Objective

To examine the association of blood pressure (BP) with incident Alzheimer's disease (AD) dementia.

Methods

This work is based on a longitudinal, cohort study of 18 years, the Chicago Health and Aging Project (CHAP) performed in 2,137 participants (55% black) with systolic BP measured around 8.1 years before incident AD dementia.

Results

The association of BP with risk of AD dementia was U-shaped, with the lowest risks of AD dementia near the center of the systolic BP (SBP) and diastolic BP (DBP) distributions, and modestly elevated risk at lower BPs, and greater risk at higher BPs. The degree of U-shape and the range of lowest risk (threshold ranges) varied with antihypertensive medication use and presence of the APOE ε4 allele. The U-shape was most prominent for the subgroup not taking antihypertensive medications and having an APOE ε4 allele. At higher BPs, those having the APOE ε4 allele and not receiving antihypertensive medication were at greater risk of AD dementia than other groups: The risk of incident AD dementia increased by 100% (relative risk [RR] = 2.00; 95% confidence interval [CI] = 1.70, 2.31) for every 10 mm Hg increase in SBP above 140 mm Hg. For DBP, the risk of incident of AD dementia increased by 57% (RR = 1.57; 95% CI = 1.33, 1.86) for every 5 mm Hg increase in DBP above 76 mm Hg.

Interpretation

The BP risk of AD dementia association is U-shaped, with elevated risk at lower and higher BPs. People having the APOE ε4 allele and not receiving antihypertensive medication with higher BPs have notably elevated risk of AD dementia. Ann Neurol 2018;83:935-944.

Objectives

To examine the effects of age and race on the association of apolipoprotein E (APOE) genotypes with cognitive decline in a population sample.

Design

Longitudinal study of 18 years' duration.

Setting

Biracial urban US population sample.

Participants

There were a total of 5807 participants, 60% African American (AA) and 40% European American (EA).

Measurements

A composite cognitive function based on individual tests of episodic memory, perceptual speed, and the Mini-Mental State Examination.

Results

The frequencies of APOE ε2/ε3 (14% vs 12%), ε2/ε4 (4% vs 2%), ε3/ε4 (29% vs 22%), and ε4/ε4 (4% vs 2%) genotypes were higher among AAs than EAs. After adjusting for demographic factors, the rate of decline in global cognition was twice as high among participants with the APOE ε4/ε4 genotype compared to participants with the APOE ε3/ε3 genotype (0.097 vs 0.048 SD units [SDUs] per year; P < .0001). This doubling was not different between AAs (0.091 vs 0.045 SDUs per year) and EAs (0.118 vs 0.059 SDUs per year) (P_interaction = .63). The APOE ε3/ε4 genotype was associated with a higher rate of decline with age (P_interaction = .021), while the APOE ε2/ε4 genotype (P_interaction = .016) and the APOE ε2/ε3 genotype (P_interaction = .043) were associated with a lower rate of decline with higher age. The APOE ε2/ε2 genotype was associated with a lower rate of decline in episodic memory, while the APOE ε2/ε4 was associated with a higher rate of decline in episodic memory and perceptual speed.

Conclusions

The association of the APOE genotypes with cognitive decline was not different between AAs and EAs. However, individuals with different APOE genotypes showed a lower or a higher rate of decline with age. J Am Geriatr Soc 67:734-740, 2019.

Objective

To examine the temporal changes in the likelihood of dementia and mild cognitive impairment (MCI) between 1993 and 2012 using a short battery of cognitive tests.

Methods

A cohort of 10,342 participants underwent a short battery of cognitive tests collected during triennial in-home interviews with 2,794 of those evaluated for the clinical diagnosis of dementia and MCI. We used a generalized logit regression model to estimate the likelihood of dementia and MCI, and a quasibinomial regression model to examine the temporal changes in those likelihood scores.

