Meta-analysis of modifiable risk factors for Alzheimer's disease 

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To cite: Xu W, Tan L, Wang H-F et al. Meta-analysis of modifiable risk factors for Alzheimer's disease. J Neurol Neurosurg Psychiatry 2015;86:1299-1306 doi:10.1136/jnnp-2015-310548.
Background
The aetiology of Alzheimer's disease 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 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 increasing risk whereas history of arthritis, heart disease, metabolic syndrome and cancer decreasing risk, and lifestyle, low education, high body mass index in mid-life and low BMI increasing the risk whereas cognitive activity, current smoking, 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.