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Hippocampus. 2017 Mar;27(3):249-262. doi: 10.1002/hipo.22690. Epub 2017 Jan 9.

White matter hyperintensities are associated with disproportionate progressive hippocampal atrophy.

Author information

1
Department of Neurodegenerative Disease, Dementia Research Centre, UCL Institute of Neurology, London, United Kingdom.
2
Statistical Innovation Group, Cambridge, AstraZeneca, United Kingdom.
3
Translational Imaging Group, Centre for Medical Image Computing, University College London, London, United Kingdom.
4
Nuffield Department of Clinical Neurosciences, FMRIB Centre, University of Oxford, United Kingdom.
5
Wellcome Trust Centre for Neuroimaging, London, United Kingdom.
6
Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus University Medical Center Utrecht, The Netherlands.
7
Pennington Biomedical Research Center, Baton Rouge, Louisiana.

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.

KEYWORDS:

Alzheimer's disease; hippocampus; mild cognitive impairment; vascular disease; white matter disease; white matter hyperintensity (WMH)

PMID:
27933676
PMCID:
PMC5324634
DOI:
10.1002/hipo.22690
[Indexed for MEDLINE]
Free PMC Article

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