MCI, Dementia Risks Up With Increasing Biological Severity of Alzheimer Disease

MONDAY, Nov. 17, 2025 (HealthDay News) — For individuals who are currently cognitively unimpaired, the lifetime and 10-year absolute risk of mild cognitive impairment (MCI) and dementia increases with increasing amyloid positron emission tomography (PET) centiloid value, according to a study published in the December issue of The Lancet Neurology.

Clifford R. Jack Jr., M.D., from the Mayo Clinic in Rochester, Minnesota, and colleagues conducted a retrospective, longitudinal cohort study to compute lifetime and 10-year absolute risks for cognitive impairment as a function of continuous amyloid PET in participants who were cognitively unimpaired and aged 50 years or older at enrollment.

The analysis included 5,158 participants who were cognitively unimpaired and 700 with MCI. The researchers observed a monotonic increase in lifetime risk for MCI and dementia with increasing centiloid value; this was the predictor with the largest effect. For male apolipoprotein E (APOE) ε4 carriers who were cognitively unimpaired at a starting age of 75 years, the lifetime risk for MCI was 56.2, 60.2, 71.0, 75.2, and 76.5 percent for centiloid 5, centiloid 25, centiloid 50, centiloid 75, and centiloid 100, respectively. For female APOE ε4 carriers who were cognitively unimpaired at a starting age of 75 years, the corresponding lifetime risks for MCI were 68.9, 71.3, 77.6, 81.2, and 83.8 percent.

“This kind of risk estimate could eventually help people and their doctors decide when to begin therapy or make lifestyle changes that may delay the onset of symptoms,” coauthor Ronald C. Peterson, M.D., also from the Mayo Clinic, said in a statement.

Several authors disclosed ties to the biopharmaceutical industry.

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