Angela L. Jefferson

OBJECTIVES: To cross‐sectionally quantify the contribution of proxy measures of cognitive reserve reflective of the lifespan, such as education, socioeconomic status (SES), reading ability, and cognitive activities, in explaining late‐life cognition. DESIGN: Prospective observational cohort study of aging. SETTING: Retirement communities across the Chicago metropolitan area. PARTICIPANTS: Nine hundred fifty‐one older adults free of clinical dementia in the Rush Memory and Aging Project (aged 79±8, 74% female). MEASUREMENTS: Baseline data on multiple life course factors included early‐, mid‐, and late‐life participation in cognitive activities; early‐life and adult SES; education; and reading ability (National Adult Reading Test; NART). Path analysis quantified direct and indirect standardized effects of life course factors on global cognition and five cognitive domains (episodic memory, semantic memory, working memory, visuospatial ability, perceptual speed). RESULTS: Adjusting for age, sex, and race, education had the strongest association with global cognition, episodic memory, semantic memory, and visuospatial ability, whereas NART (followed by education) had the strongest association with working memory. Late‐life cognitive activities had the strongest association with perceptual speed, followed by education. CONCLUSIONS: These cross‐sectional findings suggest that education and reading ability are the most‐robust proxy measures of cognitive reserve in relation to late‐life cognition. Additional research leveraging path analysis is warranted to better understand how these life course factors, reflecting the latent construct of cognitive reserve, affect abnormal cognitive aging.

Background/Aims: We hypothesized that inflammatory markers are cross-sectionally and longitudinally associated with neuropsychological indicators of early ischemia and Alzheimer’s disease. Methods: Framingham Offspring Study participants, free of clinical stroke or dementia (n = 1,878; 60 ± 9 years; 54% women), underwent neuropsychological assessment and ascertainment of 11 inflammatory markers. Follow-up neuropsychological assessments (6.3 ± 1.0 years) were conducted on 1,352 of the original 1,878 participants. Results: Multivariable linear regression related the inflammatory markers to cross-sectional performance and longitudinal change in neuropsychological performances. Secondary models included a twelfth factor, tumor necrosis factor-α (TNF-α), available on a subset of the sample (n = 1,393 cross-sectional; n = 1,213 longitudinal). Results suggest a few modest cross-sectional inflammatory and neuropsychological associations, particularly for tests assessing visual organization (C-reactive protein, p = 0.007), and a few modest relations between inflammatory markers and neuropsychological change, particularly for executive functioning (TNF-α, p = 0.004). Secondary analyses suggested that inflammatory markers were cross-sectionally (TNF-α, p = 0.004) related to reading performance. Conclusions: Our findings are largely negative, but suggest that specific inflammatory markers may have limited associations with poorer cognition and reading performance among community-dwelling adults. Because of multiple testing concerns, our limited positive findings are offered as hypothesis generating and require replication in other studies.

In light of our limited understanding of what motivates older adults to participate in clinical studies of Alzheimer's disease (AD), the current study examines incentives and barriers to participating in AD clinical research among older adults. 235 p

This study examined factors associated with brain donation program participation among African American and White elders. By postal mail, participants were recruited from an Alzheimer's research registry (all of whom had been invited to participate in the Center's brain donation program) and asked to complete surveys assessing brain donation knowledge, trust in healthcare systems, and religiousness. African American respondents completed a cultural mistrust inventory. Demographic, brain donation status, and literacy data (as assessed by the Wide Range Achievement Test-3 Reading subtest) were compiled from the respondents' most recent registry visit. The survey response rate was 60% (n=184 White and n=49 Black respondents). Logistic regression, comparing religiousness, trust in healthcare institutions, and educational attainment, identified a single predictor (ie, religiousness) in the prediction of donation status among White respondents (P=0.008), whereas no predictors were observed for donation status among the Black respondents. Using all African American donors and nondonors from the registry (n=68), comparisons revealed Wide Range Achievement Test-3 Reading score differences for African American donors (46.8±5.9) and nondonors (42.8±8.4, P=0.02). Results suggest that increased religiousness is related to White elders' decisions not to donate, whereas lower reading ability might be related to African American participants' decisions not to donate.

Background— Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with preclinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer disease in the community. Methods and Results— Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, or dementia (age, 61±9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI–assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume ( P =0.03) and information processing speed ( P =0.02) and inversely related to lateral ventricular volume ( P =0.048). When participants with clinically prevalent cardiovascular disease were excluded, the relation between cardiac index and total brain volume remained ( P =0.02). Post hoc comparisons revealed that participants in the bottom cardiac index tertile (values 2.92). Conclusions— Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging.

Purpose: To learn about African American older adults’ knowledge and perceptions of brain donation, factors that relate to participating or not participating in a brain donation research program, and methods to increase African American brain donation commitment rates in the context of an Alzheimer's disease (AD) research program. Design and Methods: African American older adults (n = 15) from the Boston University Alzheimer's Disease Core Center participant research registry enrolled in 1 of 2 focus groups of 90 min about brain donation. Seven participants were selected for a third follow-up focus group. Results: Focus group transcripts were analyzed using consensual qualitative research methods, and 8 overarching themes emerged: (a) perceptions of and misconceptions about brain donation procedures, (b) racial minorities in medical research, (c) racial disparities and discrimination in medical settings, (d) influence of religion and spirituality, (e) family perceptions of and involvement in donation, (f) family history of disease and desire to find a cure, (g) prior exposure to medical and research settings, and (h) culturally sensitive approaches to brain donation. Implications: Culturally relevant educational protocols need to be created for use with African American older adults. These protocols should include information about brain donation procedures, rates of AD among Black elders, and potential benefits of donation to Black communities; inclusion of religious figures, family, and peers in donation education and decisions; and methods to address mistrust, including cultural competence trainings for staff.

Heart failure has served as a clinically useful model for understanding how cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults, theoretically because systemic hypoperfusion disrupts cerebral perfusion,

Vascular cognitive impairment is the second most common cause of dementia after Alzheimer's disease and is expected to grow in prevalence with the aging global population. The purpose of this authoritative book is to give a broad clinical perspective on vascular cognitive impairment and thus create a foundation for the implementation of good dementia care. The book focuses on pathophysiology, diagnosis, treatment and prevention. It demonstrates the underlying causes of the disorder, such as the manner in which vascular risk-factors influence the onset of vascular cognitive impairment. The concept of mixed forms of vascular dementia, Alzheimer's dementia and other vascular diseases is discussed as well as the influence of vascular changes with regard to the onset of Alzheimer's disease. The detailed section on pathophysiology will enhance clinicians' understanding of this complex disorder. Finally there is a section on pharmacological and neuropsychological treatment of cognitive and psychiatric symptoms.