Association Between β-Amyloid Accumulation and Incident Dementia in Individuals 80 Years or Older Without Dementia

While the highest prevalence of dementia occurs in individuals older than 80 years, most imaging studies focused on younger populations. The rates of β-amyloid (Aβ) accumulation and the effect of Alzheimer disease (AD) pathology on progression to dementia in this age group remain unexplored. In this study, we examined the relationship between changes in Aβ deposition over time and incident dementia in nondemented individuals followed during a period of 11 years.

We examined 94 participants (age 85.9 + 2.8 years) who had up to 5 measurements of Pittsburgh compound-B (PiB)-PET and clinical evaluations from 2009 to 2020. All 94 participants had 2 PiB-PET scans, 76 participants had 3 PiB-PET scans, 18 participants had 4 PiB-PET scans, and 10 participants had 5 PiB-PET scans. The rates of Aβ deposition were compared with 120 nondemented individuals younger than 80 years (69.3 ± 5.4 years) from the Australian Imaging, Biomarker, and Lifestyle (AIBL) study who had 3 or more annual PiB-PET assessments.

By 2020, 49% of the participants developed dementia and 63% were deceased. There was a gradual increase in Aβ deposition in all participants whether they were considered Aβ positive or negative at baseline. In a Cox model controlled for age, sex, education level, APOE-4 allele, baseline Mini-Mental State Examination, and mortality, short-term change in Aβ deposition was not significantly associated with incident dementia (HR 2.19 (0.41-11.73). However, baseline Aβ burden, cortical thickness, and white matter lesions volume were the predictors of incident dementia. Aβ accumulation was faster (p = 0.01) in the older cohort (5.6%/year) when compared with AIBL (4.1%/year). In addition, baseline Aβ deposition was a predictor of short-term change (mean time 1.88 years).

There was an accelerated Aβ accumulation in cognitively normal individuals older than 80 years. Baseline Aβ deposition was a determinant of incident dementia and short-term change in Aβ deposition suggesting that an active Aβ pathologic process was present when these participants were cognitively normal. Consequently, age may not be a limiting factor for the use of the emergent anti-Aβ therapies.