Cognitive Reserve Hypothesis Research Articles

What Do Parents Have to Do with My Cognitive Reserve Life Course Perspectives on Twelve-Year Cognitive Decline

Background/Aims: To examine the cognitive reserve hypothesis by comparing the contribution of early childhood and life course factors related to cognitive functioning in a nationally representative sample of older Americans. Methods: We examined a prospective, national probability cohort study (Health and Retirement Study; 1998-2010) of older adults (n = 8,833) in the contiguous 48 United States. The main cognitive functioning outcome was a 35-point composite of memory (recall), mental status, and working memory tests. The main predictors were childhood socioeconomic position (SEP) and health, and individual-level adult achievement and health. Results: Individual-level achievement indicators (i.e., education, income, and wealth) were positively and significantly associated with baseline cognitive function, while adult health was negatively associated with cognitive function. Controlling for individual-level adult achievement and other model covariates, childhood health presented a relatively small negative, but statistically significant association with initial cognitive function. Neither individual achievement nor childhood SEP was statistically linked to decline over time. Conclusions: Cognitive reserve purportedly acquired through learning and mental stimulation across the life course was associated with higher initial global cognitive functioning over the 12-year period in this nationally representative study of older Americans. We found little supporting evidence that childhood economic conditions were negatively associated with cognitive function and change, particularly when individual-level achievement is considered.

Life-span cognitive activity, neuropathologic burden, and cognitive aging

To test the hypothesis that cognitive activity across the life span is related to late-life cognitive decline not linked to common neuropathologic disorders. On enrollment, older participants in a longitudinal clinical-pathologic cohort study rated late-life (i.e., current) and early-life participation in cognitively stimulating activities. After a mean of 5.8 years of annual cognitive function testing, 294 individuals had died and undergone neuropathologic examination. Chronic gross infarcts, chronic microscopic infarcts, and neocortical Lewy bodies were identified, and measures of β-amyloid burden and tau-positive tangle density in multiple brain regions were derived. In a mixed-effects model adjusted for age at death, sex, education, gross and microscopic infarction, neocortical Lewy bodies, amyloid burden, and tangle density, more frequent late-life cognitive activity (estimate = 0.028, standard error [SE] = 0.008, p < 0.001) and early-life cognitive activity (estimate = 0.034, SE = 0.013, p = 0.008) were each associated with slower cognitive decline. The 2 measures together accounted for 14% of the residual variability in cognitive decline not related to neuropathologic burden. The early-life-activity association was attributable to cognitive activity in childhood (estimate = 0.027, SE = 0.012, p = 0.026) and middle age (estimate = 0.029, SE = 0.013, p = 0.025) but not young adulthood (estimate = -0.020, SE = 0.014, p = 0.163). More frequent cognitive activity across the life span has an association with slower late-life cognitive decline that is independent of common neuropathologic conditions, consistent with the cognitive reserve hypothesis.

Lifelong Exposure to Multilingualism: New Evidence to Support Cognitive Reserve Hypothesis

ObjectiveInvestigate the protective effect of multilingualism on cognition in seniors.MethodsAs part of the MemoVie study conducted on 232 non-demented volunteers aged 65 and more, neurogeriatric and neuropsychological evaluations were performed. Participants were classified as presenting either cognitive impairment without dementia (CIND) or being free of any cognitive impairment (CIND-free). Language practices, socio-demographic data and lifestyle habits were recorded. In this retrospective nested case-control design, we used as proxies of multilingualism: number of languages practiced, age of acquisition and duration of practice, emphasizing the temporal pattern of acquisition, and the resulting practice of several languages sequentially or concomitantly during various periods of life. This special angle on the matter offered to our work a dimension particularly original and innovative.Results44 subjects (19%) had CIND, the others were cognitively normal. All practiced from 2 to 7 languages. When compared with bilinguals, participants who practiced more than 2 languages presented a lower risk of CIND, after adjustment for education and age (odds ratio (OR) = 0.30, 95% confidence limits (95%CL) = [0.10–0.92]). Progressing from 2 to 3 languages, instead of staying bilingual, was associated with a 7-fold protection against CIND (OR = 0.14, 95%CL = [0.04–0.45], p = 0.0010). A one year delay to reach multilingualism (3 languages practiced being the threshold) multiplied the risk of CIND by 1.022 (OR = 1.022, 95%CL = [1.01–1.04], p = 0.0044). Also noteworthy, just as for multilingualism, an impact of cognitively stimulating activities on the occurrence of CIND was found as well (OR = 0.979, 95%CL = [0.961–0.998], p = 0.033).ConclusionThe study did not show independence of multilingualism and CIND. Rather it seems to show a strong association toward a protection against CIND. Practicing multilingualism from early life on, and/or learning it at a fast pace is even more efficient. This protection might be related to the enhancement of cognitive reserve and brain plasticity, thereby preserving brain functions from alterations during aging.

