Age‐related atrophy persists after screening for preclinical Alzheimer disease

• Published in: Alzheimer's & dementia Vol. 17; no. S4
• Main Authors: Koenig, Lauren N., LaMontagne, Pamela J., Glasser, Matthew F., Gordon, Brian A., Morris, John C., Shimony, Joshua S., Benzinger, Tammie L.S.
• Format: Journal Article
• Language: English
• Published: 01.12.2021
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.051098

Background Brain atrophy has been shown to occur with age, but it is unclear if this is misattribution of undetected preclinical Alzheimer disease (AD). Here we determine regional patterns of age‐related atrophy in a cross‐sectional cohort screened for the confounding influence of preclinical Alzheimer disease. Method We assembled two dementia‐free cohorts ‐ a Normal Aging Cohort (n=383) and a Preclinical AD Cohort (n=115) ‐ using participants from The Open Access Series of Imaging Studies and non‐mutation carriers from the Dominantly Inherited Alzheimer Network. The Preclinical AD Cohort was positive by amyloid PET scan. The Normal Aging Cohort was amyloid negative and remained cognitively normal longitudinally. Linear models assessed age‐related atrophy for volumes and cortical thicknesses directly and by using the estimated derivative of smoothed aging curves to assess non‐linear patterns. Amyloid positivity by regional volume/thickness was modeled using multiple linear regressions on the subset of the Normal Aging Cohort above age 60 and the Preclinical Alzheimer Disease Cohort. Result The greatest age‐related atrophy was seen in the temporal lobe and subcortical regions, but nearly all regions showed some level of atrophy (Figure 1A). The age‐derivative pattern (Figure 1B) indicated that the temporal lobe linearly declined with age, subcortical regions declined faster at later ages, and frontal regions declined to a lower extend in late life than at midlife. This pattern was significantly associated with an average T1/T2 myelin map from a separate cohort, while the linear measure of age‐related atrophy was not. Volumes and cortical thicknesses in our Preclinical Alzheimer Disease Cohort were not detectably different than our Normal Aging Cohort, with no regions showing significance for amyloid status or age*amyloid status after multiple comparisons correction. Conclusion Regional variability exists both in the amount of atrophy that occurs with age and in the pattern of decline observed, the second of which may be related to myelination. Regional measures of age‐related atrophy do not appear to require screening from preclinical Alzheimer disease.