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PubMed1997

Premorbid brain size as a determinant of reserve capacity against intellectual decline in Alzheimer's disease.

OBJECTIVE: Both the magnitude of brain atrophy and premorbid brain size determine the volume of the brain affected by Alzheimer's disease. To examine the possibility that premorbid brain volume is a determinant of cognitive reserve in patients with Alzheimer's disease, the relation between diffuse brain atrophy and cognitive decline and the impact of premorbid brain size on cognitive decline were studied in patients with Alzheimer's disease. METHOD: By measuring whole brain volume and intracranial volume in 60 patients with probable Alzheimer's disease, mild to moderate in severity, with the use of high-resolution magnetic resonance imaging and image processing, the authors studied the impact of premorbid brain volume and magnitude of diffuse brain atrophy on cognitive functions. On the basis of the normative brain-calvarium relationship derived from data an 28 healthy adults and the total intracranial volume measure of each patient, the magnitude of brain atrophy and premorbid brain volume were estimated. RESULTS: After control for the effects of age, sex, and education as confounding factors, it was found that the Alzheimer's disease patients' intelligence was correlated both positively with premorbid brain volume and negatively with magnitude of brain atrophy, while impairments in language and memory were correlated with magnitude of brain atrophy but not with premorbid brain volume. CONCLUSIONS: These findings partially support the hypothesis that premorbid brain volume is a determinant of reserves against intellectual decline in Alzheimer's disease.

Adult↗
PubMed2002

Dementia epidemiology.

Determining the incidence and prevalence of dementia is an inexact science. Dementia is difficult to define and detect in the population. Even with the difficulties of determining prevalence and incidence, it is clear that dementia causes a substantial burden on our society. Problems with diagnostic inaccuracy and insidious disease onset influence our ability to observe risk factor associations; factors related to survival may be mistaken for risk/protective factors. Current studies suggest that factors influencing brain development or cognitive reserve may delay the onset of AD, perhaps through a protective mechanism or a delay in diagnosis caused by improved performance on cognitive tests. The recent identification of genes that cause dementia suggests that these genes or their biochemical pathways may be involved in the pathogenesis of nonfamilial cases. The contribution of genes that cause disease in and of themselves may be smaller than that of genes that act to metabolize or potentiate environmental exposures. The interaction between gene and environment should be increasingly well studied in the future. Epidemiology must take advantage of these molecular advances. The tasks of public health and epidemiology should still involve prevention, the nonrandom occurrence of disease, and its environmental context in addition to heredity. The tools to address these tasks should continue to be refined.

Aged↗
PubMed2000

Estimated premorbid intelligence mediates neurobehavioral change in individuals infected with HIV across 12 months.

This study tested whether estimated premorbid intelligence moderates worsening neurobehavioral dysfunction in HIV infection. 155 homosexual men (54 controls, 49 HIV+ asymptomatic, 24 HIV+ symptomatic, 28 AIDS) with stable disease status were tested on measures of executive function at baseline and 12-month follow-up. Premorbid intelligence was estimated on the basis of a demographically-based regression equation (Hamsher, 1984), and participants were classified as average or above-average intelligence. Regardless of disease status, participants with above-average IQ showed no declines on measures of executive function across time. In contrast, among those with average IQ, symptomatic groups showed declines, whereas the asymptomatic group did not. The findings support the hypothesis that estimated premorbid intelligence mediates declines in neuropsychological function in patients with stable HIV status. These findings are consistent with theoretical models of cognitive reserve capacity.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Influence of education on the benton visual retention test performance as mediated by a strategic search component.

Age-related cognitive decline has been reported by several studies. However, little investigations have dealt with the effect of education on this decline. In the present study, we examined the influence of educational level on visual working memory, evaluated by the Benton Visual Retention Test (BVRT in recognition format) in 829 elderly participants of the PAQUID study. A multivariate linear model suggested that the effect of education on BVRT performance was not mediated by visual discrimination abilities suggesting that it was mainly supported by better executive abilities. Moreover, the analysis of success and error location suggested that subjects with higher educational level use a more exhaustive exploration strategy during the recognition phase than subjects with lower educational level, which permit them to better perform. The ability of high educational level subjects to use more efficient strategies may participate to the 'cognitive reserve' capacity.

