Association of cardiovascular disease management drugs with Lewy body dementia: a case-control study.

Lewy body dementia is the second most common neurodegenerative dementia after Alzheimer's disease. Disease-modifying therapies for this disabling neuropsychiatric condition are critically needed. To identify drugs associated with the risk of developing Lewy body dementia, we performed a population-based case-control study of 148 170 US Medicare participants diagnosed with Lewy body dementia between 1 January 2008 and 31 December 2014 and of 1 253 043 frequency-matched controls. We estimated odds ratios and 95% confidence intervals for the association of Lewy body dementia risk with 1017 prescription drugs overall and separately for the three major racial groups (Black, Hispanic and White Americans). We identified significantly reduced Lewy body dementia risk associated with drugs used to treat cardiovascular diseases (anti-hypertensives: odds ratio = 0.72, 95% confidence interval = 0.70-0.74, P-value = 0; cholesterol-lowering agents: odds ratio = 0.85, 95% confidence interval = 0.83-0.87, P-value = 0; anti-diabetics: odds ratio = 0.83, 95% confidence interval = 0.62-0.72, P-value = 0). Notably, anti-diabetic medications were associated with a larger risk reduction among Black Lewy body dementia patients compared with other racial groups (Black: odds ratio = 0.67, 95% confidence interval = 0.62-0.72, P-value = 0; Hispanic: odds ratio = 0.86, 95% = 0.80-0.92, P-value = 5.16 × 10-5; White: odds ratio = 0.85, 95% confidence interval = 0.82-0.88, P-value = 0). To independently confirm the epidemiological findings, we looked for evidence of genetic overlap between Lewy body dementia and cardiovascular traits using whole-genome sequence data generated for 2591 Lewy body dementia patients and 4027 controls. Bivariate mixed modelling identified shared genetic risk between Lewy body dementia and low-density lipoprotein cholesterol levels, Type 2 diabetes and hypertension. By combining epidemiological and genomic data, we demonstrated that drugs treating cardiovascular diseases are associated with reduced Lewy body dementia risk, and these associations varied across racial groups. Future randomized clinical trials need to confirm our findings, but our data suggest that assiduous management of cardiovascular diseases may be beneficial in this understudied form of dementia.

Associations between cancer and Alzheimer's disease in a U.S. Medicare population.

Several studies have reported bidirectional inverse associations between cancer and Alzheimer's disease (AD). This study evaluates these relationships in a Medicare population. Using Surveillance, Epidemiology, and End Results (SEER) linked to Medicare data, 1992-2005, we evaluated cancer risks following AD in a case-control study of 836,947 cancer cases and 142,869 controls as well as AD risk after cancer in 742,809 cancer patients and a non-cancer group of 420,518. We applied unconditional logistic regression to estimate odds ratios (ORs) and Cox proportional hazards models to estimate hazards ratios (HRs). We also evaluated cancer in relation to automobile injuries as a negative control to explore potential study biases. In the case-control analysis, cancer cases were less likely to have a prior diagnosis of AD than controls (OR = 0.86; 95% CI = 0.81-0.92). Cancer cases were also less likely than controls to have prior injuries from automobile accidents to the same degree (OR = 0.83; 95% CI = 0.78-0.88). In the prospective cohort, there was a lower risk observed in cancer survivors, HR = 0.87 (95% CI = 0.84-0.90). In contrast, there was no association between cancer diagnosis and subsequent automobile accident injuries (HR = 1.03; 95% CI = 0.98-1.07). That cancer risks were similarly reduced after both AD and automobile injuries suggest biases against detecting cancer in persons with unrelated medical conditions. The modestly lower AD risk in cancer survivors may reflect underdiagnosis of AD in those with a serious illness. This study does not support a relationship between cancer and AD.

Individual, environmental, and meteorological predictors of daily personal ultraviolet radiation exposure measurements in a United States cohort study.

BACKGROUND: Individual exposure to ultraviolet radiation (UVR) is challenging to measure, particularly for diseases with substantial latency periods between first exposure and diagnosis of outcome, such as cancer. To guide the choice of surrogates for long-term UVR exposure in epidemiologic studies, we assessed how well stable sun-related individual characteristics and environmental/meteorological factors predicted daily personal UVR exposure measurements. METHODS: We evaluated 123 United States Radiologic Technologists subjects who wore personal UVR dosimeters for 8 hours daily for up to 7 days (N = 837 days). Potential predictors of personal UVR derived from a self-administered questionnaire, and public databases that provided daily estimates of ambient UVR and weather conditions. Factors potentially related to personal UVR exposure were tested individually and in a model including all significant variables. RESULTS: The strongest predictors of daily personal UVR exposure in the full model were ambient UVR, latitude, daily rainfall, and skin reaction to prolonged sunlight (R(2) = 0.30). In a model containing only environmental and meteorological variables, ambient UVR, latitude, and daily rainfall were the strongest predictors of daily personal UVR exposure (R(2) = 0.25). CONCLUSIONS: In the absence of feasible measures of individual longitudinal sun exposure history, stable personal characteristics, ambient UVR, and weather parameters may help estimate long-term personal UVR exposure.