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Abstract
Objective To investigate the contribution of Alzheimer disease (AD) vs non-AD neuropathologies to hippocampal atrophy.
Methods The Religious Orders Study and Rush Memory and Aging Project are clinicopathologic cohort studies of aging. The current study included 547 participants who had undergone brain autopsy and postmortem hippocampal volume measurement by November 1, 2018. Hippocampal volume was measured with postmortem MRI via a 3D region of interest applied to the hippocampal formation. Neuropathologies were measured via uniform structured evaluations. Linear regression analyses estimated the proportion of variance of hippocampal volume attributable to AD and non-AD neuropathologies.
Results The average age at death was 90 years, and the average hippocampal volume was 2.1 mL. AD, transactive response DNA-binding protein 43 (TDP), hippocampal sclerosis (HS), and atherosclerosis were associated with hippocampal volume. After demographics and total hemisphere volume were controlled for, 7.0% of the variance (95% bootstrapped confidence interval [CI] 4.3%–10.5%) of hippocampal volume was attributable to AD pathology. TDP/HS explained an additional 4.5% (95% CI 2.2%–7.6%). Among individuals with Alzheimer dementia (n = 232), 3.1% (95% CI 0.6%–7.7%) of the variance was attributable to AD pathology, and TDP/HS explained an additional 6.1% (95% CI 2.2%–11.6%). Among those without Alzheimer dementia (n = 307), 3.2% (95% CI 0.9%–7.3%) of the variance was attributable to AD pathology, and TDP/HS explained an additional 1.1%, which did not reach statistical significance. Lewy bodies and vascular diseases had modest contribution to the variance of hippocampal volume.
Conclusions Both AD and TDP/HS contribute to hippocampal volume loss in older-old persons, with TDP/HS more strongly associated with hippocampal volume than AD in Alzheimer dementia.
Glossary
- AD=
- Alzheimer disease;
- CERAD=
- Consortium to Establish a Registry for Alzheimer's Disease;
- CI=
- confidence interval;
- HS=
- hippocampal sclerosis;
- NIA=
- National Institute on Aging;
- PHF=
- paired helical filament;
- ROSMAP=
- Religious Orders Study and Rush Memory and Aging Project;
- TDP=
- transactive response DNA-binding protein 43
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received March 13, 2019.
- Accepted in final form July 10, 2019.
- © 2019 American Academy of Neurology
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