The Association Between Physical Activity and Cognition in a Racially/Ethnically Diverse Cohort of Older Adults: Results From the Kaiser Healthy Aging and Diverse Life Experiences Study.

OBJECTIVE: Most prior research on physical activity (PA) and cognition is based on predominantly white cohorts and focused on associations of PA with mean (average) cognition versus the distribution of cognition. Quantile regression offers a novel way to quantify how PA affects cognition across the entire distribution. METHODS: The Kaiser Healthy Aging and Diverse Life Experiences study includes 30% white, 19% black, 25% Asian, and 26% Latinx adults age 65+ living in Northern California (n = 1600). The frequency of light or heavy PA was summarized as 2 continuous variables. Outcomes were z-scored executive function, semantic memory, and verbal episodic memory. We tested associations of PA with mean cognition using linear regression and used quantile regression to estimate the association of PA with the 10th-90th percentiles of cognitive scores. RESULTS: Higher levels of PA were associated with higher mean semantic memory (b = 0.10; 95% CI: 0.06, 0.14) and executive function (b = 0.05; 95% CI: 0.01, 0.09). Associations of PA across all 3 cognitive domains were stronger at low quantiles of cognition. CONCLUSION: PA is associated with cognition in this racially/ethnically diverse sample and may have larger benefits for individuals with low cognitive scores, who are most vulnerable to dementia.

A Combined Treatment Approach to Support Everyday Function and Promote Brain Health in Older Adults: A Pilot Study.

Objective: Subtle changes in functional abilities are an early indicator of cognitive impairment. Early intervention may be key to prolonging independence. This study describes the development and program evaluation of an intervention designed to (1) bolster the use of compensation strategies that support everyday executive and memory functioning and (2) utilize these strategies to promote engagement in brain health activities.Method: Older adults (n = 35) with subjective cognitive complaints completed an eight-week group program targeting compensation strategies (e.g., calendars) and brain health activities (e.g., physical exercise). Participants completed outcome measures at first, last, and 3 month follow-up sessions.Results: Compensation strategy use can be successfully taught to and implemented by older adults, and increasing engagement in brain health behaviors is possible, although particular lifestyle changes are challenging to implement.Conclusion: Findings support the use of interventions aimed at increased engagement in compensation strategies to aid everyday memory and executive functioning.Clinical Implications: Early intervention may help to promote prolonged functional independence.

Progression from normal cognition to mild cognitive impairment in a diverse clinic-based and community-based elderly cohort.

INTRODUCTION: Investigation of the conversion rates from normal cognition (NC) to mild cognitive impairment (MCI) is important, as effective early intervention could potentially prevent or substantially delay the onset of dementia. However, reported conversion rates differ across studies and recruitment source. Our study examined predictors of conversion from NC to MCI in a racially and ethnically diverse sample drawn both from community and clinic recruitment sources. METHODS: Rates and predictors of conversion were assessed in an ongoing prospective longitudinal study at University of California, Davis, Alzheimer's Disease Center from 2000 to 2015. Participants (n = 254) were recruited through a clinic (5%) and community sample (95%). They were clinically confirmed as cognitively normal at baseline and followed up to seven years. Recruitment source, demographic factors (age, gender, race/ethnicity, year of education, APOE ε4 positive), cognitive measures (SENAS test scores), functional assessments (CDR sum of boxes), and neuroimaging measures (total brain volume, total hippocampal volume, white hyperintensity volume) were assessed as predictors of conversion from cognitively normal to mild cognitive impairment using proportional hazards models. RESULTS: Of 254 participants, 62 (11 clinic, 51 community) progressed to MCI. The clinic-based sample showed an annual conversion rate of 30% (95% CI 17%-54%) per person-year, whereas the community-based sample showed a conversion rate of 5% (95% CI 3%-6%) per person-year. Risk factors for conversion include clinic-based recruitment, being older, lower executive function and worse functional assessment at baseline, and smaller total brain volume. DISCUSSION: Older adults who sought out a clinical evaluation, even when they are found to have normal cognition, have increased risk of subsequent development of MCI. Results are consistent with other studies showing subjective cognitive complaints are a risk for future cognitive impairment, but extend such findings to show that those who seek evaluation for their complaints are at particularly high risk. Moreover, these individuals have subtle, but significant differences in functional and cognitive abilities that, in the presence of concerns and evidence of atrophy on by brain imaging, warrant continued clinical follow-up. These risk factors could also be used as stratification variables for dementia prevention clinical trial design.

