Alzheimer's Imaging Consortium.

Area of Science:

• Neurology
• Biomarkers
• Aging

Background:

• Limited data exists on the absolute risk of mild cognitive impairment (MCI) in cognitively unimpaired (CU) individuals with abnormal Alzheimer's disease (AD) biomarkers, especially considering competing risks like death.
• This knowledge gap is critical for developing disease-modifying treatments for preclinical AD.
• The study focuses on the predictive value of AD amyloid stages determined by amyloid PET Centiloid values.

Purpose of the Study:

• To evaluate AD amyloid stage as a predictor of clinical progression to MCI or dementia.
• To predict 10-year and lifetime risks of MCI and dementia, accounting for competing risks of death.
• To assess the influence of amyloid PET stages, sex, APOE4 status, and baseline age on cognitive decline.

Main Methods:

• Included 5,858 participants from the Mayo Clinic Study of Aging (MCSA).
• Utilized long-term follow-up data on death and dementia to mitigate bias.
• Employed a hidden Markov model to predict risks based on amyloid PET stages, sex, APOE4 status, and age.

Main Results:

• AD amyloid staging using Centiloid values was the strongest predictor of lifetime risk for MCI or dementia.
• Higher Centiloid levels amplified age effects on MCI risk; for dementia, amyloid stage effects surpassed age effects.
• Age dominated 10-year risk prediction, while amyloid stages were more influential for lifetime risk. APOE4 status and male sex also showed associations with increased risk.

Conclusions:

• AD amyloid staging is a critical predictor of lifetime cognitive impairment risk, vital for guiding future treatment decisions in preclinical AD.
• Patient evaluation should prioritize biomarker-based amyloid staging over simple binary classification.
• Comprehensive benefit-risk assessments for therapeutic strategies require careful consideration of age, sex, and APOE4 status.