On 6 April, Dr Reisa Sperling and co-investigators published the results of a cross-sectional analysis of participants in the Anti-Amyloid Treatment in Aymptomatic Alzheimer’s Disease (A4) prevention trial. These results indicate that elevated amyloid-beta is an early marker of Alzheimer’s disease (AD) in the brains of older individuals, associated with lower scores on cognitive tests and correlated with family history and ApoE4 risk factors.
The A4 study is an interventional Phase 3 multi-center study testing the anti-amyloid drug, solanezumab, in cognitively normal older adults who have brain PET scans showing evidence of amyloid buildup. The trial is funded as a public-private partnership between the US National Institute of Health (NIH), Eli Lilly and several philanthropic organisations. Prescreening of participants from 67 clinical sites started in early 2014, and by 2017 investigators had identified 1323 individuals aged >65 with elevated brain amyloid (Aß+) who were eligible to continue in the A4 study. Clinical and brain imaging data were also collected from 3163 age-matched, prescreened participants who did not have positive PET scans for amyloid (Aß-). By comparing clinical, cognitive, demographic and lifestyle characteristics between these two groups (Aß+ and Aß- individuals), the researchers hoped to tease out any potential associations between these characteristics and elevated amyloid in the brain.
When the demographic characteristics of Aß+ and Aß- groups were compared, no differences due to sex, education, marital or retirement status were observed. Moreover, the researchers did not find any differences between the two groups in self-reported lifestyle parameters such as exercise, walking, sleep time, alcohol or caffeine intake. However, those in the Aß+ group were more likely to have a family history of AD, and within the Aß+ group, carriers of the ApoE4 genetic risk allele showed a higher level of amyloid deposition in the brain, as measured by PET scans. Consistent with previous reports demonstrating its protective effect against AD, ApoE2 was underrepresented in the Aß+ group. Finally, Aß+ individuals did not perform as well in the PACC cognitive tests, also reporting greater subjective cognitive declines in cognitive function over the last year. Together, these cross-sectional findings provide additional support for the hypothesis that elevated brain amyloid deposition in cognitively normal people represents a preclinical stage of AD, identifying a group of high-risk individuals for clinical trials of disease-modifying treatments.
The original article was published in JAMA Neurology and can be found here: https://jamanetwork.com/journals/jamaneurology/fullarticle/2763540?resultClick=3