Dataset Information

Race, APOE?4, and Long-Term Cognitive Trajectories in a Biracial Population Sample.

ABSTRACT: BACKGROUND:The association of the APOE?4 allele with incident Alzheimer's dementia is higher among European Americans (EAs) than African Americans (AAs), but similar for the rate of cognitive decline. OBJECTIVE:To examine the racial differences in the association of the APOE?4 allele with incident Alzheimer's dementia and cognitive decline. METHODS:Using a population-based sample of 5,117 older adults (66% AAs and 63% females), we identified cognitive trajectory groups from a latent class mixed model and examined the association of the APOE?4 allele with these groups. RESULTS:The frequency of the APOE?4 allele was higher among AAs than EAs (37% versus 26%). Four cognitive trajectories were identified: slow, mild, moderate, and rapid. Overall, AAs had a lower baseline global cognition than EAs, and a higher proportion had rapid (7% versus 5%) and moderate (20% versus 15%) decline, but similar mild (44% versus 46%), and lesser slow (29% versus 34%) decline compared to EAs. Additionally, 25% of AAs (13% of EAs) with mild and 5% (<1% of EAs) with slow decline were diagnosed with incident Alzheimer's dementia. The APOE?4 allele was associated with higher odds of rapid and moderate decline compared to slow decline among AAs and EAs, but not with mild decline. CONCLUSIONS:AAs had lower cognitive levels and were more likely to meet the cognitive threshold for Alzheimer's dementia among mild and slow decliners, explaining the attenuated association of the ?4 allele with incident Alzheimer's dementia among AAs.

SUBMITTER: Rajan KB

PROVIDER: S-EPMC6914259 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Race, APOEɛ4, and Long-Term Cognitive Trajectories in a Biracial Population Sample.

Rajan Kumar B KB McAninch Elizabeth A EA Wilson Robert S RS Weuve Jennifer J Barnes Lisa L LL Evans Denis A DA

Journal of Alzheimer's disease : JAD 20190101 1

<h4>Background</h4>The association of the APOEɛ4 allele with incident Alzheimer's dementia is higher among European Americans (EAs) than African Americans (AAs), but similar for the rate of cognitive decline.<h4>Objective</h4>To examine the racial differences in the association of the APOEɛ4 allele with incident Alzheimer's dementia and cognitive decline.<h4>Methods</h4>Using a population-based sample of 5,117 older adults (66% AAs and 63% females), we identified cognitive trajectory groups from ...[more]

PMID: 31561363

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Project description:ImportanceHospitalizations are associated with cognitive decline in older adults.ObjectiveTo determine the association between hospitalization characteristics and the trajectory of cognitive function in older adults.DesignPopulation-based longitudinal study of cognitive aging.SettingOlmsted Medical Center and Mayo Clinic, the only centers in Olmsted County, Minnesota, with hospitalization capacity.ParticipantsIndividuals without dementia at baseline, with consecutive cognitive assessments from 2004 through 2017, and at least one visit after the age of 60.MeasurementsThe primary outcome was longitudinal changes in global cognitive z-score. Secondary outcomes were changes in four cognitive domains: memory, attention/executive function, language, and visuospatial skills. Hospitalization characteristics analyzed included elective versus nonelective, medical versus surgical, critical care versus no critical care admission, and long versus short duration admissions.ResultsOf 4,587 participants, 1,622 had 1 and more hospital admission. Before hospitalization, the average slope of the global z-score was -0.031 units/year. After hospitalization, the rate of annual global z-score accelerated by -0.051 (95% CI = -0.057, -0.045) units, P < .001, resulting in an estimated annual slope after the first hospitalization of -0.082. The accelerated decline was found in all four cognitive domains (memory, visuospatial, language, and executive, all P < .001). The acceleration of the decline in global z-score following hospitalization was greater for medical compared to surgical hospitalizations (slope change following hospitalization = -0.064 vs -0.034 for medical vs surgical, P < .001), and nonelective compared to elective admissions (slope change following hospitalization = -0.075 vs -0.037 for nonelective vs elective, P < .001). The acceleration of cognitive decline was not different for hospitalization with intensive care unit admission versus not.ConclusionsHospitalization of older adults is associated with accelerated decline of global and domain-specific cognitive domains, with the rate of decline dependent upon type of admission. The clinical impact of this accelerated decline will depend on the individual's baseline cognitive reserve and expected longevity.

Project description:BackgroundBoth Alzheimer's disease (AD) genetic risk factors and indices of cognitive reserve (CR) influence risk of cognitive decline, but it remains unclear whether they interact. This study examined whether a CR index score modifies the relationship between AD genetic risk factors and long-term cognitive trajectories in a large sample of individuals with normal cognition.MethodsAnalyses used data from the Preclinical AD Consortium, including harmonized data from 5 longitudinal cohort studies. Participants were cognitively normal at baseline (M baseline age = 64 years, 59% female) and underwent 10 years of follow-up, on average. AD genetic risk was measured by (i) apolipoprotein-E (APOE) genetic status (APOE-ε2 and APOE-ε4 vs. APOE-ε3; N = 1819) and (ii) AD polygenic risk scores (AD-PRS; N = 1175). A CR index was calculated by combining years of education and literacy scores. Longitudinal cognitive performance was measured by harmonized factor scores for global cognition, episodic memory, and executive function.ResultsIn mixed-effects models, higher CR index scores were associated with better baseline cognitive performance for all cognitive outcomes. APOE-ε4 genotype and AD-PRS that included the APOE region (AD-PRSAPOE) were associated with declines in all cognitive domains, whereas AD-PRS that excluded the APOE region (AD-PRSw/oAPOE) was associated with declines in executive function and global cognition, but not memory. There were significant 3-way CR index score × APOE-ε4 × time interactions for the global (p = 0.04, effect size = 0.16) and memory scores (p = 0.01, effect size = 0.22), indicating the negative effect of APOE-ε4 genotype on global and episodic memory score change was attenuated among individuals with higher CR index scores. In contrast, levels of CR did not attenuate APOE-ε4-related declines in executive function or declines associated with higher AD-PRS. APOE-ε2 genotype was unrelated to cognition.ConclusionsThese results suggest that APOE-ε4 and non-APOE-ε4 AD polygenic risk are independently associated with global cognitive and executive function declines among individuals with normal cognition at baseline, but only APOE-ε4 is associated with declines in episodic memory. Importantly, higher levels of CR may mitigate APOE-ε4-related declines in some cognitive domains. Future research is needed to address study limitations, including generalizability due to cohort demographic characteristics.

Dataset Information

Race, APOE?4, and Long-Term Cognitive Trajectories in a Biracial Population Sample.

Publications

Race, APOEɛ4, and Long-Term Cognitive Trajectories in a Biracial Population Sample.

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