Cognitive impairment and functional disability in the absence of psychiatric diagnosis

Data from the 1981 East Baltimore Mental Health Survey were used to examine the relationship between cognitive impairment and psychiatric diagnosis in an adult population. The Mini-Mental State Examination was administered to 3841 household respondents and a subset of 810 received psychiatric evaluations. Of the 810, 23% were found to be cognitively impaired. Over one-third of those with cognitive impairment, however, did not meet DSM-III criteria for a psychiatric diagnosis. Education, geographical background, race and neurological status were predictive of cognitive performance. There was no linear effect of age on cognitive performance with disease status and education controlled. In addition to their cognitive impairment these individuals, who ranged in age from 19 to 89, were found to have significant functional disabilities. Cognitive performance itself, along with physical and emotional health, predicted total functional disability.     

Self- and informant reports of executive function on the BRIEF-A in MCI and older adults with cognitive complaints.

Amnestic mild cognitive impairment (MCI) is characterized by impaired episodic memory, although subtle executive problems have been noted on neuropsychological tests. Recent research also has described a group of healthy, non-depressed older adults with significant cognitive complaints (CC) but normal performance on neuropsychological testing. These individuals show structural and functional brain changes intermediate between those seen in MCI and healthy older adults without such complaints (HC). We evaluated executive functions in MCI and CC using the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A), a newly developed self- and informant report questionnaire in 29 patients with amnestic MCI, 28 CCs, and 30 demographically matched HCs. MCI and CC participants reported significant difficulties with selective aspects of executive functioning relative to HCs despite clinically normal performance on neuropsychological tests of this cognitive domain. Scores were generally in the pattern of MCI>CC>HC, and findings were most pronounced for working memory. Additionally, MCI and CC participants were more likely than their informants to report clinically meaningful executive problems, though informants identified a similar pattern of difficulty overall. Results failed to reveal strong relations between the BRIEF-A and standardized neuropsychological tests of executive function. Overall findings indicate that the BRIEF-A is sensitive to subtle executive changes in MCI and CC and suggest the need for research to determine if executive complaints are predictive of clinical course.     

Sleep and its associations with perceived and objective cognitive impairment in individuals with multiple sclerosis

Problems with sleep and cognitive impairment are common among people with multiple sclerosis (MS). The present study examined the relationship between self‐reported sleep and both objective and perceived cognitive impairment in MS. Data were obtained from the baseline assessment of a multi‐centre intervention trial (NCT00841321). Participants were 121 individuals with MS. Nearly half (49%) of participants met the criteria for objective cognitive impairment; however, cognitively impaired and unimpaired participants did not differ on any self‐reported sleep measures. Nearly two‐thirds (65%) of participants met the criteria for ‘poor’ sleep, and poorer sleep was significantly associated with greater levels of perceived cognitive impairment. Moreover, the relationships between self‐reported sleep and perceived cognitive impairment were significant beyond the influence of clinical and demographic factors known to influence sleep and cognitive functioning (e.g. age, sex, education level, disability severity, type of MS, disease duration, depression and fatigue). However, self‐reported sleep was not associated with any measures of objective cognitive impairment. Among different types of perceived cognitive impairment, poor self‐reported sleep was most commonly related to worse perceived executive function (e.g. planning/organization) and prospective memory. Results from the present study emphasize that self‐reported sleep is significantly and independently related to perceived cognitive impairment in MS. In terms of clinical implications, interventions focused on improving sleep may help improve perceived cognitive function and quality of life in this population; however, the impact of improved sleep on objective cognitive function requires further investigation.     

Association Between Sleep Problems and Perceived Cognitive Dysfunction Over 12 Months in Individuals with Multiple Sclerosis

Sleep problems are highly prevalent among individuals with multiple sclerosis (MS); however, the relationship between sleep problems and cognitive dysfunction is poorly understood in this population. In the present study, 163 individuals with MS and depression, fatigue, or pain completed self-report measures of sleep, cognitive dysfunction, and relevant demographic and clinical characteristics (e.g., disability severity, depressive symptomatology, pain intensity, fatigue impact) at four time points over 12 months. Mixed-effects regression demonstrated that poorer sleep was independently associated with worse perceived cognitive dysfunction (β = –0.05, p = .001), beyond the influence of depressive symptomatology. Fatigue impact was found to partially mediate this relationship. Results suggest that for individuals with MS and depression, fatigue, or pain, self-reported sleep problems are related to perceived cognitive dysfunction, and that fatigue impact accounts for part of this relationship.     

