Progression of β-Amyloid Deposition and Consequences on Cognitive Impairment

Decreasing b-amyloid (Ab) deposition in the brains of patients with Alzheimer disease (AD) should be a priority early in the care for AD in order to decrease transition rates from Ab- to Ab+, according to study findings published in Neurology.

Researchers from the University of California, Berkeley conducted a long-term neuroimaging study. They analyzed [¹⁸F]florbetapir (FBP) positron emission tomography (PET) scans collected by the AD Neuroimaging Initiative (ADNI). Between 2 and 6 scans were collected from 139 cognitively normal (CN) Ab- controls, 88 CN Ab+ individuals, and 248 cognitively impaired Ab+ patients. Individuals were assessed for conversion to Ab+ and cognitive decline up to 9 years from baseline.

Participants who were CN Ab-, CN Ab+, or impaired Ab+ were aged 73.8 (standard deviation [SD], ±6.7), 75.7 (SD, ±6.5), and 74.4 (SD, ±7.6 years), respectively. 56%, 62%, and 45% were women, and 27%, 50%, and 69% were carriers of apolipoprotein e4, respectively.

The standardized uptake value ratio (SUVR) between FBP at baseline and follow-up was observed to be more of a quadratic (R², 0.110) than linear (R², 0.028) function, peaking at 0.87 SUVR and increasing by 0.013 SUVR per year. These findings indicated the amyloid accumulation began to slow 3.8 years after conversion to Ab+. Among all study participants, 90% of the cognitively impaired patients were past the accumulation peak compared with 31% of the CN cohort.

Individuals who converted from Ab- to Ab+ during the study were more likely to be women (64% vs 44%; P =.02), apolipoprotein e4 carriers (33% vs 18%; P =.028), had higher baseline amyloid cortical SUVR (0.78±0.02 vs 0.74±0.03; P <.001), baseline cortical uptake (13.3 vs 1.5; P <.001), entorhinal cortex FTP SUVR at 5 years (1.19±0.13 vs 1.12±0.10; P =.004), and temporal composite FTP SUVR at 5 years (1.23±0.13 vs 1.18±0.08; P =.016).

Significant predictors of conversion included age (hazard ratio [HR], 1.12; 95% CI, 1.06-1.18; P <.001), the interaction between apolipoprotein e4 and sex (HR, 5.47; 95% CI, 1.17-25.5; P =.031), and increased centiloids (20-25: HR, 203.93; 95% CI, 32.12-1294.55; 15-20: HR, 76.60; 95% CI, 13.71-428.01; 10-15: HR, 82.96; 95% CI, 14.45-476.22; all P <.001).

Longitudinal cognitive decline was associated with age (b, -0.004; standard error [SE], 0.001; P <.001), FBP slope (b, 1.50; SE, 0.749; P =.046), and slightly with apolipoprotein e4 (β, 0.024; SE, 0.01; P =0.097). Entorhinal tau deposits were associated with FBP slope (b, 3.23; standard deviation [SD], 1.3; P =.018).

This study was primarily limited by the composition of the ADNI cohort, which may not be fully representative of older patients and patients with dementia.  

These data indicated the Ab deposit rate corresponded with future decline in memory and deposition of tau. Early Ab-lowering therapies should be administered in the AD course to delay cognitive decline.

Reference

Jagust W J, Landau S M. Temporal Dynamics of β-Amyloid Accumulation in Aging and Alzheimer Disease. Neurology. 2021;96:e1347-e1357. doi:10.1212/WNL.0000000000011524