👤 Eileen M Crimmins

Plant-based diets have been linked to slower cognitive decline, but data on long-term dietary changes and from diverse populations are limited. The primary aim of this study was to examine plant-based dietary patterns and their change over time in relation to Alzheimer disease and related dementias (ADRDs). This prospective longitudinal analysis of the Multiethnic Cohort Study, based in Hawaii and California (primarily Los Angeles County), included data on African American, Japanese American, Latino, Native Hawaiian, and White participants who completed food frequency questionnaires at baseline (1993-1996; age 45-75 years) and at 10-year follow-up (2003-2008) and whose Medicare claims were linked to identify incident ADRDs. A priori indices for the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI) were analyzed in Cox regression models for ADRD. The analysis included 92,849 participants (mean age 59.2 years, 55.1% female, 21,478 with ADRDs) for the baseline diet and 45,065 participants (8,360 with ADRDs) for the 10-year dietary change. For the baseline diet, comparing the highest vs lowest quintile, PDI and hPDI were associated with 12% (hazard ratio [HR] 0.88; 95% CI 0.85-0.92) and 7% (HR 0.93; 95% CI 0.89-0.97) lower risks of ADRD, respectively, whereas uPDI was related to a 6% higher risk (HR 1.06; 95% CI 1.01-1.10). For the dietary change over time, the strongest association with ADRD was observed for uPDI rather than for PDI or hPDI. Compared with those with a stable score (<0.5 SD change), participants with a large increase in uPDI (≥1 SD) showed a 25% higher risk (HR 1.25; 95% CI 1.15-1.36) and those with a large decrease in uPDI showed an 11% lower risk (HR 0.89; 95% CI 0.84-0.94). The associations between the plant-based diet indices and ADRD were generally similar by age group (<60 vs ≥60 years at baseline), race and ethnicity, or These findings suggest that adopting plant-based diets, specifically refraining from low-quality plant-based diets, even at an older age, is associated with a lower risk of ADRDs. Show less

The association of blood-based biomarkers of neuropathology with cognition, dementia, and mortality and how these association potentially differ by race/ethnicity, has not been examined in large, diverse, nationally-representative samples of adults. The sample included Health and Retirement Study (HRS) respondents over age 50 with blood-based neuropathology biomarker, demographic, and cognitive data (n=4,214). A When each biomarker was analyzed individually, higher A In a large nationally-representative sample of US adults, we found that NfL was the most consistent predictor of cross-sectional and incident dementia 6 years post blood collection. NfL was also the most consistent predictor across race/ethnic groups examined in our study. There are currently limited data on blood-based biomarkers of neuropathology as predictors of cognitive performance and incident dementia in diverse, population-based cohort studies.We used data from the Health and Retirement Study (n-=4,214) to examine the association between blood-based biomarkers of neuropathology and cognitive function, as well as their association with incident dementia and mortality 4 years after measurement. Mean levels of A Show less

Alzheimer's disease and related dementias (ADRD) are major public health concerns. DNA methylation (DNAm)-based biomarkers such as GrimAge and PhenoAge predict aging and health risk, but were not designed to optimize prediction of cognitive decline. We used data from the 2016 Venous Blood Study of the Health and Retirement Study (HRS), a nationally representative cohort of U.S. adults aged ≥51 years (N = 3575 with high-quality DNAm). Epigenetic g scores were computed using CpG weights from a BayesR+ model of general cognitive ability developed in Generation Scotland. Cognitive function was measured with a modified version of the Telephone Interview for Cognitive Status (TICS) at each interview wave; 6-year incident dementia was defined using the validated Langa-Weir algorithm. Linear regression estimated associations with cognitive scores; logistic regression estimated 4-year dementia risk. Models were adjusted sequentially for demographics, education, parental education, APOE ε4 status, and blood-based neurodegeneration markers (NfL, GFAP, Aβ42/40, pTau181). Higher epigenetic g was associated with better baseline cognition (β=2.55, 95% CI 1.92-3.17) and cognition at the time DNAm was measured (β=2.30, 95% CI 1.62-2.99) after demographic adjustment. Associations attenuated but remained significant with education and parental education (β=1.23-1.89). Each unit increase in epigenetic g predicted 29% lower 6-year risk of dementia (fully adjusted HR=0.71). Results were robust to adjustment for APOE ε4 and neurodegeneration biomarkers. Epigenetic g is a scalable, blood-based marker of cognitive function and dementia risk that adds predictive value beyond demographics, socioeconomic indicators, APOE, and neuropathology. Its validation in a diverse, nationally representative U.S. cohort underscores its potential for early risk profiling and for research on social determinants of cognitive aging in cross-national samples. Show less

Impaired lung function (ILF) has been associated with cognitive decline and dementia risk in multiple cohorts, yet the role of circulating Alzheimer disease (AD) biomarkers in this relationship is not well understood. We aim to assess the associations between ILF and AD biomarkers and to determine whether these biomarkers mediate the relationship between ILF and incident dementia. Serum p-Tau181 and plasma Aβ42/40, NfL, and GFAP were measured in 4,072 participants (mean age 66 ± 10; 59% women) in the 2016 Health and Retirement Study. Peak Expiratory Flow (PEF) was assessed in 2012/2014, and cognitive function was measured at four time points between 2014 and 2020 (every two years) to determine dementia status. Impaired lung function (ILF) was defined as predicted PEF <80%. Multivariable regression examined associations between lung function and AD biomarkers; causal mediation analysis evaluated their role in linking lung function to incident dementia. In total, 881 (21.6%) participants had ILF and 272 (6.8%) participants developed dementia. After adjusting for demographics, education, BMI, smoking, comorbidities, inflammation, eGFR and ILF was associated with elevated levels of neurodegeneration markers NfL and p-Tau 181, which partially mediated its relationship with dementia risk. These findings highlight the importance of monitoring blood protein biomarkers in individuals with impaired lung health to facilitate early interventions. Show less