title: Potential for primary prevention of Alzheimer's disease: an analysis of population-based data.
abstract: BACKGROUND
  Recent estimates suggesting that over half of Alzheimer's disease burden worldwide might be attributed to potentially modifiable risk factors do not take into account risk-factor non-independence. We aimed to provide specific estimates of preventive potential by accounting for the association between risk factors.
  
  
  METHODS
  Using relative risks from existing meta-analyses, we estimated the population-attributable risk (PAR) of Alzheimer's disease worldwide and in the USA, Europe, and the UK for seven potentially modifiable risk factors that have consistent evidence of an association with the disease (diabetes, midlife hypertension, midlife obesity, physical inactivity, depression, smoking, and low educational attainment). The combined PAR associated with the risk factors was calculated using data from the Health Survey for England 2006 to estimate and adjust for the association between risk factors. The potential of risk factor reduction was assessed by examining the combined effect of relative reductions of 10% and 20% per decade for each of the seven risk factors on projections for Alzheimer's disease cases to 2050.
  
  
  RESULTS
  Worldwide, the highest estimated PAR was for low educational attainment (19·1%, 95% CI 12·3-25·6). The highest estimated PAR was for physical inactivity in the USA (21·0%, 95% CI 5·8-36·6), Europe (20·3%, 5·6-35·6), and the UK (21·8%, 6·1-37·7). Assuming independence, the combined worldwide PAR for the seven risk factors was 49·4% (95% CI 25·7-68·4), which equates to 16·8 million attributable cases (95% CI 8·7-23·2 million) of 33·9 million cases. However, after adjustment for the association between the risk factors, the estimate reduced to 28·2% (95% CI 14·2-41·5), which equates to 9·6 million attributable cases (95% CI 4·8-14·1 million) of 33·9 million cases. Combined PAR estimates were about 30% for the USA, Europe, and the UK. Assuming a causal relation and intervention at the correct age for prevention, relative reductions of 10% per decade in the prevalence of each of the seven risk factors could reduce the prevalence of Alzheimer's disease in 2050 by 8·3% worldwide.
  
  
  CONCLUSIONS
  After accounting for non-independence between risk factors, around a third of Alzheimer's diseases cases worldwide might be attributable to potentially modifiable risk factors. Alzheimer's disease incidence might be reduced through improved access to education and use of effective methods targeted at reducing the prevalence of vascular risk factors (eg, physical inactivity, smoking, midlife hypertension, midlife obesity, and diabetes) and depression.
  
  
  BACKGROUND
  National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care for Cambridgeshire and Peterborough.
authors.affiliation: Psychology Department, Institute of Psychiatry, King's College London, London, UK.
authors.forename: Sam
authors.initials: S
authors.lastname: Norton
authors.affiliation: Medical Research Council Biostatistics, Institute of Public Health, Cambridge, UK.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Matthews
authors.affiliation: Department of Psychiatry, University of California, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA; San Francisco VA Medical Center, San Francisco, CA, USA.
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Barnes
authors.affiliation: Department of Psychiatry, University of California, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA; Department of Neurology, University of California, San Francisco, CA, USA; San Francisco VA Medical Center, San Francisco, CA, USA.
authors.forename: Kristine
authors.initials: K
authors.lastname: Yaffe
authors.affiliation: Institute of Public Health, University of Cambridge, Cambridge, UK. Electronic address: carol.brayne@medschl.cam.ac.uk.
authors.forename: Carol
authors.initials: C
authors.lastname: Brayne
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control*; D016208:Databases, Factual / Q000639:trends*; D003863:Depression / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control; D004522:Educational Status; D005060:Europe / Q000453:epidemiology; D014943:Global Health / Q000639:trends; D006306:Health Surveys / Q000379:methods / Q000639:trends; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control; D009043:Motor Activity / Q000502:physiology; D009765:Obesity / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control; D011159:Population Surveillance / Q000379:methods; D011322:Primary Prevention / Q000379:methods*; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D000074606:Smoking Prevention; D014481:United States / Q000453:epidemiology