A recent study has highlighted a concerning link between the biological severity of Alzheimer’s disease and the risk of mild cognitive impairment (MCI) and dementia in cognitively unimpaired individuals. Published in the December 2025 issue of The Lancet Neurology, the research indicates that as the amyloid positron emission tomography (PET) centiloid values increase, so does the lifetime and 10-year absolute risk of developing these cognitive issues.
Conducted by Dr. Clifford R. Jack Jr. and colleagues at the Mayo Clinic in Rochester, Minnesota, this retrospective, longitudinal cohort study analyzed a total of 5,858 cognitively unimpaired participants aged 50 years or older at the time of enrollment. Additionally, the study included 700 individuals diagnosed with MCI. The researchers found a consistent increase in the lifetime risk for both MCI and dementia as the centiloid values rose, revealing that this predictor had the most significant impact on risk assessment.
For cognitively unimpaired male carriers of the apolipoprotein E (APOE) ε4 gene, who began the study at the age of 75, the lifetime risk percentages for developing MCI were notable. These risks were calculated as follows: 56.2% at centiloid 5, 60.2% at centiloid 25, 71.0% at centiloid 50, 75.2% at centiloid 75, and 76.5% at centiloid 100.
In contrast, female APOE ε4 carriers at the same age exhibited a slightly higher risk, with lifetime probabilities of 68.9% at centiloid 5, 71.3% at centiloid 25, 77.6% at centiloid 50, 81.2% at centiloid 75, and 83.8% at centiloid 100. These findings underscore the gender differences in risk associated with amyloid levels.
Dr. Ronald C. Peterson, co-author of the study, emphasized the potential implications of these risk estimates. “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,” he stated. The research could serve as a critical tool for healthcare providers in managing patients’ cognitive health.
While the study sheds light on the correlation between amyloid levels and cognitive impairment, it is important to note that several authors have disclosed connections to the biopharmaceutical industry, which may influence the interpretation of the findings.
This groundbreaking research will likely contribute to the ongoing discourse surrounding Alzheimer’s disease and the methods used to predict and manage cognitive decline, particularly among high-risk groups. Further investigations are necessary to explore the implications of these findings on clinical practices and patient care strategies in Alzheimer’s disease management.
For more details, refer to the study by Clifford R. Jack Jr. et al., titled “Lifetime and 10-year absolute risk of cognitive impairment in relation to amyloid PET severity,” published in The Lancet Neurology.