Aged↗
PubMed1998

Senile degeneration and cognitive impairment in chronic schizophrenia.

OBJECTIVE: This study was an investigation of the role of Alzheimer-type senile degenerative abnormalities in the cognitive impairment of chronic schizophrenia. METHOD: The study group comprised 145 deceased elderly institutionalized psychiatric patients: 66 with schizophrenia, 26 with mood disorders, 36 with dementia, and 17 with other psychiatric diagnoses. The comparison group included 16 deceased elderly individuals without neurologic or psychiatric disease. Psychiatric diagnoses and cognitive status were established by standardized review of medical records. Neuritic senile plaques and neurofibrillary tangles were identified immunohistochemically and counted, by investigators blind to clinical information, in standardized regions of each brain. RESULTS: Of the subjects with schizophrenia, 68% had definite cognitive impairment, but only 8% satisfied neuropathological criteria for Alzheimer's disease. Among the schizophrenia subjects without Alzheimer's disease, definite cognitive impairment was associated with higher levels of plaques and tangles. The schizophrenia subjects without definite cognitive impairment had fewer plaques and tangles than the unimpaired nonpsychiatric subjects. CONCLUSIONS: Most cases of cognitive impairment in schizophrenia could not be attributed to Alzheimer's disease. An association of mild Alzheimer-type pathology with definite cognitive impairment was unique to schizophrenia. Enhanced sensitivity to the effects of aging on the brain may be a manifestation of diminished cognitive reserve in schizophrenia.

Aged↗
PubMed2000

Depressive symptoms and risk of Alzheimer's disease in more highly educated older people.

BACKGROUND AND OBJECTIVE: In an earlier study we observed that a depressive syndrome was highly predictive of developing Alzheimer's disease (AD) in older persons with normal baseline cognition and higher levels of education. We interpreted these findings as the depression being an early noncognitive manifestation of AD in persons with more cognitive reserve. The present study examines whether specific symptoms of depression can be identified that predict AD among older subjects with higher levels of education. DESIGN AND PARTICIPANTS: In the community-based Amsterdam Study of the Elderly (AMSTEL), a sample of 3,147 nondemented persons with normal cognition, 65 to 84 years old, was selected and divided into subjects with >8 years and < or =8 years of education. At baseline, the presence or absence of 12 specific symptoms of depression was assessed. At follow-up, patients with incident AD were diagnosed according to DSM-IV criteria in a two-step diagnostic procedure. RESULTS: After an average follow-up of 3.2 years, 1,911 persons were reevaluated, of whom 22 with > 8 years and 31 with < or =8 years of education had developed AD. Multivariate logistic regression analyses showed that among persons with >8 years of education depressed mood and subjective bradyphrenia were strongly associated with incident AD. No association between depressive symptoms and AD was observed among subjects with < or =8 years of education. CONCLUSIONS: Both depressed mood and subjective bradyphrenia seem to indicate subclinical AD in older people with higher levels of education. Clinicians should be alert that in these persons, AD may become apparent within a relatively short period of time.

Aged↗
PubMed2006

Leg length, cognitive impairment and cognitive decline in an African-Caribbean population.

BACKGROUND: Shorter leg length is associated with an adverse environment in early childhood and has been found to be associated with a variety of disorders occurring in mid- to late-life, including dementia in a Korean population. In a community population of African-Caribbean elders, in whom leg length had been measured, we sought to compare associations with cognitive impairment at baseline and cognitive decline over a three-year follow-up period. METHODS: Of 290 African-Caribbean residents in south London recruited at baseline, 216 (74%) were re-interviewed after a three-year period and 203 had sufficient data for this analysis. Cognitive impairment was derived as a binary category from a battery of cognitive tests administered at baseline and cognitive decline was derived from change in performance on a subset of these tests. Leg length (iliac crest to lateral malleolus) was also measured. RESULTS: Shorter leg length was associated with female sex, lower occupational social class and reported hypertension and diabetes. Shorter leg length (lowest quartile) was significantly associated with cognitive impairment but there were no apparent associations with cognitive decline. The association with cognitive impairment was independent of age, sex and education. Social class appeared to be an important mediating factor. CONCLUSIONS: Shorter leg length may be a marker of early life stressors which result in reduced cognitive reserve. Interestingly this association was mediated more strongly by social class (previous occupational status) than by education in this population.

