White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy
Related Experiment Video
Updated: Mar 10, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Cassidy M Fiford1, Emily N Manning1, Jonathan W Bartlett2
1Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, United Kingdom.
Abstract:
This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5-T MRI. CSF Aβ42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aβ42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.
Insights
Vascular damage, indicated by white matter hyperintensity volume, is linked to faster hippocampal atrophy in older adults, even without dementia. This suggests combined vascular and Alzheimer's disease pathology accelerates brain aging.
Area of Science:
- Neuroimaging
- Neuropathology
- Gerontology
Background:
- White matter hyperintensities (WMH) are common in aging and associated with cognitive decline.
- Alzheimer's disease (AD) pathology and vascular damage often coexist and contribute to neurodegeneration.
Purpose of the Study:
- To investigate the relationship between WMH volume, AD CSF biomarkers, and rates of brain and hippocampal atrophy.
- To determine if vascular damage exacerbates atrophy in non-demented individuals.
Main Methods:
- Serial volumetric MRI was used to quantify brain and hippocampal volume loss via boundary shift integral (BSI).
- Multiple linear regression models assessed associations between WMH burden and atrophy rates, adjusting for atrophy and CSF biomarkers (Aβ42, tau).
- Study included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects.
Main Results:
- WMH burden positively correlated with hippocampal atrophy rate in controls and MCI subjects.
- WMH burden also correlated with brain atrophy rate in controls.
- These associations persisted after adjusting for concurrent atrophy rates and CSF AD biomarkers in controls.
Conclusions:
- Vascular damage, evidenced by WMH, is associated with accelerated hippocampal atrophy in non-demented older adults.
- Combined vascular damage and AD pathology may disproportionately impact the hippocampus.
- Findings highlight the role of vascular factors in age-related brain atrophy.
More Related Videos
08:29Symmetric Bihemispheric Postmortem Brain Cutting to Study Healthy and Pathological Brain Conditions in Humans
Published on: December 18, 2016
09:38Generalized Psychophysiological Interaction PPI Analysis of Memory Related Connectivity in Individuals at Genetic Risk for Alzheimer's Disease
Published on: November 14, 2017
Related Concept Videos
01:19Role of Hippocampus in Memory
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...