Results

A short battery of cognitive tests-delayed story recall test, Symbol Digit Modalities Test, and the Mini-Mental State Examination-were associated with the clinical diagnosis of dementia and MCI. The classification accuracy of likelihood scores was 0.92 for dementia and 0.85 for MCI. After adjusting for age, race/ethnicity, and education, the likelihood of dementia in the population decreased from 21.6% (95% confidence interval [CI] 20.9%-22.3%) to 18.9% (95% CI 18.1%-19.7%) between 1993-1996 and 2000-2002 and showed no significant decline between 2000-2002 and 2009-2012 (-0.2%, 95% CI -1.1% to 0.7%). The estimated likelihood of MCI remained similar between 1993-1996 and 2009-2012 (29.0%, 95% CI 27.9%-30.1%), but showed a nonsignificant decrease in 2000-2002.

Conclusion

The likelihood scores based on a short battery of cognitive tests can serve as a measure of dementia and MCI in epidemiologic studies. The decline in the likelihood of dementia and MCI over earlier years was not sustained in later years.

Introduction

The trends in prevalence and incidence of Alzheimer's disease (AD) dementia remain uncertain.

Methods

A sample of 2794 participants with a clinical diagnosis for AD dementia were included.

Results

The 2010 census standardized prevalence of AD dementia was 14.5% (95% CI = 13.7-15.3), and annual incidence was 2.3% (1.7-2.9). Both prevalence and incidence showed substantial variation over time, but no secular trends. The prevalence of AD dementia did not change significantly from 14.6% (95% CI = 13.0, 16.2) in 1994-1997 to 14.7% (95% CI = 13.2, 16.2) in 2010-2012 (P = .84). The annual incidence of AD dementia was 2.8% (95% CI = 2.2, 3.2) in 1998-2000 and 2.2% (95% CI = 1.6, 2.8) in 2004-2006 (P = .20) and remained steady in 2010-2012. The prevalence and incidence among African Americans were approximately twice than those among European Americans.

Conclusions

The prevalence and incidence of AD dementia showed substantial variation between 1994 and 2012, but no secular trend.

Objective

The longitudinal association of the blood biomarkers total tau (t-tau), neurofilament light (Nf-L), and glial fibrillary acidic protein (GFAP) with common sporadic Alzheimer disease (AD) and cognitive decline is not established.

Methods

Using a single molecule array technology, ultrasensitive immunoassays for serum concentrations of t-tau, Nf-L, and GFAP were measured in a population sample of 1,327 participants (60% African Americans and women) who had a clinical evaluation for AD, had completed in-home cognitive assessments, and had undergone 1.5T structural magnetic resonance imaging.

Results

Higher concentrations of serum biomarkers were associated with the development of clinical AD; especially, the time-specific associations were notable: t-tau 8 to 16 years, and Nf-L and GFAP 4 to 8 years prior to clinical AD. Serum biomarkers were associated with faster cognitive decline over 16 years; baseline t-tau > 0.40pg/ml had 30% faster decline, Nf-L > 25.5pg/ml had 110% faster decline, and GFAP > 232pg/ml had 130% faster decline compared to those in the lowest quartile. Participants with baseline GFAP > 232pg/ml showed 160% faster decline in hippocampal volume compared to those with values < 160pg/ml. Additionally, higher baseline t-tau was associated with faster increase in 3rd ventricular volume, and baseline Nf-L and GFAP were associated with faster decline in cortical thickness.

Interpretation

Serum t-tau, Nf-L, and GFAP predict the development of sporadic AD and cognitive decline, and changes in structural brain characteristics, suggesting their usefulness not only as screening and predictive biomarkers, but also in capturing the pathogenesis of Alzheimer dementia. ANN NEUROL 2020;88:1065-1076.

Background

Cognitively-defined subgroups are well-documented within neurodegeneration.

Objective

We examined such profiles in diverse non-demented older adults and considered how resulting subgroups relate to modifiable factors associated with neurodegeneration.

Methods

121 non-demented (MMSE = 28.62) diverse (46%non-Latino Black, 40%non-Latino White, 15%Latino) community-dwelling adults (age = 67.7 years) completed cognitive, cardiovascular, physical activity, and diet evaluations. Latent profile analyses (LPA) employed six cognitive scores (letter fluency, letter-number sequencing, confrontational naming, 'animal' fluency, list-learning delayed recall, and recognition discriminability) to characterize cognitively-defined subgroups. Differences between resulting subgroups on cardiovascular (composite scores of overall health; specific health components including fasting blood levels) and lifestyle (sedentary behavior; moderate-to-vigorous physical activity; Mediterranean diet consumption) factors were examined using ANCOVAs adjusting for relevant confounders.

