Research published in the December 2025 issue of The Lancet Neurology reveals that individuals with higher levels of amyloid in their brains face an increased risk of developing mild cognitive impairment (MCI) and dementia. This study, led by Clifford R. Jack Jr., M.D., from the Mayo Clinic in Rochester, Minnesota, assessed the implications of amyloid positron emission tomography (PET) centiloid values in a cohort of cognitively unimpaired individuals aged 50 and older.
The retrospective, longitudinal cohort study included data from **5,158 cognitively unimpaired participants** and **700 individuals** diagnosed with MCI. Researchers found a significant correlation between increasing centiloid values and the lifetime risk of cognitive impairment. Specifically, the findings indicate that as the centiloid value rises, so does the likelihood of developing MCI and dementia.
For male carriers of the apolipoprotein E (APOE) ε4 gene who were cognitively unimpaired at age 75, the lifetime risk for MCI escalated with higher centiloid values. The risks were measured as follows: **56.2%** for a centiloid value of **5**, **60.2%** for **25**, **71.0%** for **50**, **75.2%** for **75**, and **76.5%** for **100**.
In contrast, female APOE ε4 carriers starting at the same age had even higher lifetime risks for MCI: **68.9%**, **71.3%**, **77.6%**, **81.2%**, and **83.8%** for the respective centiloid values. These figures highlight a clear trend indicating that biological severity of Alzheimer’s disease, as measured by amyloid levels, plays a critical role in cognitive decline.
The implications of these findings may extend beyond research. Co-author Ronald C. Peterson, M.D., also from the Mayo Clinic, remarked, “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.” This suggests that understanding amyloid levels may guide preventive strategies for those at risk.
While the study offers valuable insights into the relationship between amyloid levels and cognitive health, it is important to note that several authors disclosed financial ties to the biopharmaceutical industry. This raises questions about potential conflicts of interest in the research.
As the global population ages, understanding the risk factors for cognitive decline becomes increasingly vital. This study emphasizes the need for ongoing research into the biological markers of Alzheimer’s disease, which could lead to more effective prevention and intervention strategies.
For more detailed information, refer to Clifford R. Jack et al, “Lifetime and 10-year absolute risk of cognitive impairment in relation to amyloid PET severity: a retrospective, longitudinal cohort study,” published in The Lancet Neurology (2025). DOI: 10.1016/s1474-4422(25)00350-3.
