. 2022 Jun;44(3):1575-1598.

doi: 10.1007/s11357-022-00539-x. Epub 2022 Mar 16.

Investigating the contribution of white matter hyperintensities and cortical thickness to empathy in neurodegenerative and cerebrovascular diseases

Miracle Ozzoude^{1

2}, Brenda Varriano¹, Derek Beaton³, Joel Ramirez^{2

4}, Melissa F Holmes^{2

4}, Christopher J M Scott^{2

4}, Fuqiang Gao^{2

4}, Kelly M Sunderland³, Paula McLaughlin⁵, Jennifer Rabin^{4

6

7

8}, Maged Goubran^{4

7

9}, Donna Kwan^{10

11}, Angela Roberts^{12

13}, Robert Bartha¹⁴, Sean Symons^{4

15}, Brian Tan³, Richard H Swartz^{4

6

15

16}, Agessandro Abrahao^{4

7}, Gustavo Saposnik^{17

18}, Mario Masellis^{6

15}, Anthony E Lang^{6

19}, Connie Marras^{6

19}, Lorne Zinman^{4

6}, Christen Shoesmith²⁰, Michael Borrie^{21

22}, Corinne E Fischer²³, Andrew Frank^{24

25}, Morris Freedman^{3

6

26}, Manuel Montero-Odasso^{21

27

28}, Sanjeev Kumar^{29

30}, Stephen Pasternak²⁰, Stephen C Strother^{3

9}, Bruce G Pollock^{29

30}, Tarek K Rajji^{29

30

31}, Dallas Seitz³², David F Tang-Wai^{6

33}, John Turnbull^{34

35}, Dar Dowlatshahi²⁴, Ayman Hassan³⁶, Leanne Casaubon⁶, Jennifer Mandzia^{20

21}, Demetrios Sahlas^{34

35}, David P Breen^{37

38

39}, David Grimes²⁴, Mandar Jog^{20

21

40}, Thomas D L Steeves¹⁸, Stephen R Arnott³, Sandra E Black^{2

4

16

31

18}, Elizabeth Finger^{20

21}; ONDRI Investigators; Maria Carmela Tartaglia^{41

42

43}

Collaborators, Affiliations

Collaborators

ONDRI Investigators:
Michael Strong, Peter Kleinstiver, Jane Lawrence-Dewar, Natalie Rashkovan, Susan Bronskil, Julia Fraser, Bill McIlroy, Ben Cornish, Karen Van Ooteghem, Frederico Faria, Yanina Sarquis-Adamson, Alanna Black, Barry Greenberg, Wendy Hatch, Chris Hudson, Elena Leontieva, Ed Margolin, Efrem Mandelcorn, Faryan Tayyari, Sherif Defrawy, Don Brien, Ying Chen, Brian Coe, Doug Munoz, Alisia Southwell, Dennis Bulman, Allison Ann Dilliott, Mahdi Ghani, Rob Hegele, John Robinson, Ekaterina Rogaeva, Sali Farhan, Seyyed Mohammad Hassan Haddad, Nuwan Nanayakkara, Courtney Berezuk, Sabrina Adamo, Malcolm Binns, Wendy Lou, Athena Theyers, Abiramy Uthirakumaran, Guangyong Gy Zou, Sujeevini Sujanthan, Mojdeh Zamyadi, David Munoz, Roger A Dixon, John Woulfe, Brian Levine, J B Orange, Alicia Peltsch, Angela Troyer, Marvin Chum

