title: Higher rates of decline for women and apolipoprotein E epsilon4 carriers.
abstract: OBJECTIVE
  Age and the apolipoprotein E ε4 allele are well-known risk factors for Alzheimer disease, but whether female sex is also a risk factor remains controversial. It is also unclear how these risk factors affect rates of structural brain and clinical decline across the spectrum of preclinical to clinical Alzheimer disease. Our objective is to estimate the effects of apolipoprotein E ε4 and sex on age-specific rates of morphometric and clinical decline in late-onset sporadic Alzheimer disease.
  
  
  METHODS
  With the use of linear mixed-effects models, we examined the effect of age, apolipoprotein E ε4, and sex on longitudinal brain atrophy and clinical decline among cognitively normal older individuals and individuals with mild cognitive impairment and Alzheimer disease (total = 688). We also evaluated the relationship between these effects and CSF biomarkers of Alzheimer disease pathology.
  
  
  RESULTS
  Apolipoprotein E ε4 significantly accelerated rates of decline, and women in all cohorts had higher rates of decline than men. The magnitude of the sex effect on rates of decline was as large as those of ε4, yet their relationship to measures of CSF biomarkers were weaker.
  
  
  CONCLUSIONS
  These results indicate that in addition to apolipoprotein E ε4 status, diagnostic and therapeutic strategies should take into account the effect of female sex on the Alzheimer disease process.
authors.affiliation: Departments of Neurosciences.
authors.forename: D
authors.initials: D
authors.lastname: Holland
authors.forename: R S
authors.initials: RS
authors.lastname: Desikan
authors.forename: A M
authors.initials: AM
authors.lastname: Dale
authors.forename: L K
authors.initials: LK
authors.lastname: McEvoy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D015897:Comorbidity; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data; D008297:Male; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D017678:Sex Distribution; D014481:United States / Q000453:epidemiology; D016387:Women's Health / Q000706:statistics & numerical data*
chemical_list: D053327:Apolipoprotein E4; D015415:Biomarkers