title: Age, Sex, and APOE ε4 Effects on Memory, Brain Structure, and β-Amyloid Across the Adult Life Span.
abstract: OBJECTIVE
  Typical cognitive aging may be defined as age-associated changes in cognitive performance in individuals who remain free of dementia. Ideally, the full adult age spectrum should be included to assess brain imaging findings associated with typical aging.
  
  
  OBJECTIVE
  To compare age, sex, and APOE ε4 effects on memory, brain structure (adjusted hippocampal volume [HVa]), and amyloid positron emission tomography (PET) in cognitively normal individuals aged 30 to 95 years old.
  
  
  METHODS
  Cross-sectional observational study (March 2006 to October 2014) at an academic medical center. We studied 1246 cognitively normal individuals, including 1209 participants aged 50 to 95 years old enrolled in a population-based study of cognitive aging and 37 self-selected volunteers aged 30 to 49 years old.
  
  
  METHODS
  Memory, HVa, and amyloid PET.
  
  
  RESULTS
  Overall, memory worsened from age 30 years through the 90s. The HVa worsened gradually from age 30 years to the mid-60s and more steeply beyond that age. The median amyloid PET was low until age 70 years and increased thereafter. Memory was worse in men than in women overall (P < .001) and more specifically beyond age 40 years. The HVa was lower in men than in women overall (P < .001) and more specifically beyond age 60 years. There was no sex difference in amyloid PET at any age. Within each sex, memory performance and HVa were not different by APOE ε4 status at any age. From age 70 years onward, APOE ε4 carriers had significantly greater median amyloid PET than noncarriers. However, the ages at which 10% of the population were amyloid PET positive were 57 years for APOE ε4 carriers and 64 years for noncarriers.
  
  
  CONCLUSIONS
  Male sex is associated with worse memory and HVa among cognitively normal individuals, while APOE ε4 is not. In contrast, APOE ε4 is associated with greater amyloid PET (from age 70 years onward), while sex is not. Worsening memory and HVa occur at earlier ages than abnormal amyloid PET. Therefore, neuropathological processes other than β-amyloidosis must underlie declines in brain structure and memory function in middle age. Our findings are consistent with a model of late-onset Alzheimer disease in which β-amyloidosis arises in later life on a background of preexisting structural and cognitive decline that is associated with aging and not with β-amyloid deposits.
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Wiste
authors.affiliation: Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Weigand
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Vemuri
authors.affiliation: Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Mielke
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Val
authors.initials: V
authors.lastname: Lowe
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Senjem
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Gunter
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Machulda
authors.affiliation: Department of Radiology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Brian E
authors.initials: BE
authors.lastname: Gregg
authors.affiliation: Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.affiliation: Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota3Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Walter A
authors.initials: WA
authors.lastname: Rocca
authors.affiliation: Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota.
authors.forename: Ronald C
authors.initials: RC
authors.lastname: Petersen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006624:Hippocampus / Q000033:anatomy & histology*; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D008875:Middle Aged; D049268:Positron-Emission Tomography; D012737:Sex Factors
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4