Time-lagged associations between two adverse childhood experiences and later-life cognitive function through educational attainment and stroke.

OBJECTIVE: Adverse childhood experiences (ACEs) have been associated with worse cognitive health in older adulthood. This study aimed to extend findings on the specificity, persistence, and pathways of associations between two ACEs and cognition by using a comprehensive neuropsychological battery and a time-lagged mediation design. METHOD: Participants were 3304 older adults in the Health and Retirement Study Harmonized Cognitive Assessment Protocol. Participants retrospectively reported whether they were exposed to parental substance abuse or experienced parental physical abuse before age 18. Factor scores derived from a battery of 13 neuropsychological tests indexed cognitive domains of episodic memory, executive functioning, processing speed, language, and visuospatial function. Structural equation models examined self-reported years of education and stroke as mediators, controlling for sociodemographics and childhood socioeconomic status. RESULTS: Parental substance abuse in childhood was associated with worse later-life cognitive function across all domains, in part via pathways involving educational attainment and stroke. Parental physical abuse was associated with worse cognitive outcomes via stroke independent of education. CONCLUSIONS: This national longitudinal study in the United States provides evidence for broad and persistent indirect associations between two ACEs and cognitive aging via differential pathways involving educational attainment and stroke. Future research should examine additional ACEs and mechanisms as well as moderators of these associations to better understand points of intervention.

Study protocol: Behavioral economics and self-determination theory to change diabetes risk (BEST Change).

BACKGROUND: The Diabetes Prevention Program (DPP) and metformin can prevent or delay the onset of type 2 diabetes mellitus (T2DM) among patients with prediabetes. Yet, even when these evidence-based strategies are accessible and affordable, uptake is low. Thus, there is a critical need for effective, scalable, and sustainable approaches to increase uptake and engagement in these interventions. METHODS: In this randomized controlled trial, we will test whether financial incentives and automated messaging to promote autonomous motivation for preventing T2DM can increase DPP participation, metformin use, or both among adults with prediabetes. Participants (n = 380) will be randomized to one of four study arms. Control Arm participants will receive usual care and educational text messages about preventing T2DM. Incentives Arm participants will receive the Control Arm intervention plus financial incentives for DPP participation or metformin use. Tailored Messages Arm participants will receive the Control Arm intervention plus tailored messages promoting autonomous motivation for preventing T2DM. Combined Arm participants will receive the Incentives Arm and Tailored Messages Arm interventions plus messages to increase the personal salience of financial incentives. The primary outcome is change in hemoglobin A1c from baseline to 12 months. Secondary outcomes are change in body weight, DPP participation, and metformin use. DISCUSSION: If effective, these scalable and sustainable approaches to increase patient motivation to prevent T2DM can be deployed by health systems, health plans, and employers to help individuals with prediabetes lower their risk for developing T2DM.

Cumulative Genetic Risk and APOE ε4 Are Independently Associated With Dementia Status in a Multiethnic, Population-Based Cohort.

OBJECTIVE: Alzheimer disease (AD) is a common and costly neurodegenerative disorder. A large proportion of AD risk is heritable, and many genetic risk factors have been identified. The objective of this study was to test the hypothesis that cumulative genetic risk of known AD markers contributed to odds of dementia in a population-based sample. METHODS: In the US population-based Health and Retirement Study (waves 1995-2014), we evaluated the role of cumulative genetic risk of AD, with and without the APOE ε4 alleles, on dementia status (dementia, cognitive impairment without dementia, borderline cognitive impairment without dementia, and cognitively normal). We used logistic regression, accounting for demographic covariates and genetic principal components, and analyses were stratified by European and African genetic ancestry. RESULTS: In the European ancestry sample (n = 8,399), both AD polygenic score excluding the APOE genetic region (odds ratio [OR] = 1.10; 95% confidence interval [CI]: 1.00-1.20) and the presence of any APOE ε4 alleles (OR = 2.42; 95% CI: 1.99-2.95) were associated with the odds of dementia relative to normal cognition in a mutually adjusted model. In the African ancestry sample (n = 1,605), the presence of any APOE ε4 alleles was associated with 1.77 (95% CI: 1.20-2.61) times higher odds of dementia, whereas the AD polygenic score excluding the APOE genetic region was not significantly associated with the odds of dementia relative to normal cognition 1.06 (95% CI: 0.97-1.30). CONCLUSIONS: Cumulative genetic risk of AD and APOE ε4 are both independent predictors of dementia in European ancestry. This study provides important insight into the polygenic nature of dementia and demonstrates the utility of polygenic scores in dementia research.

Heavy Metals Exposure and Alzheimer's Disease and Related Dementias.

Alzheimer's disease and related dementias lack effective treatment or cures and are major public health challenges. Risk for Alzheimer's disease and related dementias is partially attributable to environmental factors. The heavy metals lead, cadmium, and manganese are widespread and persistent in our environments. Once persons are exposed to these metals, they are adept at entering cells and reaching the brain. Lead and cadmium are associated with numerous health outcomes even at low levels of exposure. Although manganese is an essential metal, deficiency or environmental exposure or high levels of the metal can be toxic. In cell and animal model systems, lead, cadmium, and manganese are well documented neurotoxicants that contribute to canonical Alzheimer's disease pathologies. Adult human epidemiologic studies have consistently shown lead, cadmium, and manganese are associated with impaired cognitive function and cognitive decline. No longitudinal human epidemiology study has assessed lead or manganese exposure on Alzheimer's disease specifically though two studies have reported a link between cadmium and Alzheimer's disease mortality. More longitudinal epidemiologic studies with high-quality time course exposure data and incident cases of Alzheimer's disease and related dementias are warranted to confirm and estimate the proportion of risk attributable to these exposures. Given the widespread and global exposure to lead, cadmium, and manganese, even small increases in the risks of Alzheimer's disease and related dementias would have a major population impact on the burden on disease. This article reviews the experimental and epidemiologic literature of the associations between lead, cadmium, and manganese on Alzheimer's disease and related dementias and makes recommendations of critical areas of future investment.