Midlife Modifiable Risk Factors for Dementia: A Systematic Review and Meta-analysis of 34 Prospective Cohort Studies

Objective: The aim of this study is to assess the association between midlife risk factors and dementia. Methods: PubMed and Cochrane library were systematically searched on May 24, 2018, to retrieve prospective cohort studies. The summary Relative Risk (RR) and 95% Confidence Interval (CI) were calculated by the random-effect model to explore the association between midlife risk factors and dementia. Sensitivity analysis and meta-regression were conducted to explore the source of heterogeneity. Publication bias was examined using Begg's and Egger's tests. Results: Thirty-four prospective cohort studies were included, among which 24 were eligible for metaanalysis. A total of 159,594 non-demented adults were enrolled at baseline before 65 years and 13,540 people were diagnosed with dementia after follow-up. The pooled results revealed that five factors could significantly increase the dementia risk by 41 to 78%, including obesity (RR, 1.78; 95% CI: 1.31-2.41), diabetes mellitus (RR, 1.69; 95% CI: 1.38-2.07), current smoking (RR, 1.61; 95%, CI: 1.32-1.95), hypercholesterolemia (RR, 1.57; 95% CI: 1.19-2.07), and hypertension (borderline blood pressure RR, 1.41; 95% CI: 1.23-1.62 and high Systolic Blood Pressure (SBP) RR, 1.72; 95% CI: 1.25-2.37). However, the sensitivity analyses found that the results of hypercholesterolemia and high SBP were not reliable, which need to be confirmed by more high-quality studies. No influences due to publication bias were revealed. In the systematic review, another three factors (hyperhomocysteinemia, psychological stress, and heavy drinking) were found to be associated with elevated dementia risk. In addition, physical exercise, a healthy diet, and hormone therapy in middle age were associated with the reduction of dementia risk. Conclusions: Middle-aged people with obesity, diabetes, hypertension, or hypercholesterolemia, and current smokers in midlife are at higher risk of developing dementia later in life.

Sex differences in cerebrovascular pathologies on FLAIR in cognitively unimpaired elderly

ObjectiveTo examine sex differences in cerebrovascular pathologies (CVPs) as seen on fluid-attenuated inversion recovery (FLAIR) MRI and in cardiovascular and metabolic risk factors in a population-based cognitively unimpaired cohort and to examine whether sex is independently associated with FLAIR findings after accounting for differences in important midlife risk factors.MethodsWe identified 1,301 cognitively normal participants (663 men and 638 women) enrolled in the Mayo Clinic Study of Aging (age ≥70 years) who had FLAIR MRI and ascertained total burden of white matter (WM) hyperintensities (WMH), subcortical infarctions, and cortical infarctions. We compared CVPs and midlife and late-life vascular risk factors between men and women. We fit regression models with each CVP as an outcome, treating age, sex, and midlife risk factors as predictors.ResultsWomen had significantly greater WMH volume relative to their WM volume compared to men (2.8% vs 2.4% of WM, p < 0.001), while men had a greater frequency of cortical infarctions compared to women (9% vs 4%, p < 0.001). Subcortical infarctions were equally common in men and women (20%). In regression modeling after adjustment for WM volume, the mean WMH volume difference between men and women was of the same magnitude as a 7-year difference in age. In contrast, men had 2.2-greater relative odds of having a cortical infarction compared to women. These sex differences persisted even after adjustment for midlife vascular risk factors.ConclusionsThere were important sex differences in CVP findings on FLAIR in cognitively unimpaired elderly. Understanding these sex differences could aid in the development of sex-specific preventive strategies.

Midlife risk factors of diseases and geriatric syndromes

Environmental risk factors for adverse health outcomes are usually evident by midlife. Genes and the ageing process modify the risk factor actions, and together become the main causes of chronic non-communicable diseases, including cardiovascular diseases, diabetes, chronic kidney disease, and the most common forms of cancer (breast, prostate, colon) later in life. The most important lifestyle-related or environmental risk factors include diet, smoking, and physical inactivity, which often contribute to traditional or medical risk factors including hypertension, dyslipidemia, obesity, and hyperglycemia, which are the downstream antecedents of many other disease states. Further, it is increasingly evident that the occurrence of common geriatric syndromes, including frailty and mild cognitive impairment, can also be predicted by midlife risk factors. Current knowledge of risk factor development during the life course, and evidence-based prevention should be better utilized in the long-term prevention of health problems in old age.