Cognitive Decline Associated With Successive Amyloid-Beta and Tau Changes

Tau proteins
Tau proteins
Older adults with an increase in amyloid-β plaques followed by increased tau neurofibrillary tangles have shown lower cognition after 7 years.

Older adults with an increase in amyloid-beta plaques followed by increased tau neurofibrillary tangles have shown lower cognition after 7 years, according to a study recently published in JAMA Neurology. Regular tau positron emission tomography (PET) is needed to track the progression of disease, while regular amyloid PET is needed to detect early changes in Alzheimer disease pathology.

This prospective cohort study included 60 participants. Thirty-five (58%) were women, and the median age was 73 years at inclusion. All participants had normal cognition at study entry. Exclusion criteria included substance abuse, serious psychiatric or medical conditions, and head trauma.

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Images collected included a median of 3 Pittsburgh compound B (PiB) PET scans for amyloid-beta pathology and 2 flortaucipir PET scans. There were multiple amyloid-beta and tau observations between 2010 and 2017. The researchers assessed cognitive changes annually using initial data and rates of change, with the Preclinical Alzheimer Cognitive Composite used to evaluate cognition. The progression to mild cognitive impairment was evaluated in yearly consensus meetings. The change in Preclinical Alzheimer Cognitive Composite, PiB, and flortaucipir over time were predicted using linear mixed models.

An initial high burden of amyloid-beta was found in 17 participants. A tau change was associated with a previous increase in amyloid-beta, with flortaucipir standardized uptake value ratios [SUVr]/PiB-SUVr of 1.07 (95% CI, 0.13-3.46; P =.02). With covarying baseline tau and amyloid-beta, cognitive changes were associated with changes in tau (-3.28 z scores/SUVR; 95% CI, -6.67 to -0.91; P =.001). The 6 participants who progressed to mild cognitive impairment showed greater tau changes than the 11 who did not (SUVr per year, 0.05; 95% CI, 0.03-0.07; P =.001). Successive amyloid-beta and tau changes had a mediating effect on the correlation between initial amyloid-beta and 7-year cognition.

Limitations of this study included a lack of tau observation at the study’s commencement, inability to test the lack of correlation between early changes in tau and later change in amyloid-beta, and a lack of generalizability due to the small sample size.

The study researchers concluded that “successive changes in [amyloid-beta] and then tau were associated with lower cognition after a 7-year follow-up. Larger samples are needed to validate the proposed sequence. Additional observations will help estimate the delay separating the trajectories of [amyloid-beta], tau, and cognition.”

Disclosure: Several authors reported financial associations with pharmaceutical companies. See the reference for complete disclosure information.


Hanseeuw BJ, Betensky RA, Jacobs HIL, et al. Association of amyloid and tau with cognition in preclinical Alzheimer disease: a longitudinal study [published online June 3, 2019]. JAMA Neurol. doi:10.1001/jamaneurol.2019.1424