Affiliations

¹ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Tower, 60 Leonard Avenue, 6th floor 6KD-407, Toronto, ON, M5T 0S8, Canada.
² L.C. Campbell Cognitive Neurology Unit, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
³ Rotman Research Institute of Baycrest Centre, Toronto, ON, Canada.
⁴ Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON, Canada.
⁵ Nova Scotia Health and Dalhousie University, Halifax, NS, Canada.
⁶ Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
⁷ Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
⁸ Rehabilitation Sciences Institute, University of Toronto, Toronto, ON, Canada.
⁹ Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
¹⁰ Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
¹¹ Queen's University, Kingston, ON, Canada.
¹² Roxelyn and Richard Pepper Department of Communication Sciences and Disorders, Northwestern University, Evanston, IL, USA.
¹³ School of Communication Sciences and Disorders, Faculty of Health Sciences, Western University, London, ON, Canada.
¹⁴ Robarts Research Institute, Western University, London, ON, Canada.
¹⁵ Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
¹⁶ Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
¹⁷ Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
¹⁸ Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
¹⁹ Edmond J Safra Program for Parkinson Disease, Movement Disorder Clinic, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.
²⁰ Department of Clinical Neurological Sciences, Western University, London, ON, Canada.
²¹ Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
²² St. Joseph's Healthcare Centre, London, ON, Canada.
²³ Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
²⁴ Department of Medicine (Neurology), University of Ottawa Brain and Mind Research Institute and Ottawa Hospital Research Institute, Ottawa, ON, Canada.
²⁵ Bruyère Research Institute, Ottawa, ON, Canada.
²⁶ Division of Neurology, Baycrest Health Sciences, Toronto, ON, Canada.
²⁷ Lawson Health Research Institute, London, ON, Canada.
²⁸ Gait and Brain Lab, Parkwood Institute, London, ON, Canada.
²⁹ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
³⁰ Adult Neurodevelopment and Geriatric Psychiatry, Centre for Addiction and Mental Health, Toronto, ON, Canada.
³¹ Toronto Dementia Research Alliance, University of Toronto, Toronto, ON, Canada.
³² Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
³³ Memory Clinic, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.
³⁴ Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
³⁵ Department of Medicine, McMaster University, Hamilton, ON, Canada.
³⁶ Thunder Bay Regional Health Research Institute, Thunder Bay, ON, Canada.
³⁷ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
³⁸ Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, UK.
³⁹ Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
⁴⁰ London Health Sciences Centre, London, ON, Canada.
⁴¹ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Tower, 60 Leonard Avenue, 6th floor 6KD-407, Toronto, ON, M5T 0S8, Canada. carmela.tartaglia@uhn.ca.
⁴² Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada. carmela.tartaglia@uhn.ca.
⁴³ Memory Clinic, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. carmela.tartaglia@uhn.ca.

PMID: 35294697
PMCID: PMC9213606
DOI: 10.1007/s11357-022-00539-x

Investigating the contribution of white matter hyperintensities and cortical thickness to empathy in neurodegenerative and cerebrovascular diseases

Miracle Ozzoude et al. Geroscience. 2022 Jun.

. 2022 Jun;44(3):1575-1598.

doi: 10.1007/s11357-022-00539-x. Epub 2022 Mar 16.

Authors

Collaborators

ONDRI Investigators:
Michael Strong, Peter Kleinstiver, Jane Lawrence-Dewar, Natalie Rashkovan, Susan Bronskil, Julia Fraser, Bill McIlroy, Ben Cornish, Karen Van Ooteghem, Frederico Faria, Yanina Sarquis-Adamson, Alanna Black, Barry Greenberg, Wendy Hatch, Chris Hudson, Elena Leontieva, Ed Margolin, Efrem Mandelcorn, Faryan Tayyari, Sherif Defrawy, Don Brien, Ying Chen, Brian Coe, Doug Munoz, Alisia Southwell, Dennis Bulman, Allison Ann Dilliott, Mahdi Ghani, Rob Hegele, John Robinson, Ekaterina Rogaeva, Sali Farhan, Seyyed Mohammad Hassan Haddad, Nuwan Nanayakkara, Courtney Berezuk, Sabrina Adamo, Malcolm Binns, Wendy Lou, Athena Theyers, Abiramy Uthirakumaran, Guangyong Gy Zou, Sujeevini Sujanthan, Mojdeh Zamyadi, David Munoz, Roger A Dixon, John Woulfe, Brian Levine, J B Orange, Alicia Peltsch, Angela Troyer, Marvin Chum

Affiliations

¹ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Tower, 60 Leonard Avenue, 6th floor 6KD-407, Toronto, ON, M5T 0S8, Canada.
² L.C. Campbell Cognitive Neurology Unit, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
³ Rotman Research Institute of Baycrest Centre, Toronto, ON, Canada.
⁴ Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, ON, Canada.
⁵ Nova Scotia Health and Dalhousie University, Halifax, NS, Canada.
⁶ Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
⁷ Harquail Centre for Neuromodulation, Hurvitz Brain Sciences Program, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
⁸ Rehabilitation Sciences Institute, University of Toronto, Toronto, ON, Canada.
⁹ Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
¹⁰ Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada.
¹¹ Queen's University, Kingston, ON, Canada.
¹² Roxelyn and Richard Pepper Department of Communication Sciences and Disorders, Northwestern University, Evanston, IL, USA.
¹³ School of Communication Sciences and Disorders, Faculty of Health Sciences, Western University, London, ON, Canada.
¹⁴ Robarts Research Institute, Western University, London, ON, Canada.
¹⁵ Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
¹⁶ Heart & Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
¹⁷ Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
¹⁸ Division of Neurology, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, ON, Canada.
¹⁹ Edmond J Safra Program for Parkinson Disease, Movement Disorder Clinic, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.
²⁰ Department of Clinical Neurological Sciences, Western University, London, ON, Canada.
²¹ Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
²² St. Joseph's Healthcare Centre, London, ON, Canada.
²³ Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
²⁴ Department of Medicine (Neurology), University of Ottawa Brain and Mind Research Institute and Ottawa Hospital Research Institute, Ottawa, ON, Canada.
²⁵ Bruyère Research Institute, Ottawa, ON, Canada.
²⁶ Division of Neurology, Baycrest Health Sciences, Toronto, ON, Canada.
²⁷ Lawson Health Research Institute, London, ON, Canada.
²⁸ Gait and Brain Lab, Parkwood Institute, London, ON, Canada.
²⁹ Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
³⁰ Adult Neurodevelopment and Geriatric Psychiatry, Centre for Addiction and Mental Health, Toronto, ON, Canada.
³¹ Toronto Dementia Research Alliance, University of Toronto, Toronto, ON, Canada.
³² Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
³³ Memory Clinic, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.
³⁴ Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada.
³⁵ Department of Medicine, McMaster University, Hamilton, ON, Canada.
³⁶ Thunder Bay Regional Health Research Institute, Thunder Bay, ON, Canada.
³⁷ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
³⁸ Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, UK.
³⁹ Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
⁴⁰ London Health Sciences Centre, London, ON, Canada.
⁴¹ Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Krembil Discovery Tower, 60 Leonard Avenue, 6th floor 6KD-407, Toronto, ON, M5T 0S8, Canada. carmela.tartaglia@uhn.ca.
⁴² Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada. carmela.tartaglia@uhn.ca.
⁴³ Memory Clinic, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. carmela.tartaglia@uhn.ca.

