Causal effect of household income on Alzheimer's disease risk and mediation by cognitive performance: a bidirectional, two‑sample, two‑stage mendelian randomization study

Combined Effects of Social Determinants of Health on Alzheimer's Disease: Insights from Bibliometric and NHANES Analyses.

Investigating the Causal Relationship between Neuroticism and Alzheimer's Disease Using Mendelian Randomization and the Mediating Role of Modifiable Risk Factors

Depression, hypertension, hypertension, and alcohol consumption were identified as significant mediators of the relationship between higher neuroticism and increased AD risk, suggesting that the neuroticism-AD relationship is unlikely to be causal.

The Joint Effects of Life's Essential 8 and Genetics on Mild Cognitive Impairment and Dementia Risk in People With Diabetes: Findings From the UK Biobank and All of Us.

OBJECTIVE We examined how cardiovascular health (CVH), measured by Life's Essential 8 (LE8), and genetic risk are jointly associated with risks of mild cognitive impairment (MCI), dementia, and related cognitive outcomes in people with diabetes. RESEARCH DESIGN AND METHODS We analyzed 41,374 participants without dementia from the UK Biobank (UKB) and 9,766 from All of Us (AoU). LE8, comprising diet, physical activity, nicotine exposure, sleep, body mass index, lipids, blood glucose, and blood pressure, was scored from 0 to 100 and categorized as low, moderate, or high. Genetic risk was assessed using APOE ε4 alleles and polygenic risk scores (PRS) for Alzheimer disease. We used Cox regression to examine associations of LE8 with MCI and dementia and linear regression to assess MRI-based brain functional measures and cognitive test outcomes, adjusting for covariates. Interactions between LE8 and genetic risk were tested on multiplicative and additive scales. RESULTS Over 15 years of follow-up (UKB), moderate or high CVH versus low CVH was associated with a lower risk of MCI (hazard ratio 0.82 [95% CI 0.71, 0.95], P < 0.05) but not with risk of all-cause dementia (0.97 [0.84, 1.11], P = 0.63). In participants at high genetic risk (high PRS), moderate or high CVH was associated with a lower risk of MCI (0.78 [0.62, 0.98], P for additive interaction < 0.05). AoU results were consistent. CONCLUSIONS Better CVH was significantly associated with a lower risk of MCI in people with diabetes, accounting for genetic risk. The association between CVH and MCI and dementia was stronger among individuals with low or moderate genetic risk and appeared attenuated among those with high genetic risk.

Genetic evidence for a causal role of depression in late-onset Alzheimer disease: A Mendelian randomization study

Genetic evidence supporting a causal role for depression in the etiology of late-onset AD is provided, a link not observed for other major psychiatric disorders tested and highlighted the specific importance of managing depression as a potential strategy for mitigating AD risk.

Evidence from European ancestry genome-wide association studies and a case-control study suggests several selenoproteins are linked to a decreased risk of Alzheimer's disease

Genetic and clinical evidence is provided that specific selenoproteins are associated with a decreased risk of AD and highlight the potential role of these proteins in AD pathophysiology and suggest their promise as biomarkers or therapeutic targets, warranting further investigation.

Inflammatory dietary patterns and mental health traits in middle/old-aged adults: A bi-directional Mendelian Randomization study