016-05-01

This paper provides an overview of cognitive impairment due to vascular brain damage, which is referred to as vascular cognitive impairment (VCI). Over the past decades, we have seen marked progress in detecting VCI, both through maturation of diagnostic concepts and through advances in brain imaging, especially MRI. Yet in daily practice, it is often challenging to establish the diagnosis, particularly in patients where there is no evident temporal relation between a cerebrovascular event and cognitive dysfunction. Because vascular damage is such a common cause of cognitive dysfunction, it provides an obvious target for treatment. In patients whose cognitive dysfunction follows directly after a stroke, the etiological classification of this stroke will direct treatment. In many patients however, VCI develops due to so-called "silent vascular damage," without evident cerebrovascular events. In these patients, small vessel diseases (SVDs) are the most common cause. Yet no SVD-specific treatments currently exist, which is due to incomplete understanding of the pathophysiology. This review addresses developments in this field. It offers a framework to translate diagnostic criteria to daily practice, addresses treatment, and highlights some future perspectives. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau, and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

The influence of cognitive dysfunction on benefit from learning and memory rehabilitation in MS: A sub-analysis of the MEMREHAB trial.

PubMed

Chiaravalloti, Nancy D; DeLuca, John

2015-10-01

This study examined the influence of processing speed (PS) on benefit from treatment with the modified Story Memory Technique(©) (mSMT), a behavioral intervention shown to improve new learning and memory in multiple sclerosis (MS). This double-blind, placebo-controlled, randomized clinical trial included 85 participants with clinically definite MS, 45 assigned to the treatment group and 40 to the placebo-control group. Participants completed baseline and follow-up neuropsychological assessment. The present study represents a post-hoc analysis to examine the role of PS on treatment efficacy. The treatment group showed a significantly improved CVLT learning slope relative to the placebo group post-treatment, after co-varying PS performance. SDMT performance was a significant predictor of benefit from mSMT treatment, beyond group assignment. Post-hoc analysis indicated a significant correlation between the SDMT and overall cognition, indicating that the SDMT may be serving as a proxy for overall cognitive impairment. Performance on measures of cognitive dysfunction aside from learning and memory impact the benefit of mSMT treatment. While the current study focused on PS as a critical factor, PS may be serving as a marker for generalized cognitive dysfunction. Implications for cognitive rehabilitation in MS are discussed. © The Author(s), 2015.

Interictal epileptic discharge correlates with global and frontal cognitive dysfunction in temporal lobe epilepsy.

PubMed

Dinkelacker, Vera; Xin, Xu; Baulac, Michel; Samson, Séverine; Dupont, Sophie

2016-09-01

Temporal lobe epilepsy (TLE) with hippocampal sclerosis has widespread effects on structural and functional connectivity and often entails cognitive dysfunction. EEG is mandatory to disentangle interactions in epileptic and physiological networks which underlie these cognitive comorbidities. Here, we examined how interictal epileptic discharges (IEDs) affect cognitive performance. Thirty-four patients (right TLE=17, left TLE=17) were examined with 24-hour video-EEG and a battery of neuropsychological tests to measure intelligence quotient and separate frontal and temporal lobe functions. Hippocampal segmentation of high-resolution T1-weighted imaging was performed with FreeSurfer. Partial correlations were used to compare the number and distribution of clinical interictal spikes and sharp waves with data from imagery and psychological tests. The number of IEDs was negatively correlated with executive functions, including verbal fluency and intelligence quotient (IQ). Interictal epileptic discharge affected cognitive function in patients with left and right TLE differentially, with verbal fluency strongly related to temporofrontal spiking. In contrast, IEDs had no clear effects on memory functions after corrections with partial correlations for age, age at disease onset, disease duration, and hippocampal volume. In patients with TLE of long duration, IED occurrence was strongly related to cognitive deficits, most pronounced for frontal lobe function. These data suggest that IEDs reflect dysfunctional brain circuitry and may serve as an independent biomarker for cognitive comorbidity. Copyright © 2016. Published by Elsevier Inc.

Brain 18F-FDG PET Metabolic Abnormalities in Patients with Long-Lasting Macrophagic Myofascitis.

PubMed

Van Der Gucht, Axel; Aoun Sebaiti, Mehdi; Guedj, Eric; Aouizerate, Jessie; Yara, Sabrina; Gherardi, Romain K; Evangelista, Eva; Chalaye, Julia; Cottereau, Anne-Ségolène; Verger, Antoine; Bachoud-Levi, Anne-Catherine; Abulizi, Mukedaisi; Itti, Emmanuel; Authier, François-Jérôme

2017-03-01

The aim of this study was to characterize brain metabolic abnormalities in patients with macrophagic myofascitis (MMF) and the relationship with cognitive dysfunction through the use of PET with 18 F-FDG. Methods: 18 F-FDG PET brain imaging and a comprehensive battery of neuropsychological tests were performed in 100 consecutive MMF patients (age [mean ± SD], 45.9 ± 12 y; 74% women). Images were analyzed with statistical parametric mapping (SPM12). Through the use of analysis of covariance, all 18 F-FDG PET brain images of MMF patients were compared with those of a reference population of 44 healthy subjects similar in age (45.4 ± 16 y; P = 0.87) and sex (73% women; P = 0.88). The neuropsychological assessment identified 4 categories of patients: those with no significant cognitive impairment ( n = 42), those with frontal subcortical (FSC) dysfunction ( n = 29), those with Papez circuit dysfunction ( n = 22), and those with callosal disconnection ( n = 7). Results: In comparison with healthy subjects, the whole population of patients with MMF exhibited a spatial pattern of cerebral glucose hypometabolism ( P < 0.001) involving the occipital lobes, temporal lobes, limbic system, cerebellum, and frontoparietal cortices, as shown by analysis of covariance. The subgroup of patients with FSC dysfunction exhibited a larger extent of involved areas (35,223 voxels vs. 13,680 voxels in the subgroup with Papez circuit dysfunction and 5,453 voxels in patients without cognitive impairment). Nonsignificant results were obtained for the last subgroup because of its small population size. Conclusion: Our study identified a peculiar spatial pattern of cerebral glucose hypometabolism that was most marked in MMF patients with FSC dysfunction. Further studies are needed to determine whether this pattern could represent a diagnostic biomarker of MMF in patients with chronic fatigue syndrome and cognitive dysfunction. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Validity of Montreal Cognitive Assessment in non-english speaking patients with Parkinson's disease.

PubMed

Krishnan, Syam; Justus, Sunitha; Meluveettil, Radhamani; Menon, Ramshekhar N; Sarma, Sankara P; Kishore, Asha

2015-01-01

The Montreal Cognitive Assessment is a brief and easy screening tool for accurately testing cognitive dysfunction in Parkinson's disease. We tested its validity for use in non-English (Malayalam) speaking patients with Parkinson's disease. We developed a Malayalam (a south-Indian language) version of Montreal Cognitive Assessment and applied to 70 patients with Parkinson's disease and 60 age- and education-matched healthy controls. Metric properties were assessed, and the scores were compared with the performance in validated Malayalam versions of Mini Mental Status Examination and Addenbrooke's Cognitive Examination. The Montreal Cognitive Assessment-Malayalam showed good internal consistency and test-retest reliability and its scores correlated with Mini Mental Status Examination (patients: R = 0.70; P < 0.001; healthy controls: R = 0.26; P = 0.04) and Addenbrooke's Cognitive Examination (patients: R = 0.8; P < 0.001; healthy controls: R = 0.52; P < 0.001) scores. This study establishes the reliability of cross-cultural adaptation of Montreal Cognitive Assessment for assessing cognition in Malayalam-speaking Parkinson's disease patients for early screening and potential future interventions for cognitive dysfunction.

Postoperative cognitive dysfunction in older adults: a call for nursing involvement.

PubMed

Sorrell, Jeanne M

2014-11-01

As the population continues to age and new medical developments make surgery at advanced ages increasingly possible, it is important to consider how older adults tolerate surgery and anesthesia. Considerable evidence shows that older adults have a higher risk of developing postoperative cognitive dysfunction (POCD), which leads to transient and sometimes long-term cognitive changes that may affect quality of life. Because little is known about how to prevent or treat POCD, it is important that nurses identify ways in which they can intervene to help patients who experience this disorder. Copyright 2014, SLACK Incorporated.

Dysfunctional Attitudes and Affective Responses to Daily Stressors: Separating Cognitive, Genetic, and Clinical Influences on Stress Reactivity

PubMed Central

Conway, Christopher C.; Slavich, George M.; Hammen, Constance

2016-01-01

Despite decades of research examining diathesis-stress models of emotional disorders, it remains unclear whether dysfunctional attitudes interact with stressful experiences to shape affect on a daily basis and, if so, how clinical and genetic factors influence these associations. To address these issues, we conducted a multi-level daily diary study that examined how dysfunctional attitudes and stressful events relate to daily fluctuations in negative and positive affect in 104 young adults. Given evidence that clinical and genetic factors underlie stress sensitivity, we also examined how daily affect is influenced by internalizing and externalizing symptoms and brain-derived neurotrophic factor (BDNF) genotype, which have been shown to influence neural, endocrine, and affective responses to stress. In multivariate models, internalizing symptoms and BDNF Val66Met genotype independently predicted heightened negative affect on stressful days, but dysfunctional attitudes did not. Specifically, the BDNF Met allele and elevated baseline internalizing symptomatology predicted greater increases in negative affect in stressful circumstances. These data are the first to demonstrate that BDNF genotype and stress are jointly associated with daily fluctuations in negative affect, and they challenge the assumption that maladaptive beliefs play a strong independent role in determining affective responses to everyday stressors. The results may thus inform the development of new multi-level theories of psychopathology and guide future research on predictors of affective lability. PMID:27041782

Gratitude influences sleep through the mechanism of pre-sleep cognitions.

PubMed

Wood, Alex M; Joseph, Stephen; Lloyd, Joanna; Atkins, Samuel

2009-01-01

To test whether individual differences in gratitude are related to sleep after controlling for neuroticism and other traits. To test whether pre-sleep cognitions are the mechanism underlying this relationship. A cross-sectional questionnaire study was conducted with a large (186 males, 215 females) community sample (ages=18-68 years, mean=24.89, S.D.=9.02), including 161 people (40%) scoring above 5 on the Pittsburgh Sleep Quality Index, indicating clinically impaired sleep. Measures included gratitude, the Pittsburgh Sleep Quality Index (PSQI), self-statement test of pre-sleep cognitions, the Mini-IPIP scales of Big Five personality traits, and the Social Desirability Scale. Gratitude predicted greater subjective sleep quality and sleep duration, and less sleep latency and daytime dysfunction. The relationship between gratitude and each of the sleep variables was mediated by more positive pre-sleep cognitions and less negative pre-sleep cognitions. All of the results were independent of the effect of the Big Five personality traits (including neuroticism) and social desirability. This is the first study to show that a positive trait is related to good sleep quality above the effect of other personality traits, and to test whether pre-sleep cognitions are the mechanism underlying the relationship between any personality trait and sleep. The study is also the first to show that trait gratitude is related to sleep and to explain why this occurs, suggesting future directions for research, and novel clinical implications.

Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer's Disease-Like Models.

PubMed

Huh, Eugene; Kim, Hyo Geun; Park, Hanbyeol; Kang, Min Seo; Lee, Bongyong; Oh, Myung Sook

2014-05-01

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.

Houttuynia cordata Improves Cognitive Deficits in Cholinergic Dysfunction Alzheimer’s Disease-Like Models

PubMed Central

Huh, Eugene; Kim, Hyo Geun; Park, Hanbyeol; Kang, Min Seo; Lee, Bongyong; Oh, Myung Sook

2014-01-01

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer’s disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta (Aβ) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Aβ-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in Aβ-induced neurotoxicity. In mice with Aβ-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Aβ-induced neurotoxicity. Moreover, HCW, which had an IC50 value of 79.7 μg/ml for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD. PMID:25009697

The cycle of schizoaffective disorder, cognitive ability, alcoholism, and suicidality.

PubMed

Goldstein, Gerald; Haas, Gretchen L; Pakrashi, Manish; Novero, Ada M; Luther, James F

2006-02-01

In this study we investigated the putative role of cognitive dysfunction, diagnosis (schizoaffective versus schizophrenia disorder), and alcoholism as risk factors for suicidal behavior among individuals with DSM-TV schizophrenia or schizoaffective disorders. Subjects received cognitive tests and medical records were reviewed for evidence of a history of suicide attempts or suicidal ideation. Discriminant analysis was used to identify cognitive test performance measures that distinguished those with versus those without suicidal behavior. None of the cognitive measures discriminated between the two groups. The rates of suicidal behavior (suicidal ideation and suicide attempts) did not differ between participants with versus those without comorbid alcohol use. An association was found between suicidal behavior and the diagnosis of schizoaffective disorder. It was concluded that the history of prominent mood syndromes characteristic of schizoaffective disorder contributes to increased risk of suicidal behaviors. Cognitive dysfunction and/or alcoholism did not contribute additionally to risk in this study.

Persistent anterograde amnesia following limbic encephalitis associated with antibodies to the voltage-gated potassium channel complex.

PubMed

Butler, Christopher R; Miller, Thomas D; Kaur, Manveer S; Baker, Ian W; Boothroyd, Georgie D; Illman, Nathan A; Rosenthal, Clive R; Vincent, Angela; Buckley, Camilla J

2014-04-01

Limbic encephalitis (LE) associated with antibodies to the voltage-gated potassium channel complex (VGKC) is a potentially reversible cause of cognitive impairment. Despite the prominence of cognitive dysfunction in this syndrome, little is known about patients' neuropsychological profile at presentation or their long-term cognitive outcome. We used a comprehensive neuropsychological test battery to evaluate cognitive function longitudinally in 19 patients with VGKC-LE. Before immunotherapy, the group had significant impairment of memory, processing speed and executive function, whereas language and perceptual organisation were intact. At follow-up, cognitive impairment was restricted to the memory domain, with processing speed and executive function having returned to the normal range. Residual memory function was predicted by the antibody titre at presentation. The results show that, despite broad cognitive dysfunction in the acute phase, patients with VGKC-LE often make a substantial recovery with immunotherapy but may be left with permanent anterograde amnesia.

Assessment of subjective and objective cognitive function in bipolar disorder: Correlations, predictors and the relation to psychosocial function.

PubMed

Demant, Kirsa M; Vinberg, Maj; Kessing, Lars V; Miskowiak, Kamilla W

2015-09-30

Cognitive dysfunction is prevalent in bipolar disorder (BD). However, the evidence regarding the association between subjective cognitive complaints, objective cognitive performance and psychosocial function is sparse and inconsistent. Seventy seven patients with bipolar disorder who presented cognitive complaints underwent assessment of objective and subjective cognitive function and psychosocial functioning as part of their participation in two clinical trials. We investigated the association between global and domain-specific objective and subjective cognitive function and between global cognitive function and psychosocial function. We also identified clinical variables that predicted objective and subjective cognitive function and psychosocial functioning. There was a correlation between global subjective and objective measures of cognitive dysfunction but not within the individual cognitive domains. However, the correlation was weak, suggesting that cognitive complaints are not an assay of cognition per se. Self-rated psychosocial difficulties were associated with subjective (but not objective) cognitive impairment and both subjective cognitive and psychosocial difficulties were predicted by depressive symptoms. Our findings indicate that adequate assessment of cognition in the clinical treatment of BD and in drug trials targeting cognition requires implementation of not only subjective measures but also of objective neuropsychological tests. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Electroencephalogram power changes as a correlate of chemotherapy-associated fatigue and cognitive dysfunction.

PubMed

Moore, Halle C F; Parsons, Michael W; Yue, Guang H; Rybicki, Lisa A; Siemionow, Wlodzimierz

2014-08-01

Persistent fatigue and cognitive dysfunction are poorly understood potential long-term effects of adjuvant chemotherapy. In this pilot study, we assessed the value of electroencephalogram (EEG) power measurements as a means to evaluate physical and mental fatigue associated with chemotherapy. Women planning to undergo adjuvant chemotherapy for breast cancer and healthy controls underwent neurophysiologic assessments at baseline, during the time of chemotherapy treatment, and at 1 year. Repeated measures analysis of variance was used to analyze the data. Compared with controls, patients reported more subjective fatigue at baseline that increased during chemotherapy and did not entirely resolve by 1 year. Performance on endurance testing was similar in patients versus controls at all time points; however, values of EEG power increased after a physical task in patients during chemotherapy but not controls. Compared with controls, subjective mental fatigue was similar for patients at baseline and 1 year but worsened during chemotherapy. Patients performed similarly to controls on formal cognitive testing at all time points, but EEG activity after the cognitive task was increased in patients only during chemotherapy. EEG power measurement has the potential to provide a sensitive neurophysiologic correlate of cancer treatment-related fatigue and cognitive dysfunction.

Does True Neurocognitive Dysfunction Contribute to Minnesota Multiphasic Personality Inventory-2nd Edition-Restructured Form Cognitive Validity Scale Scores?

PubMed

Martin, Phillip K; Schroeder, Ryan W; Heinrichs, Robin J; Baade, Lyle E

2015-08-01

Previous research has demonstrated RBS and FBS-r to identify non-credible reporters of cognitive symptoms, but the extent that these scales might be influenced by true neurocognitive dysfunction has not been previously studied. The present study examined the relationship between these cognitive validity scales and neurocognitive performance across seven domains of cognitive functioning, both before and after controlling for PVT status in 120 individuals referred for neuropsychological evaluations. Variance in RBS, but not FBS-r, was significantly accounted for by neurocognitive test performance across most cognitive domains. After controlling for PVT status, however, relationships between neurocognitive test performance and validity scales were no longer significant for RBS, and remained non-significant for FBS-r. Additionally, PVT failure accounted for a significant proportion of the variance in both RBS and FBS-r. Results support both the convergent and discriminant validity of RBS and FBS-r. As neither scale was impacted by true neurocognitive dysfunction, these findings provide further support for the use of RBS and FBS-r in neuropsychological evaluations. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cognitive dysfunction and depression in adult kidney transplant recipients: baseline findings from the FAVORIT Ancillary Cognitive Trial (FACT)

USDA-ARS?s Scientific Manuscript database

Hyperhomocysteinemia and B-vitamin deficiency may be treatable risk factors for cognitive impairment and decline. Hyperhomocysteinemia, cognitive impairment and depression all are common in individuals with kidney disease, including kidney transplant recipient. Accordingly, we assessed the prevalenc...

The Influence of Depression on Cognitive Control: Disambiguating Approach and Avoidance Tendencies.

PubMed

Huang, He; Movellan, Javier; Paulus, Martin P; Harlé, Katia M

2015-01-01

Dysfunctions of approach and avoidance motivation play an important role in depression, which in turn may affect cognitive control, i.e., the ability to regulate thoughts and action to achieve internal goals. We use a novel experimental paradigm, i.e. a computer simulated driving-task, to study the impact of depression on cognitive control by measuring approach and avoidance actions in continuous time. In this task, 39 subjects with minimal to severe depression symptoms were instructed to use a joystick to move a virtual car as quickly as possible to a target point without crossing a stop-sign or crashing into a wall. We recorded their continuous actions on a joystick and found that depression 1) leads to further stopping distance to task target; and 2) increases the magnitude of late deceleration (avoidance) but not early acceleration (approach), which was only observed in the stop-sign condition. Taken together, these results are consistent with the hypothesis that depressed individuals have greater avoidance motivation near stopping target, but are minimally affected by approach motivation.

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.

Spatial localization deficits and auditory cortical dysfunction in schizophrenia

PubMed Central

Perrin, Megan A.; Butler, Pamela D.; DiCostanzo, Joanna; Forchelli, Gina; Silipo, Gail; Javitt, Daniel C.

2014-01-01

Background Schizophrenia is associated with deficits in the ability to discriminate auditory features such as pitch and duration that localize to primary cortical regions. Lesions of primary vs. secondary auditory cortex also produce differentiable effects on ability to localize and discriminate free-field sound, with primary cortical lesions affecting variability as well as accuracy of response. Variability of sound localization has not previously been studied in schizophrenia. Methods The study compared performance between patients with schizophrenia (n=21) and healthy controls (n=20) on sound localization and spatial discrimination tasks using low frequency tones generated from seven speakers concavely arranged with 30 degrees separation. Results For the sound localization task, patients showed reduced accuracy (p=0.004) and greater overall response variability (p=0.032), particularly in the right hemifield. Performance was also impaired on the spatial discrimination task (p=0.018). On both tasks, poorer accuracy in the right hemifield was associated with greater cognitive symptom severity. Better accuracy in the left hemifield was associated with greater hallucination severity on the sound localization task (p=0.026), but no significant association was found for the spatial discrimination task. Conclusion Patients show impairments in both sound localization and spatial discrimination of sounds presented free-field, with a pattern comparable to that of individuals with right superior temporal lobe lesions that include primary auditory cortex (Heschl’s gyrus). Right primary auditory cortex dysfunction may protect against hallucinations by influencing laterality of functioning. PMID:20619608

The role of objective cognitive dysfunction in subjective cognitive complaints after stroke.

PubMed

van Rijsbergen, M W A; Mark, R E; Kop, W J; de Kort, P L M; Sitskoorn, M M

2017-03-01

Objective cognitive performance (OCP) is often impaired in patients post-stroke but the consequences of OCP for patient-reported subjective cognitive complaints (SCC) are poorly understood. We performed a detailed analysis on the association between post-stroke OCP and SCC. Assessments of OCP and SCC were obtained in 208 patients 3 months after stroke. OCP was evaluated using conventional and ecologically valid neuropsychological tests. Levels of SCC were measured using the CheckList for Cognitive and Emotional (CLCE) consequences following stroke inventory. Multivariate hierarchical regression analyses were used to evaluate the association of OCP with CLCE scores adjusting for age, sex and intelligence quotient. Analyses were performed to examine the global extent of OCP dysfunction (based on the total number of impaired neuropsychological tests, i.e. objective cognitive impairment index) and for each OCP test separately using the raw neuropsychological (sub)test scores. The objective cognitive impairment index for global OCP was positively correlated with the CLCE score (Spearman's rho = 0.22, P = 0.003), which remained significant in multivariate adjusted models (β = 0.25, P = 0.01). Results for the separate neuropsychological tests indicated that only one task (the ecologically valid Rivermead Behavioural Memory Test) was independently associated with the CLCE in multivariate adjusted models (β = -0.34, P < 0.001). Objective neuropsychological test performance, as measured by the global dysfunction index or an ecologically valid memory task, was associated with SCC. These data suggest that cumulative deficits in multiple cognitive domains contribute to subjectively experienced poor cognitive abilities in daily life in patients post-stroke. © 2016 EAN.

Children with chronic lung diseases have cognitive dysfunction as assessed by event-related potential (auditory P300) and Stanford-Binet IQ (SB-IV) test.

PubMed

Kamel, Terez Boshra; Abd Elmonaem, Mahmoud Tarek; Khalil, Lobna Hamed; Goda, Mona Hamdy; Sanyelbhaa, Hossam; Ramzy, Mourad Alfy

2016-10-01

Chronic lung disease (CLD) in children represents a heterogeneous group of many clinico-pathological entities with risk of adverse impact of chronic or intermittent hypoxia. So far, few researchers have investigated the cognitive function in these children, and the role of auditory P300 in the assessment of their cognitive function has not been investigated yet. This study was designed to assess the cognitive functions among schoolchildren with different chronic pulmonary diseases using both auditory P300 and Stanford-Binet test. This cross-sectional study included 40 school-aged children who were suffering from chronic chest troubles other than asthma and 30 healthy children of similar age, gender and socioeconomic state as a control group. All subjects were evaluated through clinical examination, radiological evaluation and spirometry. Audiological evaluation included (basic otological examination, pure-tone, speech audiometry and immittancemetry). Cognitive function was assessed by auditory P300 and psychological evaluation using Stanford-Binet test (4th edition). Children with chronic lung diseases had significantly lower anthropometric measures compared to healthy controls. They had statistically significant lower IQ scores and delayed P300 latencies denoting lower cognitive abilities. Cognitive dysfunction correlated to severity of disease. P300 latencies were prolonged among hypoxic patients. Cognitive deficits in children with different chronic lung diseases were best detected using both Stanford-Binet test and auditory P300. P300 is an easy objective tool. P300 is affected early with hypoxia and could alarm subtle cognitive dysfunction.

Cognitive Impairment in Chronic Alcoholics: Some Cause for Optimism.

ERIC Educational Resources Information Center

Goldman, Mark S.

1983-01-01

It appears that, although the cognitive functioning of many alcoholics remains impaired even after drinking has stopped, considerable recovery can occur. New findings now suggest the possibility of reducing cognitive dysfunction and enhancing alcoholism treatment outcomes. (CMG)

Postoperative Structural Brain Changes and Cognitive Dysfunction in Patients with Breast Cancer.

PubMed

Sato, Chiho; Sekiguchi, Atsushi; Kawai, Masaaki; Kotozaki, Yuka; Nouchi, Rui; Tada, Hiroshi; Takeuchi, Hikaru; Ishida, Takanori; Taki, Yasuyuki; Kawashima, Ryuta; Ohuchi, Noriaki

2015-01-01

The primary purpose of this study was to clarify the influence of the early response to surgery on brain structure and cognitive function in patients with breast cancer. It was hypothesized that the structure of the thalamus would change during the early response after surgery due to the effects of anesthesia and would represent one aspect of an intermediate phenotype of postoperative cognitive dysfunction (POCD). We examined 32 postmenopausal females with breast cancer and 20 age-matched controls. We assessed their cognitive function (attention, memory, and executive function), and performed brain structural MRI 1.5 ± 0.5 days before and 5.6 ± 1.2 days after surgery. We found a significant interaction between regional grey matter volume (rGMV) in the thalamus (P < 0.05, familywise error (FWE), small volume correction (SVC)) and one attention domain subtest (P = 0.001, Bonferroni correction) after surgery in the patient group compared with the control group. Furthermore, the changes in attention were significantly associated with sevoflurane anesthetic dose (r2 = 0.247, β = ‒0.471, P = 0.032) and marginally associated with rGMV changes in the thalamus (P = 0.07, FWE, SVC) in the Pt group. Our findings suggest that alterations in brain structure, particularly in the thalamus, may occur shortly after surgery and may be associated with attentional dysfunction. This early postoperative response to anesthesia may represent an intermediate phenotype of POCD. It was assumed that patients experiencing other risk factors of POCD, such as the severity of surgery, the occurrence of complications, and pre-existing cognitive impairments, would develop clinical POCD with broad and multiple types of cognitive dysfunction.

Hydrogen Sulfide Ameliorates Homocysteine-Induced Cognitive Dysfunction by Inhibition of Reactive Aldehydes Involving Upregulation of ALDH2.

PubMed

Li, Min; Zhang, Ping; Wei, Hai-Jun; Li, Man-Hong; Zou, Wei; Li, Xiang; Gu, Hong-Feng; Tang, Xiao-Qing

2017-04-01

Homocysteine, a risk factor for Alzheimer's disease, induces cognitive dysfunction. Reactive aldehydes play an important role in cognitive dysfunction. Aldehyde-dehydrogenase 2 detoxifies reactive aldehydes. Hydrogen sulfide, a novel neuromodulator, has neuroprotective effects and regulates learning and memory. Our previous work confirmed that the disturbance of hydrogen sulfide synthesis is invovled in homocysteine-induced defects in learning and memory. Therefore, the present work was to explore whether hydrogen sulfide ameliorates homocysteine-generated cognitive dysfunction and to investigate whether its underlying mechanism is related to attenuating accumulation of reactive aldehydes by upregulation of aldehyde-dehydrogenase 2. The cognitive function of rats was assessed by the Morris water maze test and the novel object recognition test. The levels of malondialdehyde, 4-hydroxynonenal, and glutathione as well as the activity of aldehyde-dehydrogenase 2 were determined by enzyme linked immunosorbent assay; the expression of aldehyde-dehydrogenase 2 was detected by western blot. The behavior experiments, Morris water maze test and novel objects recognition test, showed that homocysteine induced deficiency in learning and memory in rats, and this deficiency was reversed by treatment of NaHS (a donor of hydrogen sulfide). We demonstrated that NaHS inhibited homocysteine-induced increases in generations of MDA and 4-HNE in the hippocampus of rats and that hydrogen sulfide reversed homocysteine-induced decreases in the level of glutathione as well as the activity and expression of aldehyde-dehydrogenase 2 in the hippocampus of rats. Hydrogen sulfide ameliorates homocysteine-induced impairment in cognitive function by decreasing accumulation of reactive aldehydes as a result of upregulations of glutathione and aldehyde-dehydrogenase 2. © The Author 2016. Published by Oxford University Press on behalf of CINP.

