Relationship Between Amyloid-β Positivity and Progression to Mild Cognitive Impairment or Dementia over 8 Years in Cognitively Normal Older Adults

Abstract

Aβ+ is an important prognostic marker for progression from CN to MCI/dementia in older adults and APOEɛ4 carriage provides further predictive value in the presence of Aβ+. These data suggest that Aβ-associated clinical progression is consistent with clinical-pathological models of AD, whereas progression in the absence of elevated Aβ deposition may be the result of neuropathological processes other than AD that accumulate with age.

Dementia prevention, intervention, and care: 2020 report of the Lancet Commission

“…Similarly, an 8-year follow-up study of 599 volunteers (average age 70 years) in Australia found that cognitively normal PET amyloid-positive people had an elevated risk of developing Alzheimer's disease compared with amyloid negative (17·7% vs 8·1%; OR 2·4, 95% CI 1·5–4·0). 184 Over 80% of the 266 people who were PET amyloid-positive did not go onto develop a cognitive impairment within 8 years, showing positive status does not predict impairment for most people in a timeframe that might be a useful prognostic window. Follow-up at 5 years of amyloid-positive participants with normal cognition or mild cognitive impairment versus amyloid negative people found the same pattern of increased risk (2·6, 1·4–4·9).…”

Clinical meaningfulness of subtle cognitive decline on longitudinal testing in preclinical AD

“…In the same vein, FDA draft guidance offers the possibility of conducting studies long enough to follow individuals over the course of stage 2 until they show functional impairment . However, disease progression is protracted, with a recent study showing that only 20% of stage 1/2 participants progress to MCI/dementia diagnosis after 8 years . Thus, an alternative, more efficient approach is to determine the magnitude of cognitive decline on longitudinal testing that may serve as a proxy for future functional impairment.…”

“…3 However, disease progression is protracted, with a recent study showing that only 20% of stage 1/2 participants progress to MCI/dementia diagnosis after 8 years. 6 Thus, an alternative, more efficient approach is to determine the magnitude of cognitive decline on longitudinal testing that may serve as a proxy for future functional impairment. If a treatment slows this cognitive decline and reduces the likelihood of clinical progression, this would provide evidence for a clinically meaningful therapeutic response.…”

Rates of age‐ and amyloid β‐associated cortical atrophy in older adults with superior memory performance

“…PET neuroimaging was conducted using one of the four Ab radiotracers: 11 C-Pittsburgh compound-B (PiB, n 5 137), 18 F-NAV4694 (NAV, n 5 38), 18 F-Florbetapir (FBP, n 5 88), or 18 F-Flutemetamol (FLUTE, n 5 81). Detailed PET methods and procedures are described elsewhere [36,37].…”

“…SuperAging may also reflect some protection from AD [16]. Abnormally high levels of amyloid β (Aβ+) and carriage of the APOE ε4 allele are AD risk factors [18]; however, prevalence of Aβ+ and APOE ε4 carriage are consistently similar between individuals with superior memory performance and typical older adults [3,7,8,10,16]. These individuals maintain superior cognitive ability despite Aβ+ [3,7,8] or substantial markers of AD neuropathology upon post‐mortem examination [19], suggesting that any resilience to AD pathogenesis experienced by SuperAgers either ameliorates or acts independently from the risk conferred by Aβ+ and APOE ε4.…”