Cognitive reserve and cortical atrophy in multiple sclerosis

To test the cognitive reserve (CR) hypothesis in the model of multiple sclerosis (MS) by assessing the interactions among CR, brain atrophy, and cognitive efficiency in patients with relapsing-remitting MS. A Cognitive Reserve Index was calculated including education, premorbid leisure activities, and IQ. Brain atrophy was assessed through magnetic resonance quantitative parameters of normalized total brain volume and normalized cortical volume. Cognitive function was measured using Rao's Brief Repeatable Battery. Fifty-two patients with relapsing-remitting MS were evaluated at baseline and 35 of them were reassessed after a 1.6-year follow-up period. At baseline, higher CR predicted better performance on most of the Brief Repeatable Battery tests, independent of brain atrophy and clinical and demographic characteristics (p ≤ 0.021). An interaction between CRI and normalized cortical volume predicted better cognitive performance on tasks of verbal memory and attention/information processing speed (p < 0.005). However, at the follow-up examination, progressing cortical atrophy (β = 0.45; p = 0.008) and older age (β = -0.33; p = 0.044) were the only predictors of deteriorating cognitive performance. Our findings suggest that higher CR in individuals with MS may mediate between cognitive performance and brain pathology. CR-related compensation may, however, fail with progression of damage. The time window of opportunity for therapeutic approaches aimed at intellectual enhancement most likely lies in the earliest disease stages.

Low Education Is Related to Cortical Thinning in 1180 Normal Subjects: Cognitive Battering Hypothesis vs. Cognitive Reserve Hypothesis (P06.039)

Low Education Is Related to Cortical Thinning in 1180 Normal Subjects: Cognitive Battering Hypothesis vs. Cognitive Reserve Hypothesis (P06.039)

Beyond cognitive reserve: Behavioural reserve hypothesis in Frontotemporal Dementia

BackgroundThe brain reserve hypothesis posits that there are individual differences in the ability to cope with brain pathology, and that brain damage extent and clinical symptoms are not tightly linked. If cognitive reserve hypothesis has been demonstrated in Alzheimer Disease and Frontotemporal Dementia (FTD), no evidence of reserve mechanisms on behavioural disturbances has been corroborated yet. In FTD, distinct behavioural phenotypes may be identified. ObjectiveTo test the behavioural reserve hypothesis in behavioural variant FTD (bvFTD). MethodsAs previously demonstrated, bvFTD patients were grouped into four behavioural phenotypes, i.e. “disinhibited”, “apathetic”, “language”, and “aggressive”, by means of Confirmatory Factor Analysis on behavioural assessment. Educational achievement was considered as proxy measure of reserve on behavioural disturbances, and cerebral SPECT as an indirect expression of brain pathology. On each group, the effect of education on brain damage was assessed by slope analysis. ResultsA specific effect of education attainment on “disinhibited” phenotype was observed, the higher the education, the greater the hypoperfusion in the right inferior frontal gyrus and the left medial frontal gyrus and right caudate (P<0.001). On the other behavioural phenotypes, no effect of education was reported in modulating brain damage. ConclusionsWe suggest that in neurodegenerative diseases the concept of brain reserve might be extended, as compensatory mechanisms are in action not only for cognitive deficits but for behavioural disturbances as well.