The measurement of everyday cognition (ECog): scale development and psychometric properties

This article describes the development and validation of an instrument to assess cognitively mediated functional abilities in older adults, Everyday Cognition (ECog). The ECog is an informant-rated questionnaire comprised of multiple subscales. Confirmatory factor analysis (CFA) was used to examine its factor structure. Convergent validity was evaluated by comparing it to established measures of everyday function. External validity was evaluated by comparing ECog results across different clinical groups [cognitively normal, mild cognitive impairment (MCI), dementia]. CFA supported a seven-factor model including one global factor and six domain-specific factors (Everyday Memory, Language, Visuospatial Abilities, Planning, Organization, and Divided attention). The ECog correlated with established measures of functional status and global cognition, but only weakly with age and education. The clinical groups performed differently in each domain. In addition to the global factor, the Everyday Memory factor independently differentiated MCI from Normal, while the Everyday Language domain differentiated Dementia from MCI. Different subtypes of MCI also showed different patterns. Results suggest the ECog shows promise as a useful tool for the measurement of general and domain-specific everyday functions in the elderly.     

Relationship of the Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) to functional, emotional, and neuropsychological outcomes

OBJECTIVE: To explore the relationship of the Multiple Sclerosis Neuropsychology Questionnaire (MSNQ; [Benedict, R. H. B., Cox, D., Thompson, L. L., Foley, F., Weinstock-Guttman, B., & Munschauer, F. (2004). Reliable screening for neuropsychological impairment in multiple sclerosis. Multiple Sclerosis, 10, 675-678; Benedict, R. H. B., Munschauer, F., Linn, R., Miller, C., Murphy, E., Foley, F., et al. (2003). Screening for multiple sclerosis cognitive impairment using a self-administered 15-item questionnaire. Multiple Sclerosis, 9, 95-101]), a self-report screening measure of neuropsychological functioning in multiple sclerosis (MS), with everyday life functioning, neuropsychological functioning, and mood in MS. Additionally, to investigate the validity, sensitivity, and specificity of the MSNQ to predict cognitive impairment in persons with MS. STUDY DESIGN: Cross-sectional, correlational analyses; analyses of sensitivity and specificity. SETTING: Neuropsychology lab-based study with adults from the community including persons with MS (n=48) and healthy adults (n=40). MAIN OUTCOME MEASURES: Subjective and objective measures of everyday life functioning, neuropsychological functioning, and mood; ROC curve of MSNQ-Self report and MSNQ-Informant report, sensitivity and specificity of MSNQ-S and MSNQ-I. RESULTS: Correlational analyses indicate the MSNQ-S is significantly correlated with mood and self-reports of functioning, but not with objectively measures daily functioning and to only few neuropsychological tests. The MSNQ-I was not significantly correlated to mood, self-report of daily functioning or objectively measured daily functioning, but was significantly correlated with several measures of neuropsychological functioning. CONCLUSION: The MSNQ-S was not supported as a sensitive screen for neuropsychological impairment in MS. However, the MSNQ-I was supported as a valid and sensitive screen of cognitive impairment in persons with MS, although further research is needed to determine an optimal cutoff score for this measure.     

Longitudinal Neuropsychological Assessment in Pediatric Multiple Sclerosis

Although Multiple Sclerosis (MS) occurring in childhood and adolescence has received increasing attention in recent years, the impact of the disease on cognitive function in this subgroup remains poorly understood. It has been posited that children and adolescents with MS may be particularly susceptible to cognitive dysfunction because the pathological processes, including inflammation, blood brain barrier breakdown, and demyelination, occur concurrently with ongoing myelination. Early work has documented that a number of these children present with cognitive deficits. However, there is no available information on the progression of these deficits, or on what clinical factors may predict further decline. The current article reviews what is currently known about pediatric MS and follows a cohort of pediatric MS patients and assesses cognitive function longitudinally. Participants were evaluated with a brief neuropsychological test battery on two separate occasions and correlational analyses assessed the relations between changes in cognition and several clinical variables including level of neurologic impairment, number of relapses prior to baseline assessment, number of interim relapses, age of disease onset, and disease length. The results indicate that a number of these patients experience further cognitive decline over time, or decline from previously normal functioning. Baseline level of neurologic disability was significantly correlated with changes in cognition. The number of interim relapses (i.e., relapses occurring between baseline assessment and re-evaluation) showed a modest relationship to changes in cognitive function, but this did not reach statistical significance.     

