Strategic white matter hyperintensity locations for cognitive impairment: A multicenter lesion-symptom mapping study in 3525 memory clinic patients

Mirthe Coenen¹, Hugo J Kuijf², Irene M C Huenges Wajer^{1

3}, Marco Duering^{4

5}, Frank J Wolters^{6

7

8}, Evan F Fletcher⁹, Pauline M Maillard⁹; Alzheimer's Disease Neuroimaging Initiative¹; Frederik Barkhof^{10

11}, Josephine Barnes¹², Thomas Benke¹³, Jooske M F Boomsma¹⁴, Christopher P L H Chen^{15

16}, Peter Dal-Bianco¹⁷, Anna Dewenter⁴, Christian Enzinger^{18

19}, Michael Ewers⁴, Lieza G Exalto^{1

2}, Nicolai Franzmeier⁴, Onno Groeneveld^{1

20}, Saima Hilal^{15

16

21}, Edith Hofer^{22

23}, Dineke L Koek²⁴, Andrea B Maier^{16

25}, Cheryl R McCreary²⁶, Catarina S Padilla¹, Janne M Papma^{8

27}, Ross W Paterson¹², Yolande A L Pijnenburg¹⁴, Anna Rubinski⁴, Reinhold Schmidt²², Jonathan M Schott¹², Catherine F Slattery¹², Eric E Smith²⁶, Rebecca M E Steketee^{6

8}, Carole H Sudre²⁸, Esther van den Berg^{8

27}, Wiesje M van der Flier¹⁴, Narayanaswamy Venketasubramanian^{16

29}, Meike W Vernooij^{6

7

8}, Xu Xin^{15

16}, Charles DeCarli⁹, Geert Jan Biessels¹, J Matthijs Biesbroek^{1

30}

Affiliations

¹ Department of Neurology and Neurosurgery, UMC Utrecht, Brain Center, Utrecht, The Netherlands.
² Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
³ Experimental Psychology, Helmholtz Institute, Utrecht University, Utrecht, The Netherlands.
⁴ Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
⁵ Medical Image Analysis Center (MIAC) and Department of Biomedical Engineering, University of Basel, Basel, Switzerland.
⁶ Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
⁷ Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
⁸ Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
⁹ Department of Neurology, University of California at Davis, Davis, California, USA.
¹⁰ Radiology & Nuclear Medicine, Amsterdam UMC, location Vrije Universiteit, Amsterdam, The Netherlands.
¹¹ UCL Institute of Neurology, London, UK.
¹² Dementia Research Centre, UCL Queen Square Institute of Neurology, UCL, London, UK.
¹³ Clinic of Neurology, Medical University Innsbruck, Innsbruck, Austria.
¹⁴ Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
¹⁵ Department of Pharmacology, National University of Singapore, Singapore, Singapore.
¹⁶ Memory, Aging and Cognition Center, National University Health System, Singapore, Singapore.
¹⁷ Department of Neurology, Medical University Vienna, Vienna, Austria.
¹⁸ Division of General Neurology, Department of Neurology, Medical University Graz, Graz, Austria.
¹⁹ Division of Neuroradiology, Interventional and Vascular Radiology, Department of Radiology, Medical University of Graz, Graz, Austria.
²⁰ Department of Neurology, Isala MS Centre, Isala Hospital, Meppel, The Netherlands.
²¹ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
²² Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.
²³ Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
²⁴ Department of Geriatric Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
²⁵ Department of Medicine, National University of Singapore, Singapore, Singapore.
²⁶ Department of Clinical Neurosciences and Radiology and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
²⁷ Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
²⁸ MRC Unit for Lifelong Health and Ageing, the Centre for Medical Image Computing, UCL, London, UK.
²⁹ Raffles Neuroscience Center, Raffles Hospital, Singapore, Singapore.
³⁰ Department of Neurology, Diakonessenhuis Hospital, Utrecht, The Netherlands.

PMID: 36504357
DOI: 10.1002/alz.12827

Multicenter Study

Strategic white matter hyperintensity locations for cognitive impairment: A multicenter lesion-symptom mapping study in 3525 memory clinic patients

Mirthe Coenen et al. Alzheimers Dement. 2023 Jun.