Hydrogen Sulfide Ameliorates Homocysteine-Induced Cognitive Dysfunction by Inhibition of Reactive Aldehydes Involving Upregulation of ALDH2

PubMed Central

Li, Min; Zhang, Ping; Wei, Hai-jun; Li, Man-Hong; Li, Xiang; Gu, Hong-Feng

2017-01-01

Abstract Background: Homocysteine, a risk factor for Alzheimer’s disease, induces cognitive dysfunction. Reactive aldehydes play an important role in cognitive dysfunction. Aldehyde-dehydrogenase 2 detoxifies reactive aldehydes. Hydrogen sulfide, a novel neuromodulator, has neuroprotective effects and regulates learning and memory. Our previous work confirmed that the disturbance of hydrogen sulfide synthesis is invovled in homocysteine-induced defects in learning and memory. Therefore, the present work was to explore whether hydrogen sulfide ameliorates homocysteine-generated cognitive dysfunction and to investigate whether its underlying mechanism is related to attenuating accumulation of reactive aldehydes by upregulation of aldehyde-dehydrogenase 2. Methods: The cognitive function of rats was assessed by the Morris water maze test and the novel object recognition test. The levels of malondialdehyde, 4-hydroxynonenal, and glutathione as well as the activity of aldehyde-dehydrogenase 2 were determined by enzyme linked immunosorbent assay; the expression of aldehyde-dehydrogenase 2 was detected by western blot. Results: The behavior experiments, Morris water maze test and novel objects recognition test, showed that homocysteine induced deficiency in learning and memory in rats, and this deficiency was reversed by treatment of NaHS (a donor of hydrogen sulfide). We demonstrated that NaHS inhibited homocysteine-induced increases in generations of MDA and 4-HNE in the hippocampus of rats and that hydrogen sulfide reversed homocysteine-induced decreases in the level of glutathione as well as the activity and expression of aldehyde-dehydrogenase 2 in the hippocampus of rats. Conclusion: Hydrogen sulfide ameliorates homocysteine-induced impairment in cognitive function by decreasing accumulation of reactive aldehydes as a result of upregulations of glutathione and aldehyde-dehydrogenase 2. PMID:27988490

Development of norms for executive functions in typically-developing Indian urban preschool children and its association with nutritional status.

PubMed

Selvam, Sumithra; Thomas, Tinku; Shetty, Priya; Thennarasu, K; Raman, Vijaya; Khanna, Deepti; Mehra, Ruchika; Kurpad, Anura V; Srinivasan, Krishnamachari

2018-02-01

Executive functions (EFs) are essential and important for achieving success in children's everyday lives and play a fundamental role in children's cognitive, academic, social, emotional and behavioral functioning. A cross-sectional study was carried out to develop age- and sex-specific norms for EFs using the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P) among 2- to 5-year-olds from urban Bangalore, India. In addition, the association between EFs and anthropometric measures, a marker of nutritional status, is also examined. Primary caregivers of 412 children, equally distributed by age and sex, participated. Raw scores for each domain and indices were converted to standard t-scores and percentiles were computed. A t-score at or above 63 corresponding to the 90th percentile was considered as the cutoff for executive dysfunction in this sample. The prevalence of executive dysfunction is 10% based on the Global Executive Composite score of the BRIEF-P. The cutoff score for identifying executive dysfunction using existing United States (US) norms is higher compared to the cutoff score obtained in the current study. Therefore, using US norms for Indian children could result in the prevalence of executive dysfunction been underestimated. Multiple linear regression analysis revealed that stunted and underweight children have significantly elevated EF scores after adjusting for age, sex and socioeconomic status (SES; p < .01). A greater understanding of EFs in preschool children is important for the early identification of executive dysfunction and implementing interventions to improve their future prospects. This study also shows that undernourished children are more likely to have executive dysfunction.

Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies

PubMed Central

Solé, Brisa; Jiménez, Esther; Torrent, Carla; Reinares, Maria; Bonnin, Caterina del Mar; Torres, Imma; Varo, Cristina; Grande, Iria; Valls, Elia; Salagre, Estela; Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Carvalho, André F

2017-01-01

Abstract Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients’ psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients. PMID:28498954

Cerebral blood flow regulation during cognitive tasks

PubMed Central

Sorond, Farzaneh A.; Schnyer, D.M.; Serrador, J.M.; Milberg, W.P.; Lipsitz, L.A.

2008-01-01

Aging is associated with frontal subcortical microangiopathy and executive cognitive dysfunction, suggesting that elderly individuals may have impaired metabolic activation of cerebral blood flow to the frontal lobes. We used transcranial Doppler (TCD) ultrasound to examine the cerebral blood flow response to executive control and visual tasks in the anterior and posterior cerebral circulations and to determine the effects of healthy aging on cerebral blood flow regulation during cognitive tasks. Continuous simultaneous anterior cerebral artery (ACA) and posterior cerebral artery (PCA) blood flow velocities (BFVs) and mean arterial pressure (MAP) were measured in response to word stem completion (WSC) and a visual search (VS) task in 29 healthy subjects (14 young, 30 ± 1.5 years; 15 old, 74 ± 1.4 years). We found that: (1) ACA and PCA blood flow velocities are both significantly increased during WSC and VS cognitive tasks, (2) ACA and PCA activations were task specific in our young volunteers, with ACA > PCA BFV during the WSC task and PCA > ACA BFV during the VS task, (3) while healthy elderly subjects also had PCA > ACA BFV during the VS task, they did not have ACA > PCA activation during the WSC task, and (4) healthy elderly subjects tend to have overall greater increases in BFV during both cognitive tasks. We conclude that TCD can be used to monitor cerebrovascular hemodynamics during the performance of cognitive tasks. Our data suggest that there is differential blood flow increase in the ACA and PCA in young versus elderly subjects during cognitive tasks. PMID:18387547

T cell deficiency leads to cognitive dysfunction: Implications for therapeutic vaccination for schizophrenia and other psychiatric conditions

PubMed Central

Kipnis, Jonathan; Cohen, Hagit; Cardon, Michal; Ziv, Yaniv; Schwartz, Michal

2004-01-01

The effects of the adaptive immune system on the cognitive performance and abnormal behaviors seen in mental disorders such as schizophrenia have never been documented. Here, we show that mice deprived of mature T cells manifested cognitive deficits and behavioral abnormalities, which were remediable by T cell restoration. T cell-based vaccination, using glatiramer acetate (copolymer-1, a weak agonist of numerous self-reactive T cells), can overcome the behavioral and cognitive abnormalities that accompany neurotransmitter imbalance induced by (+)dizocilpine maleate (MK-801) or amphetamine. The results, by suggesting that peripheral T cell deficit can lead to cognitive and behavioral impairment, highlight the importance of properly functioning adaptive immunity in the maintenance of mental activity and in coping with conditions leading to cognitive deficits. These findings point to critical factors likely to contribute to age- and AIDS-related dementias and might herald the development of a therapeutic vaccination for fighting off cognitive dysfunction and psychiatric conditions. PMID:15141078

Neurofeedback and its possible relevance for the treatment of Tourette syndrome.

PubMed

Farkas, Aniko; Bluschke, Annet; Roessner, Veit; Beste, Christian

2015-04-01

Neurofeedback is an increasingly recognized therapeutic option in various neuropsychiatric disorders to treat dysfunctions in cognitive control as well as disorder-specific symptoms. In this review we propose that neurofeedback may also reflect a valuable therapeutic option to treat executive control functions in Gilles-de-la-Tourette syndrome (GTS). Deficits in executive control functions when ADHD symptoms appear in GTS likely reflect pathophysiological processes in cortico-thalamic-striatal circuits and may also underlie the motor symptoms in GTS. Such executive control deficits evident in comorbid GTS/ADHD depend on neurophysiological processes well-known to be modifiable by neurofeedback. However, so far efforts to use neurofeedback to treat cognitive dysfunctions are scarce. We outline why neurofeedback should be considered a promising treatment option, what forms of neurofeedback may prove to be most effective and how neurofeedback may be implemented in existing intervention strategies to treat comorbid GTS/ADHD and associated dysfunctions in cognitive control. As cognitive control deficits in GTS mostly appear in comorbid GTS/ADHD, neurofeedback may be most useful in this frequent combination of disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Unifying the field: developing an integrative paradigm for behavior therapy.

PubMed

Eifert, G H; Forsyth, J P; Schauss, S L

1993-06-01

The limitations of early conditioning models and treatments have led many behavior therapists to abandon conditioning principles and replace them with loosely defined cognitive theories and treatments. Systematic theory extensions to human behavior, using new concepts and processes derived from and built upon the basic principles, could have prevented the divisive debates over whether psychological dysfunctions are the results of conditioning or cognition and whether they should be treated with conditioning or cognitive techniques. Behavior therapy could also benefit from recent advances in experimental cognitive psychology that provide objective behavioral methods of studying dysfunctional processes. We suggest a unifying paradigm for explaining abnormal behavior that links and integrates different fields of study and processes that are frequently believed to be incompatible or antithetical such as biological vulnerability variables, learned behavioral repertoires, and that also links historical and current antecedents of the problem. An integrative paradigmatic behavioral approach may serve a unifying function in behavior therapy (a) by promoting an understanding of the dysfunctional processes involved in different disorders and (b) by helping clinicians conduct functional analyses that lead to theory-based, individualized, and effective treatments.

Protective effect of curcumin (Curcuma longa) against D-galactose-induced senescence in mice.

PubMed

Kumar, Anil; Prakash, Atish; Dogra, Samrita

2011-01-01

Brain senescence plays an important role in cognitive dysfunction and neurodegenerative disorders. Curcumin was reported to have beneficial effect against several neurodegenerative disorders including Alzheimer's disease. Therefore, the present study was conducted in order to explore the possible role of curcumin against D-galactose-induced cognitive dysfunction, oxidative damage, and mitochondrial dysfunction in mice. Chronic administration of D-galactose for 6 weeks significantly impaired cognitive function (both in Morris water maze and elevated plus maze), locomotor activity, oxidative defense (raised lipid peroxidation, nitrite concentration, depletion of reduced glutathione and catalase activity), and mitochondrial enzyme complex activities (I, II, and III) as compared to vehicle treated group. Curcumin (15 and 30 mg/kg) and galantamine (5 mg/kg) treatment for 6 weeks significantly improved cognitive tasks, locomotor activity, oxidative defense, and restored mitochondrial enzyme complex activity as compared to control (D-galactose). Chronic D-galactose treatment also significantly increased acetylcholine esterase activity that was attenuated by curcumin (15 and 30 mg/kg) and galantamine (5 mg/kg) treatment. In conclusion, the present study highlights the therapeutic potential of curcumin against d-galactose induced senescence in mice.

Neural Substrates of Inhibitory Control Deficits in 22q11.2 Deletion Syndrome†

PubMed Central

Montojo, C.A.; Jalbrzikowski, M.; Congdon, E.; Domicoli, S.; Chow, C.; Dawson, C.; Karlsgodt, K.H.; Bilder, R.M.; Bearden, C.E.

2015-01-01

22q11.2 deletion syndrome (22q11DS) is associated with elevated levels of impulsivity, inattention, and distractibility, which may be related to underlying neurobiological dysfunction due to haploinsufficiency for genes involved in dopaminergic neurotransmission (i.e. catechol-O-methyltransferase). The Stop-signal task has been employed to probe the neural circuitry involved in response inhibition (RI); findings in healthy individuals indicate that a fronto-basal ganglia network underlies successful inhibition of a prepotent motor response. However, little is known about the neurobiological substrates of RI difficulties in 22q11DS. Here, we investigated this using functional magnetic resonance imaging while 45 adult participants (15 22q11DS patients, 30 matched controls) performed the Stop-signal task. Healthy controls showed significantly greater activation than 22q11DS patients within frontal cortical and basal ganglia regions during successful RI, whereas 22q11DS patients did not show increased neural activity relative to controls in any regions. Using the Barratt Impulsivity Scale, we also investigated whether neural dysfunction during RI was associated with cognitive impulsivity in 22q11DS patients. RI-related activity within left middle frontal gyrus and basal ganglia was associated with severity of self-reported cognitive impulsivity. These results suggest reduced engagement of RI-related brain regions in 22q11DS patients, which may be relevant to characteristic behavioral manifestations of the disorder. PMID:24177988

Restoring effective sleep tranquility (REST): A feasibility and pilot study.

PubMed

Eakman, Aaron M; Schmid, Arlene A; Henry, Kimberly L; Rolle, Natalie R; Schelly, Catherine; Pott, Christine E; Burns, Joshua E

2017-06-01

The purpose of this pilot study was to establish the feasibility of completing a future controlled trial of a multi-component cognitive behavioral therapy for insomnia program for military veterans with sleep disturbance. This was a single-arm feasibility and pilot study. Participants were United States post-9/11 veterans with service-connected injuries, university students, and had self-reported sleep disturbances. Restoring Effective Sleep Tranquility was a multi-component cognitive behavioral therapy for insomnia intervention consisting of seven sessions of group therapy and eight 1:1 sessions delivered by occupational therapists. Feasibility and pilot indicators were process, resources, management, and scientific, including pre-post-assessments of sleep difficulties, dysfunctional sleep beliefs, participation, and pain interference. Indicators were supportive of feasibility, including reduced sleep difficulties (for example Medical Outcomes Study Sleep Measure [ t  = 3.29, p  = .02]), reduced nightmares: t  = 2.79, p  = .03; fewer dysfunctional sleep beliefs: t  = 3.63, p  = .01, and greater ability to participate in social roles: t  = -2.86, p  = .03, along with trends towards improved satisfaction with participation and reduced pain interference. The Restoring Effective Sleep Tranquility program may reduce sleep difficulties and improve participation in US veterans with service-connected injuries, and evidence indicates a controlled trial would be feasible to deliver.

Restoring effective sleep tranquility (REST): A feasibility and pilot study

PubMed Central

Schmid, Arlene A; Henry, Kimberly L; Rolle, Natalie R; Schelly, Catherine; Pott, Christine E; Burns, Joshua E

2017-01-01

Introduction The purpose of this pilot study was to establish the feasibility of completing a future controlled trial of a multi-component cognitive behavioral therapy for insomnia program for military veterans with sleep disturbance. Method This was a single-arm feasibility and pilot study. Participants were United States post-9/11 veterans with service-connected injuries, university students, and had self-reported sleep disturbances. Restoring Effective Sleep Tranquility was a multi-component cognitive behavioral therapy for insomnia intervention consisting of seven sessions of group therapy and eight 1:1 sessions delivered by occupational therapists. Feasibility and pilot indicators were process, resources, management, and scientific, including pre–post-assessments of sleep difficulties, dysfunctional sleep beliefs, participation, and pain interference. Findings Indicators were supportive of feasibility, including reduced sleep difficulties (for example Medical Outcomes Study Sleep Measure [t = 3.29, p = .02]), reduced nightmares: t = 2.79, p = .03; fewer dysfunctional sleep beliefs: t = 3.63, p = .01, and greater ability to participate in social roles: t = –2.86, p = .03, along with trends towards improved satisfaction with participation and reduced pain interference. Conclusion The Restoring Effective Sleep Tranquility program may reduce sleep difficulties and improve participation in US veterans with service-connected injuries, and evidence indicates a controlled trial would be feasible to deliver. PMID:28626295

Cocoa flavanol consumption improves cognitive function, blood pressure control, and metabolic profile in elderly subjects: the Cocoa, Cognition, and Aging (CoCoA) Study--a randomized controlled trial.

PubMed

Mastroiacovo, Daniela; Kwik-Uribe, Catherine; Grassi, Davide; Necozione, Stefano; Raffaele, Angelo; Pistacchio, Luana; Righetti, Roberta; Bocale, Raffaella; Lechiara, Maria Carmela; Marini, Carmine; Ferri, Claudio; Desideri, Giovambattista

2015-03-01

Recent evidence has indicated that flavanol consumption may have many health benefits in humans, including improved cognitive activities. The aim was to evaluate the effect of flavanol consumption on cognitive performance in cognitively intact elderly subjects. This was a double-blind, controlled, parallel-arm study conducted in 90 elderly individuals without clinical evidence of cognitive dysfunction who were randomly assigned to consume daily for 8 wk a drink containing 993 mg [high flavanol (HF)], 520 mg [intermediate flavanol (IF)], or 48 mg [low flavanol (LF)] cocoa flavanols (CFs). Cognitive function was assessed at baseline and after 8 wk by using the Mini-Mental State Examination (MMSE), the Trail Making Test (TMT) A and B, and the Verbal Fluency Test (VFT). The changes in MMSE score in response to the 3 different treatments were not different. In contrast, there was a positive impact of the intervention on specific aspects of cognitive function. Mean changes (±SEs) in the time required to complete the TMT A and B after consumption of the HF (-8.6 ± 0.4 and -16.5 ± 0.8 s, respectively) and IF (-6.7 ± 0.5 and -14.2 ± 0.5 s, respectively) drinks significantly (P < 0.0001) differed from that after consumption of the LF drinks (-0.8 ± 1.6 and -1.1 ± 0.7 s, respectively). Similarly, VFT scores significantly improved among all treatment groups, but the magnitude of improvement in the VFT score was significantly (P < 0.0001) greater in the HF group (7.7 ± 1.1 words/60 s) than in the IF (3.6 ± 1.2 words/60 s) and LF (1.3 ± 0.5 words/60 s) groups. Significantly different improvements in insulin resistance (P < 0.0001), blood pressure (P < 0.0001), and lipid peroxidation (P = 0.001) were also observed for the HF and IF groups in comparison with the LF group. Changes in insulin resistance explained ∼17% of changes in composite z score (partial r² = 0.1703, P < 0.0001). This dietary intervention study provides evidence that regular CF consumption can reduce some measures of age-related cognitive dysfunction, possibly through an improvement in insulin sensitivity. These data suggest that the habitual intake of flavanols can support healthy cognitive function with age. © 2015 American Society for Nutrition.

Effects of chronic intermittent ethanol exposure on orbitofrontal and medial prefrontal cortex-dependent behaviors in mice

PubMed Central

Badanich, Kimberly A.; Becker, Howard C.; Woodward, John J.

2011-01-01

In humans, stroke or trauma-induced damage to the orbitofrontal cortex (OFC) or medial prefrontal cortex (mPFC) results in impaired cognitive flexibility. Alcoholics also exhibit similar deficits in cognitive flexibility suggesting that the OFC and mPFC are susceptible to alcohol-induced dysfunction. The present experiments investigated this issue using an attention set-shifting assay in ethanol dependent adult male C57BL/6J mice. Ethanol dependence was induced by exposing mice to repeated cycles of chronic intermittent ethanol (CIE) vapor inhalation. Behavioral testing was conducted 72 hours or 10 days following CIE exposure to determine whether ethanol-induced changes in OFC-dependent (reversal learning) and mPFC-dependent (set-shifting) behaviors are long-lasting. During early ethanol abstinence (72 hrs), CIE mice showed reduced reversal learning performance as compared to controls. Reversal learning deficits were revealed as greater number of trials to criterion, more errors made and a greater difficulty in performing a reversal learning task relative to baseline performance. Furthermore, the magnitude of the impairment was greater during reversal of a simple discrimination rather than reversal of an intradimensional shift. Reversal learning deficits were no longer present when mice were tested 10 days after CIE exposure suggesting that ethanol-induced changes in OFC function can recover. Unexpectedly, performance on the set-shifting task was not impaired during abstinence from ethanol. These data suggest reversal learning, but not attention set-shifting, is transiently disrupted during short-term abstinence from CIE. Given that reversal learning requires an intact OFC, these findings support the idea that the OFC may be vulnerable to the cognitive impairing actions of ethanol. PMID:22122149

[Minimal emotional dysfunction and first impression formation in personality disorders].

PubMed

Linden, M; Vilain, M

2011-01-01

"Minimal cerebral dysfunctions" are isolated impairments of basic mental functions, which are elements of complex functions like speech. The best described are cognitive dysfunctions such as reading and writing problems, dyscalculia, attention deficits, but also motor dysfunctions such as problems with articulation, hyperactivity or impulsivity. Personality disorders can be characterized by isolated emotional dysfunctions in relation to emotional adequacy, intensity and responsivity. For example, paranoid personality disorders can be characterized by continuous and inadequate distrust, as a disorder of emotional adequacy. Schizoid personality disorders can be characterized by low expressive emotionality, as a disorder of effect intensity, or dissocial personality disorders can be characterized by emotional non-responsivity. Minimal emotional dysfunctions cause interactional misunderstandings because of the psychology of "first impression formation". Studies have shown that in 100 ms persons build up complex and lasting emotional judgements about other persons. Therefore, minimal emotional dysfunctions result in interactional problems and adjustment disorders and in corresponding cognitive schemata.From the concept of minimal emotional dysfunctions specific psychotherapeutic interventions in respect to the patient-therapist relationship, the diagnostic process, the clarification of emotions and reality testing, and especially an understanding of personality disorders as impairment and "selection, optimization, and compensation" as a way of coping can be derived.

Electrophysiological Evidence for Hyperfocusing of Spatial Attention in Schizophrenia.

PubMed

Kreither, Johanna; Lopez-Calderon, Javier; Leonard, Carly J; Robinson, Benjamin M; Ruffle, Abigail; Hahn, Britta; Gold, James M; Luck, Steven J

2017-04-05

A recently proposed hyperfocusing hypothesis of cognitive dysfunction in schizophrenia proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more narrowly but more intensely than healthy control subjects (HCS). The present study tests a key prediction of this hypothesis, namely, that PSZ will hyperfocus on information presented at the center of gaze. This should lead to greater filtering of peripheral stimuli when the task requires focusing centrally but reduced filtering of central stimuli when the task requires attending broadly in the periphery. These predictions were tested in a double oddball paradigm, in which frequent standard stimuli and rare oddball stimuli were presented at central and peripheral locations while event-related potentials were recorded. Participants were instructed to discriminate between the standard and oddball stimuli at either the central location or at the peripheral locations. PSZ and HCS showed opposite patterns of spatial bias at the level of early sensory processing, as assessed with the P1 component: PSZ exhibited stronger sensory suppression of peripheral stimuli when the task required attending narrowly to the central location, whereas HCS exhibited stronger sensory suppression of central stimuli when the task required attending broadly to the peripheral locations. Moreover, PSZ exhibited a stronger stimulus categorization response than HCS, as assessed with the P3b component, for central stimuli when the task required attending to the peripheral region. These results provide strong evidence of hyperfocusing in PSZ, which may provide a unified mechanistic account of multiple aspects of cognitive dysfunction in schizophrenia. SIGNIFICANCE STATEMENT Schizophrenia clearly involves impaired attention, but attention is complex, and delineating the precise nature of attentional dysfunction in schizophrenia has been difficult. The present study tests a new hyperfocusing hypothesis, which proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more intensely but more narrowly than healthy control subjects (HCS). Using electrophysiological measures of sensory and cognitive processing, we found that PSZ were actually superior to HCS in focusing attention at the point of gaze and filtering out peripheral distractors when the task required a narrow focusing of attention. This finding of superior filtering in PSZ supports the hyperfocusing hypothesis, which may provide the mechanism underlying a broad range of cognitive impairments in schizophrenia. Copyright © 2017 the authors 0270-6474/17/373813-11$15.00/0.

Electrophysiological Evidence for Hyperfocusing of Spatial Attention in Schizophrenia

PubMed Central

Kreither, Johanna; Lopez-Calderon, Javier; Leonard, Carly J.; Robinson, Benjamin M.; Ruffle, Abigail; Hahn, Britta; Gold, James M.

2017-01-01

A recently proposed hyperfocusing hypothesis of cognitive dysfunction in schizophrenia proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more narrowly but more intensely than healthy control subjects (HCS). The present study tests a key prediction of this hypothesis, namely, that PSZ will hyperfocus on information presented at the center of gaze. This should lead to greater filtering of peripheral stimuli when the task requires focusing centrally but reduced filtering of central stimuli when the task requires attending broadly in the periphery. These predictions were tested in a double oddball paradigm, in which frequent standard stimuli and rare oddball stimuli were presented at central and peripheral locations while event-related potentials were recorded. Participants were instructed to discriminate between the standard and oddball stimuli at either the central location or at the peripheral locations. PSZ and HCS showed opposite patterns of spatial bias at the level of early sensory processing, as assessed with the P1 component: PSZ exhibited stronger sensory suppression of peripheral stimuli when the task required attending narrowly to the central location, whereas HCS exhibited stronger sensory suppression of central stimuli when the task required attending broadly to the peripheral locations. Moreover, PSZ exhibited a stronger stimulus categorization response than HCS, as assessed with the P3b component, for central stimuli when the task required attending to the peripheral region. These results provide strong evidence of hyperfocusing in PSZ, which may provide a unified mechanistic account of multiple aspects of cognitive dysfunction in schizophrenia. SIGNIFICANCE STATEMENT Schizophrenia clearly involves impaired attention, but attention is complex, and delineating the precise nature of attentional dysfunction in schizophrenia has been difficult. The present study tests a new hyperfocusing hypothesis, which proposes that people with schizophrenia (PSZ) tend to concentrate processing resources more intensely but more narrowly than healthy control subjects (HCS). Using electrophysiological measures of sensory and cognitive processing, we found that PSZ were actually superior to HCS in focusing attention at the point of gaze and filtering out peripheral distractors when the task required a narrow focusing of attention. This finding of superior filtering in PSZ supports the hyperfocusing hypothesis, which may provide the mechanism underlying a broad range of cognitive impairments in schizophrenia. PMID:28283557

Cerebrovascular Complications of Diabetes: Focus on Cognitive Dysfunction

PubMed Central

Hardigan, Trevor; Ward, Rebecca; Ergul, Adviye

2017-01-01

The incidence of diabetes has more than doubled in the United States in the last 30 years and the global disease rate is projected to double by 2030. Cognitive impairment has been associated with diabetes, worsening quality of life in patients. The structural and functional interaction of neurons with the surrounding vasculature is critical for proper function of the central nervous system including domains involved in learning and memory. Thus, in this review we explore cognitive impairment in patients and experimental models, focusing on links to vascular dysfunction and structural changes. Lastly, we propose a role for the innate immunity--mediated inflammation in neurovascular changes in diabetes. PMID:27634842

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles

PubMed Central

Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2017-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8–9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits. PMID:28101068

Heterogeneity of Developmental Dyscalculia: Cases with Different Deficit Profiles.

PubMed

Träff, Ulf; Olsson, Linda; Östergren, Rickard; Skagerlund, Kenny

2016-01-01

Developmental Dyscalculia (DD) has long been thought to be a monolithic learning disorder that can be attributed to a specific neurocognitive dysfunction. However, recent research has increasingly recognized the heterogeneity of DD, where DD can be differentiated into subtypes in which the underlying cognitive deficits and neural dysfunctions may differ. The aim was to further understand the heterogeneity of developmental dyscalculia (DD) from a cognitive psychological perspective. Utilizing four children (8-9 year-old) we administered a comprehensive cognitive test battery that shed light on the cognitive-behavioral profile of each child. The children were compared against norm groups of aged-matched peers. Performance was then contrasted against predominant hypotheses of DD, which would also give insight into candidate neurocognitive correlates. Despite showing similar mathematical deficits, these children showed remarkable interindividual variability regarding cognitive profile and deficits. Two cases were consistent with the approximate number system deficit account and also the general magnitude-processing deficit account. These cases showed indications of having domain-general deficits as well. One case had an access deficit in combination with a general cognitive deficit. One case suffered from general cognitive deficits only. The results showed that DD cannot be attributed to a single explanatory factor. These findings support a multiple deficits account of DD and suggest that some cases have multiple deficits, whereas other cases have a single deficit. We discuss a previously proposed distinction between primary DD and secondary DD, and suggest hypotheses of dysfunctional neurocognitive correlates responsible for the displayed deficits.

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.

