Advancing age is associated with a decline in cognitive functioning—the ability to think, process, and remember information. Although many older adults report some decline in these abilities, some experience sharper declines, and others may be diagnosed with neurodegenerative conditions such as Alzheimer’s disease, which is characterized by severe difficulties with many cognitive abilities, particularly remembering information.
Many clinical studies conducted using brain imaging, as well as autopsy studies, have confirmed the presence of amyloid and tau—two hallmark proteins—in the brains of individuals with Alzheimer’s disease, and at times, in those without a formal diagnosis. These protein levels can be measured in several ways, including in the cerebrospinal fluid (CSF), and have been shown to predict the clinical symptoms in older adults with Alzheimer’s disease. However, amyloid and tau pathology are also present in older adults without any diagnosed neurodegenerative condition, and it remains unclear whether higher levels of these proteins are associated with declines in cognitive functioning within this population.
In a 2025 study published in Neuropsychology, Michael Mckenna, Oyetunde Gbadeyan, Rebecca Andridge, Matt W. Schroeder, Erika A. Pugh, Dough W. Scharre, and Ruchika S. Prakash examined whether abnormal levels of amyloid and tau in CSF are linked to changes in cognitive functioning over time. The study included older adults with no impairment to mild cognitive impairment and with Alzheimer’s disease.
The study team analyzed data from the National Institutes of Health—funded Alzheimer’s Disease Neuroimaging Initiative (ADNI)—one of the most comprehensive publicly available resources for studying both healthy and pathological aging. The study included 1,215 participants: 367 older adults without cognitive impairment, 619 with mild cognitive impairment, and 229 with Alzheimer’s disease. To measure cognitive changes over a two-year period, the researchers used well-established summary scores from the ADNI dataset that reflect overall cognition, memory, and executive functioning (EF)—abilities often impacted in those with Alzheimer’s disease.
The results showed that the combined metric of amyloid and tau pathology was linked to a steeper decline in overall cognition and memory, but only among those with pre-existing cognitive impairment. In other words, among older adults with mild cognitive impairment or Alzheimer’s disease, higher levels of pathology were associated with worse functioning in thinking and memory skills. In contrast, the combined measure of amyloid and tau pathology was associated with a worse decline in EF—a broad domain of cognition that includes planning, multi-tasking, and managing daily activities such as shopping—even among older adults without any diagnosed neurodegenerative condition. These findings suggest that the hallmark characteristics of Alzheimer’s disease—amyloid and tau—may also be associated with higher-order cognitive abilities in older adults without a clinical diagnosis.
These results highlight the importance of understanding the effects of amyloid and tau pathology even before a clinical diagnosis is made. Moreover, the finding that EF abilities were associated with Alzheimer’s disease pathology across all participants suggests that these abilities may be sensitive to early pathophysiological changes and should be assessed early in the disease course.