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Subtle Cognitive Decline Predicts Alzheimer’s Pathology

March 04, 2020

Low-cost, noninvasive cognitive testing may help identify people at risk of progressing to the first stage of Alzheimer’s disease, according to a study published online in Biological Psychiatry.

“Stage 1 of the National Institute on Aging–Alzheimer’s Association’s proposed Alzheimer’s disease continuum is defined as amyloid-β (Aβ) positive but cognitively normal. Identifying at-risk individuals before Aβ reaches pathological levels could have great benefits for early intervention,” researchers wrote.

“Although Aβ levels become abnormal long before severe cognitive impairments appear, increasing evidence suggests that subtle cognitive changes may begin early, potentially before Aβ surpasses the threshold for abnormality.”

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To investigate where cognitive performance would predict progression of Aβ from normal to abnormal levels, the Preclinical Alzheimer Cognitive Composite and the Alzheimer’s Disease Neuroimaging Initiative memory factor composite tests were administered to 292 people in the Alzheimer’s Disease Neuroimaging Initiative. All participants were below the Aβ threshold for Alzheimer’s disease diagnosis (Aβ-negative) and displayed no signs of dementia at baseline.

Among the participants, 40 eventually progressed to Aβ-positivity during follow-up. Poorer performance on the cognitive tests, according to the study, was significantly linked with increased odds of progressing to Aβ-positivity, even after researchers controlled for baseline biomarker levels of subthreshold Aβ and cerebrospinal fluid phosphorylated tau.

“Once a person reaches the point of being Aβ-positive, it means that there is already substantial underlying pathology,” said study first author Jeremy A. Elman, PhD, assistant professor in the psychiatry department at the University of California San Diego School of Medicine. “It would be advantageous to identify at-risk individuals before they develop substantial amyloid burden to improve treatment efficacy and slow progression to Alzheimer’s disease dementia.”

—Jolynn Tumolo


Elman JA, Panizzon MS, Gustavson DE, et al. Amyloid-β positivity predicts cognitive decline but cognition predicts progression to amyloid-β positivity. Biological Psychiatry. 2020 January 7;[Epub ahead of print].

LaFee S. Subtle decline in cognition predicts progression to Alzheimer’s pathology [press release]. La Jolla, California: University of California San Diego; February 14, 2020.

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