Advances in Alzheimer’s disease (AAD): Standing firm at its first anniversary

Advances in Alzheimer’s Disease (AAD) is an international journal launched last year, dedicated to promote basic, translational and clinical research on Alzheimer’s Disease (AD) and brain aging (http://www.scirp.org/journal/aad/). On its first anniversary, the journal has made substantial achievements and shows a great promise for its future. AAD published the first issue on June 26 last year, followed by the second and third issues in September and December. The first issue of this year was published in March as scheduled. The current issue publishes 3 original and review articles. The published papers were contributed by investigators over the world, mostly outside China, covering broad and diverse topics on AD, from mechanistic study to disease diagnosis, care and treatment. These papers have attracted considerable attention in the field, with total views near 40 thousand and full article downloads over 6 thousand to date. AD is the most common type of dementia in the elderly. It attacks individuals aged over 65 in most cases, at a prevalence around 5%, which doubles every decade as the age goes further up. In 2013, an estimated 5 million Americans aged 65 and older have AD. The advances in modern medicine and the improvement in social and envi ronmental conditions will further increase human lifeexpectancy in the coming years, so do for the number of people who will develop this neurodegenerative disease. It is projected that 14 million Americans will live with AD by 2050 (http://www.alz.org/alzheimers_disease_facts_and_figur es.asp?type=alzchptfooter) [1,2]. The situation in China is perhaps even worse and more alarming because of its population in the world, which is rapidly aging. While there is little official epidemiological record, China may already have more than 6 8 million AD patients today. What’s more, the overall life-expectancy for Chinese is now about 76 years (http://en.wikipedia.org/wiki/List_of_countries_by_life_ expectancy), but it will catch up the current mid-80s records in most western/developed countries within 10 years or so. Together with other problems and difficulties (e.g., the one-child policy), China may soon face one of the greatest socioeconomic and healthcare challenges in her journey to modernization (http://charls.ccer.edu.cn). AD is pathologically characterized by amyloid plaques, neurofibrillary tangles, neuritic pathology, gliosis, and neuronal and synaptic loss in vulnerable brain regions especially in the limbic and neocortical areas [3-5]. Aging is the greatest risk factor, while vascular and metabolic deficits, trauma, inflammation, environmental insults, genetic predisposition, and physiological “wasting” of cognitive and physical reserve are also potential etiological factors. Many theories have been proposed for the pathogenesis of this disease. Among all, the amyloid hypothesis emphasizes accumulation of β-amyloid peptides (Aβ) being the leading pathogenic factor. The mitochondria/metabolic stress cascade hypothesis considers age-inherent metabolic failure or oxidative damages to mitochondrial DNA, RNA, lipid and protein as the primary pathogenic mechanism. The cognitive reserve hypothesis suggests that reduced brain use plays an important role in dementia and AD development. The calcium hypothesis posits Ca homeostatic deregulation contributing to neuronal death and functional decline in brain aging and AD [5-9]. Evidence exists in supporting each of these hypotheses, reflecting the nature of complexity and multi-dimensional abnormalities of this disease. At present, efforts are particularly needed to identify the fundamental molecular/cellular mechanism that may unify the risk factors, pathological manifestations and functional loss in this disease [8,9]. Because there are no

Reserve Mechanisms in Neurodegenerative Diseases: From Bench to Bedside and Back Again

In the course of neurodegenerative disorders there are several mechanisms that may counteract the pathological process, mitigating the clinical manifestations of the disease. Usually referred as cognitive reserve hypothesis, this theoretical framework posits that individuals with enriched cognitive status (i.e. with higher educational and occupational levels and higher individual social achievement) may cope better with the occurrence of cognitive decline by a more efficient recruitment of neural networks sustaining higher-level functions. Cognitive reserve was initially studied in Alzheimer's disease, but this concept has been soon after extended also to other neurodegenerative disorders, such as Frontotemporal Dementia, Parkinson's disease, and Huntington's disease, suggesting a general applicability of cortical plasticity phenomena in contrasting neurodegeneration. The neural underpinnings of these dynamic compensatory mechanisms open the possibility for strategic interventions based on environmental approaches. In this continuously growing field, the aim of the present review is to explore new acquisitions, derived from basic research and clinical grounds, on cognitive reserve mechanisms and the potential application as novel therapeutic targets in neurodegenerative diseases.