Aged↗
PubMedDate not supplied

Dementia-free centenarians.

BACKGROUND: A small percentage of centenarians, about 15-25%, are functionally cognitively intact. Among those who are not cognitively intact at 100, approximately 90% delayed the onset of clinically evident impairment at least until the average age of 92 yr. OBJECTIVE: To review current and past findings related to the prevalence and incidence of dementia amongst the exceptionally long-lived. METHODS: Findings from the various centenarian studies, world-wide, are reviewed. RESULTS: Neuropsychological and neuropathological correlations thus far suggest that there are centenarians who demonstrate no evidence of neurodegenerative disease. There also appear to be centenarians who despite the substantial presence of neuropathological markers of Alzheimer's disease did not meet clinical criteria for having dementia, thus suggesting the existence of cognitive reserve. Epigenic studies suggest a significant familial component to these survival advantages. CONCLUSION: Centenarians are of scientific interest as a human model of relative resistance to dementia.

Aged↗
PubMed2005

Circadian preference and cognitive functioning among rehabilitation inpatients.

The influence of circadian preference was examined among 56 morning-oriented rehabilitation inpatients with cognitive (n=28) and noncognitive (n=28) impairments. Each individual was tested twice: morning (preferred time) and evening (nonpreferred time); sessions and test batteries were counterbalanced to control for practice effects. Standard measures assessed attention, language, memory, visuospatial, and executive functions. Persons with cognitive impairment showed disproportionate vulnerability to the effects of circadian preference and time of testing, performing more poorly at nonpreferred than preferred times. Substantial effects (eta2 .12 to .48) were found on tests of executive functioning and tasks incorporating similar higher-order demands (e/g/. complex figure copy). Results are supported by tympanic temperature changes during a vigilance task, and index of cerebral blood flow in response to cognitive challenge. Cognitive reserve theory is suggested as an explanation for the differential effects. These findings may have implications for inpatient therapeutic interventions and discharge planning.

Adult↗
PubMed2005

Does arm length indicate cognitive and functional reserve?

BACKGROUND: This study aimed to examine whether arm length and height were associated with cognitive and functional abilities. METHODS: Screening interviews were conducted in 235 community dwelling individuals aged 65 and over. The assessment scales included the Korean version of modified Mini-Mental State Examination (K-mMMSE) for cognition, and the Korean Instrumental Activities of Daily Living (K-IADL) for functional ability. All the participants were examined clinically and a diagnosis of dementia was ascertained. Anthropometric measurements included total arm span and height. RESULTS: Both arm length and height correlated significantly with the cognitive and functional scales. In the multivariate regression models, their associations were significant, independent of age, sex, education, and other variables. Shorter arm length was also significantly associated with dementia; while, height lost significance after an adjustment for the potential confounders. CONCLUSIONS: Arm length and height could indicate cognitive and functional ability. Arm length, which was known to be less prone to degenerative processes, might be more stable as an indicator for cognitive and functional reserve capacity than height.

Activities of Daily Living↗
PubMedDate not supplied

[Influence of factors not related with HIV infection on neuropsychological performance of HIV-seropositive patients].

INTRODUCTION: The presence of neuropsychological impairment related to HIV infection has generated abundant literature whose results are disparate. Keeping in mind that it has been suggested that neuropsychological impairment could be associated to the presence of certain factors that would coexist with the own HIV, it is necessary to determine factors which contribute to transform a seropositive into a subject more neuropsychologically vulnerable. DEVELOPMENT: In this work we present a revision of those factors related with HIV infection that can influence neuropsychological performance of the patients as the antecedents of neurological and psychiatric pathology, depressed mood, drugs abuse, and cognitive reserve. CONCLUSIONS: The study of the influence of these factors can not only contribute to clarify the controversy on the presence of neuropsychological deficits, but also to understand why some seropositive patients are more neuropsychologically vulnerable than others, and ultimately to better understand the neuropsychological implications derived of HIV infection.