Insulin-like growth factor-1: a possible marker for emotional and cognitive disturbances, and treatment effectiveness in major depressive disorder.

PubMed

Levada, Oleg A; Troyan, Alexandra S

2017-01-01

Depression and cognitive dysfunction share a common neuropathological platform. Abnormal neural plasticity in the frontolimbic circuits has been linked to changes in the expression of neurotrophic factors, including IGF-1. These changes may result in clinical abnormalities observed over the course of major depressive disorder (MDD), including cognitive dysfunction. The present review aimed to summarize evidence regarding abnormalities of peripheral IGF-1 in MDD patients and assess a marker and predictive role of the neurotrophin for emotional and cognitive disturbances, and treatment effectiveness. A literature search of the PubMed database was conducted for studies, in which peripheral IGF-1 levels were evaluated. Our analysis revealed four main findings: (1) IGF-1 levels in MDD patients mismatch across the studies, which may arise from various factors, e.g., age, gender, the course of the disease, presence of cognitive impairment, ongoing therapy, or general health conditions; (2) the initial peripheral IGF-1 levels may predict the occurrence of depression in future; (3) peripheral IGF-1 levels may reflect cognitive dysfunction, although the data is limited; (4) it is difficult to evaluate the influence of treatment on IGF-1 levels as there is discrepancy of this growth factor among the studies at baseline, although most of them showed a decrease in IGF-1 levels after treatment.

Conversion of elderly to Alzheimer's dementia: role of confluence of hypothermia and senescent stigmata--the plausible pathway.

PubMed

Daulatzai, Mak Adam

2010-01-01

Aging is a consequence of progressive decline in special and somatosensory functions and specific brain stem nuclei. Many senescent stigmata, including hypoxia, hypoxemia, depressed cerebral blood flow and glucose metabolism, diseases of senescence, and their medications all enhance hypothermia as do alcohol, cold environment, and malnutrition. Hypothermia is a critical factor having deleterious impact on brain stem and neocortical functions. Additionally, anesthesia in elderly also promotes hypothermia; anesthetics not only cause consciousness (sensory and motor) changes, but memory impairment as well. Anesthesia inhibits cholinergic pathways, reticular and thalamocortical systems, cortico-cortical connectivity, and causes post-operative delirium and cognitive dysfunction. Increasing evidence indicates that anesthetic exposures may contribute to dementia onset and Alzheimer's disease (AD) in hypothermic elderly. Inhaled anesthetics potentiate caspases, BACE, tau hyperphosphorylation, and apoptosis. This paper addresses the important question: "Why do only some elderly fall victim to AD"? Based on information on the pathogenesis of early stages of cognitive dysfunction in elderly (i.e., due to senescent stigmata), and the effects of anesthesia superimposed, a detailed plausible neuropathological substrate (mechanism/pathway) is delineated here that reveals the possible cause(s) of AD. Basically, it encompasses several risk factors for cognitive dysfunction during senescence plus several hypothermia-enhancing routes; they all converge and tip the balance towards dementia onset. This knowledge of the confluence of heterogeneous risk factors in perpetuating dementia relentlessly is of importance in order to: (a) avoid their convergence; (b) take measures to stop/reverse cognitive dysfunction; and (c) to develop therapeutic strategies to enhance cognitive function and attenuate AD.

Amyloid-β Homeostasis Bridges Inflammation, Synaptic Plasticity Deficits and Cognitive Dysfunction in Multiple Sclerosis.

PubMed

Stampanoni Bassi, Mario; Garofalo, Sara; Marfia, Girolama A; Gilio, Luana; Simonelli, Ilaria; Finardi, Annamaria; Furlan, Roberto; Sancesario, Giulia M; Di Giandomenico, Jonny; Storto, Marianna; Mori, Francesco; Centonze, Diego; Iezzi, Ennio

2017-01-01

Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines. Although mechanisms of inflammation-induced hippocampal pathology in MS are not completely understood, alteration of Amyloid-β (Aβ) metabolism is emerging as a key factor linking together inflammation, synaptic plasticity and neurodegeneration in different neurological diseases. We explored the correlation between concentrations of Aβ 1-42 and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β), IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα), interferon γ (IFNγ)) in the cerebrospinal fluid (CSF) of 103 remitting MS patients. CSF levels of Aβ 1-42 were negatively correlated with the proinflammatory cytokine IL-8 and positively correlated with the anti-inflammatory molecules IL-10 and interleukin-1 receptor antagonist (IL-1ra). Other correlations, although noticeable, were either borderline or not significant. Our data show that an imbalance between proinflammatory and anti-inflammatory cytokines may lead to altered Aβ homeostasis, representing a key factor linking together inflammation, synaptic plasticity and cognitive dysfunction in MS. This could be relevant to identify novel therapeutic approaches to hinder the progression of cognitive dysfunction in MS.

Cognitive sequelae of methanol poisoning involve executive dysfunction and memory impairment in cross-sectional and long-term perspective.

PubMed

Bezdicek, O; Michalec, J; Vaneckova, M; Klempir, J; Liskova, I; Seidl, Z; Janikova, B; Miovsky, M; Hubacek, J; Diblik, P; Kuthan, P; Pilin, A; Kurcova, I; Fenclova, Z; Petrik, V; Navratil, T; Pelclova, D; Zakharov, S; Ruzicka, E

2017-03-01

Methanol poisoning leads to lesions in the basal ganglia and subcortical white matter, as well as to demyelination and atrophy of the optic nerve. However, information regarding cognitive deficits in a large methanol sample is lacking. The principal aim of the present study was to identify the cognitive sequelae of methanol poisoning and their morphological correlates. A sample of 50 patients (METH; age 48 ± 13 years), 3-8 months after methanol poisoning, and 57 control subjects (CS; age 49 ± 13 years) were administered a neuropsychological battery. Forty-six patients were followed in 2 years' perspective. Patients additionally underwent 1.5T magnetic resonance imaging (MRI). Three biochemical and toxicological metabolic markers and a questionnaire regarding alcohol abuse facilitated the classification of 24 patients with methanol poisoning without alcohol abuse (METHna) and 22 patients with methanol poisoning and alcohol abuse (METHa). All groups were compared to a control group of similar size, and matched for age, education, premorbid intelligence level, global cognitive performance, and level of depressive symptoms. Using hierarchical multiple regression we found significant differences between METH and CS, especially in executive and memory domains. METHa showed a similar pattern of cognitive impairment with generally more severe executive dysfunction. Moreover, all METH patients with extensive involvement on brain MRI (lesions in ≥2 anatomical regions) had a more severe cognitive impairment. From a longitudinal perspective, we did not find any changes in their cognitive functioning after 2 years' follow-up. Our findings suggest that methanol poisoning is associated with executive dysfunction and explicit memory impairment, supposedly due to basal ganglia dysfunction and disruption of frontostriatal circuitry proportional to the number of brain lesions, and that these changes are persistent after 2 years' follow-up. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of silent information regulator 1 in the protective effect of hydrogen sulfide on homocysteine-induced cognitive dysfunction: Involving reduction of hippocampal ER stress.

PubMed

Tang, Yi-Yun; Wang, Ai-Ping; Wei, Hai-Jun; Li, Man-Hong; Zou, Wei; Li, Xiang; Wang, Chun-Yan; Zhang, Ping; Tang, Xiao-Qing

2018-04-16

Homocysteine (Hcy) causes cognitive deficits and hippocampal endoplasmic reticulum (ER) stress. Our previous study has confirmed that Hydrogen sulfide (H 2 S) attenuates Hcy-induced cognitive dysfunction and hippocampal ER stress. Silent information regulator 1 (Sirt-1) is indispensable in the formation of learning and memory. Therefore, the aim of this study was to explore the role of Sirt-1 in the protective effect of H 2 S against Hcy-induced cognitive dysfunction. We found that NaHS (a donor of H 2 S) markedly up-regulated the expression of Sirt-1 in the hippocampus of Hcy-exposed rats. Sirtinol, a specific inhibitor of Sirt-1, reversed the improving role of NaHS in the cognitive function of Hcy-exposed rats, as evidenced by that sirtinol increased the escape latency and the swim distance in the acquisition trial of morris water maze (MWM) test, decreased the times crossed through and the time spent in the target quadrant in the probe trail of MWM test, and reduced the discrimination index in the novel object recognition test (NORT) in the rats cotreated with NaHS and Hcy. We also found that sirtinol reversed the protection of NaHS against Hcy-induced hippocampal ER-stress, as evidenced by up-regulating the expressions of GRP78, CHOP, and cleaved caspase-12 in the hippocampus of rats cotreated with NaHS and Hcy. These results suggested the contribution of upregulation of hippocampal Sirt-1 to the improving role of H 2 S in the cognitive function of Hcy-exposed rats, which involves suppression of hippocampal ER stress. Our finding provides a new insight into the mechanism underlying the inhibitory role of H 2 S in Hcy-induced cognitive dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

Coping with cancer-related cognitive dysfunction: a scoping review of the literature.

PubMed

Sleight, Alix

2016-01-01

Cancer-related cognitive dysfunction (CRCD) impacts memory, attention, concentration, language, multi-tasking, and organizational skills and decreases participation and quality of life for cancer survivors. The objectives of this article are: (1) to outline the neuroscience of CRCD, its risk factors, and its effect on participation; and (2) to identify and summarize the literature on rehabilitation interventions and coping techniques for CRCD in cancer survivors. A scoping review of articles cited in PubMed, MEDLINE, PsychINFO, and CINAHL was performed. To be included, articles must have been published in a peer-reviewed scientific journal between 1996 and 2014, written in English, and included a quantitative or qualitative non-pharmacological study of interventions and/or coping strategies for adult cancer survivors experiencing CRCD. Ten articles met the inclusion criteria for final review. Six studies tested the efficacy of rehabilitation treatments on CRCD. Three involved cognitive-behavioral therapy (CBT), while three tested neuropsychological and/or cognitive training interventions. Four qualitative studies investigated coping strategies used by survivors with CRCD. CBT-based treatments and neuropsychological/cognitive training methods may ameliorate symptoms of CRCD. The most commonly-reported coping strategy is utilization of assistive technology and memory aids. Further research is needed about efficacious rehabilitation techniques for this population. Implications for Rehabilitation Cancer-related cognitive dysfunction (CRCD) may impact up to 50% of cancer survivors. CRCD can significantly decrease participation and quality of life during survivorship. Cognitive-behavioral therapy (CBT) and neuropsychological/cognitive training methods may ameliorate symptoms of CRCD. The most common coping strategy reported by cancer survivors with CRCD is the use of assistive technology and memory aids.

Kidney function and cognitive decline in frail elderly: two faces of the same coin?

PubMed

Coppolino, Giuseppe; Bolignano, Davide; Gareri, Pietro; Ruberto, Carmen; Andreucci, Michele; Ruotolo, Giovanni; Rocca, Maurizio; Castagna, Alberto

2018-06-04

Cognitive and renal impairment are pervasive among elderly frails, a high-risk, geriatric sub-population with peculiar clinical characteristics. In a series of frail individuals with non-advanced chronic kidney disease (CKD), we aimed at assessing the entity of functional, general health and cognitive impairment and the possible relationship between these types of dysfunction and the severity of renal impairment. 2229 geriatric subjects were screened for frailty and CKD. Severity of CKD was assessed by eGFR (CKD-EPI formula). Frailty was established by the Fried Index. Functional, general health and cognitive status were assessed by validated score measures. Final analysis included 271 frail CKD subjects (162 women, 109 men). Mean eGFR was 64.25 ± 25.04 mL/min/1.73 m 2 . Prevalence of mild-to-moderate CKD (stage 3-4) was 44%. Twenty-six percent of patients had severe cognitive impairment, while mild and moderate impairment was found in 7 and 67% of individuals, respectively. All subjects had poor functional and general health status. Cognitive capacities significantly decreased across CKD stages (p for trend < 0.0001). In fully adjusted multivariate analyses, cognitive status remained an independent predictor of eGFR (β = 0.465; p < 0.0001). Mild-to-moderate CKD is highly pervasive among frail elderly individuals and the severity of renal dysfunction is independently correlated with that of cognitive impairment. Future studies are advocated to clarify whether the combination of kidney and mental dysfunction may portend a higher risk of worsen outcomes in this high-risk population.

Obstructive sleep apnea exaggerates cognitive dysfunction in stroke patients.

PubMed

Zhang, Yan; Wang, Wanhua; Cai, Sijie; Sheng, Qi; Pan, Shenggui; Shen, Fang; Tang, Qing; Liu, Yang

2017-05-01

Obstructive sleep apnea (OSA) is very common in stroke survivors. It potentially worsens the cognitive dysfunction and inhibits their functional recovery. However, whether OSA independently damages the cognitive function in stroke patients is unclear. A simple method for evaluating OSA-induced cognitive impairment is also missing. Forty-four stroke patients six weeks after onset and 24 non-stroke patients with snoring were recruited for the polysomnographic study of OSA and sleep architecture. Their cognitive status was evaluated with a validated Chinese version of Cambridge Prospective Memory Test. The relationship between memory deficits and respiratory, sleeping, and dementia-related clinical variables were analyzed with correlation and multiple linear regression tests. OSA significantly and independently damaged time- and event-based prospective memory in stroke patients, although it had less power than the stroke itself. The impairment of prospective memory was correlated with increased apnea-hypopnea index, decreased minimal and mean levels of peripheral oxygen saturation, and disrupted sleeping continuity (reduced sleep efficiency and increased microarousal index). The further regression analysis identified minimal levels of peripheral oxygen saturation and sleep efficiency to be the two most important predictors for the decreased time-based prospective memory in stroke patients. OSA independently contributes to the cognitive dysfunction in stroke patients, potentially through OSA-caused hypoxemia and sleeping discontinuity. The prospective memory test is a simple but sensitive method to detect OSA-induced cognitive impairment in stroke patients. Proper therapies of OSA might improve the cognitive function and increase the life quality of stroke patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Experiential Avoidance as a Mediator of Relationships between Cognitions and Hair-Pulling Severity

ERIC Educational Resources Information Center

Norberg, Melissa M.; Wetterneck, Chad T.; Woods, Douglas W.; Conelea, Christine A.

2007-01-01

Cognitive-behavioral models suggest that certain cognitions and beliefs are functionally related to hair pulling in persons with trichotillomania (TTM), but little empirical data have been collected to test such claims. This study assessed dysfunctional beliefs about appearance, shameful cognitions, and fear of negative evaluation and their…

Neurobiology of cognitive remediation therapy for schizophrenia: a systematic review.

PubMed

Thorsen, Anders Lillevik; Johansson, Kyrre; Løberg, Else-Marie

2014-01-01

Cognitive impairment is an important aspect of schizophrenia, where cognitive remediation therapy (CRT) is a promising treatment for improving cognitive functioning. While neurobiological dysfunction in schizophrenia has been the target of much research, the neural substrate of cognitive remediation and recovery has not been thoroughly examined. The aim of the present article is to systematically review the evidence for neural changes after CRT for schizophrenia. The reviewed studies indicate that CRT affects several brain regions and circuits, including prefrontal, parietal, and limbic areas, both in terms of activity and structure. Changes in prefrontal areas are the most reported finding, fitting to previous evidence of dysfunction in this region. Two limitations of the current research are the few studies and the lack of knowledge on the mechanisms underlying neural and cognitive changes after treatment. Despite these limitations, the current evidence suggests that CRT is associated with both neurobiological and cognitive improvement. The evidence from these findings may shed light on both the neural substrate of cognitive impairment in schizophrenia, and how better treatment can be developed and applied.

CSF tau and tau/Aβ42 predict cognitive decline in Parkinson's disease.

PubMed

Liu, Changqin; Cholerton, Brenna; Shi, Min; Ginghina, Carmen; Cain, Kevin C; Auinger, Peggy; Zhang, Jing

2015-03-01

A substantial proportion of patients with Parkinson's disease (PD) have concomitant cognitive dysfunction. Identification of biomarker profiles that predict which PD patients have a greater likelihood for progression of cognitive symptoms is pressingly needed for future treatment and prevention approaches. Subjects were drawn from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) study, a large clinical trial that enrolled initially untreated PD patients. For the current study, Phase One encompassed trial baseline until just prior to levodopa administration (n = 403), and Phase Two spanned the initiation of levodopa treatment until the end of cognitive follow-up (n = 305). Correlations and linear mixed models were performed to determine cross-sectional and longitudinal associations between baseline amyloid β1-42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) and measures of memory and executive function. Analyses also considered APOE genotype and tremor- vs. rigidity-dominant phenotype. No association was found between baseline CSF biomarkers and cognitive test performance during Phase One. However, once levodopa treatment was initiated, higher p-tau and p-tau/Aβ42 predicted subsequent decline on cognitive tasks involving both memory and executive functions. The interactions between biomarkers and cognition decline did not appear to be influenced by levodopa dosage, APOE genotype or motor phenotype. The current study has, for the first time, demonstrated the possible involvement of tau species, whose gene (MAPT) has been consistently linked to the risk of PD by genome-wide association studies, in the progression of cognitive symptoms in PD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Executive functioning and depressed mood before and after unilateral frontal lobe resection for intractable epilepsy.

PubMed

Dulay, Mario F; Busch, Robyn M; Chapin, Jessica S; Jehi, Lara; Najm, Imad

2013-06-01

Executive dysfunction occurs in a variety of patients who have sustained damage to the frontal lobes. In individuals with frontal lobe epilepsy (FLE) or after unilateral frontal lobe resection (FLR), a unique neuropsychological profile linking executive functions (EF) with the frontal lobe has been elusive, with conflicting findings in the literature. Some studies show greater risk of executive impairment with left-sided FLE or FLR, while others report greater risk for right-sided patients. Some studies report no relationship between FLE and EF impairment, while others show EF impairment regardless of side of seizure foci or surgery. In patients with temporal lobe epilepsy, executive dysfunction is associated with depressed mood possibly reflecting disruption of cortical-limbic pathways and/or frontal-striatal circuitry. Although not previously examined, depression level may affect executive functioning in those with FLE or FLR. We hypothesized that FLE patients with poor mood state would show greater executive dysfunction than FLE patients without poor mood state. The relationship among EF, side of surgery and depressed mood before and 8 months after unilateral FLR was evaluated in 64 patients using validated measures of EF and mood state (Beck Depression Inventory-II). Results indicated that individuals with depressed mood before surgery had greater difficulty on a task of mental flexibility compared to patients without preoperative depressed mood. Further, individuals with depressed mood before surgery had significant increases in perseverative responding and completed fewer categories on a card-sorting task after surgery compared to patients without preoperative depressed mood. Regression analyses showed that among side of surgery, seizure freedom status after surgery and depression status, only pre-surgical depression status explained a significant amount of variance in executive functioning performance after surgery. Results suggest that clinically elevated depressive symptoms before surgery are a risk factor for moderate declines in EF after surgery. Results may be attributable to reduced cognitive reserve in patients with depressive symptoms, or may reflect a common cause attributable to damage to unilateral dorsal and ventral lateral frontal lobe. Copyright © 2012 Elsevier Ltd. All rights reserved.

Association of Anxiety and Depression With Microtubule-Associated Protein 2– and Synaptopodin-Immunolabeled Dendrite and Spine Densities in Hippocampal CA3 of Older Humans

PubMed Central

Soetanto, Ainie; Wilson, Robert S.; Talbot, Konrad; Un, Ashley; Schneider, Julie A.; Sobiesk, Mark; Kelly, Jeremiah; Leurgans, Sue; Bennett, David A.; Arnold, Steven E.

2010-01-01

Context Chronic psychological distress has deleterious effects on many of the body’s physiological systems. In experimental animal models, chronic stress leads to neuroanatomic changes in the hippocampus, in particular a decrease in the length and branching of dendrites as well as a decrease in the number of dendritic spines. Objectives To examine whether analogous distress-related neuroanatomic changes occur in humans and whether such changes might also be related to cognitive dysfunction observed in older people who report greater psychological distress. Design Postmortem study of brain tissues from participants of the Religious Orders Study, an ongoing population-based clinicopathological study of aging and cognition. Setting The Rush University Religious Orders Study and the University of Pennsylvania Cellular and Molecular Neuropathology Program. Participants Seventy-two deceased participants of the Religious Orders Study. Main Outcome Measures Densities of microtubule-associated protein 2–immunolabeled dendrites and synaptopodin-immunolabeled dendritic spines in the CA3 subfield of the hippocampus, quantified using semiautomated image acquisition and analysis. Results Higher levels of trait anxiety and longitudinal depression scores were associated with decreased densities of dendrites and spines in CA3. Dendrite and spine densities did not correlate with an index of global cognition or with densities of common age-related pathological changes. Conclusions Regressive neuronal changes occur in humans who experience greater psychological distress. These changes are analogous to neuronal changes in animal models of chronic stress. PMID:20439826

Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice

PubMed Central

Madathil, Sindhu K.; Carlson, Shaun W.; Brelsfoard, Jennifer M.; Ye, Ping; D’Ercole, A. Joseph; Saatman, Kathryn E.

2013-01-01

Traumatic brain injury (TBI) survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1), a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal) overexpression of IGF-1 using the controlled cortical impact (CCI) injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d) hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI. PMID:23826235

Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice.

PubMed

Madathil, Sindhu K; Carlson, Shaun W; Brelsfoard, Jennifer M; Ye, Ping; D'Ercole, A Joseph; Saatman, Kathryn E

2013-01-01

Traumatic brain injury (TBI) survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1), a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal) overexpression of IGF-1 using the controlled cortical impact (CCI) injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d) hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI.

Cognitive Impairment in Bipolar Disorder: Treatment and Prevention Strategies.

PubMed

Solé, Brisa; Jiménez, Esther; Torrent, Carla; Reinares, Maria; Bonnin, Caterina Del Mar; Torres, Imma; Varo, Cristina; Grande, Iria; Valls, Elia; Salagre, Estela; Sanchez-Moreno, Jose; Martinez-Aran, Anabel; Carvalho, André F; Vieta, Eduard

2017-08-01

Over the last decade, there has been a growing appreciation of the importance of identifying and treating cognitive impairment associated with bipolar disorder, since it persists in remission periods. Evidence indicates that neurocognitive dysfunction may significantly influence patients' psychosocial outcomes. An ever-increasing body of research seeks to achieve a better understanding of potential moderators contributing to cognitive impairment in bipolar disorder in order to develop prevention strategies and effective treatments. This review provides an overview of the available data from studies examining treatments for cognitive dysfunction in bipolar disorder as well as potential novel treatments, from both pharmacological and psychological perspectives. All these data encourage the development of further studies to find effective strategies to prevent and treat cognitive impairment associated with bipolar disorder. These efforts may ultimately lead to an improvement of psychosocial functioning in these patients. © The Author 2017. Published by Oxford University Press on behalf of CINP.

Reduced Physical Fitness in Patients With Heart Failure as a Possible Risk Factor for Impaired Driving Performance

PubMed Central

Alosco, Michael L.; Penn, Marc S.; Spitznagel, Mary Beth; Cleveland, Mary Jo; Ott, Brian R.

2015-01-01

OBJECTIVE. Reduced physical fitness secondary to heart failure (HF) may contribute to poor driving; reduced physical fitness is a known correlate of cognitive impairment and has been associated with decreased independence in driving. No study has examined the associations among physical fitness, cognition, and driving performance in people with HF. METHOD. Eighteen people with HF completed a physical fitness assessment, a cognitive test battery, and a validated driving simulator scenario. RESULTS. Partial correlations showed that poorer physical fitness was correlated with more collisions and stop signs missed and lower scores on a composite score of attention, executive function, and psychomotor speed. Cognitive dysfunction predicted reduced driving simulation performance. CONCLUSION. Reduced physical fitness in participants with HF was associated with worse simulated driving, possibly because of cognitive dysfunction. Larger studies using on-road testing are needed to confirm our findings and identify clinical interventions to maximize safe driving. PMID:26122681

Piracetam improves children's memory after general anaesthesia.

PubMed

Fesenko, Ułbołgan A

2009-01-01

Surgery and anaesthesia may account for postoperative complications including cognitive impairment. The purpose of the study was to assess the influence of general anaesthetics on children's memory and effectiveness of piracetam for prevention of postoperative cognitive dysfunction. The study included patients receiving different kinds of anaesthesia for various surgical procedures, randomly allocated to two groups. According to immediate postoperative treatment, the study group received intravenous piracetam 30 mg kg(-1) and the control group--placebo. The cognitive functions were examined preoperatively and within 10 consecutive postoperative days using the ten-word memory test. The study group consisted of 123 children, the control one--of 127. Declines in memory indexes were observed in all anaesthetized patients. The most injured function was long-term memory. The intravenous administration of piracetam improved this cognitive function. The study results confirm that general anaesthesia affects the memory function in children. Piracetam is effective for prevention of postoperative cognitive dysfunction after anaesthesia.

GABA neuron alterations, cortical circuit dysfunction and cognitive deficits in schizophrenia.

PubMed

Gonzalez-Burgos, Guillermo; Fish, Kenneth N; Lewis, David A

2011-01-01

Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions.

The Link Between Physical Activity and Cognitive Dysfunction in Alzheimer Disease.

PubMed

Phillips, Cristy; Baktir, Mehmet Akif; Das, Devsmita; Lin, Bill; Salehi, Ahmad

2015-07-01

Alzheimer disease (AD) is a primary cause of cognitive dysfunction in the elderly population worldwide. Despite the allocation of enormous amounts of funding and resources to studying this brain disorder, there are no effective pharmacological treatments for reducing the severity of pathology and restoring cognitive function in affected people. Recent reports on the failure of multiple clinical trials for AD have highlighted the need to diversify further the search for new therapeutic strategies for cognitive dysfunction. Thus, studies detailing the neuroprotective effects of physical activity (PA) on the brain in AD were reviewed, and mechanisms by which PA might mitigate AD-related cognitive decline were explored. A MEDLINE database search was used to generate a list of studies conducted between January 2007 and September 2014 (n=394). These studies, along with key references, were screened to identify those that assessed the effects of PA on AD-related biomarkers and cognitive function. The search was not limited on the basis of intensity, frequency, duration, or mode of activity. However, studies in which PA was combined with another intervention (eg, diet, pharmacotherapeutics, ovariectomy, cognitive training, behavioral therapy), and studies not written in English were excluded. Thirty-eight animal and human studies met entry criteria. Most of the studies suggested that PA attenuates neuropathology and positively affects cognitive function in AD. Although the literature lacked sufficient evidence to support precise PA guidelines, convergent evidence does suggest that the incorporation of regular PA into daily routines mitigates AD-related symptoms, especially when deployed earlier in the disease process. Here the protocols used to alter the progression of AD-related neuropathology and cognitive decline are highlighted, and the implications for physical therapist practice are discussed. © 2015 American Physical Therapy Association.

Affective and cognitive reactivity to mood induction in chronic depression.

PubMed

Guhn, Anne; Sterzer, Philipp; Haack, Friderike H; Köhler, Stephan

2018-03-15

Chronic depression (CD) is strongly associated with childhood maltreatment, which has been proposed to lead to inefficient coping styles that are characterized by abnormal affective responsiveness and dysfunctional cognitive attitudes. However, while this notion forms an important basis for psychotherapeutic strategies in the treatment of CD, there is still little direct empirical evidence for a role of altered affective and cognitive reactivity in CD. The present study therefore experimentally investigated affective and cognitive reactivity to two forms of negative mood induction in CD patients versus a healthy control sample (HC). For the general mood induction procedure, a combination of sad pictures and sad music was used, while for individualized mood induction, negative mood was induced by individualized scripts with autobiographical content. Both experiments included n = 15 CD patients versus n = 15 HC, respectively. Interactions between affective or cognitive reactivity and group were analyzed by repeated measurements ANOVAs. General mood induction neither revealed affective nor cognitive reactivity in the patient group while the control group reported the expected decrease of positive affect [interaction (IA) affective reactivity x group: p = .011, cognitive reactivity x group: n.s.]. In contrast, individualized mood induction specifically increased affective reactivity (IA: p = .037) as well as the amount of dysfunctional cognitions in patients versus controls (IA: p = .014). The experiments were not balanced in a crossover design, causal conclusions are thus limited. Additionally, the differences to non-chronic forms of depression are still outstanding. The results suggest that in patients with CD, specific emotional activation through autobiographical memories is a key factor in dysfunctional coping styles. Psychotherapeutic interventions aimed at modifying affective and cognitive reactivity are thus of high relevance in the treatment of CD. Copyright © 2018 Elsevier B.V. All rights reserved.