Reserve Mechanisms in Neurodegenerative Diseases: From Bench to Bedside and Back Again

In the course of neurodegenerative disorders there are several mechanisms that may counteract the pathological process, mitigating the clinical manifestations of the disease. Usually referred as cognitive reserve hypothesis, this theoretical framework posits that individuals with enriched cognitive status (i.e. with higher educational and occupational levels and higher individual social achievement) may cope better with the occurrence of cognitive decline by a more efficient recruitment of neural networks sustaining higher-level functions. Cognitive reserve was initially studied in Alzheimer’s disease, but this concept has been soon after extended also to other neurodegenerative disorders, such as Frontotemporal Dementia, Parkinson’s disease, and Huntington’s disease, suggesting a general applicability of cortical plasticity phenomena in contrasting neurodegeneration. The neural underpinnings of these dynamic compensatory mechanisms open the possibility for strategic interventions based on environmental approaches. In this continuously growing field, the aim of the present review is to explore new acquisitions, derived from basic research and clinical grounds, on cognitive reserve mechanisms and the potential application as novel therapeutic targets in neurodegenerative diseases. Keywords: Reserve mechanisms, cognitive reserve, neurodegenerative disease, Alzheimer's Disease, Frontotemporal Dementia, Frontotemporal Lobar degeneration, MRI, PET, education, occupation

P3‐210: Association of cognitive decline with cerebral metabolism and education in amnestic MCI: Implications for the cognitive reserve hypothesis

P3‐210: Association of cognitive decline with cerebral metabolism and education in amnestic MCI: Implications for the cognitive reserve hypothesis

Education and Dementia in the Context of the Cognitive Reserve Hypothesis: A Systematic Review with Meta-Analyses and Qualitative Analyses

BackgroundCognitive reserve (CR) or brain reserve capacity explains why individuals with higher IQ, education, or occupational attainment have lower risks of developing dementia, Alzheimer’s disease (AD) or vascular dementia (VaD). The CR hypothesis postulates that CR reduces the prevalence and incidence of AD or VaD. It also hypothesizes that among those who have greater initial cognitive reserve (in contrast to those with less reserve) greater brain pathology occurs before the clinical symptoms of disease becomes manifest. Thus clinical disease onset triggers a faster decline in cognition and function, and increased mortality among those with initial greater cognitive reserve. Disease progression follows distinctly separate pathological and clinical paths. With education as a proxy we use meta-analyses and qualitative analyses to review the evidence for the CR hypothesis.Methodology/Principal FindingsWe searched PubMed, PsycoINFO, EMBASE, HealthStar, and Scopus databases from January 1980 to June 2011 for observational studies with clear criteria for dementia, AD or VaD and education. One hundred and thirty-three articles with a variety of study designs met the inclusion criteria. Prevalence and incidence studies with odds ratios (ORs), relative risks or original data were included in the meta-analyses. Other studies were reviewed qualitatively. The studies covered 437,477 subjects. Prevalence and incidence studies with pooled ORs of 2.61 (95%CI 2.21–3.07) and 1.88 (95%CI 1.51–2.34) respectively, showed low education increased the risk of dementia. Heterogeneity and sensitivity tests confirmed the evidence. Generally, study characteristics had no effect on conclusions. Qualitative analyses also showed the protective effects of higher education on developing dementia and with clinical disease onset hastening a decline in cognition and function, and greater brain pathology.Conclusion/SignificanceThis systematic review and meta-analyses covering a wide range of observational studies and diverse settings provides robust support for the CR hypothesis. The CR hypothesis suggests several avenues for dementia prevention.

Dementia incidence and mortality in middle-income countries, and associations with indicators of cognitive reserve: a 10/66 Dementia Research Group population-based cohort study

