Reserve and Alzheimer's disease genetic risk: Effects on hospitalization and mortality.

INTRODUCTION: Cognitive reserve predicts delayed diagnosis of Alzheimer's disease (AD) and faster postdiagnosis decline. The net impact of cognitive reserve, combining both prediagnosis and postdiagnosis risk, on adverse AD-related outcomes is unknown. We adopted a novel approach, using AD genetic risk scores (AD-GRS), to evaluate this. METHODS: Using 242,959 UK Biobank participants age 56+ years, we evaluated whether cognitive reserve (operationalized as education) modified associations between AD-GRS and mortality or hospitalization (total count, fall-related, and urinary tract infection-related). RESULTS: AD-GRS predicted mortality and hospitalization outcomes. Education did not modify AD-GRS effects on mortality, but had a nonsignificantly (interaction P = .10) worse effect on hospitalizations due to urinary tract infection or falls among low education (OR = 1.07 [95% CI: 1.02, 1.12]) than high education (OR = 1.01 [0.95, 1.07]) individuals. DISCUSSION: Education did not convey differential survival advantages to individuals with higher genetic risk of AD, but may reduce hospitalization risk associated with AD genetic risk.

Neuropathological Diagnoses of Demented Hispanic, Black, and Non-Hispanic White Decedents Seen at an Alzheimer's Disease Center.

Our nation is becoming increasingly diverse; however, few autopsy studies examine multiple ethnoracial groups, especially Hispanics. We examined differences in neuropathological diagnoses of 423 deceased participants with dementia from three ethnoracial groups (35 Black, 28 Hispanic, and 360 non-Hispanic White) evaluated at the University of California Davis Alzheimer's Disease Center. We used novel applications of bootstrap resampling and logistic regression standardization to project neuropathological diagnostic rates for non-Hispanic Whites to minority sample characteristics to improve inference of findings. Alzheimer's disease (AD) without significant cerebrovascular disease (CVD) or other dementia-related pathologies (AD (non-mixed)) was present in 15 Black (43%), 4 Hispanic (14%), and 156 (43%) non-Hispanic Whites. CVD sufficient to contribute to dementia was confirmed in 14 Black (40%), 15 Hispanic (54%), and 101 (28%) non-Hispanic White decedents. The observed CVD prevalence of 40% in Blacks exceeded the predicted 29% [95% CI: 22%-36%]. Despite being outside the 95% confidence interval, the difference between observed and predicted was not statistically significant after bootstrap testing. Conversely, for Hispanics, the observed proportion at 54% exceeded significantly the predicted prevalence of 24% from non-Hispanic Whites [95% CI: 16%-34%], avg. p = 0.008). An identical analysis using AD (non-mixed) as the outcome predicted AD (non-mixed) in Blacks averaging 41% [95% CI: 34%-48%], nearly equal to observed prevalence. For Hispanics, however, the observed proportion at 14%, was well below predictions (mean = 42%, 95% CI: 32%-53%], avg. p = 0.008). We conclude mixed diagnoses and CVD are more common in Hispanic and Black decedents than Non-Hispanic Whites with dementia in our cohort. The increased prevalence of vascular co-morbidity may be a potential opportunity to intervene more effectively in dementia treatment of those individuals.

Staging of amyloid ß, t-tau, regional atrophy rates, and cognitive change in a nondemented cohort: Results of serial mediation analyses.

INTRODUCTION: Current models posit a sequence of amyloid ß (Aß), tau, atrophy, and cognitive change leading to Alzheimer's disease, but ambiguities remain. We examined these sequences via serial mediations. METHODS: We studied normal controls, early mild cognitive impairment, and late mild cognitive impairment individuals from the Alzheimer's Disease Neuroimaging Initiative 2 database for the mediation of baseline cerebrospinal fluid Aß effects on 2-year cognitive change via regional longitudinal atrophy rate (AR) alone or AR and tau. RESULTS: In normal controls, Aß correlated directly with regional ARs and memory loss, with no mediations. In early mild cognitive impairment, tau and lateral temporal ARs serially mediated the influence of Aß on memory while Aß affected memory via hippocampal AR. Late mild cognitive impairment consistently showed serial mediations of tau followed by atrophy. However, Aß effects on memory also continued to be specifically mediated by medial temporal ARs without intermediate tau. DISCUSSION: Biomarker sequences vary by region and disease state, suggesting the need to refine current cascade models.