Dearborn, Jennifer L.

Background: Midlife obesity is associated with dementia in later life, but how the metabolic syndrome (MetS) relates to cognitive change is less understood. We hypothesized that MetS would be more predictive of 6-year cognitive decline than its individual components in a large biethnic cohort (the ARIC study) and that combinations of risk factors would further increase likelihood of change. Methods: The MetS was defined in 1987-89 on 10,687 participants with two cognitive assessments at two time points. In subjects aged 44 to 66, obesity measures included body mass index (BMI) and waist-to-hip ratio (WTHR). The main outcome measure was change in 1990-92 to 96-99 of three cognitive tests: Delayed Word Recall (DWR), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT). Linear and logistic regressions were all adjusted for age, combined race-center, sex, education, smoking, drinking, coronary artery disease and prior stroke. Change was measured as the difference divided by the number of years between visits. Results: At baseline, the prevalence of MetS was 22% (mean age 54 years, 27% black, 55% female, and 28% BMI>30 kg/m2). Subjects with MetS performed in the lowest test quintile (adjusted ORs: DWR 1.3 95% CI 1.1-1.4) in 1996-99, and much of this effect size was explained by an elevated WTHR (DWR OR 1.3 CI 1.1-1.5) and diabetes (DWR OR 1.4 CI 1.2-1.7). MetS was not associated with annual cognitive change, and diabetes was the only significant component associated with change (adjusted beta: DWR 0.03 p=.01, DSST 0.2 p<.001, WFT 0.09 p=.01). Conclusion: MetS at ages 44 to 66 was associated with worse cognitive function at follow-up, but not with annual cognitive decline over several years. Elevated WTHR and diabetes explained most of the association of MetS with cognitive function measures, and diabetes with cognitive decline. Until we have a definition of the MetS more based on pathophysiology, the components of the MetS should be the focus of analysis in future studies.

Background: A healthy diet may be protective against cognitive decline by mechanisms that involve improved vascular risk factors such as hypertension and dysglycemia, and reduced systemic inflammation. In this population-based study, we hypothesized that midlife diet pattern would be associated with cognitive decline over 21-years. Methods: This study included 13,603 participants in the ARIC population-based cohort recruited from four U.S. sites who were aged 45 to 64 at baseline (1987-89) when diet was measured. Participants recorded diet using a 66-item food frequency questionnaire. Two dietary patterns, called “Meat and Fried” and the “Balanced Diet”, were named after the most representative foods that emerged from constructs derived from a principal component analysis of 30 food groups. A higher diet pattern score represented greater adherence. Cognitive testing, including the digit symbol substitution, the word fluency and delayed word recall tests, were combined to a z-score at each visit (visits 2, 1990-92; 4, 1996-98 and 5, 2011-2013). Test scores for participants not attending subsequent visits were imputed using Multiple Imputation by Chained Equations to account for cohort attrition. Cognitive performance at visit 2 was compared by tertile (T) of each diet pattern. Using mixed effects models with a random slope and intercept , we determined the 21-year change in cognitive function by diet pattern tertile, adjusting for demographics and medical history. Results: At visit 2, adherence to the Meat and Fried pattern was associated with lower cognitive test scores (z-score T3: -0.172, SD 0.985; T1: 0.149, SD 0.981, p-trend <0.001). Adherence to the Balanced Diet was not associated with differences in cognitive performance (z-score T3: 0.013, SD 0.988; T1 -0.036, SD 1.001, p-trend 0.10). 21-year change in cognitive function did not differ by adherence to diet pattern with adjustments (difference of the change in z-score for Meat and Fried, T3 vs. T1: 0.02, [CI -0.05 to 0.08]; Balanced Diet T3 vs. T1: -0.03, [CI -0.09 to 0.02]). Conclusion: Although participants with a diet pattern high in meat and fried foods had lower cognition at time of first assessment, diet patterns at midlife did not carry independent associations with cognitive decline.

Background: Increasing evidence points to intracranial atherosclerosis as a risk factor not only for stroke but also for dementia, but whether it is linked to Alzheimer’s disease-specific pathology itself is less understood. In the community-based Atherosclerosis Risk in Communities (ARIC) study, we evaluated the cross-sectional association between intracranial atherosclerosis and cerebral amyloid deposition, in nondemented participants. Methods: In 2011-2014, a subset of participants from the ARIC Neurocognitive Study underwent both a brain MRI, including high-resolution vessel wall imaging, and florbetapir PET, as a marker of amyloid deposition. We analyzed the association between elevated amyloid (defined as a global cortical florbetapir standardized uptake value ratio (SUVR)>1.2) and intracranial arterial plaque presence, frequency, and extent of stenosis, with adjustment for demographic and vascular risk factors. We tested effect modification by APOE ε4 genotype. Results: In 300 participants (mean age of 76y, 44% African-American, 56% female, 31% carriers of at least one APOE ε4 allele), intracranial plaque was found in 105 (35%) participants. Mean SUVR was higher in individuals with vs without plaque (1.34 ± 0.29 vs 1.27 ± 0.23, p=0.03). In adjusted models, plaque presence was not associated significantly with elevated SUVR in the total sample, nor was number of plaques. Associations between plaque presence and extent were generally stronger in APOE ε4 carriers than noncarriers (p<0.05 for interaction for some plaque features; see Table). Conclusions: Although intracranial arterial plaque or stenosis was not definitively associated with brain amyloid in this sample of nondemented older adults, associations with brain amyloid appeared stronger in carriers of an APOE ε4 allele, consistent with studies demonstrating a similar relationship as that seen with other more traditionally measured vascular risk factors.