Longitudinal patterns of β-amyloid deposition in nondemented older adults

Abstract

Background: High levels of β-amyloid (Aβ) characterize Alzheimer disease.

Objective: To investigate whether longitudinal changes in Aβ deposition can be detected in vivo in older adults without dementia (hereafter referred to as nondemented).

Design: Prospective study.

Setting: Community-dwelling older adults.

Participants: Twenty-four nondemented participants (4 with a baseline Clinical Dementia Rating Scale score of 0.5; mean [SD] age, 79.2 [8.1] years) in the Baltimore Longitudinal Study of Aging underwent serial carbon 11-labeled Pittsburgh Compound B-positron emission tomography ([(11)C]PiB-PET) (follow-up at a mean [SD] of 1.5 [0.5] years), with 5 participants undergoing a third [(11)C]PiB-PET examination.

Main outcome measures: Annual changes in distribution volume ratio (DVR) were evaluated using a global index of cortical DVR (cDVR) and region-of-interest analyses. Given the variability of cDVR at the initial PiB-PET, annual changes in cDVR in those with minimal vs those with elevated initial cDVR were compared.

Results: In nondemented older adults, annual increase in [(11)C]PiB retention is 0.011 DVR per year (0.9%; P = .01), which localizes to the prefrontal, parietal, lateral temporal, occipital, and anterior and posterior cingulate cortices. Annual change in cDVR is greater in older adults with elevated cDVR than in those with a minimal initial cDVR (P = .006).

Conclusions: Fibrillar Aβ detected by [(11)C]PiB-PET increases over time even in nondemented older adults. Individuals with higher initial [(11)C]PiB retention have greater rates of Aβ deposition, providing evidence of differential rates of Aβ deposition. Moreover, regional vulnerabilities to Aβ deposition allow for more targeted investigation of early Aβ changes.

Figure 1

Trajectories of longitudinal changes in carbon 11-labeled Pittsburgh Compound B retention in 24 nondemented older adults, including 5 individuals with a third follow-up scan. The Clinical Dementia Rating Scale (CDR) score at each time point is noted. cDVR indicates mean cortical distribution volume ratio.

Figure 2

Annual changes in mean cortical carbon 11-labeled Pittsburgh Compound B ([¹¹C]PiB) retention. A, Nondemented older adults as a group. B, Older adults with minimal vs elevated initial [¹¹C]PiB retention. Triangles represent individuals with a Clinical Dementia Rating (CDR) Scale total score of 0.5. Two individuals with CDR=0.5 have an annual change in mean cortical distribution volume ratio (cDVR) of 0.02. The horizontal line in the middle of each box indicates the median, and the top and bottom borders of the box mark the 90^th and 10^th percentiles, respectively. The points beyond the whiskers are outliers beyond the 90^th or 10^th percentiles.