Rehabilitation needs and participation restriction in patients with cognitive disorder in the chronic phase of traumatic brain injury

PubMed Central

Sashika, Hironobu; Takada, Kaoruko; Kikuchi, Naohisa

2017-01-01

Abstract The purpose of this study was to clarify psychosocial factors/problems, social participation, quality of life (QOL), and rehabilitation needs in chronic-phase traumatic brain injury (TBI) patients with cognitive disorder discharged from the level-1 trauma center (L1-TC), and to inspect the effects of rehabilitation intervention to these subjects. A mixed-method research (cross-sectional and qualitative study) was conducted at an outpatient rehabilitation department. Inclusion criteria of subjects were transfer to the L1-TC due to TBI; acute-stage rehabilitation treatment received in the L1-TC from November 2006 to October 2011; age of ≥18 and <70 years at the time of injury; a score of 0–3 on the Modified Rankin Scale at discharge and that of 4–5 due to physical or severe aggressive behavioral comorbid disorders. Study details were sent, via mail, to 84 suitable candidates, of whom 36 replied. Thirty-one subjects (median age: 33.4 years; male: 17; and average time since injury: 48.1 months), who had consented to study participation, were participated. Cognitive function, social participation, QOL, psychosocial factors/problems, rehabilitation needs, and chronic-phase rehabilitation outcomes were evaluated using the Wechsler Adult Intelligence Scale, Third Edition, the Wechsler Memory Scale-Revised, the Zung Self-Rating Depression Scale, the Sydney Psychosocial Reintegration Scale, Version 2, and the Short Form 36, Version 2, qualitative analysis of semistructured interviews, etc. Participants were classified into achieved-social-participation (n = 11; employed: 8), difficult-social-participation (n = 12; unemployed: 8), and no-cognitive-dysfunction groups (n = 8; no social participation restriction). Relative to the achieved-social-participation group, the difficult-social-participation group showed greater injury and cognitive dysfunction and lower Sydney Psychosocial Reintegration Scale and Short Form 36 role/social component summary scores (64.9/49.1 vs 44.3/30.4, respectively, P < 0.05). Linear regression analysis showed that the social participation status was greatly affected by the later cognitive disorders and psychosocial factors/problems not by the severity of TBI. No changes were observed in these scores following chronic-phase rehabilitation intervention. Chronic-phase TBI with cognitive disorder led to rehabilitation needs, and improvement of subjects’ psychosocial problems and QOL was difficult. PMID:28121947

Rehabilitation needs and participation restriction in patients with cognitive disorder in the chronic phase of traumatic brain injury.

PubMed

Sashika, Hironobu; Takada, Kaoruko; Kikuchi, Naohisa

2017-01-01

The purpose of this study was to clarify psychosocial factors/problems, social participation, quality of life (QOL), and rehabilitation needs in chronic-phase traumatic brain injury (TBI) patients with cognitive disorder discharged from the level-1 trauma center (L1-TC), and to inspect the effects of rehabilitation intervention to these subjects.A mixed-method research (cross-sectional and qualitative study) was conducted at an outpatient rehabilitation department.Inclusion criteria of subjects were transfer to the L1-TC due to TBI; acute-stage rehabilitation treatment received in the L1-TC from November 2006 to October 2011; age of ≥18 and <70 years at the time of injury; a score of 0-3 on the Modified Rankin Scale at discharge and that of 4-5 due to physical or severe aggressive behavioral comorbid disorders. Study details were sent, via mail, to 84 suitable candidates, of whom 36 replied. Thirty-one subjects (median age: 33.4 years; male: 17; and average time since injury: 48.1 months), who had consented to study participation, were participated. Cognitive function, social participation, QOL, psychosocial factors/problems, rehabilitation needs, and chronic-phase rehabilitation outcomes were evaluated using the Wechsler Adult Intelligence Scale, Third Edition, the Wechsler Memory Scale-Revised, the Zung Self-Rating Depression Scale, the Sydney Psychosocial Reintegration Scale, Version 2, and the Short Form 36, Version 2, qualitative analysis of semistructured interviews, etc.Participants were classified into achieved-social-participation (n = 11; employed: 8), difficult-social-participation (n = 12; unemployed: 8), and no-cognitive-dysfunction groups (n = 8; no social participation restriction). Relative to the achieved-social-participation group, the difficult-social-participation group showed greater injury and cognitive dysfunction and lower Sydney Psychosocial Reintegration Scale and Short Form 36 role/social component summary scores (64.9/49.1 vs 44.3/30.4, respectively, P < 0.05). Linear regression analysis showed that the social participation status was greatly affected by the later cognitive disorders and psychosocial factors/problems not by the severity of TBI. No changes were observed in these scores following chronic-phase rehabilitation intervention.Chronic-phase TBI with cognitive disorder led to rehabilitation needs, and improvement of subjects' psychosocial problems and QOL was difficult.

Kant, cognitive psychotherapy, and the hardening of the categories.

PubMed

Nevid, Jeffrey S

2007-12-01

Contemporary models of psychotherapy owe a considerable intellectual debt to philosophy, even though the contributions of philosophers to contemporary practice in the field often go unrecognized. A case in point is Kant's epistemology, which is foundational to cognitive approaches to psychotherapy. Here, it is argued that the rigid use of certain judgments represented in Kant's conceptual scheme underlies patterns of distorted or dysfunctional thinking associated with emotional disorders. Kantian judgments of necessity, disjunction, particularity and universality have counterpoints in contemporary conceptions of cognitive distortions. Moreover, Kantian epistemology has important therapeutic implications with respect to helping people with emotional disorders recognize and challenge rigidly held judgments or categories of understanding. The Kantian perspective also leads us to consider the cognitive frameworks or thought structures that underlie dysfunctional thinking patterns.

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.

Sleep disruption among cancer patients following autologous hematopoietic cell transplantation.

PubMed

Nelson, Ashley M; Jim, Heather S L; Small, Brent J; Nishihori, Taiga; Gonzalez, Brian D; Cessna, Julie M; Hyland, Kelly A; Rumble, Meredith E; Jacobsen, Paul B

2018-03-01

Despite a high prevalence of sleep disruption among hematopoietic cell transplant (HCT) recipients, relatively little research has investigated its relationships with modifiable cognitive or behavioral factors or used actigraphy to characterize sleep disruption in this population. Autologous HCT recipients who were 6-18 months post transplant completed self-report measures of cancer-related distress, fear of cancer recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors upon enrollment. Patients then wore an actigraph for 7 days and completed a self-report measure of sleep disruption on day 7 of the study. Among the 84 participants (age M = 60, 45% female), 41% reported clinically relevant sleep disruption. Examination of actigraph data confirmed that, on average, sleep was disrupted (wake after sleep onset M = 66 min) and sleep efficiency was less than recommended (sleep efficiency M = 78%). Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors were related to self-reported sleep disruption (p values<0.05) but not objective sleep indices. Results suggest that many HCT recipients experience sleep disruption after transplant. Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and maladaptive sleep behaviors are related to self-reported sleep disruption and should be considered targets for cognitive behavioral intervention in this population.

Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa.

PubMed

Imam, Aminu; Ajao, Moyosore Saliu; Amin, Abdulbasit; Abdulmajeed, Wahab Imam; Ibrahim, Abdulmumin; Olajide, Olayemi Joseph; Ajibola, Musa Iyiola; Alli-Oluwafuyi, Abdulmusawir; Balogun, Wasiu Gbolahan

2016-09-01

Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days. The Morris water maze (MWM) paradigm was used to assess the memory index, the elevated plus maze was used for anxiety-like behaviour, and the open field test was used for locomotor activities; thereafter, the rats were sacrificed and their brains were removed for histopathologic studies. Cannabis-like Scopolamine caused memory impairment, delayed latency in the MWM, and anxiety-like behaviour, coupled with alterations in the cerebello-hippocampal neurons. The post-treatment of rats with NSO mitigated cannabis-induced cognitive dysfunction as with scopolamine and impaired anxiety-like behaviour by increasing open arm entry, line crossing, and histological changes. The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis.

Radiation-induced cognitive dysfunction and cerebellar oxidative stress in mice: protective effect of alpha-lipoic acid.

PubMed

Manda, Kailash; Ueno, Megumi; Moritake, Takashi; Anzai, Kazunori

2007-02-12

Reactive oxygen species are implicated in neurodegeneration and cognitive disorders due to higher vulnerability of neuronal tissues. The cerebellum is recently reported to be involved in cognitive function. Therefore, present study aimed at investigating the role alpha-lipoic acid against radiation-induced oxidative stress and antioxidant status in cerebellum and its correlation with cognitive dysfunction. We observed spontaneous motor activities and spatial memory task of mice using pyroelectric infrared sensor and programmed video tracking system, respectively. Whole body X-irradiation (6 Gy) of mice substantially impaired the reference memory and motor activities of mice. However, acute intraperitoneal treatment of mice with alpha-lipoic acid prior to irradiation significantly attenuated such cognitive dysfunction. Alpha-lipoic acid pretreatment exerted a very high magnitude of protection against radiation-induced augmentation of protein carbonyls and thiobarbituric acid reactive substance (TBARS) in mice cerebellum. Further, radiation-induced deficit of total, nonprotein and protein-bound sulfhydryl (T-SH, NP-SH, PB-SH) contents of cerebellum and plasma ferric reducing power (FRAP) was also inhibited by alpha-lipoic acid pre-treatment. Moreover, alpha-lipoic acid treated mice showed an intact cytoarchitecture of cerebellum, higher counts of intact Purkinje cells and granular cells in comparison to untreated irradiated mice. Results clearly indicate that alpha-lipoic acid is potent neuroprotective antioxidant.

Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa

PubMed Central

Imam, Aminu; Ajao, Moyosore Saliu; Amin, Abdulbasit; Abdulmajeed, Wahab Imam; Ibrahim, Abdulmumin; Olajide, Olayemi Joseph; Ajibola, Musa Iyiola; Alli-Oluwafuyi, Abdulmusawir; Balogun, Wasiu Gbolahan

2016-01-01

Background Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. Methods Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days. The Morris water maze (MWM) paradigm was used to assess the memory index, the elevated plus maze was used for anxiety-like behaviour, and the open field test was used for locomotor activities; thereafter, the rats were sacrificed and their brains were removed for histopathologic studies. Results Cannabis-like Scopolamine caused memory impairment, delayed latency in the MWM, and anxiety-like behaviour, coupled with alterations in the cerebello-hippocampal neurons. The post-treatment of rats with NSO mitigated cannabis-induced cognitive dysfunction as with scopolamine and impaired anxiety-like behaviour by increasing open arm entry, line crossing, and histological changes. Conclusions The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis. PMID:27904421

Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players.

PubMed

Montenigro, Philip H; Alosco, Michael L; Martin, Brett M; Daneshvar, Daniel H; Mez, Jesse; Chaisson, Christine E; Nowinski, Christopher J; Au, Rhoda; McKee, Ann C; Cantu, Robert C; McClean, Michael D; Stern, Robert A; Tripodis, Yorghos

2017-01-15

The term "repetitive head impacts" (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), quantitative analysis of this relationship has not yet been examined because of the lack of validated tools to quantify lifetime RHI exposure. The objectives of this study were: 1) to develop a metric to quantify cumulative RHI exposure from football, which we term the "cumulative head impact index" (CHII); 2) to use the CHII to examine the association between RHI exposure and long-term clinical outcomes; and 3) to evaluate its predictive properties relative to other exposure metrics (i.e., duration of play, age of first exposure, concussion history). Participants included 93 former high school and collegiate football players who completed objective cognitive and self-reported behavioral/mood tests as part of a larger ongoing longitudinal study. Using established cutoff scores, we transformed continuous outcomes into dichotomous variables (normal vs. impaired). The CHII was computed for each participant and derived from a combination of self-reported athletic history (i.e., number of seasons, position[s], levels played), and impact frequencies reported in helmet accelerometer studies. A bivariate probit, instrumental variable model revealed a threshold dose-response relationship between the CHII and risk for later-life cognitive impairment (p < 0.0001), self-reported executive dysfunction (p < 0.0001), depression (p < 0.0001), apathy (p = 0.0161), and behavioral dysregulation (p < 0.0001). Ultimately, the CHII demonstrated greater predictive validity than other individual exposure metrics.

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.

Cognitive-behavioural suicide prevention for male prisoners: a pilot randomized controlled trial.

PubMed

Pratt, D; Tarrier, N; Dunn, G; Awenat, Y; Shaw, J; Ulph, F; Gooding, P

2015-12-01

Prisoners have an exceptional risk of suicide. Cognitive-behavioural therapy for suicidal behaviour has been shown to offer considerable potential, but has yet to be formally evaluated within prisons. This study investigated the feasibility of delivering and evaluating a novel, manualized cognitive-behavioural suicide prevention (CBSP) therapy for suicidal male prisoners. A pilot randomized controlled trial of CBSP in addition to treatment as usual (CBSP; n = 31) compared with treatment as usual (TAU; n = 31) alone was conducted in a male prison in England. The primary outcome was self-injurious behaviour occurring within the past 6 months. Secondary outcomes were dimensions of suicidal ideation, psychiatric symptomatology, personality dysfunction and psychological determinants of suicide, including depression and hopelessness. The trial was prospectively registered (number ISRCTN59909209). Relative to TAU, participants receiving CBSP therapy achieved a significantly greater reduction in suicidal behaviours with a moderate treatment effect [Cohen's d = -0.72, 95% confidence interval -1.71 to 0.09; baseline mean TAU: 1.39 (S.D. = 3.28) v. CBSP: 1.06 (S.D. = 2.10), 6 months mean TAU: 1.48 (S.D. = 3.23) v. CBSP: 0.58 (S.D. = 1.52)]. Significant improvements were achieved on measures of psychiatric symptomatology and personality dysfunction. Improvements on psychological determinants of suicide were non-significant. More than half of the participants in the CBSP group achieved a clinically significant recovery by the end of therapy, compared with a quarter of the TAU group. The delivery and evaluation of CBSP therapy within a prison is feasible. CBSP therapy offers significant promise in the prevention of prison suicide and an adequately powered randomized controlled trial is warranted.

Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players

PubMed Central

Montenigro, Philip H.; Alosco, Michael L.; Martin, Brett M.; Daneshvar, Daniel H.; Mez, Jesse; Chaisson, Christine E.; Nowinski, Christopher J.; Au, Rhoda; McKee, Ann C.; Cantu, Robert C.; McClean, Michael D.; Tripodis, Yorghos

2017-01-01

Abstract The term “repetitive head impacts” (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), quantitative analysis of this relationship has not yet been examined because of the lack of validated tools to quantify lifetime RHI exposure. The objectives of this study were: 1) to develop a metric to quantify cumulative RHI exposure from football, which we term the “cumulative head impact index” (CHII); 2) to use the CHII to examine the association between RHI exposure and long-term clinical outcomes; and 3) to evaluate its predictive properties relative to other exposure metrics (i.e., duration of play, age of first exposure, concussion history). Participants included 93 former high school and collegiate football players who completed objective cognitive and self-reported behavioral/mood tests as part of a larger ongoing longitudinal study. Using established cutoff scores, we transformed continuous outcomes into dichotomous variables (normal vs. impaired). The CHII was computed for each participant and derived from a combination of self-reported athletic history (i.e., number of seasons, position[s], levels played), and impact frequencies reported in helmet accelerometer studies. A bivariate probit, instrumental variable model revealed a threshold dose-response relationship between the CHII and risk for later-life cognitive impairment (p < 0.0001), self-reported executive dysfunction (p < 0.0001), depression (p < 0.0001), apathy (p = 0.0161), and behavioral dysregulation (p < 0.0001). Ultimately, the CHII demonstrated greater predictive validity than other individual exposure metrics. PMID:27029716

Role of Oxidative Stress in the Neurocognitive Dysfunction of Obstructive Sleep Apnea Syndrome.

PubMed

Zhou, Li; Chen, Ping; Peng, Yating; Ouyang, Ruoyun

2016-01-01

Obstructive sleep apnea syndrome (OSAS) is characterized by chronic nocturnal intermittent hypoxia and sleep fragmentations. Neurocognitive dysfunction, a significant and extraordinary complication of OSAS, influences patients' career, family, and social life and reduces quality of life to some extent. Previous researches revealed that repetitive hypoxia and reoxygenation caused mitochondria and endoplasmic reticulum dysfunction, overactivated NADPH oxidase, xanthine oxidase, and uncoupling nitric oxide synthase, induced an imbalance between prooxidants and antioxidants, and then got rise to a series of oxidative stress (OS) responses, such as protein oxidation, lipid peroxidation, and DNA oxidation along with inflammatory reaction. OS in brain could trigger neuron injury especially in the hippocampus and cerebral cortex regions. Those two regions are fairly susceptible to hypoxia and oxidative stress production which could consequently result in cognitive dysfunction. Apart from continuous positive airway pressure (CPAP), antioxidant may be a promising therapeutic method to improve partially reversible neurocognitive function. Understanding the role that OS played in the cognitive deficits is crucial for future research and therapeutic strategy development. In this paper, recent important literature concerning the relationship between oxidative stress and cognitive impairment in OSAS will be summarized and the results can provide a rewarding overview for future breakthrough in this field.

White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies

PubMed Central

Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Cui, Chengcheng; Zhang, Li; Li, Qingjiang; Lu, Mei; Zhang, Talan; Liu, Amy; Chen, Jieli

2016-01-01

We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia (VaD) using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p<0.05) cognitive decline that worsens with age starting at 2 weeks, which persists until at least 6 weeks after MMI. RB rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 (AQP-4) expression around blood vessels. MMI induced glymphatic dysfunction with delayed cerebrospinal fluid (CSF) penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases AQP-4 and induces glymphatic dysfunction which may play an important role in MMI induced axonal/WM damage and cognitive deficits. PMID:27940353

White matter damage and glymphatic dysfunction in a model of vascular dementia in rats with no prior vascular pathologies.

PubMed

Venkat, Poornima; Chopp, Michael; Zacharek, Alex; Cui, Chengcheng; Zhang, Li; Li, Qingjiang; Lu, Mei; Zhang, Talan; Liu, Amy; Chen, Jieli

2017-02-01

We investigated cognitive function, axonal/white matter (WM) changes and glymphatic function of vascular dementia using a multiple microinfarction (MMI) model in retired breeder (RB) rats. The MMI model induces significant (p < 0.05) cognitive decline that worsens with age starting at 2 weeks, which persists until at least 6 weeks after MMI. RB rats subjected to MMI exhibit significant axonal/WM damage identified by decreased myelin thickness, oligodendrocyte progenitor cell numbers, axon density, synaptic protein expression in the cortex and striatum, cortical neuronal branching, and dendritic spine density in the cortex and hippocampus compared with age-matched controls. MMI evokes significant dilation of perivascular spaces as well as water channel dysfunction indicated by decreased Aquaporin-4 expression around blood vessels. MMI-induced glymphatic dysfunction with delayed cerebrospinal fluid penetration into the brain parenchyma via paravascular pathways as well as delayed waste clearance from the brain. The MMI model in RB rats decreases Aquaporin-4 and induces glymphatic dysfunction which may play an important role in MMI-induced axonal/WM damage and cognitive deficits. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebrospinal fluid neurofilament tracks fMRI correlates of attention at the first attack of multiple sclerosis.

PubMed

Tortorella, C; Direnzo, V; Taurisano, P; Romano, R; Ruggieri, M; Zoccolella, S; Mastrapasqua, M; Popolizio, T; Blasi, G; Bertolino, A; Trojano, M

2015-04-01

Identifying markers of cognitive dysfunction in multiple sclerosis (MS) is extremely challenging since it means supplying potential biomarkers for neuroprotective therapeutic strategies. The aim of this study is to investigate the relationship between fMRI correlates of attention performance and cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels in patients with clinically isolated syndrome (CIS) suggestive of MS. Twenty-one untreated, cognitively preserved CIS patients underwent BOLD-fMRI while performing the Variable Attentional Control (VAC) task, a cognitive paradigm requiring increasing levels of attentional control processing. CSF NFL was assessed by ELISA technique. SPM8 random-effects models were used for statistical analyses of fMRI data (p<0.05 corrected). Repeated-measures ANOVA on imaging data showed an interaction between attentional control load and NFL levels in the right putamen. At the high level of attentional control demand CIS patients with "low NFL levels" showed greater activity in the putamen compared with subjects with "high NFL levels" (p=0.001). These results are independent of cognitive impairment index. Our findings suggest a relationship between CSF NFL levels and load-dependent failure of putaminal recruitment pattern during sustained attention in CIS and suggest a role of CSF NFL as a marker of subclinical abnormality of cognitive pathway recruitment in CIS. © The Author(s), 2014.

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.

Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility

PubMed Central

Murray, Andrew J.; Woloszynowska-Fraser, Marta U.; Ansel-Bollepalli, Laura; Cole, Katy L. H.; Foggetti, Angelica; Crouch, Barry; Riedel, Gernot; Wulff, Peer

2015-01-01

Dysfunction of parvalbumin (PV)-positive GABAergic interneurons (PVIs) within the prefrontal cortex (PFC) has been implicated in schizophrenia pathology. It is however unclear, how impaired signaling of these neurons may contribute to PFC dysfunction. To identify how PVIs contribute to PFC-dependent behaviors we inactivated PVIs in the PFC in mice using region- and cell-type-selective expression of tetanus toxin light chain (TeLC) and compared the functional consequences of this manipulation with non-cell-type-selective perturbations of the same circuitry. By sampling for behavioral alterations that map onto distinct symptom categories in schizophrenia, we show that dysfunction of PVI signaling in the PFC specifically produces deficits in the cognitive domain, but does not give rise to PFC-dependent correlates of negative or positive symptoms. Our results suggest that distinct aspects of the complex symptomatology of PFC dysfunction in schizophrenia can be attributed to specific prefrontal circuit elements. PMID:26608841

Age-Associated Differences in Cognitive Performance in Older Community Dwelling Schizophrenia Patients: Differential Sensitivity of Clinical Neuropsychological and Experimental Information Processing Tests

PubMed Central

Bowie, Christopher R.; Reichenberg, Abraham; McClure, Margaret M.; Leung, Winnie L.; Harvey, Philip D.

2008-01-01

Cognitive dysfunction is a common feature of schizophrenia and deficits are present before the onset of psychosis, and are moderate to severe by the time of the first episode. Controversy exists over the course of cognitive dysfunction after the first episode. This study examined age-associated differences in performance on clinical neuropsychological (NP) and information processing tasks in a sample of geriatric community living schizophrenia patients (n=172). Compared to healthy control subjects (n=70), people with schizophrenia did not differ on NP tests across age groups but showed evidence for age-associated cognitive worsening on the more complex components of an information-processing test. Age-related changes in cognitive function in schizophrenia may be a function of both the course of illness and the processing demands of the cognitive measure of interest. Tests with fixed difficulty, such as clinical NP tests, may differ in their sensitivity from tests for which parametric difficulty manipulations can be performed. PMID:18053687

Pharmacological cognitive enhancement: treatment of neuropsychiatric disorders and lifestyle use by healthy people.

PubMed

Sahakian, Barbara J; Morein-Zamir, Sharon

2015-04-01

Neuropsychiatric disorders typically manifest as problems with attentional biases, aberrant learning, dysfunctional reward systems, and an absence of top-down cognitive control by the prefrontal cortex. In view of the cost of common mental health disorders, in terms of distress to the individual and family in addition to the financial cost to society and governments, new developments for treatments that address cognitive dysfunction should be a priority so that all members of society can flourish. Cognitive enhancing drugs, such as cholinesterase inhibitors and methylphenidate, are used as treatments for the cognitive symptoms of Alzheimer's disease and attention deficit hyperactivity disorder. However, these drugs and others, including modafinil, are being increasingly used by healthy people for enhancement purposes. Importantly for ethical and safety reasons, the drivers for this increasing lifestyle use of so-called smart drugs by healthy people should be considered and discussions must occur about how to ensure present and future pharmacological cognitive enhancers are used for the benefit of society. Copyright © 2015 Elsevier Ltd. All rights reserved.

Micro-RNAs in cognition and cognitive disorders: Potential for novel biomarkers and therapeutics.

PubMed

Woldemichael, Bisrat T; Mansuy, Isabelle M

2016-03-15

Micro-RNAs (miRNAs) are small regulatory non-coding RNAs involved in the regulation of many biological functions. In the brain, they have distinct expression patterns depending on region, cell-type and developmental stage. Their expression profile is altered by neuronal activation in response to behavioral training or chemical/electrical stimulation. The dynamic changes in miRNA level regulate the expression of genes required for cognitive processes such as learning and memory. In addition, in cognitive dysfunctions such as dementias, expression levels of many miRNAs are perturbed, not only in brain areas affected by the pathology, but also in peripheral body fluids such as serum and cerebrospinal fluid. This presents an opportunity to utilize miRNAs as biomarkers for early detection and assessment of cognitive dysfunctions. Further, since miRNAs target many genes and pathways, they may represent key molecular signatures that can help understand the mechanisms of cognitive disorders and the development of potential therapeutic agents. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive outcome of cerebral fat embolism.

PubMed

Manousakis, Georgios; Han, Dong Y; Backonja, Miroslav

2012-11-01

Cerebral fat embolism is an uncommon but serious complication of long-bone fracture. We report a young adult patient who sustained fat embolism after a femoral fracture. He developed stupor and coma within 24 hours from his injury. His acute recovery was characterized by marked frontal dysfunction. A comprehensive neuropsychological evaluation 4 months later revealed overall normal cognitive function, except for mild residual frontal dysfunction and weakness of verbal memory. Copyright © 2012 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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

Altered caudate connectivity is associated with executive dysfunction after traumatic brain injury

PubMed Central

De Simoni, Sara; Jenkins, Peter O; Bourke, Niall J; Fleminger, Jessica J; Jolly, Amy E; Patel, Maneesh C; Leech, Robert; Sharp, David J

2018-01-01

Abstract Traumatic brain injury often produces executive dysfunction. This characteristic cognitive impairment often causes long-term problems with behaviour and personality. Frontal lobe injuries are associated with executive dysfunction, but it is unclear how these injuries relate to corticostriatal interactions that are known to play an important role in behavioural control. We hypothesized that executive dysfunction after traumatic brain injury would be associated with abnormal corticostriatal interactions, a question that has not previously been investigated. We used structural and functional MRI measures of connectivity to investigate this. Corticostriatal functional connectivity in healthy individuals was initially defined using a data-driven approach. A constrained independent component analysis approach was applied in 100 healthy adult dataset from the Human Connectome Project. Diffusion tractography was also performed to generate white matter tracts. The output of this analysis was used to compare corticostriatal functional connectivity and structural integrity between groups of 42 patients with traumatic brain injury and 21 age-matched controls. Subdivisions of the caudate and putamen had distinct patterns of functional connectivity. Traumatic brain injury patients showed disruption to functional connectivity between the caudate and a distributed set of cortical regions, including the anterior cingulate cortex. Cognitive impairments in the patients were mainly seen in processing speed and executive function, as well as increased levels of apathy and fatigue. Abnormalities of caudate functional connectivity correlated with these cognitive impairments, with reductions in right caudate connectivity associated with increased executive dysfunction, information processing speed and memory impairment. Structural connectivity, measured using diffusion tensor imaging between the caudate and anterior cingulate cortex was impaired and this also correlated with measures of executive dysfunction. We show for the first time that altered subcortical connectivity is associated with large-scale network disruption in traumatic brain injury and that this disruption is related to the cognitive impairments seen in these patients. PMID:29186356

"Boomerang Neuropathology" of Late-Onset Alzheimer's Disease is Shrouded in Harmful "BDDS": Breathing, Diet, Drinking, and Sleep During Aging.

