Investigating Predictors of Preserved Cognitive Function in Older Women Using Machine Learning: Women's Health Initiative Memory Study

Background: Identification of factors that may help to preserve cognitive function in late life could elucidate mechanisms and facilitate interventions to improve the lives of millions of people. However, the large number of potential factors associated with cognitive function poses an analytical challenge. Objective: We used data from the longitudinal Women's Health Initiative Memory Study (WHIMS) and machine learning to investigate 50 demographic, biomedical, behavioral, social, and psychological predictors of preserved cognitive function in later life. Methods: Participants in WHIMS and two consecutive follow up studies who were at least 80 years old and had at least one cognitive assessment following their 80th birthday were classified as cognitively preserved. Preserved cognitive function was defined as having a score ≥39 on the most recent administration of the modified Telephone Interview for Cognitive Status (TICSm) and a mean score across all assessments ≥39. Cognitively impaired participants were those adjudicated by experts to have probable dementia or at least two adjudications of mild cognitive impairment within the 14 years of follow-up and a last TICSm score < 31. Random Forests was used to rank the predictors of preserved cognitive function. Results: Discrimination between groups based on area under the curve was 0.80 (95%-CI-0.76-0.85). Women with preserved cognitive function were younger, better educated, and less forgetful, less depressed, and more optimistic at study enrollment. They also reported better physical function and less sleep disturbance, and had lower systolic blood pressure, hemoglobin, and blood glucose levels. Conclusion: The predictors of preserved cognitive function include demographic, psychological, physical, metabolic, and vascular factors suggesting a complex mix of potential contributors

Population differences in associations of serotonin transporter promoter polymorphism (5HTTLPR) di- and triallelic genotypes with blood pressure and hypertension prevalence

Based on prior research finding the 5HTTLPR L allele associated with increased cardiovascular reactivity to laboratory stressors and increased risk of myocardial infarction, we hypothesized that the 5HTTLPR L allele will be associated with increased blood pressure (BP) and increased hypertension prevalence in 2 large nationally representative samples in the United States and Singapore. Methods Logistic regression and linear models tested associations between triallelic (L′S′, based on rs25531) 5HTTLPR genotypes and hypertension severity and mean systolic and diastolic blood pressure (SBP and DBP) collected during the Wave IV survey of the National Longitudinal Study of Adolescent to Adult Health (Add Health, N = 11,815) in 2008–09 and during 2004–07 in 4196 Singaporeans. Results In US Whites, L′ allele carriers had higher SBP (0.9 mm Hg, 95% CI = 0.26-1.56) and greater odds (OR = 1.23, 95% CI = 1.10-1.38) of more severe hypertension than those with S′S′ genotypes. In African Americans, L′ carriers had lower mean SBP (−1.27 mm Hg, 95% CI = −2.53 to −0.01) and lower odds (OR = 0.78, 95% CI = 0.65-0.94) of more severe hypertension than those with the S′S′ genotype. In African Americans, those with L′L′ genotypes had lower DBP (−1.13 mm Hg, 95% CI = −2.09 to −0.16) than S′ carriers. In Native Americans, L′ carriers had lower SBP (−6.05 mm Hg, 95% CI = −9.59 to −2.51) and lower odds of hypertension (OR = 0.34, 95% CI = 0.13-0.89) than those with the S′S′ genotype. In Asian/Pacific Islanders those carrying the L′ allele had lower DBP (−1.77 mm Hg, 95% CI = −3.16 to −0.38) and lower odds of hypertension (OR = 0.68, 95% CI = 0.48-0.96) than those with S′S′. In the Singapore sample S′ carriers had higher SBP (3.02 mm Hg, 95% CI = 0.54-5.51) and DBP (1.90 mm Hg, 95% CI = 0.49-3.31) than those with the L′L′ genotype. Conclusions These findings suggest that Whites carrying the L′ allele, African Americans and Native Americans with the S′S′ genotype, and Asians carrying the S′ allele will be found to be at higher risk of developing cardiovascular disease and may benefit from preventive measures