Longitudinal neuropsychological assessment in pediatric multiple sclerosis

Although Multiple Sclerosis (MS) occurring in childhood and adolescence has received increasing attention in recent years, the impact of the disease on cognitive function in this subgroup remains poorly understood. It has been posited that children and adolescents with MS may be particularly susceptible to cognitive dysfunction because the pathological processes, including inflammation, blood brain barrier breakdown, and demyelination, occur concurrently with ongoing myelination. Early work has documented that a number of these children present with cognitive deficits. However, there is no available information on the progression of these deficits, or on what clinical factors may predict further decline. The current article reviews what is currently known about pediatric MS and follows a cohort of pediatric MS patients and assesses cognitive function longitudinally. Participants were evaluated with a brief neuropsychological test battery on two separate occasions and correlational analyses assessed the relations between changes in cognition and several clinical variables including level of neurologic impairment, number of relapses prior to baseline assessment, number of interim relapses, age of disease onset, and disease length. The results indicate that a number of these patients experience further cognitive decline over time, or decline from previously normal functioning. Baseline level of neurologic disability was significantly correlated with changes in cognition. The number of interim relapses (i.e., relapses occurring between baseline assessment and re-evaluation) showed a modest relationship to changes in cognitive function, but this did not reach statistical significance.     

Effects of cerebrovascular disease and amyloid beta burden on cognition in subjects with subcortical vascular cognitive impairment

Cerebrovascular disease (CVD) and amyloid burden are the most frequent pathologies in subjects with cognitive impairment. However, the relationship between CVD, amyloid burden, and cognition are largely unknown. We aimed to evaluate whether CVD (lacunes, white matter hyperintensities, and microbleeds) and amyloid burden (Pittsburgh compound B [PiB] retention ratio) contribute to cognitive impairment independently or interactively. We recruited 136 patients with subcortical vascular cognitive impairment who underwent magnetic resonance imaging, PiB–positron emission tomography, and neuropsychological testing. The number of lacunes was associated with memory, frontal dysfunctions, and disease severity. The volume of white matter hyperintensities and the PiB retention ratio were associated only with memory dysfunction. There was no direct correlation between CVD markers and PiB retention ratio except that the number of lacunes was negatively correlated with the PiB retention ratio. In addition, there were no interactive effects of CVD and PiB retention ratio on cognition. Our findings suggest that CVD and amyloid burden contribute independently and not interactively to specific patterns of cognitive dysfunction in patients with subcortical vascular cognitive impairment.     

Coffee with jelly or unbuttered toast: commissions and omissions are dissociable aspects of everyday action impairment in Alzheimer's disease

Relative to our understanding of the memory and language deficits associated with Alzheimer's disease (AD), little is known about problems with everyday action performance (i.e., meal preparation, grooming). The resource theory proposes that everyday action problems are best explained by a unitary deficit in general cognitive resources. However, recent research suggests that omission and commission errors may reflect dissociable aspects of action impairment, with only omissions associated with resource limitations. This study examined everyday action performance in 70 participants with AD who also underwent a neuropsychological evaluation. First, correlation and principal component analyses were performed to examine the construct(s) that might explain everyday action impairment. Second, relations between everyday task component(s) and neuropsychological tests were examined by using correlation and regression analyses. Third, differences in everyday action error patterns were examined among participants of comparable overall impairment levels. Results showed omission and commission errors were uncorrelated and distinct components of everyday action performance, predicted by different neuropsychological tests, and differentially distributed even among participants with comparable overall impairment.     

