title: Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis.
abstract: BACKGROUND
  Cognitive impairment, including dementia, is a major health concern with the increasing aging population. Preventive measures to delay cognitive decline are of utmost importance. Alzheimer's disease (AD) is the most frequent cause of dementia, increasing in prevalence from <1% below the age of 60 years to >40% above 85 years of age.
  
  
  METHODS
  We systematically reviewed selected modifiable factors such as education, smoking, alcohol, physical activity, caffeine, antioxidants, homocysteine (Hcy), n-3 fatty acids that were studied in relation to various cognitive health outcomes, including incident AD. We searched MEDLINE for published literature (January 1990 through October 2012), including cross-sectional and cohort studies (sample sizes > 300). Analyses compared study finding consistency across factors, study designs and study-level characteristics. Selecting studies of incident AD, our meta-analysis estimated pooled risk ratios (RR), population attributable risk percent (PAR%) and assessed publication bias.
  
  
  RESULTS
  In total, 247 studies were retrieved for systematic review. Consistency analysis for each risk factor suggested positive findings ranging from ~38.9% for caffeine to ~89% for physical activity. Education also had a significantly higher propensity for "a positive finding" compared to caffeine, smoking and antioxidant-related studies. Meta-analysis of 31 studies with incident AD yielded pooled RR for low education (RR = 1.99; 95% CI: 1.30-3.04), high Hcy (RR = 1.93; 95% CI: 1.50-2.49), and current/ever smoking status (RR = 1.37; 95% CI: 1.23-1.52) while indicating protective effects of higher physical activity and n-3 fatty acids. Estimated PAR% were particularly high for physical activity (PAR% = 31.9; 95% CI: 22.7-41.2) and smoking (PAR% = 31.09%; 95% CI: 17.9-44.3). Overall, no significant publication bias was found.
  
  
  CONCLUSIONS
  Higher Hcy levels, lower educational attainment, and decreased physical activity were particularly strong predictors of incident AD. Further studies are needed to support other potential modifiable protective factors, such as caffeine.
authors: Laboratory of Epidemiology and Population Sciences, National Institute on Aging, NIA/NIH/IRP, 251 Bayview Blvd,, Suite 100, Room #: 04B118, Baltimore, MD 21224, USA. baydounm@mail.nih.gov.
authors: May A
authors: MA
authors: Beydoun
authors: Hind A
authors: HA
authors: Beydoun
authors: Alyssa A
authors: AA
authors: Gamaldo
authors: Alison
authors: A
authors: Teel
authors: Alan B
authors: AB
authors: Zonderman
authors: Youfa
authors: Y
authors: Wang
mesh_terms: D000428:Alcohol Drinking; D000544:Alzheimer Disease / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D000975:Antioxidants / Q000627:therapeutic use; D002110:Caffeine / Q000494:pharmacology; D003071:Cognition; D003072:Cognition Disorders / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D003704:Dementia / Q000209:etiology; D004032:Diet; D004522:Educational Status; D015444:Exercise; D015525:Fatty Acids, Omega-3 / Q000097:blood / Q000627:therapeutic use; D005260:Female; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D008297:Male; D012907:Smoking
chemical_list: D000975:Antioxidants; D015525:Fatty Acids, Omega-3; D006710:Homocysteine; D002110:Caffeine