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Early predictors of Alzheimer's disease may not occur in fixed, specific sequence

Study findings published in the Journal of Alzheimer’s Disease suggest that the number of abnormal biological and cognitive markers of Alzheimer’s disease a patient has, regardless of temporal sequence, are the strongest predictors of future cognitive decline.

“The [National Institute of Aging and the Alzheimer’s Association] criteria for ‘preclinical’ Alzheimer’s disease propose a staging method in which [Alzheimer’s disease] biomarkers follow an invariable temporal sequence in accordance with the amyloid cascade hypothesis. However, recent findings do not align with the proposed temporal sequence and ‘subtle cognitive decline,’ which has not been definitively operationalized, may occur earlier than suggested in preclinical [Alzheimer’s disease],” study researcher Emily C. Edmonds, PhD, of the University of California, San Diego, and colleagues wrote. “We aimed to define ‘subtle cognitive decline’ using sensitive and reliable neuropsychological tests, and to examine the number and sequence of biomarker abnormalities in the Alzheimer’s Disease Neuroimaging Initiative.”

Researchers assessed 570 cognitively normal patients from the Alzheimer’s Disease Neuroimaging Initiative and then separately evaluated them based on the presence of abnormal biological and cognitive markers associated with preclinical Alzheimer’s disease.

The analysis indicated neurodegeneration was 2.5 times more common than amyloid accumulation at baseline.

Patients who progressed to diagnosis with mild cognitive impairment were more likely to exhibit neurodegeneration as the first sign of early Alzheimer’s disease.

Amyloid accumulation and subtle cognitive decline had equal odds of being the first sign of early Alzheimer’s disease among patients who progressed to diagnosis with mild cognitive impairment.

“At present, it is much more common for assessment of cognition to be based on insensitive screening measures or reports of cognitive problems by patients or their family members. These blunt screening tools can be very unreliable, which might explain why cognitive decline has traditionally been viewed as occurring later in the disease process,” Edmonds said in a press release. “The integration of sensitive neuropsychological measures with assessment of biomarkers of [Alzheimer’s disease] can enhance our ability to more accurately identify individuals who are at risk for future progression to [Alzheimer’s disease].” – by Amanda Oldt

Disclosure: Edmonds reports no relevant financial disclosures. Please see the full study for a list of all other authors’ relevant financial disclosures.