Subtle cognitive decline could predict Alzheimer’s disease

Alzheimer’s disease (AD) is progressive but slow to develop—or at least to reveal itself.

In a new study, researchers found that early, subtle differences in cognitive performance, such as fewer words recalled on a memory test, are a sign that harmful proteins are accumulating in the brain, even if levels of those proteins do not yet qualify as dangerous.

The research was conducted by a team at the University of California San Diego and elsewhere.

Pathologically, AD is primarily characterized by the accumulation of protein plaques called β-amyloid (Aβ), which gradually accumulate in the brain, disrupting cell function and eventually killing affected neurons.

The second type of protein, called tau, also accumulates abnormally inside neurons, damaging functions.

In the progression of AD, Aβ levels build in the brain, but the process leading to abnormally high levels is typically long. It is often years or decades before consequential symptoms of severe cognitive impairment appear.

A new framework from the National Institute on Aging and Alzheimer’s Association defines the first stage of AD to be individuals with abnormal levels of Aβ who are still cognitively normal.

In the study, the team sought to determine whether poor cognitive performance, however subtle, might be a predictor that current Aβ-negative levels (accumulations below the threshold for AD diagnosis) were likely to become Aβ-positive.

The researchers conducted a pair of non-invasive cognitive tests on 292 participants.

All of the participants were Aβ-negative at baseline testing and displayed no dementia; 40 participants would progress to Aβ-positivity during the study and follow-up period.

The scientists found that participants who tested with lower baseline cognition were at a much higher risk of progressing to Aβ-positivity.

That is, low test scores indicating poorer cognitive function suggested amyloid plaque levels that, while not yet considered to be problematic, were likely rising and would ultimately reach the threshold definition of AD.

The findings, according to the researchers, suggest that low-cost, non-invasive cognitive testing is useful for identifying people who may be at risk for developing AD, making them ideal candidates for therapeutic intervention and clinical trials.

The lead author of the study is Jeremy A. Elman, Ph.D., an assistant professor in the Department of Psychiatry at UC San Diego School of Medicine.

The study is published in the journal Biological Psychiatry.

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