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Research paper
Meta-analysis of modifiable risk factors for Alzheimer's disease
  1. Wei Xu1,
  2. Lan Tan1,2,3,
  3. Hui-Fu Wang2,
  4. Teng Jiang2,
  5. Meng-Shan Tan1,
  6. Lin Tan3,
  7. Qing-Fei Zhao1,
  8. Jie-Qiong Li1,
  9. Jun Wang1,
  10. Jin-Tai Yu1,2,3,4
  1. 1Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, China
  2. 2Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, China
  3. 3College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China
  4. 4Department of Neurology, Memory and Aging Center, University of California, San Francisco, California, USA
  1. Correspondence to Dr Jin-Tai Yu, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, Box 1207, San Francisco, CA 94158, USA; yu-jintai{at}


Background The aetiology of Alzheimer's disease (AD) is believed to involve environmental exposure and genetic susceptibility. The aim of our present systematic review and meta-analysis was to roundly evaluate the association between AD and its modifiable risk factors.

Methods We systematically searched PubMed and the Cochrane Database of Systematic Reviews from inception to July 2014, and the references of retrieved relevant articles. We included prospective cohort studies and retrospective case–control studies.

Results 16 906 articles were identified of which 323 with 93 factors met the inclusion criteria for meta-analysis. Among factors with relatively strong evidence (pooled population >5000) in our meta-analysis, we found grade I evidence for 4 medical exposures (oestrogen, statin, antihypertensive medications and non-steroidal anti-inflammatory drugs therapy) as well as 4 dietary exposures (folate, vitamin E/C and coffee) as protective factors of AD. We found grade I evidence showing that one biochemical exposure (hyperhomocysteine) and one psychological condition (depression) significantly increase risk of developing AD. We also found grade I evidence indicative of complex roles of pre-existing disease (frailty, carotid atherosclerosis, hypertension, low diastolic blood pressure, type 2 diabetes mellitus (Asian population) increasing risk whereas history of arthritis, heart disease, metabolic syndrome and cancer decreasing risk) and lifestyle (low education, high body mass index (BMI) in mid-life and low BMI increasing the risk whereas cognitive activity, current smoking (Western population), light-to-moderate drinking, stress, high BMI in late-life decreasing the risk) in influencing AD risk. We identified no evidence suggestive of significant association with occupational exposures.

Conclusions Effective interventions in diet, medications, biochemical exposures, psychological condition, pre-existing disease and lifestyle may decrease new incidence of AD.

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