Cognition Disorders↗
PubMed2002

Dementia, asymmetry of temporal lobe structures, and apolipoprotein E genotype: relationships to cerebral atrophy and neuropsychological impairment.

We examined asymmetry of hippocampal volume as well as other temporal lobe structures (temporal lobe, temporal horn of the lateral ventricular system, parahippocampal and fusiform gyri) in 194 subjects from the Cache County, Utah study, with varying disorders [85 with Alzheimer's disease (AD), 59 with some cognitive or neuropsychiatric disorder-referenced as a Mixed Neuropsychiatric group, 30 with mild ambiguous/mild cognitive impairment (MA/MCI) and 20 controls] and APOE genotypes. Asymmetry was determined by subtracting left-side volume from the right corrected by total intracranial volume. No significant asymmetry was observed to be associated with presence of the epsilon4 allele. Since the AD-epsilon4 allele risk effect may be expressed early in the course of the disorder, we also examined asymmetry indices in AD, MA/MCI and Mixed Neuropsychiatric subjects early in the course of their disorder (2 years or less) to those with longer duration illness (greater than 2 years). We observed a leftward asymmetry (i.e., left side larger) regardless of APOE genotype in hippocampal volume where both AD and MCI subjects demonstrated a leftward shift in hippocampal size when length of disease (LOD) was less but not more than 2 years. Leftward asymmetry was not associated with LOD in the Mixed Neuropsychiatric group. These findings do not support an association between epsilon4 and hippocampal asymmetry in dementia. We also examined whether asymmetry influenced neuropsychological performance, but minimal effects were observed. Where significance or strong trends were observed, better neuropsychological performance was associated with larger parenchymal volume of temporal lobe structures. These findings were interpreted as representing cognitive reserve effects where larger volume was protective against impairment. The role of asymmetry research in understanding neuropsychological performance in dementia is discussed.

Aged↗
PubMed2025

Heterogeneity Analysis of Associations Involving the Large-Scale Online MindCrowd Survey Memory Test.

INTRODUCTION: Alzheimer's disease and related disorders (ADRDs), as well as general age-related cognitive decline, are known to be multifactorial with heterogeneous etiologies. Identifying and accommodating heterogeneity in any one ADRD-related data set can be pursued using different analytical techniques, each with different assumptions or purposes. For example, whereas a great deal of research has explored clustering individuals or variables that exhibit greater similarity in some way, little research has explored evidence for heterogeneity in the relationships between relevant outcomes, such as performance on a memory test, and risk factors such as environmental exposures, behaviors, or genetic factors among individuals. METHODS: We explored evidence of heterogeneity in the relationships between ability on a memory test, specifically the paired associate learning (PAL) test, and multiple social and demographic risk factors using the large MindCrowd study database (n > 90,000 individuals). We focused on mixtures of regression models but compared models assuming many interaction effects among independent variables as well as random effects. RESULTS: We ultimately find substantial evidence for heterogeneity and offer an intuitive explanation for it involving individual motivation for participating in the MindCrowd study. Basically, we argue that our mixture of regression model analysis results suggest that a smaller group of individuals (&#x223c;16%) likely participated in the MindCrowd study out of a concern for their cognitive abilities as they exhibit stronger and statistically significant negative associations between age, number of medications they are on, some ancestries, and the number correct on the PAL test. They also exhibit stronger positive associations between education and PAL test results in a dose-dependent manner suggesting that a "cognitive reserve" associated with greater education could benefit them. Analysis models assuming interaction terms and random effects suggested that other forms of heterogeneity in the relationships between variables exist in the data set, but their results do not carry with them the same intuitive explanation that the results of the mixture model analyses do. CONCLUSION: We find evidence for heterogeneity in the relationships between social and demographic variables and PAL test results in the large MindCrowd study database. This heterogeneity is likely due to individuals with and without concerns for their cognitive abilities participating in the study. We also find other types of evidence in the data set. Our results should motivate caution in the use of large epidemiological study or survey-oriented data sets to build predictive models of clinical or subclinical pathologies without exploring or accommodating heterogeneity. Our results also suggest that one should include questions about motivation to participate in large epidemiological studies since different motivations may impact important relationships between independent and dependent variables.