Insulin resistance is associated with cognition among HIV-1-infected patients: the Hawaii Aging With HIV cohort

OBJECTIVE: To determine if insulin resistance (IR) is associated with lower cognitive performance among HIV-1-infected adults and to determine if advanced age magnifies risk. DESIGN: Cross-sectional analysis within the Hawaii Aging With HIV Cohort. METHODS: We calculated the homeostasis model assessment of insulin resistance (HOMA-IR) among 145 cohort participants. Values were compared to concurrent neuropsychological test performance and cognitive diagnoses. RESULTS: Hypertension, body mass index (BMI), and non-Caucasian self-identity were directly related to insulin resistance (IR); however, age, CD4 lymphocyte count, and rates of treatment with HAART were not. In logistic regression analyses and stratifying cognition status on a 3-tiered scale (normal, minor cognitive motor disorder (MCMD), and HIV-associated dementia (HAD)), we identified an increased risk of meeting a higher diagnostic category as HOMA-IR increased (OR, 1.12; 95% CI: 1.003 to 1.242 per unit of HOMA-IR, P = 0.044). In linear regression models and among nondiabetic participants, an increasing degree of IR was associated with lower performance on neuropsychological summary scores. CONCLUSIONS: IR is associated with cognitive dysfunction in this contemporary HIV-1 cohort enriched with older individuals. Metabolic dysfunction may contribute to the multifactorial pathogenesis of cognitive impairment in the era of HAART.     

The ecological validity of clinical tests of memory and attention in multiple sclerosis.

Ecological validity--the degree to which clinical tests of cognitive functioning predict functional impairment--has recently become an area of interest in neuropsychology. The current study used a sample of 31 cognitively and functionally impaired multiple sclerosis (MS) patients to determine if tests commonly used to assess memory and attentional functioning in MS are ecologically valid. Two methods of improving the ecological validity of cognitive testing were employed. Stepwise multiple regression analyses suggested that tests of memory and attention more analogous to everyday tasks are better predictors of functional impairment in MS than both standard clinical tests of memory and attention, and memory questionnaires completed by the patient or a significant other. Nonetheless, both standard clinical tests and more ecologically valid tests significantly predicted functional impairment. Importantly, they were not significantly correlated with one another, suggesting that the inclusion of both types of tests in evaluating MS patients is warranted.     

The ability of the Dementia Rating Scale to predict everyday functioning.

The Dementia Rating Scale (DRS) is a brief neuropsychological assessment battery designed to assess five areas of cognitive functioning in the elderly. The relationship between DRS performance and everyday functioning was examined for 50 psychogeriatric patients. Everyday functioning was assessed with a standardized performance measure examining self-care, safety, money management, cooking, medication administration, and community utilization. Regression analyses were conducted for each of the six functional domains. In addition, correlations between the DRS subscales and the functional areas were computed. Results revealed significant predictive relationships (p <.01) between performance on the DRS and most functional domains. The multiple Rs ranged from .52 - .70, accounting for 27% to 49% of the variance. The Initiation/Perseveration subscale was most heavily weighted in each analysis. Significant correlations were obtained between subdomains of cognition and most functional areas. The findings provide evidence of relationships between DRS performance and functional ability.     

The relationship between neuropsychological performance and daily functioning in individuals with Alzheimer's disease: ecological validity of neuropsychological tests.

The current study examined the relationship between neuropsychological test performance and functional status in 42 individuals diagnosed with Alzheimer's disease. A comprehensive battery of cognitive tests was employed in order to assess a wide range of neuropsychological abilities. Functional status was measured through the use of both a performance-based scale of activities of daily living (an expanded version of the Direct Assessment of Functional Status; DAFS, Loewenstein et al., 1989), and by a caregiver/informant-based rating scale (Instrumental Activities of Daily Living; IADL, Lawton & Brody, 1969). Findings suggest that neuropsychological functioning is moderately predictive of functional status. Using multiple regression analyses, neuropsychological variables accounted for 25% of the variance in the IADL and 50% of the variance in the DAFS. Individual domains of both functional measures were also significantly predicted by the neuropsychological variables. The findings provide evidence of a relationship between neuropsychological test performance and ADLs in an Alzheimer disease patient population.     

