Elevated levels of β-amyloid with or without elevated tau in cerebrospinal fluid (CSF) is associated with a higher risk for cognitive decline in at-risk, middle-age, and older adults, according to study findings published in Neurology.

Investigators included middle-age and older community-dwelling adults (N=392) from the Wisconsin Registry for Alzheimer’s Prevention (n=141) and the Wisconsin Alzheimer’s Disease Research Center clinical core (n=251) longitudinal cohort studies. Participants were either cognitively healthy or impaired, had a family history of Alzheimer’s disease (AD), had completed a lumbar puncture, and underwent ≥2 biennial or annual neuropsychological assessments. A total of 215 study participants were biomarker negative for AD (preclinical AD stage 0), whereas 46 (15%) were Aβ+ only (preclinical AD stage 1), 25 (8%) were Aβ+ and tau+ (preclinical AD stage 2), and 28 (9%) were tau+ only.

Preclinical AD stages 1 and 2 demonstrated higher rates of linear cognitive decline with age, particularly with regard to story memory and processing speed measures (B = 0.01; P =.03). In addition, these groups demonstrated greater nonlinear cognitive decline on set-shifting and list-learning measures when compared with preclinical AD stage 0 participants. There was no difference between the tau+ only and stage 0 groups with regard to cognitive decline rates.

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Only CSF AD biomarkers were included in this analysis, precluding the ability to improve classification of preclinical AD with additional molecular neuroimaging biomarkers. Also, the findings from this study were primarily limited to the participants in this cohort, most of whom were highly educated white adults from the Midwest.

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The findings from this analysis “in the context of the literature suggests that Aβ may be associated with subtle decline in midlife, whereas tau may contribute to more pronounced clinical symptoms as the disease progresses.”


Clark LR, Berman SE, Norton D, et al. Age-accelerated cognitive decline in asymptomatic adults with CSF β-amyloid [published online March 9, 2018]. Neurology. doi:10.1212/WNL.0000000000005291