Early Cognitively Based Functional Limitations Predict Loss of Independence in Instrumental Activities of Daily Living in Older Adults.

Older adults with early forms of neurodegenerative disease are at risk for functional disability, which is often defined by the loss of independence in instrumental activities of daily living (IADLs). The current study investigated the influence of mild changes in everyday functional abilities (referred to as functional limitations) on risk for development of incident functional disability. A total of 407 participants, who were considered cognitively normal or diagnosed with mild cognitive impairment (MCI) at baseline, were followed longitudinally over an average 4.1 years (range=0.8-9.2 years). Informant-based ratings from the Everyday Cognition (ECog; Farias et al., 2008) and the Instrumental Activities of Daily Living (Lawton & Brody, 1969) scales assessed the degree of functional limitations and incident IADL disability, respectively. Cox proportional hazards models revealed that more severe functional limitations (as measured by the Total ECog score) at baseline were associated with approximately a four-fold increased risk of developing IADL disability a few years later. Among the ECog domains, functional limitations in Everyday Planning, Everyday Memory, and Everyday Visuospatial domains were associated with the greatest risk of incident functional disability. These results remained robust even after controlling for participants' neuropsychological functioning on tests of executive functions and episodic memory. Current findings indicate that early functional limitations have prognostic value in identifying older adults at risk for developing functional disability. Findings highlight the importance of developing interventions to support everyday abilities related to memory, executive function, and visuospatial skills in an effort to delay loss of independence in IADLs.

Self-rated and informant-rated everyday function in comparison to objective markers of Alzheimer's disease.

It is recognized that individuals with mild cognitive impairment (MCI) already demonstrate difficulty in aspects of daily functioning, which predicts disease progression. This study examined the relationship between self- versus informant-report of functional ability, and how those reports relate to objective disease measures across the disease spectrum (i.e. cognitively normal, MCI, Alzheimer's disease). A total of 1080 subjects with self- and/or informant-rated Everyday Cognition questionnaires were included. Objective measures included cognitive functioning, structural brain atrophy, cerebrospinal fluid abnormalities, and a marker of amyloid deposition using positron emission tomography with [18F]AV45 (florbetapir). Overall, informant-report was consistently more associated with objective markers of disease than self-report although self-reported functional status may still have some utility in early disease.

Vietnamese Insights into Cognitive Aging Program (VIP): Objectives, study design, and cohort description.

Introduction: There is a dearth of research on cognitive aging and dementia in Asian Americans, particularly in Vietnamese Americans, the fourth largest Asian subgroup in the United States. Methods: The Vietnamese Insights into Cognitive Aging Program (VIP) investigates early life adversity and war-related trauma and their associations with cognitive health in a community-based sample of older Vietnamese Americans in Northern California (i.e., Sacramento and Santa Clara counties). Baseline measurements include a comprehensive neuropsychological battery, including measures of global cognition along with executive function, semantic memory, and episodic memory. Data also include measures of functioning, early life adversity and trauma exposure, and psychosocial and traditional cardiovascular disease risk factors. Cognitive assessments will be repeated twice over the course of the data collection period, approximately 12- and 24- months post-baseline. Blood samples collected during Wave 2 will be assayed for biochemical risk factors. Results: Baseline assessments were conducted from January 2022 to November 2023, with N = 548 Vietnamese Americans; mean age ± SD was 73 ± 5.31 years and 55% of participants were women. There were significant differences in social factors by site, with Santa Clara participants having higher education (some college or higher: Sacramento, ≈25%; Santa Clara: ≈48%) and marginally higher incomes compared to Sacramento participants. A higher percentage of Santa Clara participants reported speaking English well or very well (24%) compared to Sacramento participants (13%), although the majority of the entire sample (81%) reported speaking some to no English (response options: not at all; some/a little bit; well/very well). Discussion: This longitudinal study providea a unique opportunity to more fully delineate psychosocial factors that contribute to dementia disparities in diverse and under-engaged populations. Future work will examine cognition, the prevalence of mild cognitive impairment and dementia, and other health outcomes, while controlling for site differences in all analyses. Highlights: Vietnamese Insights into Cognitive Aging Program (VIP) is a new study.VIP has detailed early life and health data on 548 older Vietnamese Americans.History of war and trauma may contribute to Alzheimer's disease and related dementias (ADRD)-related burden.VIP may provide insight into ADRD burden in other understudied groups.

