Using subjective cognitive decline to identify high global amyloid in community-based samples: A cross-cohort study

Area of Science:

• Neuroscience
• Clinical Trials
• Biomarkers

Background:

• Alzheimer's disease (AD) clinical trials require efficient recruitment of individuals with specific biomarkers.
• Beta-amyloid (Aβ) positivity is a key criterion for enrolling participants in many AD trials.
• Subjective cognitive decline (SCD) is being investigated as a potential early indicator of AD pathology.

Purpose of the Study:

• To evaluate the effectiveness of subjective cognitive decline (SCD) in identifying individuals with elevated beta-amyloid (Aβ) levels.
• To determine if SCD can reduce the number of Aβ positron emission tomography (PET) scans needed for clinical trial recruitment.
• To assess the impact of SCD, apolipoprotein E (APOE) genotype, and sex on Aβ positivity.

Main Methods:

• Analysis of three independent cohorts comprising 890 clinically normal individuals.
• Dichotomization of SCD status from a single question.
• Logistic regression modeling to classify Aβ positivity based on SCD, APOE ε4 status, sex, and age.

Main Results:

• SCD was associated with a 1.58-fold increased odds of being Aβ+ compared to non-SCD.
• Female APOE ε4 carriers with SCD showed significantly higher odds of Aβ+ (OR=3.34).
• Incorporating SCD reduced Aβ PET scan requirements by 13% (9% if APOE ε4 status was known).

Conclusions:

• Subjective cognitive decline (SCD) is a valuable tool for classifying individuals with high Aβ burden, independent of APOE genotype.
• Collecting SCD information is a practical strategy for targeting recruitment in AD clinical trials.
• SCD may help identify individuals on an early Alzheimer's disease trajectory.