Meta-analysis of modifiable risk factors for Alzheimer's disease
2015/08/20 by Wei Xu, Lan Tan, Hui-Fu Wang +11 · 582 citations
Environmental Science · Medicine · #Alzheimer's disease research and treatments #Body mass index #Cohort study #Dementia and Cognitive Impairment Research #Depression (economics) #Diabetes mellitus #Disease #Endocrinology #Environmental health #Family history #Gerontology #Health, Environment, Cognitive Aging #Internal medicine #Medicine #Meta-analysis #Population
paper · doi:10.1136/jnnp-2015-310548
published in Journal of Neurology Neurosurgery & Psychiatry 86(12), jnnp-2015 (BMJ)
openalex publication_date 2015/08/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/30
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.
Citations
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- Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease. [europepmc]
- Subclinical Cardiovascular Disease and Death, Dementia, and Coronary Heart Disease in Patients 80+ Years. [europepmc]
- Environmental risk factors for dementia: a systematic review. [europepmc]
- Traumatic brain injury history is associated with earlier age of onset of Alzheimer disease. [europepmc]
- Sex and the development of Alzheimer's disease. [europepmc]
- Impact of Hypertension on Cognitive Function: A Scientific Statement From the American Heart Association. [europepmc]
- Enhanced neural activation with blueberry supplementation in mild cognitive impairment. [europepmc]
- Modifiable pathways in Alzheimer's disease: Mendelian randomisation analysis. [europepmc]
- Vulnerability and resilience to Alzheimer's disease: early life conditions modulate neuropathology and determine cognitive reserve. [europepmc]
- Alcohol use and dementia: a systematic scoping review. [europepmc]
- Frailty as a Predictor of Cognitive Disorders: A Systematic Review and Meta-Analysis. [europepmc]
- A Systematic Review of Meta-Analyses that Evaluate Risk Factors for Dementia to Evaluate the Quantity, Quality, and Global Representativeness of Evidence. [europepmc]
- Associations between blood pressure across adulthood and late-life brain structure and pathology in the neuroscience substudy of the 1946 British birth cohort (Insight 46): an epidemiological study. [europepmc]
- Common risk factors for major noncommunicable disease, a systematic overview of reviews and commentary: the implied potential for targeted risk reduction. [europepmc]
- Associations Between Vascular Risk Across Adulthood and Brain Pathology in Late Life: Evidence From a British Birth Cohort. [europepmc]
- Late-life obesity is a protective factor for prodromal Alzheimer's disease: a longitudinal study. [europepmc]
- Lifestyle Modifications and Nutritional Interventions in Aging-Associated Cognitive Decline and Alzheimer's Disease. [europepmc]
- Role of Alcohol Drinking in Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis. [europepmc]
- Modeling Neurodegenerative Disorders in Drosophila melanogaster . [europepmc]
- Cholesterol and Alzheimer's Disease Risk: A Meta-Meta-Analysis. [europepmc]
- Education and Cognitive Functioning Across the Life Span. [europepmc]
- Resveratrol and Neuroprotection: Impact and Its Therapeutic Potential in Alzheimer's Disease. [europepmc]
- Association of sex differences in dementia risk factors with sex differences in memory decline in a population-based cohort spanning 20-76 years. [europepmc]
- Relationship of body mass index with frailty and all-cause mortality among middle-aged and older adults. [europepmc]
- Use of Antihypertensives, Blood Pressure, and Estimated Risk of Dementia in Late Life: An Individual Participant Data Meta-Analysis. [europepmc]
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