Results

Based on sample means across cognitive scores, LPA resulted in the following cognitive subgroups: 1) high-average cognition, 55%non-Latino White and 64%female participants; 2) average cognition, 58%non-Latino Black and 68%male participants; 3) lower memory, 58%non-Latino Black participants; and 4) lower executive functioning, 70%Latinos. The high-average subgroup reported significantly higher Mediterranean diet consumption than the average subgroup (p = 0.001). The lower executive functioning group had higher fasting glucose and hemoglobin A1c than all other subgroups (p-values<0.001).

Conclusion

LPA revealed two average subgroups reflecting level differences in cognition previously reported between non-Latino White and Black adults, and two lower cognition subgroups in domains similar to those documented in neurodegeneration. These subgroups, and their differences, suggest the importance of considering social determinants of health in cognitive aging and modifiable risk.

Purpose

We examined the association of Stroke Belt birth state with late-life cognition in The Study of Healthy Aging in African Americans (STAR).

Methods

STAR enrolled 764 Black Americans ages 50+ who were long-term Kaiser Permanente Northern California members. Participants completed Multiphasic Health Check-ups (MHC; 1964-1985) where early-life overweight/obesity, hypertension, diabetes, and hyperlipidemia were measured. At STAR (2018), birth state, self-reported early-life socioeconomic status (SES), and executive function, verbal episodic memory, and semantic memory scores were collected. We used linear regression to examine the association between Stroke Belt birth and late-life cognition adjusting for birth year, gender, and parental education. We evaluated early-life SES and cardiovascular risk factors (CVRF) as potential mechanisms.

Results

Twenty-seven percent of participants were born in the Stroke Belt with a mean age of 69 (standard deviation = 9) at STAR. Stroke Belt birth was associated with worse late-life executive function (β [95% confidence interval]: -0.18 [-0.33, -0.02]) and semantic memory (-0.37 [-0.53, -0.21]), but not verbal episodic memory (-0.04 [-0.20, 0.12]). Adjustment for SES and CVRF attenuated associations of Stroke Belt birth with cognition (executive function [-0.05 {-0.25, 0.14}]; semantic memory [-0.28 {-0.49, -0.07}]).

Conclusions

Black Americans born in the Stroke Belt had worse late-life cognition than those born elsewhere, underscoring the importance of early-life exposures on brain health.

Objectives

Adverse childhood experiences (ACEs) are associated with higher risk of chronic disease, but little is known about the association with late life cognitive decline. We examined the longitudinal association between ACEs and late-life cognitive decline in the Study of Healthy Aging in African Americans (STAR).

Design

Linear mixed models with random intercepts and slope examined the association of individual and composite ACEs with cognitive change adjusting for years from baseline (timescale), baseline age, sex, parental education, childhood socioeconomic status and childhood social support. Participants reported whether they had experienced nine types of ACEs. Executive function and verbal episodic memory were measured up to three times over a 3-year period using the Spanish and English Neuropsychological Assessment Scales.

Settings

Kaiser Permanente Northern California members living in the Bay Area.

Participants

STAR is a cohort study of cognitive ageing launched in 2018 that has enrolled 764 black Americans ages ≥50 years (mean age=67.5; SD=8.5).

Results

Twenty-one per cent of participants reported no ACEs, 24% one ACE, 20% two ACEs, 17% three ACEs and 17% four or more ACEs. Compared with no ACEs, two ACEs (β=0.117; 95% CI 0.052 to 0.182), three ACEs (β=0.075; 95% CI 0.007 to 0.143) and four or more ACEs (β=0.089; 95% CI 0.002 to 0.158) were associated with less decline in executive function. There were no significant associations between number of ACEs and baseline or longitudinal verbal episodic memory or between individual ACEs and executive function or verbal episodic memory.