. 2023 Jun;19(6):2420-2432.

doi: 10.1002/alz.12827. Epub 2022 Dec 12.

Authors

Affiliations

¹ Department of Neurology and Neurosurgery, UMC Utrecht, Brain Center, Utrecht, The Netherlands.
² Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
³ Experimental Psychology, Helmholtz Institute, Utrecht University, Utrecht, The Netherlands.
⁴ Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.
⁵ Medical Image Analysis Center (MIAC) and Department of Biomedical Engineering, University of Basel, Basel, Switzerland.
⁶ Department of Radiology & Nuclear Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
⁷ Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
⁸ Alzheimer Center Erasmus MC, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
⁹ Department of Neurology, University of California at Davis, Davis, California, USA.
¹⁰ Radiology & Nuclear Medicine, Amsterdam UMC, location Vrije Universiteit, Amsterdam, The Netherlands.
¹¹ UCL Institute of Neurology, London, UK.
¹² Dementia Research Centre, UCL Queen Square Institute of Neurology, UCL, London, UK.
¹³ Clinic of Neurology, Medical University Innsbruck, Innsbruck, Austria.
¹⁴ Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
¹⁵ Department of Pharmacology, National University of Singapore, Singapore, Singapore.
¹⁶ Memory, Aging and Cognition Center, National University Health System, Singapore, Singapore.
¹⁷ Department of Neurology, Medical University Vienna, Vienna, Austria.
¹⁸ Division of General Neurology, Department of Neurology, Medical University Graz, Graz, Austria.
¹⁹ Division of Neuroradiology, Interventional and Vascular Radiology, Department of Radiology, Medical University of Graz, Graz, Austria.
²⁰ Department of Neurology, Isala MS Centre, Isala Hospital, Meppel, The Netherlands.
²¹ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.
²² Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.
²³ Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
²⁴ Department of Geriatric Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
²⁵ Department of Medicine, National University of Singapore, Singapore, Singapore.
²⁶ Department of Clinical Neurosciences and Radiology and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
²⁷ Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
²⁸ MRC Unit for Lifelong Health and Ageing, the Centre for Medical Image Computing, UCL, London, UK.
²⁹ Raffles Neuroscience Center, Raffles Hospital, Singapore, Singapore.
³⁰ Department of Neurology, Diakonessenhuis Hospital, Utrecht, The Netherlands.

PMID: 36504357
DOI: 10.1002/alz.12827

Abstract

Introduction: Impact of white matter hyperintensities (WMH) on cognition likely depends on lesion location, but a comprehensive map of strategic locations is lacking. We aimed to identify these locations in a large multicenter study.

Methods: Individual patient data (n = 3525) from 11 memory clinic cohorts were harmonized. We determined the association of WMH location with attention and executive functioning, information processing speed, language, and verbal memory performance using voxel-based and region of interest tract-based analyses.

Results: WMH in the left and right anterior thalamic radiation, forceps major, and left inferior fronto-occipital fasciculus were significantly related to domain-specific impairment, independent of total WMH volume and atrophy. A strategic WMH score based on these tracts inversely correlated with performance in all domains.

Discussion: The data show that the impact of WMH on cognition is location-dependent, primarily involving four strategic white matter tracts. Evaluation of WMH location may support diagnosing vascular cognitive impairment.

Highlights: We analyzed white matter hyperintensities (WMH) in 3525 memory clinic patients from 11 cohorts The impact of WMH on cognition depends on location We identified four strategic white matter tracts A single strategic WMH score was derived from these four strategic tracts The strategic WMH score was an independent determinant of four cognitive domains.

Keywords: cognitive impairment; lesion symptom mapping; location; memory clinic patients; white matter hyperintensities.

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References

REFERENCES

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1. Prins ND, Scheltens P. White matter hyperintensities, cognitive impairment and dementia: an update. Nat Rev Neurol. 2015;11(3):157-165. doi:10.1038/nrneurol.2015.10
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Strategic white matter hyperintensity locations for cognitive impairment: A multicenter lesion-symptom mapping study in 3525 memory clinic patients

Affiliations

Strategic white matter hyperintensity locations for cognitive impairment: A multicenter lesion-symptom mapping study in 3525 memory clinic patients

Authors

Affiliations

Abstract

References

REFERENCES

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources