Volume 19, Issue 1 p. 194-207
FEATURED ARTICLE

White matter hyperintensities and longitudinal cognitive decline in cognitively normal populations and across diagnostic categories: A meta-analysis, systematic review, and recommendations for future study harmonization

Austyn D Roseborough

Austyn D Roseborough

Vulnerable Brain Laboratory, Department of Anatomy and Cell Biology, The Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada

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Lorenzo Saad

Lorenzo Saad

Vulnerable Brain Laboratory, Department of Anatomy and Cell Biology, The Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada

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Maren Goodman

Maren Goodman

Western Libraries, The University of Western Ontario, London, Ontario, Canada

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Lauren E Cipriano

Lauren E Cipriano

Ivey Business School and Department of Epidemiology and Biostatistics, The University of Western Ontario, London, Ontario, Canada

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Vladimir C Hachinski

Vladimir C Hachinski

Department of Clinical Neurological Sciences, The Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada

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Shawn N Whitehead

Corresponding Author

Shawn N Whitehead

Vulnerable Brain Laboratory, Department of Anatomy and Cell Biology, The Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada

Correspondence

Shawn Whitehead, Department of Anatomy and Cell Biology, 458 Medical Sciences Building, The University of Western Ontario, London, ON N6A 3K7, Canada.

Email: [email protected]

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First published: 23 March 2022
Citations: 7

Abstract

Introduction

The primary aim of this paper is to improve the clinical interpretation of white matter hyperintensities (WMHs) and provide an overarching summary of methodological approaches, allowing researchers to design future studies targeting current knowledge gaps.

Methods

A meta-analysis and systematic review was performed investigating associations between baseline WMHs and longitudinal cognitive outcomes in cognitively normal populations, and populations with mild cognitive impairment (MCI), Alzheimer's disease (AD), and stroke.

Results

Baseline WMHs increase the risk of cognitive impairment and dementia across diagnostic categories and most consistently in MCI and post-stroke populations. Apolipoprotein E (APOE) genotype and domain-specific cognitive changes relating to strategic anatomical locations, such as frontal WMH and executive decline, represent important considerations. Meta-analysis reliability was assessed using multiple methods of estimation, and results suggest that heterogeneity in study design and reporting remains a significant barrier.

Discussion

Recommendations and future directions for study of WMHs are provided to improve cross-study comparison and translation of research into consistent clinical interpretation.

CONFLICTS OF INTEREST

The authors declare no conflicts of interest.