(107) Estimating the Prevalence of Preclinical Alzheimer’s Disease with Subjective Cognitive Decline among US Adults

Background: Overt cognitive impairment in the Alzheimer’s disease (AD) continuum is preceded by a preclinical phase, in which amyloid biomarkers are present yet cognition remains within normal ranges of scores. Clinical trials are increasingly focused on preclinical AD (preAD) for new therapies designed to slow disease progression. However, current estimates of the preAD population potentially eligible for trials are lacking.

Objectives: To estimate amyloid-positive (Aβ+) subjective cognitive decline (SCD) cases in the US in 2024, also considering the prevalence of consultation with healthcare providers (HCP) and potential eligibility for preAD trials.

Methods: We used a funnel approach to estimate cases. First, we estimated the number of cognitively unimpaired (CU) US adults 50+ years in 2024 by race/ethnicity and 5-year age-group, using the CDC Wonder population data stratified by race/ethnicity and age, combined with literature-based prevalence estimates to remove those with mild cognitive impairment, dementia or intellectual/developmental disorders. Next, we applied estimates of age- and race-stratified prevalence of SCD from a population-based survey (Wooten 2023) and estimates of Aβ+ from the Amyloid Biomarker Study (Jansen 2022). We then calculated the estimated number who have spoken to an HCP by applying age- and race/ethnicity data from Wooten 2023. Finally, we estimated the number potentially eligible for a preAD trial by applying relevant screen failure estimates from a phase 3 trial (Sperling 2023).

Results: In 2024, an estimated 2.6 million (M) CU in the US aged 50+ years have Aβ+ SCD, of which approximately 1.2M are estimated to discuss their cognitive symptoms with an HCP, and approximately 350,000 are estimated to potentially meet typical eligibility requirements for a modern preAD trial. Stratified by race/ethnicity, ~1.8M non-Hispanic white (NHW); ~274K NH-black (NHB); 390K Hispanic; and ~199K other race/ethnicity individuals have Aβ+ SCD in 2024. Of these, HCP discussions are estimated for ~790K NHW; ~133K NHB; ~164K Hispanic; and ~91K other race/ethnicity cases. Of these, an estimated ~240K NHW; ~40K NHB; ~50K Hispanic; and ~28K other race/ethnicity would potentially meet screening criteria for a preAD trial.

Conclusions: Among the estimated 2.6M adults 50+ years in the US with SCD in the preclinical AD phase, only about 14%, or roughly 350,000 people, are likely to speak to an HCP about cognitive concerns and potentially meet typical eligibility requirements for preclinical AD trials. These estimates are derived from a compilation of data sources and should be refined as more data become available on factors influencing help-seeking, trial enrollment, or treatment initiation.