PubMed

Daulatzai, Mak Adam

2015-07-01

Brain damage begins years before substantial neurodegeneration and Alzheimer's dementia. Crucial fundamental activities of life are breathing, eating, drinking, and sleeping. When these pivotal functions are maligned over a prolonged period, they impart escalating dyshomeostasis. The latter may lead to disastrous consequences including cognitive dysfunction and Alzheimer's disease (AD). The current theme here is that multiple pathophysiological derangements are promoted over a prolonged period by the very fundamental activities of life-when "rendered unhealthy." They may converge on several regulating/modulating factors (e.g., mitochondrial energy production, oxidative stress, innate immunity, and vascular function) and promote insidious neuropathology that culminates in cognitive decline in the aged. This is of course associated with the accumulation of amyloid beta and phosphorylated tau in the brain. Epidemiological, biomarker, and neuroimaging studies have provided significant copious evidence on the presence of indolent prodromal AD neuropathology many years prior to symptomatic onset. Progressive oxidative damage to specific gene promoters may result in gene silencing. A mechanistic link may possibly exist between epigenomic state, DNA damage, and chronically unhealthy/dysfunctional body systems. This paper, therefore, addresses and delineates the deleterious pathophysiological impact triggered by dysfunctional breathing, harmful diet, excess of alcohol consumption, and sleep deprivation; indeed, their impact may alter epigenetic state. It is mandatory, therefore, to abrogate cognitive decline and attenuate AD pathology through adoption of a healthy lifestyle, in conjunction with combination therapy with known moderators of cognitive decline. This strategy may thwart multiple concurrent and synergistic pathologies, including epigenetic dysfunction. A multi-factorial therapeutic intervention is required to overcome wide ranging neuropathology and multi-faceted disease process. Such an approach may attenuate neuropathology and ameliorate memory dysfunction.

Risk factors associated with cognitive decline in the elderly with type 2 diabetes: baseline data analysis of the Japanese Elderly Diabetes Intervention Trial.

PubMed

Umegaki, Hiroyuki; Iimuro, Satoshi; Shinozaki, Tomohiro; Araki, Atsushi; Sakurai, Takashi; Iijima, Katsuya; Ohashi, Yasuo; Ito, Hideki

2012-04-01

Recent evidence has shown that type 2 diabetes mellitus (T2DM) in the elderly is a risk factor for cognitive dysfunction or dementia. However, the precise mechanisms have not yet been elucidated. In the current study, we attempted to elucidate the association of clinical indices and diabetic complications at baseline with cognitive declines after 6-year follow up in type 2 diabetic elderly. The subjects were 261 participants who were administered the Mini-Mental State Examination (MMSE) at baseline and after 6 years, at the end of the observation period. The cognitive decline was determined as a 5-point or greater decline in MMSE scores during the observation period. Logistic regression analysis to find the factors associated with cognitive decline, adjusted for age and sex, were carried out, and factors with P-values of less than 0.2 were included in four models of multiple logistic regression analysis. We found that the existence of diabetic nephropathy, higher systolic blood pressure and higher serum triglycerides (or lower high-density lipoprotein cholesterol) at baseline were significantly associated with cognitive declines after 6 years in Japanese elderly diabetics in all four models. The comorbidity of diabetic nephropathy, hypertension and hypertriglyceridemia at baseline were associated with more than 5-point declines in MMSE. Elucidation of the underlying mechanisms of this association is warranted. © 2012 Japan Geriatrics Society.

Surgery results in exaggerated and persistent cognitive decline in a rat model of the Metabolic Syndrome.

PubMed

Feng, Xiaomei; Degos, Vincent; Koch, Lauren G; Britton, Steven L; Zhu, Yinggang; Vacas, Susana; Terrando, Niccolò; Nelson, Jeffrey; Su, Xiao; Maze, Mervyn

2013-05-01

Postoperative cognitive decline can be reproduced in animal models. In a well-validated rat model of the Metabolic Syndrome, we sought to investigate whether surgery induced a more severe and persistent form of cognitive decline similar to that noted in preliminary clinical studies. In rats that had been selectively bred for low and high exercise endurance, the low capacity runners (LCR) exhibited features of Metabolic Syndrome (obesity, dyslipidemia, insulin resistance, and hypertension). Tibial fracture surgery was performed under isoflurane anesthesia in LCR and high capacity runner (HCR) rats and cognitive function was assessed postoperatively in a trace-fear conditioning paradigm and Morris Water Maze; non-operated rats were exposed to anesthesia and analgesia (sham). Group sizes were n = 6. On postoperative D7, LCR rats had shorter freezing times than postoperative HCR rats. Five months postoperatively, LCR rats had a flatter learning trajectory and took longer to locate the submerged platform than postoperative HCR rats; dwell-time in the target quadrant in a probe trial was shorter in the postoperative LCR compared to HCR rats. LCR and HCR sham rats did not differ in any test. Postoperatively, LCR rats diverged from HCR rats exhibiting a greater decline in memory, acutely, with persistent learning and memory decline, remotely; this could not be attributed to changes in locomotor or swimming performance. This Metabolic Syndrome animal model of surgery-induced cognitive decline corroborates, with high fidelity, preliminary findings of postoperative cognitive dysfunction in Metabolic Syndrome patients.

Frontal dysfunctions of impulse control - a systematic review in borderline personality disorder and attention-deficit/hyperactivity disorder.

PubMed

Sebastian, Alexandra; Jung, Patrick; Krause-Utz, Annegret; Lieb, Klaus; Schmahl, Christian; Tüscher, Oliver

2014-01-01

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders.

Does improvement of cognitive functioning by cognitive remediation therapy effect work outcomes in severe mental illness? A secondary analysis of a randomized controlled trial.

PubMed

Ikebuchi, Emi; Sato, Sayaka; Yamaguchi, Sosei; Shimodaira, Michiyo; Taneda, Ayano; Hatsuse, Norifumi; Watanabe, Yukako; Sakata, Masuhiro; Satake, Naoko; Nishio, Masaaki; Ito, Jun-Ichiro

2017-05-01

The aim of this study was to clarify whether improvement of cognitive functioning by cognitive remediation therapy can improve work outcome in schizophrenia and other severe mental illnesses when combined with supported employment. The subjects of this study were persons with severe mental illness diagnosed with schizophrenia, major depression, or bipolar disorder (ICD-10) and cognitive dysfunction who participated in both cognitive remediation using the Thinking Skills for Work program and a supported employment program in a multisite, randomized controlled study. Logistic and multiple linear regression analyses were performed to clarify the influence of cognitive functioning on vocational outcomes, adjusting for demographic and clinical variables. Improvement of cognitive functioning with cognitive remediation significantly contributed to the total days employed and total earnings of competitive employment in supported employment service during the study period. Any baseline demographic and clinical variables did not significantly contribute to the work-related outcomes. A cognitive remediation program transferring learning skills into the real world is useful to increase the quality of working life in supported employment services for persons with severe mental illness and cognitive dysfunction who want to work competitively. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Cognitive Communication Impairments: A Family-Focused Viewpoint.

ERIC Educational Resources Information Center

DePompei, Roberta; And Others

1988-01-01

An active role is recommended for family members involved in rehabilitation of cognitive communicative impairments of head-injured individuals. The paper discusses family systems theory, dysfunctional family reactions to the cognitive communicative behaviors of the head-injured member, and methods of assisting the family to develop the…

Role of fruits, nuts, and vegetables in maintaining cognitive health

USDA-ARS?s Scientific Manuscript database

Population aging is leading to an increase in the incidence of age-related cognitive dysfunction and, with it, the health care burden of caring for older adults. Epidemiological studies have shown that consumption of fruits, nuts, and vegetables is positively associated with cognitive ability; howev...

Cognitive impairment as measured by the THINC-integrated tool (THINC-it): The association with self-reported anxiety in Major Depressive Disorder.

PubMed

Cha, Danielle S; Carmona, Nicole E; Rodrigues, Nelson B; Mansur, Rodrigo B; Lee, Yena; Subramaniapillai, Mehala; Phan, Lee; Cha, Rebekah H; Pan, Zihang; Lee, Jae Hon; Lee, JungGoo; Almatham, Fahad; Alageel, Asem; Rosenblat, Joshua D; Shekotikhina, Margarita; Rong, Carola; Harrison, John; McIntyre, Roger S

2018-06-01

This study evaluated the association between self-reported anxiety and objective/subjective measures of cognitive performance in adults with Major Depressive Disorder (MDD). Acutely depressed subjects with recurrent MDD (n = 100) and age-, sex-, and education-matched healthy controls (HC; n = 100) between the ages of 18 and 65 completed the cross-sectional validation study of the THINC-integrated tool (THINC-it; ClinicalTrials.gov: NCT02508493). Objective cognitive performance was assessed using the THINC-it, and subjective cognitive impairment with the Perceived Deficits Questionnaire for Depression-5-item. Subjects also completed the Generalized Anxiety Disorder-7-item (GAD-7) questionnaire. Subjects with MDD reported significantly more anxiety symptoms, as assessed by the GAD-7, compared to HC (p < 0.001). Linear regression analysis determined that anxiety symptoms significantly accounted for 70.4% of the variability in subjective cognitive impairment, adjusting for depression severity. Moreover, subjects' ratings of the difficulties caused by their anxiety were reported as significantly more severe among subjects with MDD when compared to HC (p < 0.001). Likewise, greater self-reported difficulties with anxiety significantly predicted 57.8% of the variability in subjective cognitive impairment, adjusting for depression severity. Neither anxiety symptoms nor impairment due to anxiety symptoms predicted objective cognitive performance. Subjects were not prospectively verified to have a clinical diagnosis of GAD. Rather, this study examined the relationships between symptoms of generalized anxiety, assessed using a brief screening tool, and subjective and objective cognitive function. Results from the current study indicate that adults with MDD and high levels of self-reported anxiety are significantly more likely to report experiencing subjective cognitive dysfunction. Copyright © 2018 Elsevier B.V. All rights reserved.

Development and validation of 26-item dysfunctional attitude scale.

PubMed

Ebrahimi, Amrollah; Samouei, Rahele; Mousavii, Sayyed Ghafour; Bornamanesh, Ali Reza

2013-06-01

Dysfunctional Attitude Scale is one of the most common instruments used to assess cognitive vulnerability. This study aimed to develop and validate a short form of Dysfunctional Attitude Scale appropriate for an Iranian clinical population. Participants were 160 psychiatric patients from medical centers affiliated with Isfahan Medical University, as well as 160 non-patients. Research instruments were clinical interviews based on the Diagnostic and Statistical Manual-IV-TR, Dysfunctional Attitude Scale and General Heath Questionnaire (GHQ-28). Data was analyzed using multicorrelation calculations and factor analysis. Based on the results of factor analysis and item-total correlation, 14 items were judged candidates for omission. Analysis of the 26-item Dysfunctional Attitude Scale (DAS-26) revealed a Cronbach's alpha of 0.92. Evidence for the concurrent criterion validity was obtained through calculating the correlation between the Dysfunctional Attitude Scale and psychiatric diagnosis (r = 0.55), GHQ -28 (r = 0.56) and somatization, anxiety, social dysfunction, and depression subscales (0.45,0.53,0.48, and 0.57, respectively). Factor analysis deemed a four-factor structure the best. The factors were labeled as success-perfectionism, need for approval, need for satisfying others, and vulnerability-performance evaluation. The results showed that the Iranian version of the Dysfunctional Attitude Scale (DAS-26) bears satisfactory psychometric properties suggesting that this cognitive instrument is appropriate for use in an Iranian cultural context. Copyright © 2012 Wiley Publishing Asia Pty Ltd.

Basal ganglia and beyond: The interplay between motor and cognitive aspects in Parkinson's disease rehabilitation.

PubMed

Ferrazzoli, Davide; Ortelli, Paola; Madeo, Graziella; Giladi, Nir; Petzinger, Giselle M; Frazzitta, Giuseppe

2018-07-01

Parkinson's disease (PD) is characterized by motor and cognitive dysfunctions, affecting the motor behaviour. We summarize evidence that the interplay between motor and cognitive approaches is crucial in PD rehabilitation. Rehabilitation is complementary to pharmacological therapy and effective in reducing the PD disturbances, probably acting by inducing neuroplastic effects. The motor behaviour results from a complex integration between cortical and subcortical areas, underlying the motor, cognitive and motivational aspects of movement. The close interplay amongst these areas makes possible to learn, control and express habitual-automatic actions, which are dysfunctional in PD. The physiopathology of PD could be considered the base for the development of effective rehabilitation treatments. As the volitional action control is spared in early-medium stages of disease, rehabilitative approaches engaging cognition permit to achieve motor benefits and appear to be the most effective for PD. We will point out data supporting the relevance of targeting both motor and cognitive aspects in PD rehabilitation. Finally, we will discuss the role of cognitive engagement in motor rehabilitation for PD. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Prevalence of Cognitive Impairment and Association With Survival Among Older Patients With Hematologic Cancers.

PubMed

Hshieh, Tammy T; Jung, Wooram F; Grande, Laura J; Chen, Jiaying; Stone, Richard M; Soiffer, Robert J; Driver, Jane A; Abel, Gregory A

2018-05-01

As the population ages, cognitive impairment has promised to become increasingly common among patients with cancer. Little is known about how specific domains of cognitive impairment may be associated with survival among older patients with hematologic cancers. To determine the prevalence of domain-specific cognitive impairment and its association with overall survival among older patients with blood cancer. This prospective observational cohort study included all patients 75 years and older who presented for initial consultation in the leukemia, myeloma, or lymphoma clinics of a large tertiary hospital in Boston, Massachusetts, from February 1, 2015, to March 31, 2017. Patients underwent screening for frailty and cognitive dysfunction and were followed up for survival. The Clock-in-the-Box (CIB) test was used to screen for executive dysfunction. A 5-word delayed recall test was used to screen for impairment in working memory. The Fried frailty phenotype and Rockwood cumulative deficit model of frailty were also assessed to characterize participants as robust, prefrail, or frail. Among 420 consecutive patients approached, 360 (85.7%) agreed to undergo frailty assessment (232 men [64.4%] and 128 women [35.6%]; mean [SD] age, 79.8 [3.9] years), and 341 of those (94.7%) completed both cognitive screening tests. One hundred twenty-seven patients (35.3%) had probable executive dysfunction on the CIB, and 62 (17.2%) had probable impairment in working memory on the 5-word delayed recall. Impairment in either domain was modestly correlated with the Fried frailty phenotype (CIB, ρ = 0.177; delayed recall, ρ = 0.170; P = .01 for both), and many phenotypically robust patients also had probable cognitive impairment (24 of 104 [23.1%] on CIB and 9 of 104 [8.7%] on delayed recall). Patients with impaired working memory had worse median survival (10.9 [SD, 12.9] vs 12.2 [SD, 14.7] months; log-rank P < .001), including when stratified by indolent cancer (log-rank P = .01) and aggressive cancer (P < .001) and in multivariate analysis when adjusting for age, comorbidities, and disease aggressiveness (odds ratio, 0.26; 95% CI, 0.13-0.50). Impaired working memory was also associated with worse survival for those undergoing intensive treatment (log-rank P < .001). Executive dysfunction was associated with worse survival only among patients who underwent intensive treatment (log-rank P = .03). These data suggest that domains of cognitive dysfunction may be prevalent in older patients with blood cancer and may have differential predictive value for survival. Targeted interventions are needed for this vulnerable patient population.

The Outward Spiral: A vicious cycle model of obesity and cognitive dysfunction.

PubMed

Hargrave, Sara L; Jones, Sabrina; Davidson, Terry L

2016-06-01

Chronic failure to suppress intake during states of positive energy balance leads to weight gain and obesity. The ability to use context - including interoceptive satiety states - to inhibit responding to previously rewarded cues appears to depend on the functional integrity of the hippocampus. Recent evidence implicates energy dense Western diets in several types of hippocampal dysfunction, including reduced expression of neurotrophins and nutrient transporters, increased inflammation, microglial activation, and blood brain barrier permeability. The functional consequences of such insults include impairments in an animal's ability to modulate responding to a previously reinforced cues. We propose that such deficits promote overeating, which can further exacerbate hippocampal dysfunction and thus initiate a vicious cycle of both obesity and progressive cognitive decline.

Child, parent and family dysfunction as predictors of outcome in cognitive-behavioral treatment of antisocial children.

PubMed

Kazdin, A E

1995-03-01

The present study examined factors that predicted favorable treatment outcomes among clinically referred conduct problem children (N = 105, ages 7-13) who received cognitive-behavioral treatment. Three domains (severity and breadth of child impairment, parent stress and psychopathology and family dysfunction) assessed at pretreatment were predicted to affect treatment outcome. The results only partially supported the prediction. Less dysfunction in each of the domains predicted who responded favorably to treatment on parent ratings of deviance and prosocial functioning but not on teacher ratings of these outcomes. The findings have implications for identifying youths who respond to available treatments. The results also underscore fundamental questions about the assessment of treatment effects and the criteria for evaluating outcome.

[Higher Brain Dysfunction in Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS)].

PubMed

Ichikawa, Hiroo

2016-02-01

Stroke-like episodes are one of the cardinal features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), and occur in 84-99% of the patients. The affected areas detected on neuroimaging do not have classical vascular distribution, and involve predominantly the temporal, parietal and occipital lobes. Thus, the neurological symptoms including higher brain dysfunction correlate with this topographical distribution. In association with the occipital lobe involvement, the most frequent symptom is cortical blindness. Other symptoms have been occasionally reported in case reports: visual agnosia, prosopagnosia, cortical deafness, auditory agnosia, topographical disorientation, various types of aphasia, hemispatial neglect, and so on. On the other hand, cognitive decline associated with more diffuse brain impairment rather than with focal stroke-like lesions has been postulated. This condition is also known as mitochondrial dementia. Domains of cognitive dysfunction include abstract reasoning, verbal memory, visual memory, language (naming and fluency), executive or constructive functions, attention, and visuospatial function. Cognitive functions and intellectual abilities may decline from initially minimal cognitive impairment to dementia. To date, the neuropsychological and neurologic impairment has been reported to be associated with cerebral lactic acidosis as estimated by ventricular spectroscopic lactate levels.

Perceptual Anomalies in Schizophrenia: Integrating Phenomenology and Cognitive Neuroscience

PubMed Central

Uhlhaas, Peter J.; Mishara, Aaron L.

2007-01-01

From phenomenological and experimental perspectives, research in schizophrenia has emphasized deficits in “higher” cognitive functions, including attention, executive function, as well as memory. In contrast, general consensus has viewed dysfunctions in basic perceptual processes to be relatively unimportant in the explanation of more complex aspects of the disorder, including changes in self-experience and the development of symptoms such as delusions. We present evidence from phenomenology and cognitive neuroscience that changes in the perceptual field in schizophrenia may represent a core impairment. After introducing the phenomenological approach to perception (Husserl, the Gestalt School), we discuss the views of Paul Matussek, Klaus Conrad, Ludwig Binswanger, and Wolfgang Blankenburg on perception in schizophrenia. These 4 psychiatrists describe changes in perception and automatic processes that are related to the altered experience of self. The altered self-experience, in turn, may be responsible for the emergence of delusions. The phenomenological data are compatible with current research that conceptualizes dysfunctions in perceptual processing as a deficit in the ability to combine stimulus elements into coherent object representations. Relationships of deficits in perceptual organization to cognitive and social dysfunction as well as the possible neurobiological mechanisms are discussed. PMID:17118973

Social cognition and self-other distinctions in neuropsychiatry: Insights from schizophrenia and Tourette syndrome.

PubMed

Eddy, Clare M

2018-03-02

Impairments in social cognition may reflect dysfunction of disorder specific or disorder general mechanisms. Although cross-disorder comparison may prove insightful, few studies have compared social cognition in different neuropsychiatric disorders. Parallel investigation of schizophrenia and Tourette syndrome (TS) is encouraged by similarities including the presence of problematic social behavior, echophenomena, emotional dysregulation and dopamine dysfunction. Focusing on tests of social cognition administered in both disorders, this review aims to summarize behavioral, neurophysiological and neuroimaging findings, before exploring how these may contribute to clinical symptoms. Studies investigating social cognition (imitation, emotion recognition, and understanding of beliefs or intentions) in patients with schizophrenia or TS were identified through Web of Science and PubMed searches. Although findings indicate that social cognitive deficits are more apparent in schizophrenia, adults with TS can exhibit similar task performance to patients with paranoia. In both disorders, behavioral and neuroimaging findings raise the possibility of increased internal simulation of others' actions and emotions, in combination with a relative under-application of mentalizing. More specifically, dysfunction in neurobiological substrates such as temporo-parietal junction and inferior frontal gyrus may underlie problems with self-other distinctions in both schizophrenia and TS. Difficulties in distinguishing between actions and mental states linked to the self and other may contribute to a range of psychiatric symptoms, including emotional dysregulation, paranoia, social anhedonia and socially disruptive urges. Comparing different patient populations could therefore reveal common neuro-cognitive risk factors for the development of problematic social behaviors, in addition to markers of resilience, coping strategies and potential neuro-compensation mechanisms. Copyright © 2017 Elsevier Inc. All rights reserved.

Elevated Cystatin C Levels Are Associated with Cognitive Impairment and Progression of Parkinson Disease.

PubMed

Hu, Wei-Dong; Chen, Jing; Mao, Cheng-Jie; Feng, Ping; Yang, Ya-Ping; Luo, Wei-Feng; Liu, Chun-Feng

2016-09-01

We investigated the relationship between serum cystatin C (CysC) levels and cognitive dysfunction and disease progression in patients with Parkinson disease. Previous studies have reported altered CysC levels in neurodegenerative disorders, but only a few studies have explored the role of CysC and its relationship to cognitive dysfunction in Parkinson disease. We measured serum levels of CysC, creatinine, urea, and uric acid in 142 patients with Parkinson disease and 146 healthy controls. We assessed disease progression using the Hoehn and Yahr scale, and cognitive function using the Montreal Cognitive Assessment (Beijing version). The patients with Parkinson disease had significantly higher CysC levels than the controls (P<0.001). CysC level correlated significantly with age (r=0.494, P<0.001), sex (r=0.150, P=0.011), and serum creatinine level (r=0.377, P<0.001), but not with levels of urea or uric acid (P>0.05). CysC level was a significant independent predictor of Parkinson disease (odds ratio=23.143, 95% confidence interval: 5.485-97.648, P<0.001) in multivariate logistic regression analysis. In the Parkinson disease group, a higher CysC level was associated with a more advanced Hoehn and Yahr stage (r=0.098, P<0.05) and a lower Montreal Cognitive Assessment score (r=-0.381, P=0.003). Serum CysC levels can predict disease severity and cognitive dysfunction in patients with Parkinson disease. The exact role of CysC remains to be determined.

Adenosine Kinase Inhibition Protects against Cranial Radiation-Induced Cognitive Dysfunction

PubMed Central

Acharya, Munjal M.; Baulch, Janet E.; Lusardi, Theresa A.; Allen, Barrett. D.; Chmielewski, Nicole N.; Baddour, Al Anoud D.; Limoli, Charles L.; Boison, Detlev

2016-01-01

Clinical radiation therapy for the treatment of CNS cancers leads to unintended and debilitating impairments in cognition. Radiation-induced cognitive dysfunction is long lasting; however, the underlying molecular and cellular mechanisms are still not well established. Since ionizing radiation causes microglial and astroglial activation, we hypothesized that maladaptive changes in astrocyte function might be implicated in radiation-induced cognitive dysfunction. Among other gliotransmitters, astrocytes control the availability of adenosine, an endogenous neuroprotectant and modulator of cognition, via metabolic clearance through adenosine kinase (ADK). Adult rats exposed to cranial irradiation (10 Gy) showed significant declines in performance of hippocampal-dependent cognitive function tasks [novel place recognition, novel object recognition (NOR), and contextual fear conditioning (FC)] 1 month after exposure to ionizing radiation using a clinically relevant regimen. Irradiated rats spent less time exploring a novel place or object. Cranial irradiation also led to reduction in freezing behavior compared to controls in the FC task. Importantly, immunohistochemical analyses of irradiated brains showed significant elevation of ADK immunoreactivity in the hippocampus that was related to astrogliosis and increased expression of glial fibrillary acidic protein (GFAP). Conversely, rats treated with the ADK inhibitor 5-iodotubercidin (5-ITU, 3.1 mg/kg, i.p., for 6 days) prior to cranial irradiation showed significantly improved behavioral performance in all cognitive tasks 1 month post exposure. Treatment with 5-ITU attenuated radiation-induced astrogliosis and elevated ADK immunoreactivity in the hippocampus. These results confirm an astrocyte-mediated mechanism where preservation of extracellular adenosine can exert neuroprotection against radiation-induced pathology. These innovative findings link radiation-induced changes in cognition and CNS functionality to altered purine metabolism and astrogliosis, thereby linking the importance of adenosine homeostasis in the brain to radiation injury. PMID:27375429

Mood and Memory Deficits in a Model of Gulf War Illness Are Linked with Reduced Neurogenesis, Partial Neuron Loss, and Mild Inflammation in the Hippocampus

PubMed Central

Parihar, Vipan K; Hattiangady, Bharathi; Shuai, Bing; Shetty, Ashok K

2013-01-01

Impairments in mood and cognitive function are the key brain abnormalities observed in Gulf war illness (GWI), a chronic multisymptom health problem afflicting ∼25% of veterans who served in the Persian Gulf War-1. Although the precise cause of GWI is still unknown, combined exposure to a nerve gas prophylaxis drug pyridostigmine bromide (PB) and pesticides DEET and permethrin during the war has been proposed as one of the foremost causes of GWI. We investigated the effect of 4 weeks of exposure to Gulf war illness-related (GWIR) chemicals in the absence or presence of mild stress on mood and cognitive function, dentate gyrus neurogenesis, and neurons, microglia, and astrocytes in the hippocampus. Combined exposure to low doses of GWIR chemicals PB, DEET, and permethrin induced depressive- and anxiety-like behavior and spatial learning and memory dysfunction. Application of mild stress in the period of exposure to chemicals exacerbated the extent of mood and cognitive dysfunction. Furthermore, these behavioral impairments were associated with reduced hippocampal volume and multiple cellular alterations such as chronic reductions in neural stem cell activity and neurogenesis, partial loss of principal neurons, and mild inflammation comprising sporadic occurrence of activated microglia and significant hypertrophy of astrocytes. The results show the first evidence of an association between mood and cognitive dysfunction and hippocampal pathology epitomized by decreased neurogenesis, partial loss of principal neurons, and mild inflammation in a model of GWI. Hence, treatment strategies that are efficacious for enhancing neurogenesis and suppressing inflammation may be helpful for alleviation of mood and cognitive dysfunction observed in GWI. PMID:23807240

Amyloid-β Homeostasis Bridges Inflammation, Synaptic Plasticity Deficits and Cognitive Dysfunction in Multiple Sclerosis

PubMed Central

Stampanoni Bassi, Mario; Garofalo, Sara; Marfia, Girolama A.; Gilio, Luana; Simonelli, Ilaria; Finardi, Annamaria; Furlan, Roberto; Sancesario, Giulia M.; Di Giandomenico, Jonny; Storto, Marianna; Mori, Francesco; Centonze, Diego; Iezzi, Ennio

2017-01-01

Cognitive deficits are frequently observed in multiple sclerosis (MS), mainly involving processing speed and episodic memory. Both demyelination and gray matter atrophy can contribute to cognitive deficits in MS. In recent years, neuroinflammation is emerging as a new factor influencing clinical course in MS. Inflammatory cytokines induce synaptic dysfunction in MS. Synaptic plasticity occurring within hippocampal structures is considered as one of the basic physiological mechanisms of learning and memory. In experimental models of MS, hippocampal plasticity is profoundly altered by proinflammatory cytokines. Although mechanisms of inflammation-induced hippocampal pathology in MS are not completely understood, alteration of Amyloid-β (Aβ) metabolism is emerging as a key factor linking together inflammation, synaptic plasticity and neurodegeneration in different neurological diseases. We explored the correlation between concentrations of Aβ1–42 and the levels of some proinflammatory and anti-inflammatory cytokines (interleukin-1β (IL-1β), IL1-ra, IL-8, IL-10, IL-12, tumor necrosis factor α (TNFα), interferon γ (IFNγ)) in the cerebrospinal fluid (CSF) of 103 remitting MS patients. CSF levels of Aβ1–42 were negatively correlated with the proinflammatory cytokine IL-8 and positively correlated with the anti-inflammatory molecules IL-10 and interleukin-1 receptor antagonist (IL-1ra). Other correlations, although noticeable, were either borderline or not significant. Our data show that an imbalance between proinflammatory and anti-inflammatory cytokines may lead to altered Aβ homeostasis, representing a key factor linking together inflammation, synaptic plasticity and cognitive dysfunction in MS. This could be relevant to identify novel therapeutic approaches to hinder the progression of cognitive dysfunction in MS. PMID:29209169

Exploring neural dysfunction in 'clinical high risk' for psychosis: a quantitative review of fMRI studies.