Cerebrovascular risk factors do not contribute to genetic variance of cognitive function: the ERF study

Impaired cognition in later life may result from Alzheimer's disease-related pathology, but also from vascular pathology. We studied to what extent vascular risk explained heritability of cognition in 780 individuals, related in one extended pedigree in a genetically isolated population, in the ERF study. Heritability was estimated using variance components modelling (SOLAR). Univariate analyses included models with and without vascular disease; bivariate analyses included both cognitive and vascular traits, such as blood pressure, serum glucose or lipids. Heritability for immediate and delayed recall, recognition, semantic fluency, Trail making B and Stroop tests was significant, with estimates from 0.16 to 0.36. Vascular factors did not affect cognitive functions, except immediate recall and the Stroop test. Heritability estimates did not change significantly when adjusted for vascular disease. We found no genetic correlation between cognition and vascular traits. Therefore, in this population vascular disease is mildly associated with cognitive dysfunction, and in those with vascular disease, the underlying genetic risk factors are not likely to account for the genetic variation in cognition at adult age.     

Growth hormone releasing hormone improves the cognition of healthy older adults

Declines in the activity of the somatotrophic axis have been implicated in the age-related changes observed in a number of physiological functions, including cognition. Such age-related changes may be arrested or partially reversed by hormonal supplementation. We examined the effect of 6 months treatment with daily growth hormone releasing hormone (GHRH) or placebo on the cognition of a group of 89 healthy older (68.0+/-0.7) adults. GHRH resulted in improved performance on WAIS-R performance IQ (p<0.01), WAIS-R picture arrangement (p<0.01), finding A's (p<0.01), verbal sets (p<0.01) and single-dual task (p<0.04). GHRH-based improvements were independent of gender, estrogen status or baseline cognitive capacity. These results demonstrate that the age-related decline in the somatotrophic axis may be related to age-related decline in cognition. Further they indicate that supplementation of this neuro-hormonal axis may partially ameliorate such cognitive declines in healthy normal older adults and potentially in individuals with impaired cognitive function (i.e., mild cognitive impairment and Alzheimer's disease).     

Cognitive intervention for persons with mild cognitive impairment: A meta-analysis

Cognitive training for persons with mild cognitive impairment (MCI) has become a hot topic. However to date it remains controversial whether persons with MCI can really benefit from cognitive intervention. We aim to further investigate this by using meta-analysis of seventeen clinical studies of cognitive intervention for MCI. The results demonstrate that after training, patients with MCI improve significantly both in overall cognition and overall self-ratings. Specifically, persons with MCI obtain moderate benefits in language, self-rated anxiety and functional ability, and receive mild benefits in episodic memory, semantic memory, executive functioning/working memory, visuo-spatial ability, attention/processing speed, MMSE, self-rated memory problem, quality of life, activities of daily life and self-rated depression. The results also suggest that persons with MCI benefit from the cognitive intervention in the follow-up data. The present meta-analysis demonstrates that cognitive intervention can be a potential efficient method to enhance cognitive and functional abilities in persons with MCI, although the improvements may be domain-specific.     

The effects of aerobic exercise and transcranial direct current stimulation on cognitive function in older adults with and without cognitive impairment: A systematic review and meta-analysis

