title: Amyloid deposition is decreasing in aging brains: an autopsy study of 1,599 older people.
abstract: OBJECTIVE
  To explore cohort effects on age- and Alzheimer disease (AD)-related neuropathologic changes.
  
  
  METHODS
  We compared amyloid deposition in autopsied cases aged 65 years and older who died between 1972 and 2006. We included consecutive cases for 1972-1975, 1980, 1985, 1990, 1995, and 2000-2006. We used linear regression models to assess period effects after adjustment for age, cognitive status, and neurofibrillary tangle (NFT) staging. We calculated amyloid/NFT stage ratios to account for possible changes in AD prevalence/severity over time.
  
  
  RESULTS
  Mean amyloid stage was significantly related to year of death (p = 0.001) in the total population (1,599 cases, mean age 82 ± 8 years) and decreased 24%, from 1.88 ± 0.89 to 1.57 ± 0.81 (p < 0.0001), in 1,265 individuals without dementia. This decrease was particularly marked in the oldest age groups; people 85 years and older in 2006 had less amyloid deposition compared with those aged 75 to 84 years in 1972. Recent cohorts had lower amyloid deposition. The amyloid/NFT stage ratio decreased from 1.51 ± 0.74 to 0.99 ± 0.56 (p < 0.0001) in cases without dementia and from 0.74 ± 0.13 to 0.56 ± 0.21 (p = 0.0019) in individuals with dementia, confirming that more recent cases had less amyloid despite higher NFT densities. Cohort effects were highly significant (p < 0.0001).
  
  
  CONCLUSIONS
  The strong cohort effect we describe may influence the performance of early amyloid-based AD markers. It also provides preclinical evidence supporting recently described decreases in AD incidence. This trend, if confirmed in community-based studies, may lead to new insights in our understanding of both normal and pathologic brain aging.
authors.affiliation: From the Departments of Mental Health and Psychiatry (E.K., C.B.), and Internal Medicine, Rehabilitation and Geriatrics (F.R.H., G.G.), University Hospitals and Medical Faculty of Geneva, Switzerland.
authors.forename: Enikö
authors.initials: E
authors.lastname: Kövari
authors.forename: François R
authors.initials: FR
authors.lastname: Herrmann
authors.forename: Constantin
authors.initials: C
authors.lastname: Bouras
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gold
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism*; D001344:Autopsy; D001921:Brain / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000378:metabolism* / Q000473:pathology; D012044:Regression Analysis
chemical_list: D000682:Amyloid