Objective: The aim of this study is to assess the association between midlife risk factors and
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
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.