Reducing b-amyloid (Ab) deposition in the brain of patients with Alzheimer’s disease (AD) should be a priority when initiating treatment for AD in order to lower transition rates from Ab- to Ab +, according to study results published in Neurology demonstrate.
Researchers at the University of California at Berkeley conducted a long-term study of imaging. They analyzed [18F]Positron Emission Tomography (PET) of florbetapir (FBP) captured by the AD Neuroimaging Initiative (ADNI). Between 2 and 6 scans were collected from 139 cognitively normal (CN) Ab controls, 88 CN Ab + subjects, and 248 cognitively impaired Ab + subjects. Individuals were screened for transition to Ab + and cognitive decline up to 9 years after the start of the study.
Participants with CN Ab-, CN Ab +, or impaired Ab + were 73.8 years old (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.
The standardized admission ratio (SUVR) between baseline FBP and follow-up was observed to be a quadratic (R2, 0.110) rather than a linear (R2, 0.028) function, peaking at 0.87 SUVR and around 0.013 SUVR increases per year. These findings indicated that amyloid accumulation began to slow 3.8 years after converting to Ab +. Among all study participants, 90% of the cognitively impaired patients were above 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% versus 44%; P = 0.02), apolipoprotein e4 carriers (33% versus 18%; P = 0.028) to be a cortical SUVR (0.78 ± 0.02 versus 0.74 ± 0.03; P <0.001), baseline cortical uptake (13.3 versus 1.5; P <0.001), entorhinal cortex FTP had higher amyloid at baseline SUVR after 5 years (1.19 ± 0.13 versus 1.12 ± 0.10; P =. 004) and time-composite FTP SUVR after 5 years (1.23 ± 0.13 versus 1.18 ± 0, 08; P = 0.016).
Important predictors for the conversion were age (hazard ratio) [HR]1.12; 95% CI, 1.06-1.18; P <0.001), the interaction between apolipoprotein e4 and gender (HR 5.47; 95% CI 1.17-25.5; P = 0.031) 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 <0.001).
Longitudinal cognitive decline was associated with age (b, -0.004; standard error) [SE]0.001; P <0.001), FBP slope (b, 1.50; SE, 0.749; P = 0.046) and easy with apolipoprotein e4 (β, 0.024; SE, 0.01; P = 0.097). Entorhinal tau deposits were associated with the FBP slope (b, 3.23; standard deviation) [SD]1.3; P = 0.018).
This study was primarily limited by the composition of the ADNI cohort, which may not be fully representative of elderly patients and those with dementia.
These data showed that the deposition rate corresponded to future memory decline and dew deposition. Early lowering therapies should be given in the AD course to delay cognitive decline.
Jagust WJ, Landau SM Temporal dynamics of β-amyloid accumulation in aging and Alzheimer’s disease. Neurology. 2021; 96: e1347-e1357. doi: 10.1212 / WNL.0000000000011524