Everyday cognition in older adults: associations with neuropsychological performance and structural brain imaging.

The recently developed Everyday Cognition scales (ECog) measure multiple cognitively relevant functional domains (e.g., Everyday Memory, Everyday Language, Everyday Visuospatial abilities, and three everyday executive domains). The present study further evaluated the validity of the ECog by examining its relationship with objective measures of neuropsychological function, and neurobiological markers of disease as reflected by structural neuroimaging. Participants included 474 older adults (244 normals, 142 with MCI, 88 with dementia). The neuropsychological domains measured were episodic memory, semantic memory, spatial ability, and executive functioning. Brain MRI volumes included total brain (BV), hippocampus (HC) and dorsolateral prefrontal cortex (DLPFC). Neuropsychological measures of episodic memory and executive function were most consistently related to the ECog domains; spatial abilities had a specific relationship to the Everyday Visuospatial ECog domain. HC and BV volumes were related to most ECog domains, while DLPFC volume was independently related to two everyday executive domains (Everyday Planning and Everyday Organization). The pattern of associations varied somewhat as a function of diagnosis. Episodic memory and HC had more consistent associations with the ECog domains in older adults with MCI/dementia than in cognitively normal elderly.

A randomized control trial of a behavioral intervention for older adults with subjective cognitive complaints that combines cognitive rehabilitation strategies and lifestyle modifications.

This study examined the effectiveness of a 10-week cognitive rehabilitation and lifestyle modifying intervention that integrated compensation strategies, engagement in brain activities, and improving everyday function. The trial was registered with ClinicalTrials.gov (NCT03549078). Older adults with subjective cognitive concerns and normal performance on a cognitive screener were randomized into the intervention (n = 28) or waitlist control (n = 29) groups. The total sample comprised 57 individuals (age, mean = 74.8, SD = 6.5), mostly female (80.4% of the total sample), and well educated (education years: mean = 15.9, SD = 2.1). Outcome measures were completed at baseline, and immediately and 3- and 6-months post-intervention. Intervention participants reported significant improvements in aspects of everyday functioning and select compensation strategies and brain health activities. Increased compensation strategy use was maintained at 6-month follow up. This intervention has benefits for improving everyday functioning and increasing engagement with compensation strategies and brain health activities.

Neighborhood socioeconomic status and segregation linked to cognitive decline.

Introduction: Few longitudinal studies have examined the joint impact of neighborhood segregation and neighborhood socioeconomic status (NSES) in cognitive decline over time. Methods: This study included non-Hispanic White (NHW, n = 209) and Black participants (n = 118) whose cognition was evaluated as part of an ongoing longitudinal study. Four distinct categories of segregation and NSES were evaluated for their association with cognitive outcomes (episodic memory, semantic memory, executive function, and spatial ability) using race-specific mixed-effects models. Results: Compared to Black participants living in higher segregation-lower NSES areas, Black participants living in lower segregation-lower NSES areas or higher segregation-higher NSES areas experienced slower decline in episodic memory over time. Compared to NHW participants living in higher segregation-lower NSES areas, NHWs living in lower segregation-higher NSES areas experienced faster decline in spatial ability. Discussion: Segregation and NSES are differentially associated with cognition depending on participant race. Further research is needed to replicate study results.

Inclusion of Vietnamese Americans: Opportunities to understand dementia disparities.