Humans↗
PubMed2001

The influence of education on clinically diagnosed dementia incidence and mortality data from the Kungsholmen Project.

BACKGROUND: The relationship between education and Alzheimer disease (AD) or dementia has been widely examined and the evidence obtained is mixed. Several hypotheses have been proposed to explain the observed association between them. OBJECTIVE: To further understand the relationship between education and incidence of clinically diagnosed AD or dementia. SUBJECTS AND METHODS: A community-based, dementia-free cohort of 1296 aged 75 years and older was followed up to detect incident AD or dementia cases using Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria. The vital status of all subjects who underwent the clinical examination at follow-up (n = 983) was ascertained for 5 years further. Data were analyzed with Cox proportional hazards model after adjustment for main potential confounders. RESULTS: Over an average (SD) of 2.8 (1.0) years of follow-up, 147 subjects were diagnosed as having dementia (109 subjects as having AD). Among those who were clinically examined at follow-up, 88 died with dementia (68 died with AD) within 5 years. Subjects with a low level of education (<8 vs > or =8 years) had a relative risk of 2.6 (95% confidence interval, 1.5-4.4) for AD and 1.7 (95% confidence interval, 1.1-2.6) for dementia. A low educational level was significantly related to all-cause mortality (relative risk, 1.3; 95% confidence interval, 1.0-1.7; P<.05), but not to the mortality of subjects with AD (relative risk, 1.1; 95% confidence interval, 0.5-2.2) or dementia (relative risk, 0.9; 95% confidence interval, 0.5-1.5). CONCLUSIONS: A low level of education is related to an increased incidence of clinical AD or dementia, but not to the mortality of subjects with AD or dementia. These findings can be accounted for by the "cognitive reserve" hypothesis. Alternatively, the observed association between educational level and incidence of AD or dementia may partly reflect detection bias, by which subjects with a low level of education tend to be clinically diagnosed at an earlier point in time.

Aged↗
PubMed2004

Relationship between cerebral energy metabolism in parietotemporal cortex and hippocampus and mental activity during aging in rats.

The present investigation demonstrates differences in both formation and utilization of the energy-rich compounds adenosine triphosphate ATP and creatine phosphate (CrP) in behaviorally well and poorly performing inbred male Wistar rats in parietotemporal cerebral cortex and hippocampus with aging from 1 to 2ys. Also, differences in learning and memory capacities (behavior) became obvious. By holeboard testing, good (GP) and poor performers (PP) have been discriminated. The pools of energy-rich phosphates as determined in parietotemporal cerebral cortex and in hippocampus under resting conditions were found to be reduced by nearly 10% for both creatine phosphate and the whole available energy pools in PP as compared to GP. Aging from 1 to 2y diminished the concentrations of energy-rich phosphates in the cerebral areas studied and in both GP and PP under resting conditions. Additionally, an age-related aggravation of the energy deficit became obvious between GP and PP. Repeated mental activation from 1y to 2y resulted in the maintenance of improvement as registered for the mean run time and the number of visited/revisited holes in GP. In contrast, PP deteriorated (mean run time), and could not maintain improvement (number of visited/revisited holes) over time. Repeated mental activation normalized the energy pool by increased formation of the energy-rich compounds ATP and CrP in both cerebral areas studied in GP and PP. However, differences became obvious between GP and PP. The energy-turnover in the latter group was found to be significantly reduced for both cerebral areas studied. GP could meet the enhanced energy demand of mental activation during aging by increasing formation and utilization of energy. PP could increase energy formation but were unable to sufficiently adapt energy utilization under the same conditions. This disturbance in energy metabolism may have impacts on energy-consuming processes in PP which may contribute to the markedly reduced cognitive reserve in PP. In human beings, PP approximately poorly educated people found to be prone to sporadic Alzheimer disease.

