The following is a summary of “Association of pathological and volumetric biomarker changes with cognitive decline in clinically normal adults: Harvard Aging Brain Study,” published in the November 2023 issue of Neurology by Hanseeuw et al.

Hippocampal volume (HV) atrophy, a hallmark of memory impairment, is less specific for Alzheimer’s disease (AD) pathology compared to amyloid-beta (Aβ) and tau imaging. This lack of specificity suggests potential comorbidities that cannot be detected in vivo.

Researchers performed a retrospective study to examine the relationships between Aβ, tau, HV, and cognitive function over a 10-year follow-up, focusing on the influence of HV atrophy on cognition after controlling for Aβ and tau levels.

They enrolled 283 older adults without dementia or overt cognitive impairment in the Harvard Aging Brain Study. Examining data from individuals with accessible longitudinal imaging and cognition information. The study included serial MRI (with a follow-up duration ranging from 1.3 to 7.0 years), neocortical Aβ imaging using PiB PET scans (ranging from 1.9 to 8.5 years), entorhinal and inferior temporal tau assessments via Flortaucipir PET scans (spanning from 0.8 to 6.0 years), and the collection of Preclinical Alzheimer Cognitive Composite data (gathered over 3.0 to 9.8 years). Assessed the longitudinal relationships among Aβ, tau, volume, and cognition data, sequentially exploring models to examine the impact of each biomarker on cognitive decline.

he results showed that 128 clinically normal older adults were analyzed, 72 (56%) women and 56 (44%) men. The median age upon inclusion was 73 years old (range: 63-87). PET imaging revealed an initial high burden in 34 participants (27%). Faster hippocampal volume (HV) atrophy demonstrated a correlation with accelerated cognitive decline (R2=0.28, p<0.0001). The HV slope was independently associated with cognitive decline, explaining 10% of the variance, and combining changes in various imaging biomarkers accounted for 45% of the variance in cognitive decline.

They concluded that in older adults, hippocampal atrophy predicts cognitive decline independently of AD biomarkers, suggesting the involvement of non-AD pathologies like TDP-43 or vascular disease.

Source: n.neurology.org/content/early/2023/11/15/WNL.0000000000207962