PubMed

Dutt, Anirban; Tseng, Huai-Hsuan; Fonville, Leon; Drakesmith, Mark; Su, Liang; Evans, John; Zammit, Stanley; Jones, Derek; Lewis, Glyn; David, Anthony S

2015-02-01

Individuals at clinical high risk (CHR) of developing psychosis present with widespread functional abnormalities in the brain. Cognitive deficits, including working memory (WM) problems, as commonly elicited by n-back tasks, are observed in CHR individuals. However, functional MRI (fMRI) studies, comprising a heterogeneous cluster of general and social cognition paradigms, have not necessarily demonstrated consistent and conclusive results in this population. Hence, a comprehensive review of fMRI studies, spanning almost one decade, was carried out to observe for general trends with respect to brain regions and cognitive systems most likely to be dysfunctional in CHR individuals. 32 studies were included for this review, out of which 22 met the criteria for quantitative analysis using activation likelihood estimation (ALE). Task related contrast activations were firstly analysed by comparing CHR and healthy control participants in the total pooled sample, followed by a comparison of general cognitive function studies (excluding social cognition paradigms), and finally by only looking at n-back working memory task based studies. Findings from the ALE implicated four key dysfunctional and distinct neural regions in the CHR group, namely the right inferior parietal lobule (rIPL), the left medial frontal gyrus (lmFG), the left superior temporal gyrus (lSTG) and the right fronto-polar cortex (rFPC) of the superior frontal gyrus (SFG). Narrowing down to relatively few significant dysfunctional neural regions is a step forward in reducing the apparent ambiguity of overall findings, which would help to target specific neural regions and pathways of interest for future research in CHR populations. Copyright © 2014. Published by Elsevier Ltd.

Heavy metals (Pb, Cd, As and MeHg) as risk factors for cognitive dysfunction: A general review of metal mixture mechanism in brain.

PubMed

Karri, Venkatanaidu; Schuhmacher, Marta; Kumar, Vikas

2016-12-01

Human exposure to toxic heavy metals is a global challenge. Concurrent exposure of heavy metals, such as lead (Pb), cadmium (Cd), arsenic (As) and methylmercury (MeHg) are particularly important due to their long lasting effects on the brain. The exact toxicological mechanisms invoked by exposure to mixtures of the metals Pb, Cd, As and MeHg are still unclear, however they share many common pathways for causing cognitive dysfunction. The combination of metals may produce additive/synergetic effects due to their common binding affinity with NMDA receptor (Pb, As, MeHg), Na + - K + ATP-ase pump (Cd, MeHg), biological Ca +2 (Pb, Cd, MeHg), Glu neurotransmitter (Pb, MeHg), which can lead to imbalance between the pro-oxidant elements (ROS) and the antioxidants (reducing elements). In this process, ROS dominates the antioxidants factors such as GPx, GS, GSH, MT-III, Catalase, SOD, BDNF, and CERB, and finally leads to cognitive dysfunction. The present review illustrates an account of the current knowledge about the individual metal induced cognitive dysfunction mechanisms and analyse common Mode of Actions (MOAs) of quaternary metal mixture (Pb, Cd, As, MeHg). This review aims to help advancement in mixture toxicology and development of next generation predictive model (such as PBPK/PD) combining both kinetic and dynamic interactions of metals. Copyright © 2016 Elsevier B.V. All rights reserved.

Oculomotor evidence for neocortical systems but not cerebellar dysfunction in autism

PubMed Central

Minshew, Nancy J.; Luna, Beatriz; Sweeney, John A.

2010-01-01

Objective To investigate the functional integrity of cerebellar and frontal system in autism using oculomotor paradigms. Background Cerebellar and neocortical systems models of autism have been proposed. Courchesne and colleagues have argued that cognitive deficits such as shifting attention disturbances result from dysfunction of vermal lobules VI and VII. Such a vermal deficit should be associated with dysmetric saccadic eye movements because of the major role these areas play in guiding the motor precision of saccades. In contrast, neocortical models of autism predict intact saccade metrics, but impairments on tasks requiring the higher cognitive control of saccades. Methods A total of 26 rigorously diagnosed nonmentally retarded autistic subjects and 26 matched healthy control subjects were assessed with a visually guided saccade task and two volitional saccade tasks, the oculomotor delayed-response task and the antisaccade task. Results Metrics and dynamic of the visually guided saccades were normal in autistic subjects, documenting the absence of disturbances in cerebellar vermal lobules VI and VII and in automatic shifts of visual attention. Deficits were demonstrated on both volitional saccade tasks, indicating dysfunction in the circuitry of prefrontal cortex and its connections with the parietal cortex, and associated cognitive impairments in spatial working memory and in the ability to voluntarily suppress context-inappropriate responses. Conclusions These findings demonstrate intrinsic neocortical, not cerebellar, dysfunction in autism, and parallel deficits in higher order cognitive mechanisms and not in elementary attentional and sensorimotor systems in autism. PMID:10102406

Innovative solutions to novel drug development in mental health

PubMed Central

Insel, T.R.; Voon, V.; Nye, J.S.; Brown, V.J.; Altevogt, B.M.; Bullmore, E.T.; Goodwin, G.M.; Howard, R.J.; Kupfer, D.J.; Malloch, G.; Marston, H.M.; Nutt, D.J.; Robbins, T.W.; Stahl, S.M.; Tricklebank, M.D.; Williams, J.H.; Sahakian, B.J.

2013-01-01

There are many new advances in neuroscience and mental health which should lead to a greater understanding of the neurobiological dysfunction in neuropsychiatric disorders and new developments for early, effective treatments. To do this, a biomarker approach combining genetic, neuroimaging, cognitive and other biological measures is needed. The aim of this article is to highlight novel approaches for pharmacological and non-pharmacological treatment development. This article suggests approaches that can be taken in the future including novel mechanisms with preliminary clinical validation to provide a toolbox for mechanistic studies and also examples of translation and back-translation. The review also emphasizes the need for clinician-scientists to be trained in a novel way in order to equip them with the conceptual and experimental techniques required, and emphasizes the need for private-public partnership and pre-competitive knowledge exchange. This should lead the way for important new holistic treatment developments to improve cognition, functional outcome and well-being of people with neuropsychiatric disorders. PMID:23563062

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.

Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats.

PubMed

Silveira, Mason M; Adams, Wendy K; Morena, Maria; Hill, Matthew N; Winstanley, Catharine A

2017-03-01

Acceptance of cannabis use is growing. However, prolonged use is associated with diminished psychosocial outcomes, potentially mediated by drug-induced cognitive impairments. Δ 9 -Tetrahydrocannabinol (THC) is the main psychoactive ingredient in cannabis, yet other phytocannabinoids in the plant, such as cannabidiol (CBD), have unique properties. Given that CBD can modulate the undesirable effects of THC, therapeutic agents, such as nabiximols, contain higher CBD:THC ratios than illicit marijuana. We tested the hypothesis that THC impairs a relevant cognitive function for long-term success, namely willingness to exert cognitive effort for greater rewards, and that CBD could attenuate such decision-making impairments. Male Long-Evans rats ( n = 29) performing the rat cognitive effort task (rCET) received acute THC and CBD, independently and concurrently, in addition to other cannabinoids. Rats chose between 2 options differing in reward magnitude, but also in the cognitive effort (attentional load) required to obtain them. We found that THC decreased choice of hard trials without impairing the animals' ability to accurately complete them. Strikingly, this impairment was correlated with CB1 receptor density in the medial prefrontal cortex - an area previously implicated in effortful decision-making. In contrast, CBD did not affect choice. Coadministration of 1:1 CBD:THC matching that in nabiximols modestly attenuated the deleterious effects of THC in "slacker" rats. Only male rats were investigated, and the THC/CBD coadministration experiment was carried out in a subset of individuals. These findings confirm that THC, but not CBD, selectively impairs decision-making involving cognitive effort costs. However, coadministration of CBD only partially ameliorates such THC-induced dysfunction.

The effects of sleep dysfunction on cognition, affect, and quality of life in individuals with cerebellar ataxia.

PubMed

Sonni, Akshata; Kurdziel, Lauri B F; Baran, Bengi; Spencer, Rebecca M C

2014-05-15

Cerebellar ataxia comprises a group of debilitating diseases that are the result of progressive cerebellar degeneration. Recent studies suggest that, like other neurodegenerative diseases, sleep impairments are common in cerebellar ataxia. In light of the role of sleep in mood regulation and cognition, we sought to assess interactions between sleep, cognition, and affect in individuals with cerebellar ataxia. A survey of 176 individuals with cerebellar ataxia was conducted. The battery of instruments included a modified International Cooperative Ataxia Rating Scale, Pittsburgh Sleep Quality Index, Restless Leg Syndrome Questionnaire, REM Behavior Disorder Questionnaire, Beck Depression Inventory, Epworth Sleepiness Scale, and a Composite Cognitive Questionnaire. Fifty-one percent of individuals indicated significant sleep disturbances on the Pittsburgh Sleep Quality Index, 73% of participants had two or more symptoms of restless leg syndrome, and 88% had two or more symptoms of REM behavior disorder. Ataxia severity, based on the modified International Cooperative Ataxia Rating Scale, predicted scores on the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale and REM Behavior Disorder Questionnaire. Median split analyses revealed that cognitive function appeared to be reduced and depressive symptoms were greater for those individuals with poor subjective sleep quality and severe RLS. Importantly, sleep appears to play a mediatory role between disease severity and depressive symptoms. These results suggest that disturbed sleep may have detrimental effects on cognition and affect in individuals with cerebellar ataxia. While objective measures are needed, such results suggest that treating sleep deficits in these individuals may improve cognitive and mental health as well as overall quality of life.

COMT genotype, gambling activity, and cognition.

PubMed

Grant, Jon E; Leppink, Eric W; Redden, Sarah A; Odlaug, Brian L; Chamberlain, Samuel R

2015-09-01

Neuropsychological studies of adults with problem gambling indicate impairments across multiple cognitive domains. Catechol-O-methyltransferase (COMT) plays a unique role in the regulation of dopamine in the prefrontal cortex, and has been implicated in the cognitive dysfunction evident in problem gambling. This study examined adults with varying levels of gambling behavior to determine whether COMT genotype was associated with differences in gambling symptoms and cognitive functioning. 260 non-treatment-seeking adults aged 18-29 years with varying degrees of gambling behavior provided saliva samples for genotyping COMT val158met (rs4680). All subjects underwent clinical evaluations and neurocognitive assessment of decision-making, working memory, and impulsivity. The Val/Val COMT genotype was associated with the largest percentage of subjects with gambling disorder (31.8%), a rate significantly different from the Val/Met (13.2%) group (p = 0.001). The Val/Val COMT group was also associated with significantly more gambling disorder diagnostic criteria being met, greater frequency of gambling behavior, and significantly worse cognitive performance on the Cambridge Gamble Task (risk adjustment and delay aversion) and the Spatial Working Memory task (total errors). This study adds to the growing literature on the role of COMT in impulsive behaviors by showing that the Val/Val genotype was associated with specific clinical and cognitive elements among young adults who gamble, in the absence of differences on demographic measures and other cognitive domains. Future work should consider using genotyping to explore whether certain polymorphisms predict subsequent development of impulsive behaviors including gambling disorder, and treatment outcomes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Associations of NEUROD2 polymorphisms and change of cognitive dysfunctions in schizophrenia and schizoaffective disorder after eight weeks of antipsychotic treatment.

PubMed

Spellmann, Ilja; Riedel, Michael; Städtler, Julia; Zill, Peter; Obermeier, Michael; Cerovecki, Anja; Dehning, Sandra; Schennach, Rebecca; Epple, Maria; Opgen-Rhein, Markus; Müller, Norbert; Bondy, Brigitta; Möller, Hans-Jürgen; Musil, Richard

2017-07-01

NEUROD2 is a neurospecific helix-loop-helix transcription factor which has an impact on the regulation of glutamatergic and GABAergic genes. We investigated an association of NEUROD2 with neurocognitive dysfunctions in schizophrenia and schizoaffective disorder patients before and during treatment with different second-generation antipsychotics. Patients were genotyped for four different polymorphisms of the NEUROD2 gene ((rs9889354(A/G), rs1877032(C/T), rs12453682(C/T) and rs11078918(C/G)). Cognitive function was assessed at baseline and week 8. Results of individual neuropsychological tests were assigned to six cognitive domains (reaction time and quality; executive function; working, verbal and visual memory) and a general cognitive index. 167 patients were included in the study. The NEUROD2 exonic polymorphism rs11078918 showed significant associations with verbal memory and executive functions, whereas the NEUROD2 polymorphism rs12453682 was significantly associated with working and verbal memory, executive functions and with a cognitive index. Significant associations were found at baseline and after eight weeks. Moreover, significant associations between the change in neuropsychological test results during antipsychotic treatment and the NEUROD2 polymorphisms rs11078918 and rs12453682 were observed. Our findings suggest that the NEUROD2 gene could play a role in the pathophysiology of neurocognitive dysfunctions as well as in the change of cognitive symptoms under antipsychotic treatment in schizophrenia and schizoaffective disorder.

Integrating Functional Brain Neuroimaging and Developmental Cognitive Neuroscience in Child Psychiatry Research

ERIC Educational Resources Information Center

Pavuluri, Mani N.; Sweeney, John A.

2008-01-01

The use of cognitive neuroscience and functional brain neuroimaging to understand brain dysfunction in pediatric psychiatric disorders is discussed. Results show that bipolar youths demonstrate impairment in affective and cognitive neural systems and in these two circuits' interface. Implications for the diagnosis and treatment of psychiatric…

The Cycle of Schizoaffective Disorder, Cognitive Ability, Alcoholism, and Suicidality

ERIC Educational Resources Information Center

Goldstein, Gerald; Haas, Gretchen L.; Pakrashi, Manish; Novero, Ada M.; Luther, James F.

2006-01-01

In this study we investigated the putative role of cognitive dysfunction, diagnosis (schizoaffective versus schizophrenia disorder), and alcoholism as risk factors for suicidal behavior among individuals with DSM-IV schizophrenia or schizoaffective disorders. Subjects received cognitive tests and medical records were reviewed for evidence of a…

New insights into environmental enteric dysfunction

USDA-ARS?s Scientific Manuscript database

Environmental enteric dysfunction (EED) has been recognised as an important contributing factor to physical and cognitive stunting, poor response to oral vaccines, limited resilience to acute infections and ultimately global childhood mortality. The aetiology of EED remains poorly defined but the ep...

Exposure therapy changes dysfunctional evaluations of somatic symptoms in patients with hypochondriasis (health anxiety). A randomized controlled trial.

PubMed

Weck, Florian; Neng, Julia M B; Schwind, Julia; Höfling, Volkmar

2015-08-01

Dysfunctional evaluations of somatic symptoms are considered a central factor in maintaining hypochondriasis. The aim of the current study was to investigate whether exposure therapy (ET) without cognitive restructuring is sufficient to change dysfunctional evaluations of somatic symptoms. The current study was based on a randomized controlled trial and compared patients with hypochondriasis (N=73) receiving ET or cognitive therapy (CT) to a wait list (WL) control group. In both the ET and CT groups, dysfunctional symptom evaluations changed significantly compared with the WL group. No differences between the ET and CT groups emerged. The relationship between the treatment condition (active treatment vs. WL) and reductions in health anxiety was mediated by changes in somatic symptom evaluations only in a specific card sorting procedure. We conclude that addressing dysfunctional symptom evaluations is a necessary precondition for the effective treatment of hypochondriasis. However, the results indicate that ET and CT appear to change those processes to a similar degree. Copyright © 2015 Elsevier Ltd. All rights reserved.

Bridging disparate symptoms of schizophrenia: a triple network dysfunction theory

PubMed Central

Nekovarova, Tereza; Fajnerova, Iveta; Horacek, Jiri; Spaniel, Filip

2014-01-01

Schizophrenia is a complex neuropsychiatric disorder with variable symptomatology, traditionally divided into positive and negative symptoms, and cognitive deficits. However, the etiology of this disorder has yet to be fully understood. Recent findings suggest that alteration of the basic sense of self-awareness may be an essential distortion of schizophrenia spectrum disorders. In addition, extensive research of social and mentalizing abilities has stressed the role of distortion of social skills in schizophrenia.This article aims to propose and support a concept of a triple brain network model of the dysfunctional switching between default mode and central executive network (CEN) related to the aberrant activity of the salience network. This model could represent a unitary mechanism of a wide array of symptom domains present in schizophrenia including the deficit of self (self-awareness and self-representation) and theory of mind (ToM) dysfunctions along with the traditional positive, negative and cognitive domains. We review previous studies which document the dysfunctions of self and ToM in schizophrenia together with neuroimaging data that support the triple brain network model as a common neuronal substrate of this dysfunction. PMID:24910597

Nicotine effects on brain function and functional connectivity in schizophrenia.

PubMed

Jacobsen, Leslie K; D'Souza, D Cyril; Mencl, W Einar; Pugh, Kenneth R; Skudlarski, Pawel; Krystal, John H

2004-04-15

Nicotine in tobacco smoke can improve functioning in multiple cognitive domains. High rates of smoking among schizophrenic patients may reflect an effort to remediate cognitive dysfunction. Our primary aim was to determine whether nicotine improves cognitive function by facilitating activation of brain regions mediating task performance or by facilitating functional connectivity. Thirteen smokers with schizophrenia and 13 smokers with no mental illness were withdrawn from tobacco and underwent functional magnetic resonance imaging (fMRI) scanning twice, once after placement of a placebo patch and once after placement of a nicotine patch. During scanning, subjects performed an n-back task with two levels of working memory load and of selective attention load. During the most difficult (dichotic 2-back) task condition, nicotine improved performance of schizophrenic subjects and worsened performance of control subjects. Nicotine also enhanced activation of a network of regions, including anterior cingulate cortex and bilateral thalamus, and modulated thalamocortical functional connectivity to a greater degree in schizophrenic than in control subjects during dichotic 2-back task performance. In tasks that tax working memory and selective attention, nicotine may improve performance in schizophrenia patients by enhancing activation of and functional connectivity between brain regions that mediate task performance.

Cognitive Impairment in Folate-Deficient Rats Corresponds to Depleted Brain Phosphatidylcholine and Is Prevented by Dietary Methionine without Lowering Plasma Homocysteine12

PubMed Central

Troen, Aron M.; Chao, Wei-Hsun; Crivello, Natalia A.; D'Anci, Kristen E.; Shukitt-Hale, Barbara; Smith, Don E.; Selhub, Jacob; Rosenberg, Irwin H.

2008-01-01

Poor folate status is associated with cognitive decline and dementia in older adults. Although impaired brain methylation activity and homocysteine toxicity are widely thought to account for this association, how folate deficiency impairs cognition is uncertain. To better define the role of folate deficiency in cognitive dysfunction, we fed rats folate-deficient diets (0 mg FA/kg diet) with or without supplemental L-methionine for 10 wk, followed by cognitive testing and tissue collection for hematological and biochemical analysis. Folate deficiency with normal methionine impaired spatial memory and learning; however, this impairment was prevented when the folate-deficient diet was supplemented with methionine. Under conditions of folate deficiency, brain membrane content of the methylated phospholipid phosphatidylcholine was significantly depleted, which was reversed with supplemental methionine. In contrast, neither elevated plasma homocysteine nor brain S-adenosylmethionine and S-adenosylhomocysteine concentrations predicted cognitive impairment and its prevention by methionine. The correspondence of cognitive outcomes to changes in brain membrane phosphatidylcholine content suggests that altered phosphatidylcholine and possibly choline metabolism might contribute to the manifestation of folate deficiency-related cognitive dysfunction. PMID:19022979

Cognition and dementia in older patients with epilepsy

PubMed Central

Sen, Arjune; Capelli, Valentina

2018-01-01

Abstract With advances in healthcare and an ageing population, the number of older adults with epilepsy is set to rise substantially across the world. In developed countries the highest incidence of epilepsy is already in people over 65 and, as life expectancy increases, individuals who developed epilepsy at a young age are also living longer. Recent findings show that older persons with epilepsy are more likely to suffer from cognitive dysfunction and that there might be an important bidirectional relationship between epilepsy and dementia. Thus some people with epilepsy may be at a higher risk of developing dementia, while individuals with some forms of dementia, particularly Alzheimer’s disease and vascular dementia, are at significantly higher risk of developing epilepsy. Consistent with this emerging view, epidemiological findings reveal that people with epilepsy and individuals with Alzheimer’s disease share common risk factors. Recent studies in Alzheimer’s disease and late-onset epilepsy also suggest common pathological links mediated by underlying vascular changes and/or tau pathology. Meanwhile electrophysiological and neuroimaging investigations in epilepsy, Alzheimer’s disease, and vascular dementia have focused interest on network level dysfunction, which might be important in mediating cognitive dysfunction across all three of these conditions. In this review we consider whether seizures promote dementia, whether dementia causes seizures, or if common underlying pathophysiological mechanisms cause both. We examine the evidence that cognitive impairment is associated with epilepsy in older people (aged over 65) and the prognosis for patients with epilepsy developing dementia, with a specific emphasis on common mechanisms that might underlie the cognitive deficits observed in epilepsy and Alzheimer’s disease. Our analyses suggest that there is considerable intersection between epilepsy, Alzheimer’s disease and cerebrovascular disease raising the possibility that better understanding of shared mechanisms in these conditions might help to ameliorate not just seizures, but also epileptogenesis and cognitive dysfunction. PMID:29506031

Neurocognitive impairment and psychosis in bipolar I disorder during early remission from an acute episode of mood disturbance.

PubMed

Levy, Boaz; Weiss, Roger D

2010-02-01

Recent studies have reported greater neurocognitive impairment in euthymic bipolar disorder patients with a history of psychosis relative to patients without such a history. To further explore the relation between psychosis and cognitive dysfunction in bipolar disorder, the current study examined the cognitive functioning of patients during early remission from a discrete episode of mood disturbance. The study aimed to determine whether the presence of psychosis during inpatient hospitalization was associated with greater cognitive impairment at the time of hospital discharge. Fifty-nine inpatients who met DSM-IV criteria for bipolar disorder (24 admitted with psychosis, 35 admitted without psychosis), ages 18-59 years, completed a neuropsychological battery and mood measures 24-48 hours before discharge. The cognitive battery included standardized tests of IQ, attention and working memory, visual memory, verbal memory, and executive functioning. A multivariate analysis of variance detected group differences on measures of verbal memory (P < .001) and executive functioning (P < .003), using mood measures and previous number of psychiatric admissions as covariates. Post hoc analysis of between-subjects effects revealed significantly poorer performance on the California Verbal Learning Test-Second Edition, logical memory subtest from Wechsler Memory Scale-Revised, Stroop Word/Color Interference test, and the Wisconsin Card Sorting Test for patients who were admitted to the hospital with psychosis. These results remained significant after matching the groups for past psychosis, with the exception of the logical memory subtest. The results of this study indicate that patients with bipolar disorder who were admitted to the hospital due to psychosis exhibited significantly more severe cognitive impairment at the time of discharge than patients admitted for an acute mood disturbance without psychosis. These findings may be important for improving discharge planning and the development of more effective outpatient services. Copyright 2010 Physicians Postgraduate Press, Inc.

The KEEPS-Cognitive and Affective Study: baseline associations between vascular risk factors and cognition.

PubMed

Wharton, Whitney; Gleason, Carey E; Dowling, N Maritza; Carlsson, Cynthia M; Brinton, Eliot A; Santoro, M Nanette; Neal-Perry, Genevieve; Taylor, Hugh; Naftolin, Frederick; Lobo, Rogerio A; Merriam, George; Manson, Joann E; Cedars, Marcelle I; Miller, Virginia M; Black, Dennis M; Budoff, Matthew; Hodis, Howard N; Harman, S Mitchell; Asthana, Sanjay

2014-01-01

Midlife vascular risk factors influence later cognitive decline and Alzheimer's disease (AD). The decrease in serum estradiol levels during menopause has been associated with cognitive impairment and increased vascular risk, such as high blood pressure (BP), which independently contributes to cognitive dysfunction and AD. We describe the extent to which vascular risk factors relate to cognition in healthy, middle-aged, recently postmenopausal women enrolled in the Kronos Early Estrogen Prevention Cognitive and Affective Study (KEEPS-Cog) at baseline. KEEPS-Cog is a double-blind, randomized, placebo-controlled, parallel group, clinical trial, investigating the efficacy of low-dose, transdermal 17β-estradiol and oral conjugated equine estrogen on cognition. All results are cross-sectional and represent baseline data only. Analyses confirm that the KEEPS-Cog cohort (n = 571) was middle aged (mean 52.7 years, range 42-59 years), healthy, and free of cognitive dysfunction. Higher systolic BP was weakly related to poorer performance in auditory working memory and attention (p = 0.004; adjusted for multiple comparisons p = 0.10). This relationship was not associated with endogenous hormone levels, and systolic BP was not related to any other cognitive domain. BP levels may be more sensitive than other vascular risk factors in detecting subtle differences in cognitive task performance in healthy, recently menopausal women. Lower BP early in menopause may affect cognitive domains known to be associated with AD.

The role of cognitive impairment in psychosocial functioning in remitted depression.

PubMed

Knight, Mattew J; Air, Tracy; Baune, Bernhard T

2018-08-01

Cognitive dysfunction is a prevalent and disabling symptom of Major Depressive Disorder (MDD), and is often retained in the remitted stage of illness. Emerging evidence suggests that cognitive impairment may be associated with dysfunction in a number of psychosocial domains (e.g., workplace productivity, social relationships). The current study explored the relationship between cognition and psychosocial functioning in remitted MDD and in healthy controls. Data were obtained from 182 participants of the Cognitive Function and Mood Study (CoFaM-S), a cross-sectional study of cognition, mood, and social cognition in mood disorders. Participants' (Remitted MDD n = 72, Healthy n = 110) cognition was assessed with a battery of cognitive tests including the Repeatable Battery for the Assessment of Neuropsychological Function (RBANS) and other standard measures of cognition (e.g., The Tower of London task). Psychosocial functioning was clinically evaluated with the Functioning Assessment Short Test (FAST). The results indicated that executive functioning was the strongest independent predictor of functioning in remitted MDD patients, whereas various cognitive domains predicted psychosocial functioning in healthy individuals. Psychosocial functioning was measured with a clinical interview, and was therefore reliant on clinicians' judgement of impairment, as opposed to more objective measures of functioning. These findings suggest that executive cognition plays an important role in functional recovery in remitted depression, and may be a crucial target in adjunctive treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

NMDA receptor agonists reverse impaired psychomotor and cognitive functions associated with hippocampal Hbegf-deficiency in mice.

PubMed

Sasaki, Keita; Omotuyi, Olaposi Idowu; Ueda, Mutsumi; Shinohara, Kazuyuki; Ueda, Hiroshi

2015-12-04

Structural and functional changes of the hippocampus are correlated with psychiatric disorders and cognitive dysfunctions. Genetic deletion of heparin-binding epidermal growth factor-like growth factor (HB-EGF), which is predominantly expressed in cortex and hippocampus, also causes similar psychiatric and cognitive dysfunctions, accompanying down-regulated NMDA receptor signaling. However, little is known of such dysfunctions in hippocampus-specific Hbegf cKO mice. We successfully developed hippocampus-specific cKO mice by crossbreeding floxed Hbegf and Gng7-Cre knock-in mice, as Gng7 promoter-driven Cre is highly expressed in hippocampal neurons as well as striatal medium spiny neurons. In mice lacking hippocampus Hbegf gene, there was a decreased neurogenesis in the subgranular zone (SGZ) of the dentate gyrus as well as down-regulation of PSD-95/NMDA-receptor-NR1/NR2B subunits and related NMDA receptor signaling. Psychiatric, social-behavioral and cognitive abnormalities were also observed in hippocampal cKO mice. Interestingly, D-cycloserine and nefiracetam, positive allosteric modulators (PAMs) of NMDA receptor reversed the apparent reduction in NMDA receptor signaling and most behavioral abnormalities. Furthermore, decreased SGZ neurogenesis in hippocampal cKO mice was reversed by nefiracetam. The present study demonstrates that PAMs of NMDA receptor have pharmacotherapeutic potentials to reverse down-regulated NMDA receptor signaling, neuro-socio-cognitive abnormalities and decreased neurogenesis in hippocampal cKO mice.