Adenosine Triphosphate↗
PubMed2004

Memory profiles in parents of patients with schizophrenia.

Recent research shows that categorizing patients with schizophrenia based on frontal-striatal and frontal-temporal memory profiles may yield neurobiologically meaningful disease subtypes. We hypothesize that parents of patients exhibit similar memory profiles. Both parents of 36 patients with schizophrenia (N = 72) and 26 healthy married control couples (N = 52) participated in this study. All subjects were physically healthy and had no history of neurological illness or alcohol/drug abuse. The presence of a psychiatric and/or personality disorder was assessed with the Comprehensive Assessment of Symptoms and History (CASH) interview, the Schedule for Affective Disorders and Schizophrenia-lifetime (SADS-L) interview and the Structured Interview for DSM-IV Personality Disorders (SIDP-IV), respectively. Cluster analysis of selected measures from the Dutch version of the California Verbal Learning Test (CVLT) delineated parents into two subgroups with distinct memory deficits and a third subgroup without impairments. Specific frontal-striatal and frontal-temporal subgroups, however, were not found. In addition, our results indicated that mothers seem to be more protected against the negative effects of genetic liability to schizophrenia than fathers. Furthermore, relatives with a higher level of intelligence may have more cognitive reserve to compensate for the negative impact of implied brain dysfunction on verbal memory than relatives with a low level of intelligence. Although the parents of patients with schizophrenia could be delineated into subgroups with primary memory deficits, frontal-striatal and frontal-temporal subgroups could not be unambiguously identified. The association that emerged between level of intelligence, gender and severity of memory impairment deserves further exploration.

Cluster Analysis↗
PubMed2004

Centenarians who avoid dementia.

Some researchers and many in the lay public believe the ageist myth that the older you get the sicker you get. If this were true, it would follow that most if not all centenarians should have Alzheimer's disease. Numerous centenarian studies disprove this assumption given that a small percentage ( approximately 15-25%) of centenarians are functionally cognitively intact. Among those who are not cognitively intact at 100, approximately 90% delayed the onset of clinically evident impairment at least until an average age of 92 years. Neuropsychological and neuropathological correlations thus far suggest that there are centenarians who demonstrate no evidence of neurodegenerative disease. There also appear to be centenarians who, despite the substantial presence of neuropathological markers of Alzheimer's disease, do not meet clinical criteria for having dementia, thus suggesting the existence of cognitive reserve. Centenarians are therefore of scientific interest as a human model of relative resistance to dementia.

Age Factors↗
PubMed2002

Effects of chronic epilepsy on intellectual functions.

Intractable epilepsy is related to various transient and chronic brain electric and neurochemical disturbances. There is increasing evidence that long-lasting chronic epilepsy may induce secondary neuronal loss and metabolic dysfunctions. Still a matter of controversy is, however, whether cognitive abilities of patients deteriorate with increasing duration of intractable epilepsy. We present results from two independent cross-sectional studies dealing with measures of global cognitive performance in two different ways. The first study investigated in 78 patients with refractory temporal lobe epilepsy (TLE) the influence of duration of epilepsy on the difference between an estimated measure of former or pre-morbid intelligence and the current performance in an intelligence test. The second study aimed at duration of epilepsy-dependent effects on current IQ measures of 209 patients with refractory TLE. Both studies showed that the duration of epilepsy contributes to the explanation of interindividual variability in IQ measures of adult TLE patients to a higher degree than age and age of epilepsy onset. Similar to several studies on hippocampal neuronal density, hippocampal volume, and glucose metabolism, the presented cross-sectional data demonstrate that a duration of chronic epilepsy exceeding two decades is associated with worse cognitive abilities. Consequently, refractory TLE seems to induce a very slow but ongoing cognitive deterioration. It is assumed that epilepsy-related noxious events and agents exhaust the compensatory capacity of brain functions. A high cognitive reserve capacity, however, might delay the onset of deterioration.

Adult↗