Estimated Age of Amyloid Onset in Participants with Early‐ versus Late‐Onset Alzheimer’s Disease: Results from the LEADS & ADNI Studies
Year: 2023
Type: article
Abstract: Background Aβ deposition is thought to start decades prior to symptom onset. Previous studies have shown that mathematical modeling enables reconstruction of Aβ‐PET trajectory and age estimation at Aβ‐PET positivity in Aβ‐positive patients. We aimed to apply this approach to determine Aβ duration and estimate age at Aβ‐PET positivity in sporadic early‐ (<65yo) and late‐ (≥65yo) onset AD (EOAD/LOAD). Method We combined PET data from the Longitudinal Early‐Onset AD Study (LEADS, n = 288) and ADNeuroimaging Initiative (ADNI, n = 915). First, we selected Aβ+ (baseline Centiloids ≥24) cognitively impaired patients with ≥2 Florbetaben‐PET scans to compare baseline and longitudinal amyloid‐PET in EOAD versus LOAD using linear mixed effects regression (Figure 1). Then, we used ADNI participants with ≥2 Florbetapir‐PET scans to assess the relationship between Aβ‐PET Centiloids and time (Figure 2). We estimated the Aβ temporal trajectory by integrating a reciprocal of the spline model from the accumulation rate and Centiloidmid‐point. Finally, we used the resulting Aβ trajectory to estimate Aβ duration and age at Aβ‐PET positivity onset for patients with EOAD and LOAD (Figure 3). Result EOAD patients had higher baseline Aβ burden than LOAD patients. Amyloid‐PET increased at similar rates in the two groups (Figure 1), allowing us to operate under the assumption that EOAD and LOAD follow the same Aβ trajectory, with a temporal shift. Aβ trajectory was estimated in ADNI Florbetapir‐PET, showing an almost linear dependency between Centiloids and Aβ duration (Figure 2). The model suggests that Aβ‐PET positivity (CL = 24) is reached after 7 years, and an additional 26 years are needed to reach 100 CL. When applied to the Florbetaben sample, we determined that 75yo LOAD patients became Aβ‐PET positive around 52yo, while 60yo patients with EOAD dementia were Aβ‐PET positive around age 31 (Figure 3). Conclusion Based on available data, the dynamic of Aβ accumulation seems similar in EOAD and LOAD, with a temporal shift indicating that EOAD patients might transition to Aβ‐PET‐positive in their early 30s. Prospective studies on early phases of Aβ accumulation in EOAD patients will be important for validation of these findings since existing data is limited.
Source: Alzheimer s & Dementia
DOI: 10.1002/alz.078744
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4390195194