title: Risk factors associated with the onset and progression of Alzheimer's disease: A systematic review of the evidence.
abstract: A systematic review was conducted to identify risk factors associated with the onset and progression of Alzheimer's disease (AD). Moderate and high quality systematic reviews were eligible for inclusion. Primary studies reporting on non-genetic risk factors associated with neuropathologically or clinically confirmed AD were considered. Eighty one systematic reviews reporting on AD onset and 12 reporting on progression satisfied the eligibility criteria. Four hundred and thirty-two relevant primary studies reporting on onset were identified; however, only those published between 2010 and 2012 (n=65) were included in the qualitative synthesis. Several factors including statins, light-to-moderate alcohol consumption, compliance with a Mediterranean diet, higher educational attainment, physically and cognitively stimulating activities, and APOE ε2 appeared to be associated with a decreased risk of AD onset. The evidence was suggestive of an increased risk of AD associated with head injury in males, age, diabetes mellitus, conjugated equine estrogen use with medroxyprogesterone acetate, current smoking, and lower social engagement. With respect to genetic factors, APOE ε4 remained the strongest predictor of AD. Physical and cognitive activities were associated with a beneficial effect on cognitive function and other indicators of dementia progression while higher educational attainment was associated with faster cognitive decline. Although suggestive of an association, the current evidence for a majority of the identified putative factors for AD onset and progression was weak, at best due to conflicting findings across studies or inadequate evidence. Further research is required to confirm the etiological or protective role of a number of risk factors.
authors.affiliation: McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada; School of Epidemiology, Public Health and Preventive Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada. Electronic address: mhersi@ohri.ca.
authors.forename: Mona
authors.initials: M
authors.lastname: Hersi
authors.affiliation: McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Brittany
authors.initials: B
authors.lastname: Irvine
authors.affiliation: McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Gupta
authors.affiliation: McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada; Environmental Health Research Unit, University of Ottawa, ON, Canada; Interdisciplinary School of Health Sciences, Faculty of Health Sciences, University of Ottawa, ON, Canada.
authors.forename: James
authors.initials: J
authors.lastname: Gomes
authors.affiliation: McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada; School of Epidemiology, Public Health and Preventive Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Birkett
authors.affiliation: McLaughlin Centre for Population Health Risk Assessment, University of Ottawa, Ottawa, Ontario, Canada; School of Epidemiology, Public Health and Preventive Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada; Risk Sciences International, Ottawa, Ontario Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Krewski
mesh_terms: D017668:Age of Onset; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000209:etiology* / Q000235:genetics; D053327:Apolipoprotein E4 / Q000235:genetics; D018450:Disease Progression; D006801:Humans; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4
keywords: Alzheimer’s disease; Dementia; Etiology; Onset; Progression; Risk factors; Systematic review