SummaryBackgroundResults of the few cohort studies from countries with low incomes or middle incomes suggest a lower incidence of dementia than in high-income countries. We assessed incidence of dementia according to criteria from the 10/66 Dementia Research Group and Diagnostic and Statistical Manual of Mental Disorders (DSM) IV, the effect of dementia at baseline on mortality, and the independent effects of age, sex, socioeconomic position, and indicators of cognitive reserve.MethodsWe did a population-based cohort study of all people aged 65 years and older living in urban sites in Cuba, the Dominican Republic, and Venezuela, and rural and urban sites in Peru, Mexico, and China, with ascertainment of incident 10/66 and DSM-IV dementia 3–5 years after cohort inception. We used questionnaires to obtain information about age in years, sex, educational level, literacy, occupational attainment, and number of household assets. We obtained information about mortality from all sites. For participants who had died, we interviewed a friend or relative to ascertain the likelihood that they had dementia before death.Findings12 887 participants were interviewed at baseline. 11 718 were free of dementia, of whom 8137 (69%) were reinterviewed, contributing 34 718 person-years of follow-up. Incidence for 10/66 dementia varied between 18·2 and 30·4 per 1000 person-years, and were 1·4–2·7 times higher than were those for DSM-IV dementia (9·9–15·7 per 1000 person-years). Mortality hazards were 1·56–5·69 times higher in individuals with dementia at baseline than in those who were dementia-free. Informant reports suggested a high incidence of dementia before death; overall incidence might be 4–19% higher if these data were included. 10/66 dementia incidence was independently associated with increased age (HR 1·67; 95% CI 1·56–1·79), female sex (0·72; 0·61–0·84), and low education (0·89; 0·81–0·97), but not with occupational attainment (1·04; 0·95–1·13).InterpretationOur results provide supportive evidence for the cognitive reserve hypothesis, showing that in middle-income countries as in high-income countries, education, literacy, verbal fluency, and motor sequencing confer substantial protection against the onset of dementia.FundingWellcome Trust Health Consequences of Population Change Programme, WHO, US Alzheimer's Association, FONACIT/ CDCH/ UCV

Load-dependent posterior–anterior shift in aging in complex visual selective attention situations

The cognitive reserve hypothesis proposes that the brain actively attempts to cope with age-related changes by using pre-existing cognitive networks (neural reserve) or enlisting compensatory processes (neural compensation). In a context of visual selective attention, the current study compared task-related activation with BOLD fMRI signals in younger (N=16) and older (N=16) adults using a letter-name-matching task with two attentional load levels. In the low-load condition, the target letter might share the same identity (e.g., a/A) with one of two probes in the display, while in the high-load condition the display included four probes. The results suggest that there is an age-related change within the frontoparietal network that underlies visual selective attention processing. In the low-load condition, the older group needed to recruit more bilateral frontal regions to successfully perform the task, while the younger participants recruited more bilateral occipital regions, in agreement with the PASA (Posterior–Anterior Shift in Aging) phenomenon and the neural compensation hypothesis of cognitive reserve. In addition, in the high-load condition, we found a load-dependent posterior–anterior shift in the older participants, which was not present in the younger ones, involving the anterior part of the cingulate cortex. By showing a load-dependent PASA, our study indicates that the PASA phenomenon is supported more by the compensation mechanism (solicited exclusively in older participants) than by the reserve.

Cognitive reserve in secondary progressive multiple sclerosis

Background: Consistent with the cognitive reserve hypothesis, lifetime intellectual enrichment protects MS patients from cognitive impairment. As studies have focused predominately on patients with relapsing–remitting courses, it is unknown whether lifetime enrichment is protective against cognitive impairment in patients with secondary-progressive MS (SPMS), a more advanced disease course. Objective: Examine whether greater lifetime intellectual enrichment moderates/reduces the deleterious effect of SPMS on memory and cognitive efficiency. Methods: Twenty-five SPMS patients and 25 healthy controls (HC) completed neuropsychological tasks, yielding two composite scores: memory and cognitive efficiency. An estimate of lifetime enrichment was created from educational attainment and vocabulary knowledge. Regression analyses predicted memory and cognitive efficiency, with age, sex, intellectual enrichment and group (SPMS, HC) controlled in step one, and the interaction between intellectual enrichment and group evaluated within step two. Results: Interactions emerged between intellectual enrichment and group when predicting memory (R 2Δ=0.081, p = 0.041) and cognitive efficiency (R 2Δ=0.064, p = 0.024), such that SPMS patients exhibited deficits relative to HCs at lower levels of enrichment, but these SPMS-related cognitive deficits were absent at higher levels of enrichment. Conclusion: Intellectual enrichment protects SPMS patients from cognitive impairment, thereby extending the cognitive reserve hypothesis to this more advanced MS disease course.

