Amyloid-PET imaging predicts functional decline in clinically normal individuals

Area of Science:

• Neuroimaging and Biomarkers
• Alzheimer's Disease Research
• Clinical Neuropsychology

Background:

• Elevated amyloid-beta (Aβ) positron emission tomography (PET) signal is linked to cognitive decline in clinically normal (CN) individuals.
• The association between Aβ burden and decline in daily living activities in CN individuals requires further investigation.
• Optimal Aβ-PET Centiloid (CL) thresholds for predicting functional decline are not yet established.

Purpose of the Study:

• To investigate the association between Aβ burden, measured by Aβ-PET Centiloids (CL), and functional decline in daily living activities among clinically normal (CN) individuals.
• To establish optimal Aβ-PET CL thresholds for predicting functional decline in CN individuals.

Main Methods:

• Analysis of the European amyloid-PET imaging AMYPAD-PNHS dataset, including 1032 CN individuals and 228 with questionable functional impairment.
• Amyloid-PET was assessed using Centiloid (CL) scale and categorized into Aβ-, Aβ-intermediate/Aβ±, and Aβ+ groups.
• Functional abilities were assessed using the Clinical Dementia Rating (Global-CDR, CDR-SOB) and Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q).

Main Results:

• Cross-sectional analysis showed CL values associated with Clinical Dementia Rating (CDR) outcomes.
• Longitudinal analysis revealed that baseline CL values predicted prospective changes in CDR-SOB and A-IADL-Q scores in CN participants.
• Optimal thresholds for predicting decline were identified at 41 CL for CDR-SOB and 28 CL for A-IADL-Q.

Conclusions:

• Amyloid-PET quantification effectively identifies clinically normal individuals at risk of functional decline.
• Established Aβ-PET CL thresholds can aid in predicting the trajectory of functional impairment.