Conclusion

In this cohort of older black Americans, there was no association between ACEs and baseline cognition or cognitive change in verbal episodic memory; however, experiencing ≥ 2 ACEs was associated with less decline in executive function. These results may indicate that participants who survived to age 50+ and experienced ACEs may have cognitive resilience that warrants further investigation.

Background

Midlife cardiovascular risk factors (CVRF) increase risk of dementia. Black Americans experience an elevated prevalence of CVRF and dementia. However, little is known of how CVRF prior to midlife affect late-life cognition. We examined CVRF in adolescence, young adulthood, and midlife with late-life cognition in The Study of Healthy Aging in African Americans (STAR).

Methods

STAR assesses cognitive aging among 764 Black Americans ages ≥50 (mean age=69;SD=9;range 53-95). Participants' body mass index, blood pressure, glucose, and total cholesterol were collected during Multiphasic Health Check-ups (MHC;1964-1985). At STAR baseline (2018-2019), executive function, verbal episodic memory, and semantic memory were measured using the Spanish and English Neuropsychological Assessment Scales. Linear regression models examined associations between CVRF and cognition adjusting for demographics and years since MHC.

Results

At MHC, 36% of participants had 1 CVRF and 26% had ≥2. Twenty-two percent of participants were adolescents (ages:12-20), 62% young adults (ages:21-34), and 16% midlife adults (ages:35-56). Overweight/obesity was not associated with cognition. Hypertension was associated with worse executive function [β(95%CI):-0.14(-0.28,-0.0003)] and verbal episodic memory [β(95%CI):-0.22(-0.37,-0.07)] compared to normotension. Diabetes was associated with worse executive function [β(95%CI):-0.43(-0.83,-0.03)]. Having ≥2 CVRF (versus 0) was associated with worse executive function [β(95%CI):-0.19(-0.34,-0.03)] and verbal episodic memory [β(95%CI):-0.25(-0.41,-0.08)]. Adolescents with hypertension had lower late-life executive function compared to normotensive adolescents [β(95%CI):-0.39(-0.67,-0.11)]. Young adulthood hypertension [β(95%CI):-0.29(-0.49,-0.09)] and midlife hyperlipidemia [β(95%CI):-0.386(-0.70,-0.02)] were associated with lower verbal episodic memory.

Conclusions

Among Black Americans, lifecourse CVRF were associated with poorer executive function and verbal episodic memory emphasizing the importance of cardiovascular health on the aging brain.

Introduction

Black students attending predominantly White institutions (PWIs) versus historically Black colleges and universities (HBCUs) report more harmful discrimination and develop worse mental health outcomes, potentially offsetting the established benefits of college for lowering dementia incidence.

Methods

Black participants in two cohorts (the Kaiser Healthy Aging and Diverse Life Experiences [KHANDLE] and the Study of Healthy Aging in African Americans [STAR]) who had attended college (N = 716) self-reported the college name (classified as HBCU vs. PWI) and completed three waves of executive function (EF) and verbal episodic memory (VEM) assessments. HBCU effects on cognitive level and decline were estimated using adjusted linear mixed-effects models.

Results

HBCU (vs. PWI) attendees averaged better EF (β = 0.05 [-0.22, 0.32]) and VEM (β = 0.21 [-0.06, 0.46]) at age 70 though neither association was statistically significant. HBCU attendance was associated with slightly faster VEM decline (β = -0.03 [-0.05, 0.00]).

Discussion

Harmonized analyses with larger studies are needed to estimate important effects of HBCU attendance.

Highlights

Higher education is robustly linked to lower dementia risk, yet Black-White inequities persist among college-educated adults. Black students attending predominantly White institutions (PWIs) versus historically Black colleges and universities (HBCUs) report more harmful discrimination and develop worse mental health outcomes, which may offset the established benefits of college for lowering dementia incidence. HBCU (vs. non-HBCU) attendees averaged better executive function and verbal episodic memory (VEM) at average age 70, though confidence intervals were wide and associations were not statistically significant, and averaged slightly faster decline in VEM. Harmonized analyses using larger nationally representative studies are likely needed to avoid underestimating the health effects of HBCU attendance.