Table 74Summary of findings on potential risk factors and interventions for AD

Direction of associationFactorsLevel of evidence
Increased risk
  • APOE e4 genotype
  • Conjugated equine estrogen with methyl progesterone*
  • Some non-steroidal anti-inflammatory drugs*
  • Depressive disorder
  • Diabetes mellitus
  • Hyperlipidemia in mid-life
  • Traumatic brain injury in males
  • Pesticide exposure
  • Never married, less social support
  • Current tobacco use
Decreased risk
  • Mediterranean diet
  • Folic acid
  • HMG-CoA reductase inhibitors (statins)
  • Higher levels of education
  • Light to moderate alcohol intake
  • Cognitively engaging activities
  • Physical activity, particularly high levels
No association
  • Ginkgo biloba*
  • Vitamin E*
  • Cholinesterase inhibitors*
  • Anti-hypertensive medication*
  • Conjugated equine estrogen
  • Omega-3 fatty acids*
  • Vitamins B12, C, beta-carotene
  • Homocysteine
  • Hypertension
  • Obesity
  • Metabolic syndrome
  • Early childhood factors
  • Occupational level
  • Lead
Inadequate evidence to assess association
  • Saturated fat intake
  • Fruit and vegetable intake
  • Trace metals
  • High caloric intake
  • Memantine
  • Sleep apnea
  • Anxiety disorders
  • Resiliency
  • Non-cognitive, non-physical leisure activities
  • Agent Orange, Gulf War Syndrome
  • Solvents, aluminum
  • Genetic factors other than APOE
(Not applicable)

Data from observational studies and RCTs.

Abbreviations: APOE = apolipoprotein E gene; APOE e4 = epsilon 4 allele of the apolipoprotein E gene; HMG-CoA = 3-hydroxy-3-methylglutaryl-coenzyme A; RCTs = randomized controlled trials

GRADE criteria (see text)

From: 5, Conclusions

Cover of Preventing Alzheimer's Disease and Cognitive Decline
Preventing Alzheimer's Disease and Cognitive Decline.
Evidence Reports/Technology Assessments, No. 193.
Williams JW, Plassman BL, Burke J, et al.

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