Patterns of white matter hyperintensities associated with cognition in middle-aged cognitively healthy individuals

Anna Brugulat-Serrat,Anna Brugulat-Serrat,Carole H Sudre,Carole H Sudre,Oriol Grau-Rivera,Oriol Grau-Rivera,Oriol Grau-Rivera,Nina Gramunt,Juan Domingo Gispert,Juan Domingo Gispert,Juan Domingo Gispert,Marc Suárez-Calvet,Marc Suárez-Calvet,Carles Falcon,Carles Falcon,Karine Fauria,Karine Fauria,José Luis Molinuevo,Gonzalo Sánchez-Benavides,Gonzalo Sánchez-Benavides,Gonzalo Sánchez-Benavides,Gemma Salvadó,José Luis Molinuevo,Frederik Barkhof,Frederik Barkhof,Frederik Barkhof,Nina Gramunt,M Jorge Cardoso,M Jorge Cardoso

doi:10.1007/s11682-019-00151-2

Abstract

White matter hyperintensities (WMH) are commonly detected in the brain of elderly individuals and have been associated with a negative impact on multiple cognitive domains. We aim to investigate the impact of global and regional distribution of WMH on episodic memory and executive function in middle-aged cognitively unimpaired participants [N = 561 (45–75 years)] enriched for Alzheimer’s disease risk factors. WMH were automatically segmented from FLAIR, T1 and FSE MR images. WMH load was calculated both globally and regionally. At each cerebral lobe, regional WMH load was measured at four equidistant layers extending from the lateral ventricles to juxtacortical areas. Cognition was measured by The Memory Binding Test (MBT) and WAIS-IV subtests. Global composite z-scores were calculated for the two cognitive domains. Association between global and regional WMH measurements were sought against cognitive measures, both in global composite scores and in individual subtests. We adjusted cognition and WMH burden for the main sociodemographic (age, sex and education) and genetic factors (APOE-ε4). Memory and executive function were significantly associated with global WMH load. Regionally, lower executive performance was mainly associated with higher deep WMH load in frontal areas and, to a lower degree, in occipital, parietal and temporal regions. Lower episodic memory performance was correlated with higher WMH burden in deep frontal and occipital areas. Our novel methodological approach of regional analysis allowed us to reveal the association between cognition and WMH in strategic brain locations. Our results suggest that, even a small WMH load can impact cognition in cognitively unimpaired middle-aged subjects.

Highlights

White matter hyperintensities (WMH) are commonly detected through magnetic resonance imaging (MRI) in the brain of elderly individuals (Longstreth et al 1996) and are presumed to have a vascular etiology (Prins and Scheltens 2015)
We report regional patterns of WMH burden related to lower performance on memory an executive function after correcting by age, sex, education and APOE-ε4
Both global and regional WMH load were significantly associated with lower executive functioning and memory z-score composites

Summary

Introduction

White matter hyperintensities (WMH) are commonly detected through magnetic resonance imaging (MRI) in the brain of elderly individuals (Longstreth et al 1996) and are presumed to have a vascular etiology (Prins and Scheltens 2015). Even though they are relatively frequent in asymptomatic individuals (Kloppenborg et al 2014; Salvadó et al 2019), global WMH load has been shown to exert a negative impact on multiple cognitive domains (Bolandzadeh et al 2012; Lampe et al 2017; Prins et al 2005), on the onset and severity of dementia (Habes et al 2016), and to constitute an independent risk factor for cognitive decline (Bolandzadeh et al 2012). Previous studies have shown that occurrence of WMH are associated, in cognitively unimpaired individuals, to Alzheimer’s disease (AD) risk factors (Salvadó et al 2019), including the presence of two APOE-ε4 alleles, the strongest genetic risk factor for AD (Rojas et al 2017)

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