The brain health index: Towards a combined measure of neurovascular and neurodegenerative structural brain injury

Author:

Dickie David Alexander123ORCID,Valdés Hernández Maria del C234,Makin Stephen D13,Staals Julie5,Wiseman Stewart J234ORCID,Bastin Mark E23,Wardlaw Joanna M234ORCID

Affiliation:

1. Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK

2. Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, University of Glasgow, Glasgow, UK

3. Centre for Clinical Brain Sciences, Chancellor's Building, Edinburgh, UK

4. UK Dementia Research Institute at the University of Edinburgh, Edinburgh, UK

5. Department of Neurology and Cardiovascular Research Institute Maastricht (CARIM), Maastricht University Medical Center, Maastricht, the Netherlands

Abstract

Background A structural magnetic resonance imaging measure of combined neurovascular and neurodegenerative burden may be useful as these features often coexist in older people, stroke and dementia. Aim We aimed to develop a new automated approach for quantifying visible brain injury from small vessel disease and brain atrophy in a single measure, the brain health index. Materials and methods We computed brain health index in N = 288 participants using voxel-based Gaussian mixture model cluster analysis of T1, T2, T2*, and FLAIR magnetic resonance imaging. We tested brain health index against a validated total small vessel disease visual score and white matter hyperintensity volumes in two patient groups (minor stroke, N = 157; lupus, N = 51) and against measures of brain atrophy in healthy participants (N = 80) using multiple regression. We evaluated associations with Addenbrooke’s Cognitive Exam Revised in patients and with reaction time in healthy participants. Results The brain health index (standard beta = 0.20–0.59, P < 0.05) was significantly and more strongly associated with Addenbrooke’s Cognitive Exam Revised, including at one year follow-up, than white matter hyperintensity volume (standard beta = 0.04–0.08, P > 0.05) and small vessel disease score (standard beta = 0.02–0.27, P > 0.05) alone in both patient groups. Further, the brain health index (standard beta = 0.57–0.59, P < 0.05) was more strongly associated with reaction time than measures of brain atrophy alone (standard beta = 0.04–0.13, P > 0.05) in healthy participants. Conclusions The brain health index is a new image analysis approach that may usefully capture combined visible brain damage in large-scale studies of ageing, neurovascular and neurodegenerative disease.

Funder

National Institutes of Health

European Union Horizon 2020

Fondation Leducq

Lupus UK

Technology Strategy Board

Wellcome Trust

Row Fogo Charitable Trust

Publisher

SAGE Publications

Subject

Neurology

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