Sleep onset/maintenance difficulties and cognitive function in nondemented older adults: the role of cognitive reserve.

This study examined the relationship between cognitive function and sleep onset/maintenance difficulties (SO/MD) in nondemented older adults. We hypothesized that SO/MD negatively impacts cognition and that older adults with lower education would be especially vulnerable to its effects. The sample comprised 549 older adults from the Einstein Aging Study (EAS), a community-based cohort. Participants completed neuropsychological assessment and a sleep questionnaire. Univariate ANCOVAs were performed with cognitive performance as a dependent variable, SO/MD (present or absent) and education (lower: ≤ 12 years; higher: >12 years) as between-subjects factors, and age, ethnicity, gender, depression, and cardiovascular comorbidies as covariates. Participants were an average age of 79.7 ± 5.0 years (range = 71-97 years). Fifty-seven percent (n = 314) of the sample met criteria for SO/MD. Among participants with SO/MD, those with lower education performed more poorly on a test of category fluency than participants with higher education (means: 35.2 vs. 41.0; p < .001); among older adults without SO/MD, educational attainment had no measurable effect on cognition (SO/MD × education interaction (F(1,536) = 14.5; p = .00)). Consistent with the cognitive reserve hypothesis, older adults with lower education appear selectively vulnerable to the negative effects of sleep onset/maintenance difficulties on tests of verbal fluency.

Prefrontal cortex cytoarchitecture in normal aging and Alzheimer’s disease: a relationship with IQ

We have previously shown that the minicolumnar spacing of neurons in the cerebral cortex relates to cognitive ability, and that minicolumn thinning occurs in old age. The present study examines further the relationship between cognitive ability and cortical fine structure(minicolumn organization and neuropathology) in the dorsolateral prefrontal cortex (dlPFC) and the parahippocampal gyrus (PHG) in mild cognitive impairment (MCI)and Alzheimer's disease (AD). Premortem neuropsychological scores were related to postmortem microanatomy in 58 adults (20 normal controls, 18 MCI, and 20 confirmed AD patients). We found a correspondence between minicolumn thinning in the dlPFC and IQ decline in dementia.In mild impairment, IQ remained stable, as did dlPFC minicolumn width and dlPFC plaque load. IQ only declined as dlPFC minicolumn thinning occurred and dlPFC plaque load increased in more severe dementia. By contrast, plaque load increased and minicolumns became steadily thinner in the PHG, where minicolumn width correlated with declining mini-mental state examination score across both MCI and severe dementia. By including a further 14 younger control subjects, we found that in normal healthy aging, minicolumn width decreased in the dlPFC, whereas PHG minicolumn width did not change.AD patients in our dataset with higher IQ were older at time of death and had less pathology, which supports a neural basis for the cognitive reserve hypothesis.

The balance between cognitive reserve and brain imaging biomarkers of cerebrovascular and Alzheimer's diseases

The cognitive reserve hypothesis explains the disparity between clinical and pathological phenotypes and why, in two individuals with the same extent of neuropathology, one may be demented while the other remains cognitively intact. We examined the balance between brain magnetic resonance imaging measures of the two most common pathologies associated with brain ageing, cerebrovascular disease and Alzheimer's disease, and parameters of cerebral reserve in well-characterized participants born in 1936, for whom childhood intelligence is known. Brain magnetic resonance imaging was carried out at 1.5T using fluid attenuation inversion recovery and T(1)-weighted volumetric sequences in 249 participants. Cerebrovascular disease was quantified by measuring brain white matter hyperintensities on fluid attenuation inversion recovery images using Scheltens' scale and Alzheimer's disease was measured from volumetric data using FreeSurfer to extract whole brain volume and hippocampal volumes in turn. The effect of these measures of brain burden on life-long cognitive ageing from the age of 11 to 68 years was compared with the effect of educational attainment and occupational grade using structural equation modelling. Complete brain burden and reserve data were available in 224 participants. We found that educational attainment, but not occupation, has a measurable and positive effect, with a standardized regression weight of +0.23, on late life cognitive ability in people without cognitive impairment aged 68 years, allowing for the influence of childhood intelligence and the two most common subclinical brain pathological burdens in the ageing brain. In addition, we demonstrate that the magnitude of the contribution of education is greater than the negative impact of either neuropathological burden alone, with standardized regression weights of -0.14 for white matter hyperintensities and -0.20 for hippocampal atrophy. This study illustrates how education counteracts the deleterious effects of cerebrovascular disease and Alzheimer's disease and highlights the importance of quantifying cognitive reserve in dementia research.

