Association of Emerging β-Amyloid and Tau Pathology With Early Cognitive Changes in Clinically Normal Older Adults.
Level 3 - non-randomized controlled study
Prospective longitudinal observational cohort study with >=7 years of follow-up.
PubMed 35338074 · doi:10.1212/WNL.0000000000200137
What was done
Researchers analyzed 112 clinically normal older adults from the Harvard Aging Brain Study with longitudinal Pittsburgh compound B (PiB)-PET, 18F-flortaucipir (FTP)-PET, and cognitive testing followed for at least 7 years. Linear mixed-effects models evaluated the impact of emerging global amyloid-beta (PiB accumulation rate) and tau (entorhinal and inferior temporal cortex baseline levels and slopes) on individual cognitive test scores and the Preclinical Alzheimer's Cognitive Composite (PACC). Analyses evaluated participants with baseline amyloid below 20 Centiloids (CL) and expanded to those under 40 CL.
What was found
In participants below 20 CL, steeper amyloid accumulation slopes were associated with declining processing speed on the Digit Symbol Substitution Test (DSST) and Trail Making Test Part A, whereas tau showed minimal effects except for right inferior temporal tau slope correlating with memory retrieval decline. In the expanded group under 40 CL, amyloid accumulation also tracked with learning and memory retrieval decline (FCSRT-FR, Selective Reminding Test, Logical Memory), and rising tau tracked with declines across all tasks while attenuating amyloid effects on memory. A custom composite of processing speed and memory retrieval best predicted decline below 40 CL, whereas PACC remained optimal above 40 CL. Specific numerical effect sizes, test statistics, and p-values were not reported in the abstract.
Why it matters
Standard preclinical cognitive composites may miss the earliest cognitive shifts occurring at low biomarker thresholds. Combining processing speed and memory retrieval tasks provides a more sensitive cognitive endpoint for clinical trials intervening at the earliest detectable stages of amyloid and tau accumulation.
Limits
The sample size is relatively small (n = 112) and derived from a single cohort study. The abstract does not provide exact effect estimates, confidence intervals, or p-values, precluding direct assessment of effect magnitude.
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