There is a dearth of research on cognitive aging and dementia in Asian Americans, particularly Vietnamese Americans, who are the fourth largest Asian subgroup in the United States. The National Institutes of Health is mandated to make certain that racially and ethnically diverse populations are included in clinical research. Despite the widespread recognition to ensure that research findings can be generalizable to all groups, there are no estimates of the prevalence or incidence of mild cognitive impairment and Alzheimer's disease and related dementias (ADRD) in Vietnamese Americans, nor do we understand ADRD risk and protective factors in this group. In this article, we posit that studying Vietnamese Americans contributes to a better understanding of ADRD in general and offers unique opportunities for elucidating life course and sociocultural factors that contribute to cognitive aging disparities. That is, the unique context of Vietnamese Americans may provide understanding in terms of within-group heterogeneity and key factors in ADRD and cognitive aging. Here, we provide a brief history of Vietnamese American immigration and describe the large but often ignored heterogeneity of Asian Americans in the United States, elucidate how early life adversity and stress might influence late-life cognitive aging, and provide a basis for the role of sociocultural and health factors in the study of Vietnamese cognitive aging disparities. Research with older Vietnamese Americans provides a unique and timely opportunity to more fully delineate the factors that contribute to ADRD disparities for all populations.

Prevalence of Instrumental Activities of Daily Living Difficulties and Associated Cognitive Predictors Across Racial/Ethnic Groups: Findings From the KHANDLE Study.

OBJECTIVE: Cognitive functioning is associated with instrumental activity of daily living (IADL) performance among older adults. The present study examines potential differences in the prevalence of IADL difficulty and association with cognition across diverse groups. METHOD: Participants included 455 non-Hispanic Whites, 395 Blacks, 370 Asians, and 296 Latinos aged 65 years and older without a current dementia diagnosis from the Kaiser Healthy Aging and Diverse Life Experience cohort. Participants' self-reported IADL functioning and cognition was measured across episodic memory and executive functioning. RESULTS: Older age, male gender, and being Black were associated with more IADL difficulties. Executive functioning showed a stronger association with IADLs than memory, and it was independent of health status, whereas memory was not. In joint models including both cognitive domains, executive functioning remained a significant predictor of IADL difficulty, but memory did not. Results for both cognitive domains were attenuated with self-rated health added to the joint model. These relationships did not significantly differ across racial/ethnic groups. CONCLUSIONS: Our study supports previous work suggesting that Black older adults are at increased risk for IADL disability. This is the first study we are aware of that examined the association between specific cognitive domains and IADL performance across multiple racial/ethnic groups. Findings indicate that cognitive functioning has similar associations with self-reported IADL disability across diverse groups, and that executive functioning plays a particularly important role in IADL disability among older adults without dementia; however, health status largely attenuates the relationship between IADL difficulty and cognition.

Demographic, neuropsychological, and functional predictors of rate of longitudinal cognitive decline in Hispanic older adults.

OBJECTIVE: The identification of older adults who are at increased risk of future cognitive decline is often difficult, particularly in individuals of an ethnic minority. This study evaluated which baseline demographic, neuropsychological, and functional variables were most strongly associated with future longitudinal decline in global cognitive function. DESIGN/SETTING: Participants were part of a community-based prospective longitudinal study of 1,789 older Hispanics (Sacramento Area Latino Study on Aging). PARTICIPANTS: A subsample of 639 individuals was evaluated, comprising cognitively normal, mildly impaired, and dementia cases, and were followed longitudinally for up to 7 years. Sixty-three percent were tested in Spanish. MEASUREMENTS: Latent growth curve modeling of longitudinal data was used to assess the effects of age, gender, education, language of test administration (Spanish or English), acculturation, baseline measures of neuropsychological function (i.e., verbal memory and confrontation naming), and baseline everyday functioning (as measured by the Informant Questionnaire on Cognitive Decline in the Elderly) on rate of change in global cognitive impairment (measured by the 3MS). RESULTS: Less education, being tested in English, and poorer scores on the neuropsychological tests were all cross-sectionally associated with lower baseline 3MS scores. However, longitudinal decline in global cognition over time was primarily associated with older age and poorer everyday function at baseline. CONCLUSIONS: Informant-based ratings of functional impairment, which are easy to collect in a clinical setting, have significant use in identifying Hispanic older adults at increased risk for future cognitive decline.

Measuring cognitive reserve based on the decomposition of episodic memory variance.

