Amyloid deposition is decreasing in aging brains

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).

Conclusion: 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.