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Hippocampus. 2018 Oct 11. doi: 10.1002/hipo.23039. [Epub ahead of print]

Memory decline in elderly with cerebral small vessel disease explained by temporal interactions between white matter hyperintensities and hippocampal atrophy.

Author information

1
Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Donders Center for Medical Neuroscience, Radboud University Medical Centre, Nijmegen, The Netherlands.
2
Department of Clinical Neurosciences, Neurology Unit, University of Cambridge, Cambridge, United Kingdom.
3
Department of Neurology, Jeroen Bosch Ziekenhuis,'s-Hertogenbosch, The Netherlands.
4
Radboud University Medical Centre, Diagnostic Image Analysis Group, Department of Radiology and Nuclear Medicine, Nijmegen, The Netherlands.
5
Radboud University, Institute for Computing and Information Sciences, Nijmegen, The Netherlands.
6
Radboud University, Donders Institute for Brain Cognition and Behaviour, Centre for Cognitive Neuroimaging, Nijmegen, The Netherlands.
7
Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen, Germany.
8
Department of Medical Psychology, Radboud University Medical Centre, Radboud Alzheimer Centre, Nijmegen, The Netherlands.
9
Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognition, Nijmegen, The Netherlands.

Abstract

White matter hyperintensities (WMH) constitute the visible spectrum of cerebral small vessel disease (SVD) markers and are associated with cognitive decline, although they do not fully account for memory decline observed in individuals with SVD. We hypothesize that WMH might exert their effect on memory decline indirectly by affecting remote brain structures such as the hippocampus. We investigated the temporal interactions between WMH, hippocampal atrophy and memory decline in older adults with SVD. Five hundred and three participants of the RUNDMC study underwent neuroimaging and cognitive assessments up to 3 times over 8.7 years. We assessed WMH volumes semi-automatically and calculated hippocampal volumes (HV) using FreeSurfer. We used linear mixed effects models and causal mediation analyses to assess both interaction and mediation effects of hippocampal atrophy in the associations between WMH and memory decline, separately for working memory (WM) and episodic memory (EM). Linear mixed effect models revealed that the interaction between WMH and hippocampal volumes explained memory decline (WM: β = .067; 95%CI[.024-0.111]; p < .01; EM: β = .061; 95%CI[.025-.098]; p < .01), with better model fit when the WMH*HV interaction term was added to the model, for both WM (likelihood ratio test, χ2 [1] = 9.3, p < .01) and for EM (likelihood ratio test, χ2 [1] = 10.7, p < .01). Mediation models showed that both baseline WMH volume (β = -.170; p = .001) and hippocampal atrophy (β = 0.126; p = .009) were independently related to EM decline, but the effect of baseline WMH on EM decline was not mediated by hippocampal atrophy (p value indirect effect: 0.572). Memory decline in elderly with SVD was best explained by the interaction of WMH and hippocampal volumes. The relationship between WMH and memory was not causally mediated by hippocampal atrophy, suggesting that memory decline during aging is a heterogeneous condition in which different pathologies contribute to the memory decline observed in elderly with SVD.

KEYWORDS:

cerebral small vessel disease; cognitive decline; hippocampal volume; neuroimaging; working and episodic memory

PMID:
30307080
DOI:
10.1002/hipo.23039

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