Group versus individual cognitive treatment for Obsessive-Compulsive Disorder: changes in non-OCD symptoms and cognitions at post-treatment and one-year follow-up.

PubMed

Belloch, Amparo; Cabedo, Elena; Carrió, Carmen; Fernández-Alvarez, Héctor; García, Fernando; Larsson, Christina

2011-05-15

Current cognitive approaches postulate that obsessions and compulsions are caused and/or maintained by misinterpretations about their meaning. This assumption has led to the development of cognitive therapeutic (CT) procedures designed to challenge the dysfunctional appraisals and beliefs patients have about their obsessions. Nonetheless, few studies have compared the efficacy of individual and group CT in changing the dysfunctional cognitions that hypothetically underlie Obsessive-Compulsive Disorder (OCD). In this study, 44 OCD patients were assigned to individual (n=18) or group (n=24) CT. Sixteen completed the individual CT, and 22 completed the group CT. The effects of the two CT conditions on depression and worry tendencies were comparable. Individual treatment was more effective than group treatment in decreasing scores on dysfunctional beliefs (responsibility, overestimation of threat, and intolerance to uncertainty) and the use of suppression as a thought control strategy. The post-treatment changes were maintained one year later. The correlations between symptom improvement (OCD severity change) and belief changes were moderate: in the individual treatment the greatest associations were with beliefs about thoughts (importance and control), whereas in the group treatment the greatest associations were with beliefs related to anxiety in general (threat overestimation and intolerance to uncertainty). Copyright © 2010 Elsevier Ltd. All rights reserved.

Allosteric Modulators for the Treatment of Schizophrenia: Targeting Glutamatergic Networks

PubMed Central

Menniti, Frank S.; Lindsley, Craig W.; Conn, P. Jeffrey; Pandit, Jayvardhan; Zagouras, Panayiotis; Volkmann, Robert A.

2013-01-01

Schizophrenia is a highly debilitating mental disorder which afflicts approximately 1% of the global population. Cognitive and negative deficits account for the lifelong disability associated with schizophrenia, whose symptoms are not effectively addressed by current treatments. New medicines are needed to treat these aspects of the disease. Neurodevelopmental, neuropathological, genetic, and behavioral pharmacological data indicate that schizophrenia stems from a dysfunction of glutamate synaptic transmission, particularly in frontal cortical networks. A number of novel pre- and postsynaptic mechanisms affecting glutamatergic synaptic transmission have emerged as viable targets for schizophrenia. While developing orthosteric glutamatergic agents for these targets has proven extremely difficult, targeting allosteric sites of these targets has emerged as a promising alternative. From a medicinal chemistry perspective, allosteric sites provide an opportunity of finding agents with better drug-like properties and greater target specificity. Furthermore, allosteric modulators are better suited to maintaining the highly precise temporal and spatial aspects of glutamatergic synaptic transmission. Herein, we review neuropathological and genomic/genetic evidence underscoring the importance of glutamate synaptic dysfunction in the etiology of schizophrenia and make a case for allosteric targets for therapeutic intervention. We review progress in identifying allosteric modulators of AMPA receptors, NMDA receptors, and metabotropic glutamate receptors, all with the aim of restoring physiological glutamatergic synaptic transmission. Challenges remain given the complexity of schizophrenia and the difficulty in studying cognition in animals and humans. Nonetheless, important compounds have emerged from these efforts and promising preclinical and variable clinical validation has been achieved. PMID:23409764

Associations between sleep disturbance and suicidal ideation in adolescents admitted to an inpatient psychiatric unit.

PubMed

Kaplan, Sebastian G; Ali, Shahzad K; Simpson, Brittany; Britt, Victoria; McCall, W Vaughn

2014-01-01

The goals of our study were to: 1) describe the incidence of disturbances in sleep quality, sleep hygiene, sleep-related cognitions and nightmares; and 2) investigate the association between these sleep-related disturbances and suicidal ideation (SI), in adolescents admitted to a psychiatric inpatient unit. Our sample consisted of 50 adolescents between the ages of 12 and 17 years (32 females and 18 males; 41 Caucasian and nine African American). Our cross-sectional design involved the administration of the Adolescent Sleep Wake Scale (ASWS), the Adolescent Sleep Hygiene Scale (ASHS), the Dysfunctional Beliefs and Attitudes about Sleep-Short version for use with children (DBAS-C10), the Disturbing Dreams and Nightmare Scale (DDNSI), and the Suicidal Ideation Questionnaire Jr (SIQ-JR). Analyses were conducted using Pearson correlations, as well as univariate and multivariate regression. Results indicated that our sample experienced sleep disturbances and SI to a greater degree than non-clinical samples. Sleep quality was correlated with nightmares, while sleep quality and nightmares were each correlated with SI. Sleep quality, dysfunctional beliefs, and nightmares each independently predicted SI. Our study was the first to use the four sleep measures with an adolescent psychiatric inpatient sample. It is important to develop sleep-related assessment tools in high-risk populations given the link between sleep disturbances and suicidality. Furthermore, a better understanding of the relationships between SI and sleep quality, sleep-related cognitions, and nightmares is needed to develop potential prevention and treatment options for suicidality in adolescents.

Advances in the mechanisms and early warning indicators of the postoperative cognitive dysfunction after the extracorporeal circulation.

PubMed

Liu, Chao; Han, Jian-ge

2015-02-01

The high incidence of postoperative cognitive dysfunction (POCD) after extracorporeal circulation has seriously affected the prognosis and quality of life. Its mechanism may involve the inflammatory response and oxidative stress,the excessive phosphorylation of tau protein, the decreased blood volume and oxygen in the cerebral cortex. Appropriate early warning indicators of POCD after the extracorporeal circulation should be chosen to facilitate the cross validation of the results obtained different technical approaches and thus promote the early diagnosis and treatment of POCD.

Electrophysiological Studies of Autism: The Whisper of the Bang.

ERIC Educational Resources Information Center

Tanguay, Peter E.; Edwards, Rose Mary

1982-01-01

Although some have argued that the type of language and cognitive defects shown by autistic children almost certainly reflects forebrain dysfunctions, current studies point to the possibility that some autistic children may have dysfunction of neural systems in the brainstem. (Author)

Health Status and Performance of United States Air Force Airmen Following Mild Traumatic Brain Injury

DTIC Science & Technology

2010-09-01

adrenal insufficiency, hypopituitarism, hypothyroidism , growth- hormone deficiency and posterior pituitary dysfunction [53, 54, 56-60]. Growth...central hypothyroidism which can result in fatigue, apathy, decreased strength and cognitive dysfunction, symptoms commonly observed in PTSD [54

Role of Oxidative Stress in the Neurocognitive Dysfunction of Obstructive Sleep Apnea Syndrome

PubMed Central

Chen, Ping

2016-01-01

Obstructive sleep apnea syndrome (OSAS) is characterized by chronic nocturnal intermittent hypoxia and sleep fragmentations. Neurocognitive dysfunction, a significant and extraordinary complication of OSAS, influences patients' career, family, and social life and reduces quality of life to some extent. Previous researches revealed that repetitive hypoxia and reoxygenation caused mitochondria and endoplasmic reticulum dysfunction, overactivated NADPH oxidase, xanthine oxidase, and uncoupling nitric oxide synthase, induced an imbalance between prooxidants and antioxidants, and then got rise to a series of oxidative stress (OS) responses, such as protein oxidation, lipid peroxidation, and DNA oxidation along with inflammatory reaction. OS in brain could trigger neuron injury especially in the hippocampus and cerebral cortex regions. Those two regions are fairly susceptible to hypoxia and oxidative stress production which could consequently result in cognitive dysfunction. Apart from continuous positive airway pressure (CPAP), antioxidant may be a promising therapeutic method to improve partially reversible neurocognitive function. Understanding the role that OS played in the cognitive deficits is crucial for future research and therapeutic strategy development. In this paper, recent important literature concerning the relationship between oxidative stress and cognitive impairment in OSAS will be summarized and the results can provide a rewarding overview for future breakthrough in this field. PMID:27774119

Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging

PubMed Central

Toth, Peter; Tarantini, Stefano; Csiszar, Anna

2017-01-01

Increasing evidence from epidemiological, clinical and experimental studies indicate that age-related cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including Alzheimer’s disease. Understanding and targeting the age-related pathophysiological mechanisms that underlie vascular contributions to cognitive impairment and dementia (VCID) are expected to have a major role in preserving brain health in older individuals. Maintenance of cerebral perfusion, protecting the microcirculation from high pressure-induced damage and moment-to-moment adjustment of regional oxygen and nutrient supply to changes in demand are prerequisites for the prevention of cerebral ischemia and neuronal dysfunction. This overview discusses age-related alterations in three main regulatory paradigms involved in the regulation of cerebral blood flow (CBF): cerebral autoregulation/myogenic constriction, endothelium-dependent vasomotor function, and neurovascular coupling responses responsible for functional hyperemia. The pathophysiological consequences of cerebral microvascular dysregulation in aging are explored, including blood-brain barrier disruption, neuroinflammation, exacerbation of neurodegeneration, development of cerebral microhemorrhages, microvascular rarefaction, and ischemic neuronal dysfunction and damage. Due to the widespread attention that VCID has captured in recent years, the evidence for the causal role of cerebral microvascular dysregulation in cognitive decline is critically examined. PMID:27793855

Cognitive Effects of Stimulant, Guanfacine, and Combined Treatment in Child and Adolescent Attention-Deficit/Hyperactivity Disorder

PubMed Central

Bilder, Robert M.; Loo, Sandra; McGough, James J.; Whelan, Fiona; Hellemann, Gerhard; Sugar, Catherine; Del’Homme, Melissa; Sturm, Alexandra; Cowen, Jennifer; Hanada, Grant; McCracken, James T.

2016-01-01

Objective Psychostimulants are partially effective in reducing cognitive dysfunction associated with attention-deficit/hyperactivity disorder (ADHD). Cognitive effects of guanfacine, an alternative treatment, are poorly understood. Given its distinct action on α2A receptors, guanfacine may have different or complementary effects relative to stimulants. This study tested stimulant and guanfacine monotherapies relative to combined treatment on cognitive functions important in ADHD. Method Children with ADHD (n = 182; age 7–14 years) completed an eight-week double blind randomized controlled trial with three arms: d-methylphenidate (DMPH), guanfacine (GUAN), or combination treatment with DMPH and GUAN (COMB). A non-clinical comparison group (n = 93) had baseline testing, and a subset was re-tested 8 weeks later (n = 38). Analyses examined treatment effects in four cognitive domains (working memory, response inhibition, reaction time, and reaction time variability) constructed from 20 variables. Results The ADHD group showed impaired working memory relative to the non-clinical comparison group (effect size = −0.53 SD units). The treatments differed in effects on working memory but not other cognitive domains. Combination treatment improved working memory more than GUAN, but was not significantly better than DMPH alone. Treatment did not fully normalize the initial deficit in ADHD relative to the comparison group. Conclusion Combined treatment with DMPH and GUAN yielded greater improvements in working memory than placebo or GUAN alone, but the combined treatment was not superior to DMPH alone, and did not extend to other cognitive domains. Although GUAN may be a useful add-on treatment to psychostimulants, additional strategies appear necessary to achieve normalization of cognitive function in ADHD. Clinical trial registration information Single Versus Combination Medication Treatment for Children With Attention Deficit Hyperactivity Disorder; http://clinicaltrials.gov/; NCT00429273 PMID:27453080

Object recognition impairment in Fmr1 knockout mice is reversed by amphetamine: involvement of dopamine in the medial prefrontal cortex.

PubMed

Ventura, R; Pascucci, T; Catania, M V; Musumeci, S A; Puglisi-Allegra, S

2004-09-01

Fragile X syndrome is an X-linked form of mental retardation including, among others, symptoms such as stereotypic behaviour, hyperactivity, hyperarousal, and cognitive deficits. We hypothesized that hyperactivity and/or compromised attentional, cognitive functions may lead to impaired performance in cognitive tasks in Fmr1 knockout mice, the most widely used animal model of fragile X syndrome, and suggested that psychostimulant treatment may improve performance by acting on one or both components. Since hyperactivity and cognitive functions have been suggested to depend on striatal and prefrontal cortex dopaminergic dysfunction, we assessed whether amphetamine produced beneficial, positive effects by acting on dopaminergic corticostriatal systems. Our results show that Fmr1 knockout mice are not able to discriminate between a familiar object and a novel one in the object recognition test, thus showing a clear-cut cognitive impairment that, to date, has been difficult to demonstrate in other cognitive tasks. Amphetamine improved performance of Fmr1 knockout mice, leading to enhanced ability to discriminate novel versus familiar objects, without significantly affecting locomotor activity. In agreement with behavioural data, amphetamine produced a greater increase in dopamine release in the prefrontal cortex of Fmr1 knockout compared with the wild-type mice, while a weak striatal dopaminergic response was observed in Fmr1 knockout mice. Our data support the view that the psychostimulant ameliorates performance in Fmr1 knockout mice by improving merely cognitive functions through its action on prefrontal cortical dopamine, irrespective of its action on motor hyperactivity. These results indicate that prefrontal cortical dopamine plays a major role in cognitive impairments characterizing Fmr1 knockout mice, thus pointing to an important aetiological factor in the fragile X syndrome.

Design and feasibility of a memory intervention with focus on self-management for cognitive impairment in epilepsy.

PubMed

Caller, Tracie A; Secore, Karen L; Ferguson, Robert J; Roth, Robert M; Alexandre, Faith P; Henegan, Patricia L; Harrington, Jessica J; Jobst, Barbara C

2015-03-01

The aim of this study was to assess the feasibility of a self-management intervention targeting cognitive dysfunction to improve quality of life and reduce memory-related disability in adults with epilepsy. The intervention incorporates (1) education on cognitive function in epilepsy, (2) self-awareness training, (3) compensatory strategies, and (4) application of these strategies in day-to-day life using problem-solving therapy. In addition to the behavioral modification, formal working memory training was conducted by utilizing a commercially available program in a subgroup of patients. Our findings suggest that a self-management intervention targeting cognitive dysfunction was feasible for delivery to a rural population with epilepsy, with 13 of 16 enrolled participants completing the 8-session program. Qualitative data indicate high satisfaction and subjective improvement in cognitive functioning in day-to-day life. These findings provide support for further evaluation of the efficacy of this intervention through a randomized controlled trial. Copyright © 2015 Elsevier Inc. All rights reserved.

Noradrenergic System in Down Syndrome and Alzheimer's Disease A Target for Therapy.

PubMed

Phillips, Cristy; Fahimi, Atoossa; Das, Devsmita; Mojabi, Fatemeh S; Ponnusamy, Ravikumar; Salehi, Ahmad

2016-01-01

Locus coeruleus (LC) neurons in the brainstem send extensive noradrenergic (NE)-ergic terminals to the majority of brain regions, particularly those involved in cognitive function. Both Alzheimer's disease (AD) and Down syndrome (DS) are characterized by similar pathology including significant LC degeneration and dysfunction of the NE-ergic system. Extensive loss of NE-ergic terminals has been linked to alterations in brain regions vital for cognition, mood, and executive function. While the mechanisms by which NE-ergic abnormalities contribute to cognitive dysfunction are not fully understood, emergent evidence suggests that rescue of NE-ergic system can attenuate neuropathology and cognitive decline in both AD and DS. Therapeutic strategies to enhance NE neurotransmission have undergone limited testing. Among those deployed to date are NE reuptake inhibitors, presynaptic α-adrenergic receptor antagonists, NE prodrugs, and β-adrenergic agonists. Here we examine alterations in the NE-ergic system in AD and DS and suggest that NE-ergic system rescue is a plausible treatment strategy for targeting cognitive decline in both disorders.

Cognitive Control Dysfunction in Workers Exposed to Manganese-Containing Welding Fume

PubMed Central

Al-Lozi, A; Nielsen, SS; Hershey, T; Birke, A; Checkoway, H; Criswell, SR; Racette, BA

2017-01-01

Background Chronic exposure to manganese (Mn) is a health concern in occupations such as welding because of well-established motor effects due to basal ganglia dysfunction. We hypothesized that cognitive control (the ability to monitor, manipulate, and regulate ongoing cognitive demands) would also be affected by chronic Mn exposure. Methods We examined the relationship between Mn exposure and cognitive control performance in 95 workers with varying intensity and duration (median 15.5 years) of exposure to welding fume. We performed linear regression to assess the association between exposure to Mn-containing welding fume and cognitive control tasks. Results Overall performance was inversely related to intensity of welding exposure (p=0.009) and was driven by the Two-Back and Letter Number Sequencing tests that assess working memory (both p=0.02). Conclusions Occupational exposure to Mn-containing welding fume may be associated with poorer working memory performance, and workers may benefit from practices that reduce exposure intensity. PMID:27862095

Do sedation and analgesia contribute to long-term cognitive dysfunction in critical care survivors?

PubMed

Fernandez-Gonzalo, S; Turon, M; De Haro, C; López-Aguilar, J; Jodar, M; Blanch, L

2018-03-01

Deep sedation during stay in the Intensive Care Unit (ICU) may have deleterious effects upon the clinical and cognitive outcomes of critically ill patients undergoing mechanical ventilation. Over the last decade a vast body of literature has been generated regarding different sedation strategies, with the aim of reducing the levels of sedation in critically ill patients. There has also been a growing interest in acute brain dysfunction, or delirium, in the ICU. However, the effect of sedation during ICU stay upon long-term cognitive deficits in ICU survivors remains unclear. Strategies for reducing sedation levels in the ICU do not seem to be associated with worse cognitive and psychological status among ICU survivors. Sedation strategy and management efforts therefore should seek to secure the best possible state in the mechanically ventilated patient and lower the prevalence of delirium, in order to prevent long-term cognitive alterations. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

GABA Neuron Alterations, Cortical Circuit Dysfunction and Cognitive Deficits in Schizophrenia

PubMed Central

Gonzalez-Burgos, Guillermo; Fish, Kenneth N.; Lewis, David A.

2011-01-01

Schizophrenia is a brain disorder associated with cognitive deficits that severely affect the patients' capacity for daily functioning. Whereas our understanding of its pathophysiology is limited, postmortem studies suggest that schizophrenia is associated with deficits of GABA-mediated synaptic transmission. A major role of GABA-mediated transmission may be producing synchronized network oscillations which are currently hypothesized to be essential for normal cognitive function. Therefore, cognitive deficits in schizophrenia may result from a GABA synapse dysfunction that disturbs neural synchrony. Here, we highlight recent studies further suggesting alterations of GABA transmission and network oscillations in schizophrenia. We also review current models for the mechanisms of GABA-mediated synchronization of neural activity, focusing on parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose function has been strongly linked to the production of neural synchrony. Alterations of GABA signaling that impair gamma oscillations and, as a result, cognitive function suggest paths for novel therapeutic interventions. PMID:21904685

Frontal Dysfunctions of Impulse Control – A Systematic Review in Borderline Personality Disorder and Attention-Deficit/Hyperactivity Disorder

PubMed Central

Sebastian, Alexandra; Jung, Patrick; Krause-Utz, Annegret; Lieb, Klaus; Schmahl, Christian; Tüscher, Oliver

2014-01-01

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders. PMID:25232313

Executive dysfunction, obsessive-compulsive symptoms, and attention deficit and hyperactivity disorder in Systemic Lupus Erythematosus: Evidence for basal ganglia dysfunction?

PubMed

Maciel, Ricardo Oliveira Horta; Ferreira, Gilda Aparecida; Akemy, Bárbara; Cardoso, Francisco

2016-01-15

Chorea is well described in a group of patients with Systemic Lupus Erythematosus (SLE). There is less information, however, on other movement disorders as well as non-motor neuropsychiatric features such as obsessive-compulsive symptoms (OCS), executive dysfunction and attention deficit and hyperactivity disorder (ADHD) in subjects with SLE. Fifty-four subjects with SLE underwent a battery of neuropsychiatric tests that included the Mini Mental State Examination, the Montreal Cognitive Assessment, the Frontal Assessment Battery (FAB), the FAS verbal and the categorical (animals) semantic fluency tests, the Obsessive and Compulsive Inventory - Revised, the Yale-Brown Obsessive and Compulsive Scale and Beck's Anxiety and Depression Scales. ADHD was diagnosed according to DSM-IV criteria. SLE disease activity and cumulative damage were evaluated according to the modified SLE Disease Activity Index 2000 (mSLEDAI-2K) and the SLICC/ACR, respectively. Six (11.1%) and 33 (61.1%) patients had cognitive impairment according to the MMSE and MoCA, respectively. Eleven (20.4%) had abnormal FAB scores, and 5 (9.3%) had lower semantic fluency scores than expected. The overall frequency of cognitive dysfunction was 72.2% (39 patients) and of neuropsychiatric SLE was 77.8% (42 patients). Two patients (3.7%) had movement disorders. Fifteen (27.8%) had OCS and 17 (31.5%) met diagnostic criteria for ADHD. ADHD and OCS correlated with higher disease activity, p=0.003 and 0.006, respectively. Higher cumulative damage correlated with lower FAB scores (p 0.026). Executive dysfunction, ADHD, OCS, and movement disorders are common in SLE. Our finding suggests that there is frequent basal ganglia dysfunction in SLE. Copyright © 2015 Elsevier B.V. All rights reserved.

Pathophysiology and Treatment of Memory Dysfunction after Traumatic Brain Injury

PubMed Central

Paterno, Rosalia; Folweiler, Kaitlin A.; Cohen, Akiva S.

2018-01-01

Memory is fundamental to everyday life, and cognitive impairments resulting from traumatic brain injury (TBI) have devastating effects on TBI survivors. A contributing component to memory impairments caused by TBI are alterations in the neural circuits associated with memory function. In this review, we aim to bring together experimental findings that characterize behavioral memory deficits and the underlying pathophysiology of memory-involved circuits after TBI. While there is little doubt that TBI causes memory and cognitive dysfunction, it is difficult to conclude which memory phase i.e., encoding, maintenance or retrieval is specifically altered by TBI. This is most likely due to variation in behavioral protocols and experimental models. Additionally we review a selection of experimental treatments that hold translational potential to mitigate memory dysfunction following injury. PMID:28500417

Profile of cognitive problems in schizophrenia and implications for vocational functioning.

PubMed

Tan, Bhing-Leet

2009-08-01

This literature review attempts to profile specific areas of cognition that have shown unique and consistent evidence of dysfunction among people with schizophrenia. In addition, their impact on vocational functioning is illustrated, so as to highlight the importance of managing these cognitive difficulties in vocational rehabilitation. Literature search was carried out on seven key cognitive domains identified by the National Institute of Mental Health in the USA. Their impact on vocational function was also reviewed. It is found that attention, declarative and working memory, reasoning, problem-solving and social cognition are areas of impairment that have great impact on vocational functioning. Attention and memory problems affect learning of new work tasks. Executive function is particularly crucial in determining supported and open employment outcomes, as executive dysfunction cannot be easily compensated. Lastly, social cognition plays a major role in determining the success of workplace social exchanges. Occupational therapists need to have a good understanding of the profile of cognitive problems among people with schizophrenia, in order to tailor our intervention according to their cognitive strengths and difficulties. Several cognitive remediation strategies and programs have been designed specifically for people with mental illness. Equipping ourselves with skills in conducting such programs will augment our expertise in vocational rehabilitation.

Translating advances in the molecular basis of schizophrenia into novel cognitive treatment strategies.

PubMed

O'Tuathaigh, Colm M P; Moran, Paula M; Zhen, Xuechu C; Waddington, John L

2017-10-01

The presence and severity of cognitive symptoms, including working memory, executive dysfunction and attentional impairment, contributes materially to functional impairment in schizophrenia. Cognitive symptoms have proved to be resistant to both first- and second-generation antipsychotic drugs. Efforts to develop a consensus set of cognitive domains that are both disrupted in schizophrenia and are amenable to cross-species validation (e.g. the National Institute of Mental Health Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia and Research Domain Criteria initiatives) are an important step towards standardization of outcome measures that can be used in preclinical testing of new drugs. While causative genetic mutations have not been identified, new technologies have identified novel genes as well as hitherto candidate genes previously implicated in the pathophysiology of schizophrenia and/or mechanisms of antipsychotic efficacy. This review comprises a selective summary of these developments, particularly phenotypic data arising from preclinical genetic models for cognitive dysfunction in schizophrenia, with the aim of indicating potential new directions for pro-cognitive therapeutics. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc. © 2017 The British Pharmacological Society.

The Need for Screening, Assessment, and Treatment for Cognitive Dysfunction in Multiple Sclerosis

PubMed Central

Benedict, Ralph H.B.; Gromisch, Elizabeth S.; DeLuca, John

2012-01-01

Cognitive dysfunction is observed in about half of people with multiple sclerosis (MS), and MS health-care professionals face the challenge of screening, assessing, and treating patients for cognitive problems. Considering the inconsistent or limited empirical evidence to assist in this task, a multidisciplinary consensus conference of MS experts, sponsored by the Consortium of Multiple Sclerosis Centers (CMSC), was held on September 24, 2010, to address these issues. Key articles from the literature on these topics were distributed prior to the meeting, and CMSC member professionals were surveyed on clinical practices related to screening, assessment, and treatment for cognitive problems. The purpose of the meeting was threefold: 1) to achieve a multidisciplinary perspective on practices for screening, monitoring, evaluating, and treating MS patients for cognitive problems; 2) to propose consensus candidate measures for screening and/or monitoring for cognitive problems in MS that neurologists or nurses might administer on a regular basis; and 3) to propose consensus treatment approaches from a multidisciplinary perspective. This article summarizes the conclusions of the conference participants and provides preliminary suggestions for screening and brief assessment. PMID:24453735

Can the REBT theory explain loneliness? Theoretical and clinical applications.

PubMed

Hyland, Philip; McGinty, Gráinne; Karatzias, Thanos; Murphy, Jamie; Vallières, Frédérique; McHugh Power, Joanna

2018-06-05

Loneliness is a common psychological experience affecting a significant minority of the general population. Loneliness may in part be related to the existence of dysfunctional cognitive evaluations. To date, however, loneliness has yet to be explicitly assessed within a cognitive-behavioural theoretical framework. The current study sought to determine the association between negative cognitions, within the context of Rational Emotive Behaviour Therapy (REBT), and the experience of loneliness. A multinational sample of university students (n = 397) completed self-report assessments of rational and irrational beliefs, and loneliness. Structural equation modelling results found that the REBT model of psychopathology, and the REBT model of psychological health, provided satisfactory representations of loneliness, explaining 36% and 23% of variance in loneliness, respectively. Several dysfunctional ("Demandingness", "Catastrophising" and "Self-Downing" beliefs) and functional ("Preferences" and "Self-Acceptance" beliefs) cognitions were directly and indirectly associated with loneliness. These results highlight that cognitions and loneliness are meaningfully related, and indicate that cognitive-behavioural models may be useful in understanding loneliness. More specifically, current results suggest that REBT may offer a viable psychotherapeutic approach to treating loneliness.

Cognitive Characteristics of Children with Genetic Syndromes

PubMed Central

Simon, Tony J.

2008-01-01

The cognitive profile of several different populations of children, each with a distinct neurogenetic disorder that has been described as fitting the pattern of a “nonverbal learning disorder”, is examined. In particular, this paper presents the view that a cognitive endophenotype, specified in terms of specific cognitive processes involving the spatial, temporal and attentional domains, can be used to generate an explanation of the neurocognitive foundation of the common impairments found in these disorders. Methods for evaluating cognitive impairments are first compared and contrasted and the concept of “nonverbal learning disorders” is described. The paper then examines data from experimental tests of spatiotemporal and executive cognitive function acquired from children with one of several disorders to determine whether such a cognitive endophenotype holds promise for moving from descriptions of to explanations for the impairments observed and whether prescriptions for therapeutic interventions might flow from such an account. Synopsis This paper presents the cognitive profile observed in children with one of several common genetic syndromes associated with “nonverbal learning disorders”. It introduces the concept of a cognitive endophenotype in order to help explain the similar pattern of impairments across the syndromes. It explores the explanation of diverse impairments in higher-order visual, spatial, temporal, numerical and executive cognitive competencies deriving from origins in more basic attentional and spatial cognitive dysfunctions. The importance of a developmental approach to understanding dysfunction is stressed. PMID:17562581

Dietary enrichment counteracts age-associated cognitive dysfunction in canines.