Cognitive reserve masks neurobehavioral expression of human immunodeficiency virus-associated neurological disorder in older patients

Cognitive reserve masks neurobehavioral expression of human immunodeficiency virus-associated neurological disorder in older patients April D Thames1,3, Jessica M Foley2, Stella E Panos1,3, Elyse J Singer1, Suzie El-Saden1,3, Charles H Hinkin1,31University of California, Los Angeles School of Medicine, Los Angeles, CA; 2Boston VA Healthcare System/Harvard Medical School, Boston, MA; 3VA Greater Los Angeles Healthcare System, Los Angeles, CA, USABackground: Cognitive reserve theory may help to explain why some individuals are better able to withstand greater neurological insult before neurobehavioral manifestations occur. The present study provides a direct test of the cognitive reserve hypothesis in a sample particularly predisposed to cognitive impairment, ie, older human immunodeficiency virus (HIV)-positive adults.Methods: Eighteen older HIV-positive adults, of mean (standard deviation) age 53.25 &plusmn; 4.2 years, with 13.5 &plusmn; 2.0 years of education, underwent magnetic resonance imaging and neuropsychological assessment. Regions of interest in the basal ganglia were extracted from T1 weighted scans and volumetric measurements were acquired. Cognitive reserve capacity was measured using premorbid intelligence quotient estimates and years of education. Participants were matched based on global neuropsychological performance.Results: Individuals with higher levels of cognitive reserve demonstrated greater atrophy in the basal ganglia compared with individuals with lower levels of reserve, despite consistent cognitive function.Conclusion: Older HIV-positive patients with higher levels of cognitive reserve may appear cognitively healthier than their striatal integrity would suggest.Keywords: cognitive reserve, human immunodeficiency virus, magnetic resonance imaging, aging, basal ganglia

Relationship between occupation attributes and brain metabolism in frontotemporal dementia

Occupation has been associated with cognitive reserve in healthy aging and Alzheimer's disease. Here we assess the relationship between cerebral metabolic deficits in behavioral variant frontotemporal dementia (bvFTD) and occupation characteristics. Using factor analysis, we derived verbal, physical and visuospatial occupation scores from the US Department of Labor, Occupational Information Network and related these scores to regional cerebral metabolic rate of glucose utilization in 31 patients diagnosed with behavioral variant bvFTD, controlling for cognitive status (CERAD neuropsychological assessment battery), gender and education. Regression analyses showed a marked inverse association between glucose metabolism and (a) verbal occupation scores in left prefrontal cortex and, (b) physical occupation characteristics in right supplementary motor area. We concluded that, consistent with the cognitive reserve hypothesis, lifelong occupation characteristics are related to focal cerebral metabolic deficits in bvFTD. Specific occupation demands spanning decades may strengthen cognitive resistance to pathology.

Structural and Functional Imaging Correlates of Cognitive and Brain Reserve Hypotheses in Healthy and Pathological Aging

In the field of ageing and dementia, brain- or cognitive reserve refers to the capacity of the brain to manage pathology or age-related changes thereby minimizing clinical manifestations. The brain reserve capacity (BRC) hypothesis argues that this capacity derives from an individual's unique neural profile (e.g., cell count, synaptic connections, brain volume, etc.). Complimentarily, the cognitive reserve (CR) hypothesis emphasizes inter-individual differences in the effective recruitment of neural networks and cognitive processes to compensate for age-related effects or pathology. Despite an abundance of research, there is scarce literature attempting to synthesize the BRC the CR models. In this paper, we will review important aging and dementia studies using structural and functional neuroimaging techniques to investigate and attempt to assimilate both reserve hypotheses. The possibility to conceptualize reserve as reflecting indexes of brain plasticity will be proposed and novel data suggesting an intimate and complex correspondence between active and passive components of reserve will be presented.