In later adulthood brain pathology becomes common and trajectories of cognitive change are heterogeneous. Among the multiple determinants of late-life cognitive course, cognitive reserve has been proposed as an important factor that modifies or buffers the impact of brain pathology on cognitive function. This article presents and investigates a novel method for measuring and investigating such factors. The core concept is that in a population where pathology is common and variably present, 'reserve' may be defined as the difference between the cognitive performance predicted by an individual's level of pathology and that individual's actual performance. By this definition, people whose measured cognitive performance is better than predicted by pathology have high reserve, whereas those who perform worse than predicted have low reserve. To test this hypothesis, we applied a latent variable model to data from a diverse ageing cohort and decomposed the variance in a measure of episodic memory into three components, one predicted by demographics, one predicted by pathology as measured by structural MRI and a 'residual' or 'reserve' term that included all remaining variance. To investigate the plausibility of this approach, we then tested the residual component as an operational measure of reserve. Specific predictions about the effects of this putative reserve measure were generated from a general conceptual model of reserve. Each was borne from the results. The results show that the current level of reserve, as measured by this decomposition approach, modifies rates of conversion from mild cognitive impairment to dementia, modifies rates of longitudinal decline in executive function and, most importantly, attenuates the effect of brain atrophy on cognitive decline such that atrophy is more strongly associated with cognitive decline in subjects with low reserve than in those with high reserve. Decomposing the variance in cognitive function scores offers a promising new approach to the measure and study of cognitive reserve.

Neighborhood racial/ethnic segregation and cognitive decline in older adults.

Social determinants of health, including neighborhood factors, play a key role in the health of diverse older adults. However, few longitudinal studies have examined the role of neighborhood racial/ethnic segregation on cognitive decline in diverse samples. We examined older non-Hispanic White (NHW), Black, and Latino participants evaluated at an Alzheimer's Disease Research Center. Neighborhood racial/ethnic segregation was measured using the Getis-Ord Gi* statistic, a spatial measure of clustering that was created for Latino and Black clustering separately. Cognitive outcomes included episodic memory, semantic memory, and executive function. We used mixed effects multivariable regression models to evaluate associations between segregation and cognitive function and decline. We had 452 individuals: 46% NHW, 26% Black, and 21% Latino in 309 census tracts with an average of 5.2 years of follow-up data (range 0.6-15.0). In analyses that adjusted for a variety of covariates (including neighborhood SES), individuals in neighborhoods with a higher clustering of Latino residents (higher Gi* statistic) had slower declines over time on semantic memory and those in neighborhoods with a higher clustering of Black residents had slower declines over time on episodic memory. In race/ethnicity-stratified adjusted analyses: for Black participants, the association between clustering and cognition was present for episodic memory and executive function, showing lower baseline scores in highly clustered Black and Latino neighborhoods, respectively. There was no association with cognitive change. Among Latino participants, highly clustered Latino neighborhoods were associated with lower baseline scores in semantic memory, but slower declines in episodic memory; Latinos living in neighborhoods with a greater clustering of Black residents also had slower declines in episodic memory. Among NHWs, residing in neighborhoods with a higher clustering of Latino residents was associated with slower declines over time on semantic memory. Segregated neighborhoods may be differentially associated with cognitive outcomes depending on individual race/ethnicity.

Cognitive impairment in racially/ethnically diverse older adults: Accounting for sources of diagnostic bias.

INTRODUCTION: The Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study enrolled Asian, Black, Latino, and White adults ages 65+ without prior dementia diagnosis (N = 1709). We evaluated the prevalence of cognitive impairment (mild cognitive impairment or dementia) accounting for potential biases. METHODS: A random subgroup (N = 541) received clinical evaluation and others were evaluated if they failed a cognitive screen. Diagnoses were made under two conditions: (1) demographics-blind, based on clinical exam and demographically adjusted neuropsychological test scores; and (2) all available information (clinical exam, demographics, and adjusted and unadjusted test scores). RESULTS: Cognitive impairment prevalence was 28% for blinded-adjusted diagnosis and 25% using all available information. Black participants had higher impairment rates than White (both conditions) and Latino (blinded-adjusted diagnosis) participants. Incomplete assessments negatively biased prevalence estimates for White participants. DISCUSSION: Racial/ethnic disparities in cognitive impairment were amplified by attrition bias in White participants but were unaffected by type of test norms and diagnosticians' knowledge of demographics.

Age and education effects on relationships of cognitive test scores with brain structure in demographically diverse older persons.

