Epidemiological evidence suggests that vitamin D deficiency is associated with increased mortality, but it is unclear whether this is explained by reverse causation, and if there are specific causes of death for which vitamin D might be important. We conducted a systematic review of observational studies investigating associations between circulating 25-hydroxyvitamin D (25(OH)D) concentration and all-cause or cause-specific mortality in generally healthy populations. Relevant studies were identified using PubMed and EMBASE searches. After screening 722 unique records and removing those that were ineligible, 84 articles were included in this review. The vast majority of studies reported inverse associations between 25(OH)D concentration and all-cause mortality. This association appeared to be non-linear, with progressively lower mortality with increasing 25(OH)D up to a point, beyond which there was no further decrease. There is moderate evidence that vitamin D status is inversely associated with cancer mortality and death due to respiratory diseases, while for cardiovascular mortality, there is weak evidence of an association in observational studies, which is not supported by the data from intervention or Mendelian randomization studies. The relationship between vitamin D status and other causes of death remains uncertain due to limited data. Larger long-term studies are required to clarify these associations.

To examine the interaction between APOE genotypes and both treated and untreated hypertension on cognitive function in an updated analysis of Nurses’ Health Study (NHS) data. At baseline (1995–2001) and 3 biennial follow-up assessments over ~6 years, cognitive function was assessed. 8300 NHS participants aged 70+ years underwent a cognitive battery, which comprised 6 tests including the Telephone Interview for Cognitive Status (TICS) and tests of verbal memory, category fluency, and working memory. We estimated the mean differences in average cognitive scores across up to 4 assessments using multiple linear regression. We also tested for interaction between APOE e4 allele carrier status and hypertension overall, as well as for apparently untreated and treated hypertension. We confirmed that, compared with those with APOE e3/3 genotype, APOE e4 allele carriers scored lower by 0.55 units on the average TICS score (95%CI:-0.67,-0.43). We also observed a significantly worse average TICS score among women with untreated hypertension compared with women without hypertension (difference = -0.23, 95%CI:-0.37,-0.09), while no significant difference was observed for women with treated hypertension. Significant interaction was detected between the APOE e4 allele and untreated hypertension (p-int = 0.02 for the TICS; p-int = 0.045 for global score), but not with treated hypertension. Specifically, compared with normotensive women with the APOE e3/3 genotype, APOE e4 allele carriers with treated hypertension scored lower by 0.50 units (95%CI:-0.69,-0.31); however, the APOE e4 allele carriers with untreated hypertension scored lower by 1.02 units on the TICS score (95%CI:-1.29, -0.76). This interaction of APOE e4 and untreated hypertension was also consistently observed for the global score. Women with hypertension and at least one APOE e4 allele had worse average cognitive function compared with women without hypertension with the e3/3 genotype; this difference was amplified among APOE e4 allele carriers with untreated hypertension.

Background: Caffeine intake has been associated with a lower risk of Parkinson’s disease (PD). This association is robust in men, but inconsistent in women due to a possible interaction with post-menopausal hormone (PMH) use. Objective: To (1) evaluate the association between caffeine intake and PD risk and (2) assess potential effect modification of the association by PMH use among women. Methods: We examined associations between caffeine intake and incident PD risk in the Nurses’ Health Study (NHS) (N = 121,701 women) and the Health Professionals Follow-up Study (HPFS) (N = 51,529 men). Dietary data on coffee and caffeine from other sources were collected every four years using a validated semi-quantitative food frequency questionnaire for both cohorts. Information on lifestyle and incident PD diagnosis was updated biennially and PD diagnoses were confirmed by medical record review. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models. Results: We documented a total of 1,219 PD cases over the follow-up period. The multivariable-adjusted HR comparing the highest to lowest quintile of caffeine intake was 0.50 (95% CI: 0.37, 0.68; P_trend<0.0001) in the HPFS. Among women, there was a suggestion of an interaction between coffee intake and PMH use ( P = 0.08). In the pooled analyses combining men and women who have never used PMH, the risk of PD was lower as coffee intake increased ( P_trend<0.001). Conclusions: Our results support previous findings that increased caffeine intake may be associated with a decreased PD risk in men and women who have never used PMH.

Objective To prospectively examine how selected lifestyle factors and family history of Parkinson disease (PD) combine to determine overall PD risk. Methods We derived risk scores among 69,968 women in the Nurses9 Health Study (NHS) (1984–2012) and 45,830 men in the Health Professionals Follow-up Study (HPFS) (1986–2012). Risk scores were computed for each individual based on the following factors previously associated with PD risk: total caffeine intake, smoking, physical activity, and family history of PD for the NHS, and additionally total flavonoid intake and dietary urate index for the HPFS. Hazard ratios were estimated using Cox proportional hazards models. In addition, we performed tests of interactions on both the multiplicative and additive scale between pairs of risk factors. Results We documented 1,117 incident PD cases during follow-up. The adjusted hazard ratios comparing individuals in the highest category of the reduced risk score to those in the lowest category were 0.33 (95% confidence interval: 0.21, 0.49; p_trend < 0.0001) in the NHS and 0.18 (95% confidence interval: 0.10, 0.32; p_trend < 0.0001) in the HPFS. Results were similar when applying the risk scores computed by summing the predictors weighted by the log of their individual effect sizes on PD risk in these cohorts. Additive interaction was present between no family history of PD and caffeine in men and between caffeine and physical activity in women. Conclusions Our results suggest that known protective factors for PD tend to have additive or superadditive effects, so that PD risk is very low in individuals with multiple protective risk factors.

BACKGROUND: Alcohol intake may be associated with a lower risk of Parkinson's disease (PD), but findings from previous studies have been inconclusive.OBJECTIVE: To determine the association between alcohol intake and PD risk in the Million Women Study, a large, prospective study of women in the UK.METHODS: Between 1996 and 2001, approximately 1.3 million women in the UK, mean age 56 (standard deviation, 5) years, were recruited into the Million Women Study. Information on alcohol intake, lifestyle factors, and medical history was collected at recruitment by questionnaire. Information on incident cases of PD was ascertained by record linkage to national hospital admission records and death registrations. We estimated multivariable‐adjusted relative risks and corresponding 95% confidence intervals using Cox proportional hazards models according to categories of alcohol intake.RESULTS: During an average of 17.9 years of follow‐up, 11,009 women had a new record of PD among 1,309,267 women. In drinkers, the multivariable‐adjusted relative risk comparing women who drank more than 14 drinks of alcohol per week with women who drank 1 to 2 drinks of alcohol per week was 0.99 (95% confidence interval: 0.90, 1.10). Results did not materially change after excluding the first 10 years of follow‐up (relative risk_adjusted = 1.01; 95% confidence interval: 0.90, 1.13). There were no significant trends in alcohol‐related PD risk among never smokers. Additionally, examining this association by type of alcohol intake also yielded null findings.CONCLUSION: These results do not support an association between alcohol intake and PD risk in women. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.