BackgroundAerobic exercise (AE) may slow age-related cognitive decline. However, such cognition-sparing effects are not uniform across cognitive domains and studies. Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation and is also emerging as a potential alternative to pharmaceutical therapies. Like AE, the effectiveness of tDCS is also inconsistent for reducing cognitive impairment in ageing. The unexplored possibility exists that pairing AE and tDCS could produce synergistic effects and reciprocally augment cognition-improving effects in older individuals with and without cognitive impairments.Previous research found such synergistic effects on cognition when cognitive training is paired with tDCS in older individuals with and without mild cognitive impairment (MCI) or dementia.AimThe purpose of this systematic review with meta-analysis was to explore if pairing AE with tDCS could augment singular effects of AE and tDCS on global cognition (GC), working memory (WM) and executive function (EF) in older individuals with or without MCI and dementia.MethodsUsing a PRISMA-based systematic review, we compiled studies that examined the effects of AE alone, tDCS alone, and AE and tDCS combined on cognitive function in older individuals with and without mild cognitive impairment (MCI) or dementia. Using a PICOS approach, we systematically searched PubMed, Scopus and Web of Science searches up to December 2021, we focused on ‘MoCA’, ‘MMSE’, ‘Mini-Cog’ (measures) and ‘cognition’, ‘cognitive function’, ‘cognitive’, ‘cognitive performance’, ‘executive function’, ‘executive process’, ‘attention’, ‘memory’, ‘memory performance’ (outcome terms). We included only randomized controlled trials (RTC) in humans if available in English full text over the past 20 years, with participants’ age over 60. We assessed the methodological quality of the included studies (RTC) by the Physiotherapy Evidence Database (PEDro) scale.ResultsOverall, 68 studies were included in the meta-analyses. AE (ES = 0.56 [95% CI: 0.28–0.83], p = 0.01) and tDCS (ES = 0.69 [95% CI: 0.12–1.26], p = 0.02) improved GC in all three groups of older adults combined (healthy, MCI, demented). In healthy population, AE improved GC (ES = 0.46 [95% CI: 0.22–0.69], p = 0.01) and EF (ES = 0.27 [95% CI: 0.05–0.49], p = 0.02). AE improved GC in older adults with MCI (ES = 0.76 [95% CI: 0.21–1.32], p = 0.01). tDCS improved GC (ES = 0.69 [90% CI: 0.12–1.26], p = 0.02), all three cognitive function (GC, WM and EF) combined in older adults with dementia (ES = 1.12 [95% CI: 0.04–2.19], p = 0.04) and improved cognitive function in older adults overall (ES = 0.69 [95% CI: 0.20–1,18], p = 0.01).ConclusionOur systematic review with meta-analysis provided evidence that beyond the cardiovascular and fitness benefits of AE, pairing AE with tDCS may have the potential to slow symptom progression of cognitive decline in MCI and dementia. Future studies will examine the hypothesis of this present review that a potentiating effect would incrementally improve cognition with increasing severity of cognitive impairment.     

Interferon-gamma- and interleukin-4-producing T cells in Down's syndrome

Down's syndrome (DS) associates with genetic-dependent dysregulation of the interferon (IFN) system. We used intracellular cytokine staining to analyse the percentages of IFN-gamma- and interleukin (IL)-4-producing T cells in the peripheral blood of patients with DS, individuals with mental retardation (MR), and healthy controls (HCs). The percentages of IFN-gamma-producing CD4(+) and CD8(+) T cells (IFGCs), namely Th1 (mean, 21.4+/-S.D. 1.3) and Tc1 (12.6+/-1.1), and the Th1/Th2 ratio (6.1+/-0.2) in DS were significantly higher than in MR (15.9+/-1.3, 7.9+/-0.6, 4.8+/-0.3) and in HCs (15.6+/-1.9, 7.2+/-1.1, 4.6+/-0.6). Most of the DS patients with high IFGC percentages were seropositive for anti-transglutaminase IgA. We found no correlation between sex, age, APOE genotypes, coexisting autoimmune diseases, susceptibility to infections, or degree of cognitive impairment and high IFGC percentages. This abnormality might thus contribute to immune dysfunction in DS without manifest clinical correlates.     

Clinical correlations of microstructural changes in progressive supranuclear palsy

In patients with progressive supranuclear palsy (PSP), previous reports have shown a severe white matter (WM) damage involving supra and infratentorial regions including cerebellum. In the present study, we investigated potential correlations between WM integrity loss and clinical-cognitive features of patients with PSP. By using magnetic resonance imaging and diffusion tensor imaging with tract based spatial statistic analysis, we analyzed WM volume in 18 patients with PSP and 18 healthy controls (HCs). All patients and HCs underwent a detailed clinical and neuropsychological evaluation. Relative to HCs, patients with PSP showed WM changes encompassing supra and infratentorial areas such as corpus callosum, fornix, midbrain, inferior fronto-occipital fasciculus, anterior thalamic radiation, superior cerebellar peduncle, superior longitudinal fasciculus, uncinate fasciculus, cingulate gyrus, and cortico-spinal tract bilaterally. Among different correlations between motor-cognitive features and WM structural abnormalities, we detected a significant association between fronto-cerebellar WM loss and executive cognitive impairment in patients with PSP. Our findings, therefore, corroborate the hypothesis that cognitive impairment in PSP may result from both “intrinsic” and “extrinsic” frontal lobe dysfunction, likely related to cerebellar disconnection.