Body mass index (BMI) is a risk factor for Alzheimer’s disease (AD) although the relationship is complex. Obesity in midlife is associated with increased risk for AD, whereas evidence supports both higher and lower BMI increasing risk for AD in late life. This study examined the influence of individual differences in genetic risk for AD to further clarify the relationship between late-life BMI and conversion to AD. Participants included 52 individuals diagnosed as having mild cognitive impairment (MCI) at baseline who converted to AD within 24 months and 52 matched MCI participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. BMI was measured at baseline. Genetic risk for AD was assessed via genome-wide polygenic risk scores. Conditional logistic regression models were run to determine if BMI and polygenic risk predicted conversion to AD. Results showed an interaction between BMI and genetic risk, such that individuals with lower BMI and higher polygenic risk were more likely to convert to AD relative to individuals with higher BMI. These results remained significant after adjusting for cerebrospinal fluid biomarkers of AD. Exploratory sex-stratified analyses revealed this relationship only remained significant in males. These results show that higher genetic risk in the context of lower BMI predicts conversion to AD in the next 24 months, particularly among males. These findings suggest that genetic risk for AD in the context of lower BMI may serve as a prodromal risk factor for future conversion to AD.

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The goal of the present study was to examine associations between posttraumatic stress disorder (PTSD) symptom severity, the number of stressors experienced, and cognitive outcomes in a sample of U.S. Vietnam War Veterans (N = 274). Adults between 60 and 85 years of age completed a Vietnam Veterans Alzheimer's Disease Neuroimaging Initiative Project visit. A modified version of the Life Stressor Checklist‐Revised (LSC‐R) was used to assess the number of stressful experiences participants experienced, current PTSD severity scores were measured via the Clinician‐Administered PTSD Scale for DSM‐IV (CAPS‐IV), and cognition was assessed using the Montreal Cognitive Assessment (MoCA). Linear regressions were conducted to examine the effect of CAPS‐IV and LSC‐R scores on cognitive performance. Higher CAPS‐IV scores were associated with worse cognitive outcomes on the MoCA, ΔF(1, 264) = 12.686, p < .001, R2 = .142. In contrast, the number of reported stressful experiences was not associated with cognitive outcomes. After accounting for multiple comparisons, findings indicated that CAPS‐IV severity scores were significantly associated with the MoCA memory index. In a sample of older Veterans, PTSD symptom severity, but not the number of reported stressors, was associated with poorer performance on a well‐established cognitive function screening tool. Analyses of specific MoCA domains indicated that memory may be driving this association. These findings suggest that highly arousing stressors characteristic of PTSD, rather than stressful experiences more broadly, contribute to this association. Future work can use these findings to explore whether treating PTSD symptoms may help maintain cognitive function during the aging process.

Background: A complex set of interactions between biological, genetic, and environmental factors likely underlies the development of Alzheimer's disease (AD). Identifying which of these factors is most associated with AD is important for early diagnosis and treatment. Objective: We sought to examine genetic risk and structural brain volume on episodic memory in a sample of older adults ranging from cognitively normal to those diagnosed with AD. Methods: 686 adults (55-91 years old) completed a 3T MRI scan, baseline cognitive assessments, and biospecimen collection through the Alzheimer's Disease Neuroimaging Initiative. Hierarchical linear regression analyses examined main and interaction effects of medial temporal lobe (MTL) volume and polygenic hazard score (PHS), indicating genetic risk for AD, on a validated episodic memory composite score. Results: Genetic risk moderated the relationship between MTL volume and memory, such that individuals with high PHS and lower hippocampal and entorhinal volume had lower memory composite scores [ F (1,677) = 4.057, p = 0.044, R 2 = 0.002]. Further analyses showed this effect was driven by the left hippocampus [ F(1,677) = 5.256, p = 0.022, R 2 = 0.003] and right entorhinal cortex [ F (1,677) = 6.078, p = 0.014, R 2 = 0.003]. Conclusions: Among those with high genetic risk for AD, lower volume was associated with poorer memory. Results suggest that the interaction between AD genetic risk and MTL volume increases the likelihood for memory impairment among older adults. Results from this study suggest that genetic risk and brain volume should be considered key factors in tracking cognitive decline.

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