Meta-analysis of modifiable risk factors for Alzheimer's disease
Abstract
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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Metabolomic biomarkers such as reduced docosahexaenoic acid (DHA) and elevated homocysteine have demonstrated clinical utility.
“Despite variability introduced by diet and comorbid conditions, metabolomic biomarkers such as reduced docosahexaenoic acid (DHA) and elevated homocysteine have demonstrated clinical utility133,194, 195, 196, 197, 198, 199.”
From Artificial intelligence-driven multi-omics approaches in Alzheimer's disease: Progress, challenges, and future directions (2025) · cites this paper as [199]
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- Authors
- Xu, W., Tan, L., Wang, H.-F., Jiang, T., Tan, M.-S., Tan, L., Zhao, Q.-F., Li, J.-Q., Wang, J., & Yu, J.-T.
- Affiliations
- Qingdao University (CN)
- Qingdao Municipal Hospital (CN)
- Corresponding author
- Yu, Jin-Tai
- Venue
- Journal of Neurology, Neurosurgery & Psychiatry
- Publisher
- BMJ
- Published
- 2015-08-20
- Volume
- 86
- Issue
- 12
- Pages
- jnnp-2015-310548
- ISSN
- 0022-3050 (ISSN-L)
- 1468-330X
- OpenAlex
- W1932861877
- Cited by
- 573
- References
- 9
- Citations by year
- 2026: 11 · 2025: 45 · 2024: 83 · 2023: 55 · 2022: 66 · 2021: 59 · 2020: 56 · 2019: 48 · 2018: 52 · 2017: 52 · 2016: 34 · 2015: 9
- FWCI
- 6.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurology Neurosurgery & Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- Alzheimer's disease, modifiable risk factors, dementia prevention, estrogen, statins, antihypertensive drugs, nonsteroidal anti-inflammatory drugs, folic acid, vitamin E, coffee consumption, depression, frailty, carotid atherosclerosis, hypertension, type 2 diabetes, body mass index, educational attainment, cognitive activity, smoking, alcohol consumption, stress, occupational exposure
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Humans, Life Style, Motor Activity, Risk Factors, Preexisting Condition Coverage
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