PubMed

Milgram, N W; Zicker, S C; Head, E; Muggenburg, B A; Murphey, H; Ikeda-Douglas, C J; Cotman, C W

2002-01-01

Advanced age is accompanied by cognitive decline indicative of central nervous system dysfunction. One possibly critical causal factor is oxidative stress. Accordingly, we studied the effects of dietary antioxidants and age in a canine model of aging that parallels the key features of cognitive decline and neuropathology in humans. Old and young animals were placed on either a standard control food, or a food enriched with a broad spectrum of antioxidants and mitochondrial enzymatic cofactors. After 6 months of treatment, the animals were tested on four increasingly difficult oddity discrimination learning problems. The old animals learned more slowly than the young, making significantly more errors. However, this age-associated decline was reduced in the animals fed the enriched food, particularly on the more difficult tasks. These results indicate that maintenance on foods fortified with complex mixtures of antioxidants can partially counteract the deleterious effects of aging on cognition. Copyright 2002 Elsevier Science Inc.

A cognitive neuroscience perspective on psychopathy: evidence for paralimbic system dysfunction.

PubMed

Kiehl, Kent A

2006-06-15

Psychopathy is a complex personality disorder that includes interpersonal and affective traits such as glibness, lack of empathy, guilt or remorse, shallow affect, and irresponsibility, and behavioral characteristics such as impulsivity, poor behavioral control, and promiscuity. Much is known about the assessment of psychopathy; however, relatively little is understood about the relevant brain disturbances. The present review integrates data from studies of behavioral and cognitive changes associated with focal brain lesions or insults and results from psychophysiology, cognitive psychology and cognitive and affective neuroscience in health and psychopathy. The review illustrates that the brain regions implicated in psychopathy include the orbital frontal cortex, insula, anterior and posterior cingulate, amygdala, parahippocampal gyrus, and anterior superior temporal gyrus. The relevant functional neuroanatomy of psychopathy thus includes limbic and paralimbic structures that may be collectively termed 'the paralimbic system'. The paralimbic system dysfunction model of psychopathy is discussed as it relates to the extant literature on psychopathy.

Cerebral Autoregulation in Hypertension and Ischemic Stroke: A Mini Review

PubMed Central

Shekhar, Shashank; Liu, Ruen; Travis, Olivia K; Roman, Richard J; Fan, Fan

2017-01-01

Aging and chronic hypertension are associated with dysfunction in vascular smooth muscle, endothelial cells, and neurovascular coupling. These dysfunctions induce impaired myogenic response and cerebral autoregulation, which diminish the protection of cerebral arterioles to the cerebral microcirculation from elevated pressure in hypertension. Chronic hypertension promotes cerebral focal ischemia in response to reductions in blood pressure that are often seen in sedentary elderly patients on antihypertensive therapy. Cerebral autoregulatory dysfunction evokes Blood-Brain Barrier (BBB) leakage, allowing the circulating inflammatory factors to infiltrate the brain to activate glia. The impaired cerebral autoregulation-induced inflammatory and ischemic injury could cause neuronal cell death and synaptic dysfunction which promote cognitive deficits. In this brief review, we summarize the pathogenesis and signaling mechanisms of cerebral autoregulation in hypertension and ischemic stroke-induced cognitive deficits, and discuss our new targets including 20-Hydroxyeicosatetraenoic acid (20-HETE), Gamma-Adducin (Add3) and Matrix Metalloproteinase-9 (MMP-9) that may contribute to the altered cerebral vascular function. PMID:29333537

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.

Zebrafish as a Model for Epilepsy-Induced Cognitive Dysfunction: A Pharmacological, Biochemical and Behavioral Approach

PubMed Central

Kundap, Uday P.; Kumari, Yatinesh; Othman, Iekhsan; Shaikh, Mohd. Farooq

2017-01-01

Epilepsy is a neuronal disorder allied with distinct neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Impairment of the cognitive performances such as learning and memory is frequently observed in epileptic patients. Anti-epileptic drugs (AEDs) are efficient to the majority of patients. However, 30% of this population seems to be refractory to the drug treatment. These patients are not seizure-free and frequently they show impaired cognitive functions. Unfortunately, as a side effect, some AEDs could contribute to such impairment. The major problem associated with conducting studies on epilepsy-related cognitive function is the lack of easy, rapid, specific and sensitive in vivo testing models. However, by using a number of different techniques and parameters in the zebrafish, we can incorporate the unique feature of specific disorder to study the molecular and behavior basis of this disease. In the view of current literature, the goal of the study was to develop a zebrafish model of epilepsy induced cognitive dysfunction. In this study, the effect of AEDs on locomotor activity and seizure-like behavior was tested against the pentylenetetrazole (PTZ) induced seizures in zebrafish and epilepsy associated cognitive dysfunction was determined using T-maze test followed by neurotransmitter estimation and gene expression analysis. It was observed that all the AEDs significantly reversed PTZ induced seizure in zebrafish, but had a negative impact on cognitive functions of zebrafish. AEDs were found to modulate neurotransmitter levels, especially GABA, glutamate, and acetylcholine and gene expression in the drug treated zebrafish brains. Therefore, combination of behavioral, neurochemical and genenetic information, makes this model a useful tool for future research and discovery of newer and safer AEDs. PMID:28824436

Efficacy and process of cognitive bibliotherapy for the treatment of depression in jail and prison inmates.

PubMed

Pardini, Jamie; Scogin, Forrest; Schriver, Jennifer; Domino, Marla; Wilson, Dawn; LaRocca, Michael

2014-05-01

The purpose of this two-study project was to determine the effects of cognitive bibliotherapy for the treatment of depressive symptoms in jail and prison inmates. Participants in both samples were randomly assigned to either a treatment group that received the 4-week bibliotherapy program or a delayed-treatment control group. In the jail sample, which served as a pilot study for the more detailed prison study, the treatment group showed greater improvement on the A. T. Beck and R. A. Steer Beck Depression Inventory, 1993, Psychological Corporation, San Antonio, TX and the DAS (M. M. Weissman, & A. T. Beck Development and validation of the Dysfunctional Attitudes Scale: A preliminary investigation; paper presented at the meeting of the American Educational Research Association, November, 1978, Toronto, ON, Canada). In the prison sample, results indicated that the treatment group showed greater improvement on the HRSD (M. Hamilton, Development of a rating scale for primary depressive illness, British Journal of Social & Clinical Psychology, Vol. 6, 1967, pp. 278-296) and the A. T. Beck, R. A. Steer, & G. K. Brown Beck Depression Inventory (2nd ed.), 1996, Psychological Corporation, San Antonio, TX. Approximately half of the treated participants achieved clinically significant change. Analyses of the follow-up data revealed maintenance of treatment gains in the prison and jail samples. In the prison study, significant changes were also observed on a general measure of psychological distress. Overall, results suggest that cognitive bibliotherapy may be efficacious for depressed inmates. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Emotion regulation in social anxiety disorder: behavioral and neural responses to three socio-emotional tasks

PubMed Central

2013-01-01

Background Social anxiety disorder (SAD) is thought to involve deficits in emotion regulation, and more specifically, deficits in cognitive reappraisal. However, evidence for such deficits is mixed. Methods Using functional magnetic resonance imaging (fMRI) of blood oxygen-level dependent (BOLD) signal, we examined reappraisal-related behavioral and neural responses in 27 participants with generalized SAD and 27 healthy controls (HC) during three socio-emotional tasks: (1) looming harsh faces (Faces); (2) videotaped actors delivering social criticism (Criticism); and (3) written autobiographical negative self-beliefs (Beliefs). Results Behaviorally, compared to HC, participants with SAD had lesser reappraisal-related reduction in negative emotion in the Beliefs task. Neurally, compared to HC, participants with SAD had lesser BOLD responses in reappraisal-related brain regions when reappraising faces, in visual and attention related regions when reappraising criticism, and in the left superior temporal gyrus when reappraising beliefs. Examination of the temporal dynamics of BOLD responses revealed late reappraisal-related increased responses in HC, compared to SAD. In addition, the dorsomedial prefrontal cortex (DMPFC), which showed reappraisal-related increased activity in both groups, had similar temporal dynamics in SAD and HC during the Faces and Criticism tasks, but greater late response increases in HC, compared to SAD, during the Beliefs task. Reappraisal-related greater late DMPFC responses were associated with greater percent reduction in negative emotion ratings in SAD patients. Conclusions These results suggest a dysfunction of cognitive reappraisal in SAD patients, with overall reduced late brain responses in prefrontal regions, particularly when reappraising faces. Decreased late activity in the DMPFC might be associated with deficient reappraisal and greater negative reactivity. Trial registration ClinicalTrials.gov identifier: NCT00380731 PMID:24517388

Further support for the role of dysfunctional attitudes in models of real-world functioning in schizophrenia.

PubMed

Horan, William P; Rassovsky, Yuri; Kern, Robert S; Lee, Junghee; Wynn, Jonathan K; Green, Michael F

2010-06-01

According to A.T. Beck and colleagues' cognitive formulation of poor functioning in schizophrenia, maladaptive cognitive appraisals play a key role in the expression and persistence of negative symptoms and associated real-world functioning deficits. They provided initial support for this model by showing that dysfunctional attitudes are elevated in schizophrenia and account for significant variance in negative symptoms and subjective quality of life. The current study used structural equation modeling to further evaluate the contribution of dysfunctional attitudes to outcome in schizophrenia. One hundred eleven outpatients and 67 healthy controls completed a Dysfunctional Attitudes Scale, and patients completed a competence measure of functional capacity, clinical ratings of negative symptoms, and interview-based ratings of real-world functioning. Patients reported higher defeatist performance beliefs than controls and these were significantly related to lower functional capacity, higher negative symptoms, and worse community functioning. Consistent with Beck and colleagues' formulation, modeling analyses indicated a significant indirect pathway from functional capacity-->dysfunctional attitudes-->negative symptoms-->real-world functioning. These findings support the value of dysfunctional attitudes for understanding the determinants of outcome in schizophrenia and suggest that therapeutic interventions targeting these attitudes may facilitate functional recovery. (c) 2009 Elsevier Ltd. All rights reserved.

White matter and cognition: making the connection

PubMed Central

Fields, R. Douglas

2016-01-01

Whereas the cerebral cortex has long been regarded by neuroscientists as the major locus of cognitive function, the white matter of the brain is increasingly recognized as equally critical for cognition. White matter comprises half of the brain, has expanded more than gray matter in evolution, and forms an indispensable component of distributed neural networks that subserve neurobehavioral operations. White matter tracts mediate the essential connectivity by which human behavior is organized, working in concert with gray matter to enable the extraordinary repertoire of human cognitive capacities. In this review, we present evidence from behavioral neurology that white matter lesions regularly disturb cognition, consider the role of white matter in the physiology of distributed neural networks, develop the hypothesis that white matter dysfunction is relevant to neurodegenerative disorders, including Alzheimer's disease and the newly described entity chronic traumatic encephalopathy, and discuss emerging concepts regarding the prevention and treatment of cognitive dysfunction associated with white matter disorders. Investigation of the role of white matter in cognition has yielded many valuable insights and promises to expand understanding of normal brain structure and function, improve the treatment of many neurobehavioral disorders, and disclose new opportunities for research on many challenging problems facing medicine and society. PMID:27512019

Effects of stimulus salience on touchscreen serial reversal learning in a mouse model of fragile X syndrome

PubMed Central

Dickson, Price E.; Corkill, Beau; McKimm, Eric; Miller, Mellessa M.; Calton, Michele A.; Goldowitz, Daniel; Blaha, Charles D.; Mittleman, Guy

2013-01-01

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in males and the most common genetic cause of autism. Although executive dysfunction is consistently found in humans with FXS, evidence of executive dysfunction in Fmr1 KO mice, a mouse model of FXS, has been inconsistent. One possible explanation for this is that executive dysfunction in Fmr1 KO mice, similar to humans with FXS, is only evident when cognitive demands are high. Using touchscreen operant conditioning chambers, male Fmr1 KO mice and their male wildtype littermates were tested on the acquisition of a pairwise visual discrimination followed by four serial reversals of the response rule. We assessed reversal learning performance under two different conditions. In the first, the correct stimulus was salient and the incorrect stimulus was non-salient. In the second and more challenging condition, the incorrect stimulus was salient and the correct stimulus was non-salient; this increased cognitive load by introducing conflict between sensory-driven (i.e., bottom-up) and task-dependent (i.e., top-down) signals. Fmr1 KOs displayed two distinct impairments relative to wildtype littermates. First, Fmr1 KOs committed significantly more learning-type errors during the second reversal stage, but only under high cognitive load. Second, during the first reversal stage, Fmr1 KOs committed significantly more attempts to collect a reward during the timeout following an incorrect response. These findings indicate that Fmr1 KO mice display executive dysfunction that, in some cases, is only evident under high cognitive load. PMID:23747611

Efficacy of N-Butylphthalide and Hyperbaric Oxygen Therapy on Cognitive Dysfunction in Patients with Delayed Encephalopathy After Acute Carbon Monoxide Poisoning.

PubMed

Xiang, Wenping; Xue, Hui; Wang, Baojun; Li, Yuechun; Zhang, Jun; Jiang, Changchun; Pang, Jiangxia

2017-03-29

BACKGROUND Delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) is one of the most serious complications after CO poisoning. This study was conducted to explore the efficacy of the combined application of N-Butylphthalide and hyperbaric oxygenation therapy (HBO) on cognitive dysfunction in patients with DEACMP. MATERIAL AND METHODS A total of 184 patients with DEACMP were randomly assigned to either receive HBO or N-Butylphthalide and HBO. Meanwhile, all patients received conventional treatment. The total remission rate (RR) was used to assess the clinical efficacy. The Mini-Mental State Examination (MMSE) was used to assess the cognitive function, and the National Institutes of Health Stroke Scale (NIHSS) was used to assess the neurological function. RESULTS Finally, there were 90 and 94 patients in the control and experimental groups, respectively. After eight weeks of treatment, the total RR in the experimental group (47.9%) was significantly higher than that in the control group (33.3%). Compared to the control group, significantly more patients in the experimental group had MMSE scores of 24-30. The lower NIHSS score in the experimental group showed that N-Butylphthalide had the effect of preservation and restoration of neurological function. No obvious drug toxicity or liver and kidney dysfunction was observed, and there was no significant change in the level of blood glucose and blood lipids. CONCLUSIONS These results indicated that the combined application of N-Butylphthalide and HBO could significantly improve the cognitive dysfunction of patients with DEACMP and have great clinical efficacy, which should be further studied.

A role for Kalirin-7 in corticostriatal synaptic dysfunction in Huntington's disease

PubMed Central

Puigdellívol, Mar; Cherubini, Marta; Brito, Verónica; Giralt, Albert; Suelves, Núria; Ballesteros, Jesús; Zamora-Moratalla, Alfonsa; Martín, Eduardo D.; Eipper, Betty A.; Alberch, Jordi; Ginés, Silvia

2015-01-01

Cognitive dysfunction is an early clinical hallmark of Huntington's disease (HD) preceding the appearance of motor symptoms by several years. Neuronal dysfunction and altered corticostriatal connectivity have been postulated to be fundamental to explain these early disturbances. However, no treatments to attenuate cognitive changes have been successful: the reason may rely on the idea that the temporal sequence of pathological changes is as critical as the changes per se when new therapies are in development. To this aim, it becomes critical to use HD mouse models in which cognitive impairments appear prior to motor symptoms. In this study, we demonstrate procedural memory and motor learning deficits in two different HD mice and at ages preceding motor disturbances. These impairments are associated with altered corticostriatal long-term potentiation (LTP) and specific reduction of dendritic spine density and postsynaptic density (PSD)-95 and spinophilin-positive clusters in the cortex of HD mice. As a potential mechanism, we described an early decrease of Kalirin-7 (Kal7), a guanine-nucleotide exchange factor for Rho-like small GTPases critical to maintain excitatory synapse, in the cortex of HD mice. Supporting a role for Kal7 in HD synaptic deficits, exogenous expression of Kal7 restores the reduction of excitatory synapses in HD cortical cultures. Altogether, our results suggest that cortical dysfunction precedes striatal disturbances in HD and underlie early corticostriatal LTP and cognitive defects. Moreover, we identified diminished Kal7 as a key contributor to HD cortical alterations, placing Kal7 as a molecular target for future therapies aimed to restore corticostriatal function in HD. PMID:26464483

Inhibitory saccadic dysfunction is associated with cerebellar injury in multiple sclerosis.

PubMed

Kolbe, Scott C; Kilpatrick, Trevor J; Mitchell, Peter J; White, Owen; Egan, Gary F; Fielding, Joanne

2014-05-01

Cognitive dysfunction is common in patients with multiple sclerosis (MS). Saccadic eye movement paradigms such as antisaccades (AS) can sensitively interrogate cognitive function, in particular, the executive and attentional processes of response selection and inhibition. Although we have previously demonstrated significant deficits in the generation of AS in MS patients, the neuropathological changes underlying these deficits were not elucidated. In this study, 24 patients with relapsing-remitting MS underwent testing using an AS paradigm. Rank correlation and multiple regression analyses were subsequently used to determine whether AS errors in these patients were associated with: (i) neurological and radiological abnormalities, as measured by standard clinical techniques, (ii) cognitive dysfunction, and (iii) regionally specific cerebral white and gray-matter damage. Although AS error rates in MS patients did not correlate with clinical disability (using the Expanded Disability Status Score), T2 lesion load or brain parenchymal fraction, AS error rate did correlate with performance on the Paced Auditory Serial Addition Task and the Symbol Digit Modalities Test, neuropsychological tests commonly used in MS. Further, voxel-wise regression analyses revealed associations between AS errors and reduced fractional anisotropy throughout most of the cerebellum, and increased mean diffusivity in the cerebellar vermis. Region-wise regression analyses confirmed that AS errors also correlated with gray-matter atrophy in the cerebellum right VI subregion. These results support the use of the AS paradigm as a marker for cognitive dysfunction in MS and implicate structural and microstructural changes to the cerebellum as a contributing mechanism for AS deficits in these patients. Copyright © 2013 Wiley Periodicals, Inc.

Controlled randomized clinical trial of spirituality integrated psychotherapy, cognitive-behavioral therapy and medication intervention on depressive symptoms and dysfunctional attitudes in patients with dysthymic disorder.

PubMed

Ebrahimi, Amrollah; Neshatdoost, Hamid Taher; Mousavi, Seyed Ghafur; Asadollahi, Ghorban Ali; Nasiri, Hamid

2013-01-01

Due to the controversy over efficacy of cognitive-behavioral therapy for chronic depression, recently, there has been an increasingly tendency toward therapeutic methods based on the cultural and spiritual approaches. The aim of this research was to compare efficacy of spiritual integrated psychotherapy (SIPT) and cognitive-behavioral therapy (CBT) on the intensity of depression symptoms and dysfunctional attitudes of patients with dysthymic disorder. This study had a mixed qualitative and quantitative design. In the first phase, SIPT model was prepared and, in the second phase, a double-blind random clinical trial was performed. Sixty-two patients with dysthymic disorder were selected from several centers include Nour and Alzahra Medical Center, Counseling Centers of Isfahan University of Medical Sciences and Goldis in Isfahan. The participants were randomly assigned to three experimental groups and one control group. The first group received 8 sessions treatment of SIPT, second groups also had 8 sessions of cognitive-behavioral therapy, which was specific to dysthymic disorder and third group were under antidepressant treatment. Beck depression inventory and dysfunctional attitudes scale were used to evaluate all the participants in four measurement stages. The data were analyzed using MANCOVA repeated measure method. The results revealed that SIPT had more efficacy than medication based on both scales (P < 0.01); however, it was not different from CBT. SIPT was more effective on the modification of dysfunctional attitudes compared with CBT and medication (P < 0.05). These findings supported the efficacy of psychotherapy enriched with cultural capacities and religious teachings.

Current paranoid thinking in patients with delusions: the presence of cognitive-affective biases.

PubMed

Freeman, Daniel; Dunn, Graham; Fowler, David; Bebbington, Paul; Kuipers, Elizabeth; Emsley, Richard; Jolley, Suzanne; Garety, Philippa

2013-11-01

There has been renewed interest in the influence of affect on psychosis. Psychological research on persecutory delusions ascribes a prominent role to cognitive processes related to negative affect: anxiety leads to the anticipation of threat within paranoia; depressive negative ideas about the self create a sense of vulnerability in which paranoid thoughts flourish; and self-consciousness enhances feelings of the self as a target. The objective of this study was to examine such affective processes in relation to state paranoia in patients with delusions. 130 patients with delusions in the context of a nonaffective psychosis diagnosis (predominately schizophrenia) were assessed for contemporaneous levels of persecutory ideation on 5 visual analog scales. Measures were taken of anxiety, depression, threat anticipation, interpretation of ambiguity, self-focus, and negative ideas about the self. Of the patients, 85% report paranoid thinking at testing. Symptoms of anxiety and depression were highly prevalent. Current paranoid thinking was associated with anxiety, depression, greater anticipation of threat events, negative interpretations of ambiguous events, a self-focused cognitive style, and negative ideas about the self. The study provides a clear demonstration that a range of emotion-related cognitive biases, each of which could plausibly maintain delusions, are associated with current paranoid thinking in patients with psychosis. We identified biases both in the contents of cognition and in the processing of information. Links between affect and psychosis are central to the understanding of schizophrenia. We conclude that treatment of emotional dysfunction should lead to reductions in current psychotic experiences.

Effects of amyloid and small vessel disease on white matter network disruption.

PubMed

Kim, Hee Jin; Im, Kiho; Kwon, Hunki; Lee, Jong Min; Ye, Byoung Seok; Kim, Yeo Jin; Cho, Hanna; Choe, Yearn Seong; Lee, Kyung Han; Kim, Sung Tae; Kim, Jae Seung; Lee, Jae Hong; Na, Duk L; Seo, Sang Won

2015-01-01

There is growing evidence that the human brain is a large scale complex network. The structural network is reported to be disrupted in cognitively impaired patients. However, there have been few studies evaluating the effects of amyloid and small vessel disease (SVD) markers, the common causes of cognitive impairment, on structural networks. Thus, we evaluated the association between amyloid and SVD burdens and structural networks using diffusion tensor imaging (DTI). Furthermore, we determined if network parameters predict cognitive impairments. Graph theoretical analysis was applied to DTI data from 232 cognitively impaired patients with varying degrees of amyloid and SVD burdens. All patients underwent Pittsburgh compound-B (PiB) PET to detect amyloid burden, MRI to detect markers of SVD, including the volume of white matter hyperintensities and the number of lacunes, and detailed neuropsychological testing. The whole-brain network was assessed by network parameters of integration (shortest path length, global efficiency) and segregation (clustering coefficient, transitivity, modularity). PiB retention ratio was not associated with any white matter network parameters. Greater white matter hyperintensity volumes or lacunae numbers were significantly associated with decreased network integration (increased shortest path length, decreased global efficiency) and increased network segregation (increased clustering coefficient, increased transitivity, increased modularity). Decreased network integration or increased network segregation were associated with poor performances in attention, language, visuospatial, memory, and frontal-executive functions. Our results suggest that SVD alters white matter network integration and segregation, which further predicts cognitive dysfunction.

Application and validation of the barrow neurological institute screen for higher cerebral functions in a control population and in patient groups commonly seen in neurorehabilitation.

PubMed

Hofgren, Caisa; Esbjörnsson, Eva; Aniansson, Hans; Sunnerhagen, Katharina Stibrant

2007-09-01

To determine whether the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) can differentiate brain-dysfunctional patients from controls. A case-control study. A total of 92 controls and 120 patients from a neuro-rehabilitation clinic with a diagnosis of: right and left hemisphere stroke, traumatic brain injury, Parkinson's disease or anoxic brain damage. The BNIS has a maximum total score of 50 points, < 47 indicates cognitive dysfunction. Group comparisons and exploration of variables influencing the BNIS total score were made. A significant difference was found between the control group and the total patient group for the BNIS total score and for the subscales (p < 0.0005). Sensitivity was 88% and specificity 78%. Presence of disease and educational level had the greatest influence on the results of the BNIS. Patients with Parkinson's disease were shown to be the least cognitively affected and those with anoxic brain damage the most affected. The BNIS has potential value as a screening instrument for cognitive functions and is sufficiently sensitive to differentiate brain-dysfunctional patients from a control population. It appears to be applicable in a neurological rehabilitation setting, and can be used early in the process, giving a baseline cognitive functional level.

Human recombinant erythropoietin reduces sensorimotor dysfunction and cognitive impairment in rat models of chronic kidney disease.

PubMed

Reza-Zaldívar, E E; Sandoval-Avila, S; Gutiérrez-Mercado, Y K; Vázquez-Méndez, E; Canales-Aguirre, A A; Esquivel-Solís, H; Gómez-Pinedo, U; Márquez-Aguirre, A L

2017-11-10

Chronic kidney disease (CKD) can cause anaemia and neurological disorders. Recombinant human erythropoietin (rHuEPO) is used to manage anaemia in CKD. However, there is little evidence on the effects of rHuEPO on behaviour and cognitive function in CKD. This study aimed to evaluate the impact of rHuEPO in sensorimotor and cognitive functions in a CKD model. Male Wistar rats were randomly assigned to 4 groups: control and CKD, with and without rHuEPO treatment (1050 IU per kg body weight, once weekly for 4 weeks). The Morris water maze, open field, and adhesive removal tests were performed simultaneously to kidney damage induction and treatment. Markers of anaemia and renal function were measured at the end of the study. Treatment with rHuEPO reduced kidney damage and corrected anaemia in rats with CKD. We observed reduced sensorimotor dysfunction in animals with CKD and treated with rHuEPO. These rats also completed the water maze test in a shorter time than the control groups. rHuEPO reduces kidney damage, corrects anemia, and reduces sensorimotor and cognitive dysfunction in animals with CKD. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Treatment of Cognitive Impairment in Multiple Sclerosis

PubMed Central

Pierson, Susan H.; Griffith, Nathan

2006-01-01

Cognitive impairment in multiple sclerosis is an increasingly recognized entity. This article reviews the cognitive impairment of multiple sclerosis, its prevalence, its relationship to different types of multiple sclerosis, and its contribution to long-term functional prognosis. The discussion also focuses on the key elements of cognitive dysfunction in multiple sclerosis which distinguish it from other forms of cognitive impairment. Therapeutic interventions potentially effective for the cognitive impairment of multiple sclerosis are reviewed including the effects of disease modifying therapies and the use of physical and cognitive interventions. PMID:16720960

Functional aging impairs the role of feedback in motor learning.

PubMed

Liu, Yu; Cao, Chunmei; Yan, Jin H

2013-10-01

Optimal motor skill acquisition frequently requires augmented feedback or knowledge of results (KR). However, the effect of functional declines on the benefits of KR remains to be determined. The objective of this research was to examine how cognitive and motor deficits of older adults influence the use of KR for motor skill learning. A total of 57 older adults (mean 73.1 years; SD 4.2) received both cognitive and eye-hand coordination assessments, whereas 55 young controls (mean 25.8 years; SD 3.8) took only the eye-hand coordination test. All young and older participants learned a time-constrained arm movement through KR in three pre-KR and post-KR intervals. In the subsequent no-KR skill retests, absolute and variable time errors were not significantly reduced for the older learners who had KR during skill practice, especially for those with cognitive and motor dysfunctions. The finding suggests that KR results in no measureable improvement for older adults with cognitive and motor functional deficiencies. More importantly, for the older adults, longer post-KR intervals showed greater detrimental effects on feedback-based motor learning than shorter pauses after KR delivery. The findings support the hypothesis about the effects of cognitive and motor deficits on KR in motor skill learning of older adults. The dynamics of cognitive and motor aging, external feedback and internal control mechanisms collectively explain the deterioration in the sensory-motor learning of older adults. The theoretical implications and practical relevance of functional aging for motor skill learning are discussed. © 2013 Japan Geriatrics Society.

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.

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.