Hippocampal Atrophy May Flag Diseases Other Than Alzheimer’s


Hippocampal atrophy is associated with cognitive decline over time, independent of amyloid-beta (Aβ) or tau, new research shows. Investigators note the findings suggest neurological disorders other than Alzheimer’s disease (AD) may contribute to cognitive decline in older adults.


  • The study included 128 participants (median age 73 years) from the Harvard Aging Brain Study with a Global Clinical Dementia Rating of 0 and Mini Mental State Examination and Wechsler Logical Memory II delayed recall within 1 standard deviation of education-adjusted norms.

  • Researchers acquired longitudinal data from Flortaucipir and Pittsburgh Compound B PET scans to assess tau and Aβ pathology, and brain MRI to evaluate volumetric changes over a 10-year period.

  • Participants also underwent an annual battery of cognitive assessments, including tests of episodic memory, executive function, processing speed, and language.


  • The study showed both hippocampal atrophy and neocortical tauopathy are independent predictors of lower cognition, mediating the effects of initial entorhinal tau and Aβ pathology.

  • In addition to older age, faster hippocampal volume atrophy was correlated with more rapid cognitive decline (R2 = 0.28; P < .0001).

  • Hippocampal atrophy on its own accounted for 10% of the difference in cognitive decline.

  • About 45% of the variance in cognitive decline was explained by combining the change measures in the different imaging biomarkers.


The results suggest that measuring longitudinal changes in hippocampal volume as a secondary outcome in clinical trials, in addition to Aβ and tau pathologies, may help predict individual trajectories of cognitive decline and response, or lack of response, to AD drugs, write the authors.


The study was led by Bernard J. Hanseeuw, MD, PhD, Department of Radiology, Massachusetts General Hospital, Gordon Center for Medical Imaging, Boston, and colleagues. It was published online November 15 in Neurology.


Study participants were highly educated and mostly White, limiting generalizability of the findings. As the FTP tracer was not available at the start of the study, researchers couldn’t observe the sequence between early tau changes and subsequent Aβ. The study was not designed to detect atypical presentations of AD or non-AD pathologies.


The study received funding from the National Institutes of Health, Belgian Fund for Scientific Research, and the Queen Elizabeth Medical Foundation. Hanseeuw has reported receiving funding from the Belgian Fund for Scientific Research. Disclosures for the other authors are listed with the article.

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