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Novel neuroimaging data have implications for recruitment for Alzheimer’s clinical trials

JAMA Neurology
Reuters Health - 21/10/2020 - There is a quantitative association between initial beta-amyloid levels on positron emission tomography (PET) and subsequent tau accumulation on PET in older cognitively normal adults, report researchers with the Alzheimer's Disease Neuroimaging Initiative (ADNI).

This new observation could be important when recruiting cognitively normal older adults to clinical trials where tau accumulation is an outcome measure, they write in JAMA Neurology.

Tau accumulation seen on PET imaging is closely tied to cognitive problems and is a potential surrogate outcome measure for clinical trial of Alzheimer's disease, Dr. David Knopman of Mayo Clinic, in Rochester, Minnesota, and colleagues explain.

It's generally thought that elevated levels of beta-amyloid on PET are associated with elevated tau and tau accumulation. But whether the risk for tau accumulation is uniform in all older adults considered amyloid-positive or whether risk increases at higher beta-amyloid levels is not clear.

The researchers explored this question in 167 people (mean age, 74 years) with no cognitive problems from the Mayo Clinic Study of Aging (MCSA) and a similar group of 114 from the ADNI who underwent serial cognitive assessments and PET scans with the beta-amyloid trace 11C-Pittsburgh compound B and the tau tracer flortaucipir.

They stratified participants by index beta-amyloid levels on PET into low (<=8 centiloid), subthreshold (9 to 21 CL), suprathreshold (22 to 67 CL), and high beta-amyloid (>=68 CL). The main outcome of interest was the change over a mean of 2.7 (range, 1.1 to 4.1) years in flortaucipir PET in regions of interest.

In the MCSA cohort, individuals with the highest levels of beta-amyloid had much greater accumulation of flortaucipir on a subsequent PET scan and these results were partially replicated in the ADNI cohort.

In addition, the researchers say, consistent with the association between elevation in flortaucipir and declining cognition, the greatest declines in memory z-scores were seen in the high-beta-amyloid group, the group with the largest increases in flortaucipir.

Overall, write Dr. Knopman and colleagues, these results show that "substantial flortaucipir accumulation occurs when beta-amyloid levels are 68 centiloid or more, while at lower beta-amyloid levels, there is little flortaucipir accumulation; clinical trials intending to use a tau positron emission tomography tracer as an outcome measure should recruit persons with high beta-amyloid levels."

These "novel" observations require replication in other studies, they add.

By Reuters Staff

SOURCE: https://bit.ly/3o7XYhy JAMA Neurology, online October 19, 2020.

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