This study examined how age and education influence the relationship between neuropsychological test scores and brain structure in demographically diverse older adults spanning the range from normal cognition to dementia. A sample of 351 African Americans, 410 Hispanics, and 458 Whites underwent neuropsychological testing. Volumetric magnetic resonance imaging (MRI) measures of total brain, white matter hyperintensity, and hippocampus were available for 79 African Americans, 102 Hispanics, and 134 Whites. The authors used latent variable modeling to examine effects of age, education, and brain volumes on test scores and determine how much variance brain volumes explained in unadjusted and age- and education-adjusted scores. Age adjustment resulted in weaker relationships of test scores with MRI variables; adjustment for ethnicity yielded stronger relationships. Education adjustment increased relationships with MRI variables in the combined sample and Hispanics, made no difference in Whites, but decreased some associations in African Americans. Results suggest that demographic adjustment is beneficial when demographic variables are strongly related to test scores independent of measures of brain structure, but adjustment has negative consequences when effects of demographic characteristics are mediated by brain structure.

Determination of prevalence of depression in an epilepsy clinic using a brief DSM-IV-based self-report questionnaire.

Depression in epilepsy is common, underrecognized, and an indicator of quality of life. The Patient Health Questionnaire nine-item depression scale (PHQ-9) is a self-administered questionnaire based on Diagnostic and Statistical Manual, Fourth Edition (DSM-IV) criteria with high sensitivity and specificity for diagnosing depression. Using the PHQ-9, we determined that one-third of 263 patients seen in an epilepsy clinic had scores consistent with major depression. Seizure-free patients had lower depression scores than those with persistent seizures. Depression scores were not related to the number or type of antiepileptic drugs used. One-half of patients with scores consistent with major depression were not on antidepressant medication. The brevity of the PHQ-9 is conducive to routine screening of patients with epilepsy.

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.

Dementia in fragile X-associated tremor/ataxia syndrome (FXTAS): comparison with Alzheimer's disease.

Neurocognitive deficits in fragile X-associated tremor/ataxia syndrome (FXTAS) involve attentional control, working memory, executive functioning, and declarative and procedural learning. To date, no studies comparing FXTAS with other dementias have been done. We characterize the dementia in FXTAS, comparing it with Alzheimer's disease. Retrospective chart review of 68 adults (50 men, 18 women) with FXTAS. 20 men with FXTAS dementia were matched by age, gender, and education to patients with mild Alzheimer's dementia (AD). Neuropsychological measures were compared between the two groups: Boston Naming Test (BNT), phonemic fluency (Controlled Oral Word Association Test), digit span forward (DSF) and backward (DSB). Comparisons were based on analysis of covariance and t-tests to assess significant differences between groups. 50% of men with FXTAS and no women were cognitively impaired. On mean scores of verbal fluency (22.83 in FXTAS vs. 28.83 in AD, P = 0.112), working memory (DSB, 4.80 in AD vs. 5.41 in FXTAS, P = 0.359), and language (BNT, 48.54 in AD vs. 54.20 in FXTAS, P = 0.089), there were no significant differences. Digit span forward, measuring attention, was significantly higher in subjects with FXTAS dementia (8.59, vs. 7.10 in AD, P = 0.010). Individuals with FXTAS have significant cognitive deficits, on the order of those in AD although the cognitive profiles in these dementias are not similar. Further research is needed to outline the neuropsychiatric profile in FXTAS and the correlation of genetic markers with the progression and severity of cognitive loss.

Education amplifies brain atrophy effect on cognitive decline: implications for cognitive reserve.

Level of education is often regarded as a proxy for cognitive reserve in older adults. This implies that brain degeneration has a smaller effect on cognitive decline in those with more education, but this has not been directly tested in previous research. We examined how education, quantitative magnetic resonance imaging-based measurement of brain degeneration, and their interaction affect cognitive decline in diverse older adults spanning the spectrum from normal cognition to dementia. Gray matter atrophy was strongly related to cognitive decline. While education was not related to cognitive decline, brain atrophy had a stronger effect on cognitive decline in those with more education. Importantly, high education was associated with slower decline in individuals with lesser atrophy but with faster decline in those with greater atrophy. This moderation effect was observed in Hispanics (who had high heterogeneity of education) but not in African-Americans or Caucasians. These results suggest that education is an indicator of cognitive reserve in individuals with low levels of brain degeneration, but the protective effect of higher education is rapidly depleted as brain degeneration progresses.