PMID: 35294697
PMCID: PMC9213606
DOI: 10.1007/s11357-022-00539-x

Abstract

Change in empathy is an increasingly recognised symptom of neurodegenerative diseases and contributes to caregiver burden and patient distress. Empathy impairment has been associated with brain atrophy but its relationship to white matter hyperintensities (WMH) is unknown. We aimed to investigate the relationships amongst WMH, brain atrophy, and empathy deficits in neurodegenerative and cerebrovascular diseases. Five hundred thirteen participants with Alzheimer's disease/mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia (FTD), Parkinson's disease, or cerebrovascular disease (CVD) were included. Empathy was assessed using the Interpersonal Reactivity Index. WMH were measured using a semi-automatic segmentation and FreeSurfer was used to measure cortical thickness. A heterogeneous pattern of cortical thinning was found between groups, with FTD showing thinning in frontotemporal regions and CVD in left superior parietal, left insula, and left postcentral. Results from both univariate and multivariate analyses revealed that several variables were associated with empathy, particularly cortical thickness in the fronto-insulo-temporal and cingulate regions, sex (female), global cognition, and right parietal and occipital WMH. Our results suggest that cortical atrophy and WMH may be associated with empathy deficits in neurodegenerative and cerebrovascular diseases. Future work should consider investigating the longitudinal effects of WMH and atrophy on empathy deficits in neurodegenerative and cerebrovascular diseases.

Keywords: Cerebrovascular disease; Cortical thickness; Empathy; Neurodegenerative disease; Social cognition; White matter hyperintensities.

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Conflict of interest statement

TKR has received research support from Brain Canada, Brain and Behavior Research Foundation, BrightFocus Foundation, Canada Foundation for Innovation, Canada Research Chair, Canadian Institutes of Health Research, Centre for Aging and Brain Health Innovation, National Institutes of Health, Ontario Ministry of Health and Long-Term Care, Ontario Ministry of Research and Innovation, and the Weston Brain Institute. TKR also received in-kind equipment support for an investigator-initiated study from Magstim, and in-kind research accounts from Scientific Brain Training Pro. DPB is supported by a Wellcome Clinical Research Career Development Fellowship (214571/Z/18/Z). Other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

**Fig. 1**
Boxplots showing empathy scores classified by groups. a Study partner IRI-EC; b study partner IRI-PT; c participant IRI-EC; d participant IRI-PT. Notes: AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; CVD, cerebrovascular disease; EC, emotional concern; FTD, frontotemporal disease; IRI, Interpersonal Reactivity Index; MCI, mild cognitive impairment; PD, Parkinson’s disease; PT, perspective taking

**Fig. 2**
Cortical thickness analysis showing regions with cortical thinning in a CVD vs ALS; b CVD vs PD; c FTD vs AD/MCI; d FTD vs ALS; e FTD vs PD; f FTD vs CVD. Notes: AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; CVD, cerebrovascular disease; FTD, frontotemporal disease; MCI, mild cognitive impairment; LLOF, left lateral orbitofrontal; LParsO, left pars-opercularis; LPosC, left postcentral; LSP, left superior parietal; LInsu, left insula; LIT, left inferior temporal; RLOF, right lateral orbitofrontal; RST, right superior temporal; RMT, right middle temporal; RSF, right superior frontal; RIT, right inferior temporal; PD, Parkinson’s disease

**Fig. 3**
Partial least squares correlation diagram. a Component scores for IRI subscales; b component score for stable contributors. The values for all IRI subscales appear in the same direction where IRIother-PT shows the highest amount of variance on component 1. IRIself-PT was not a stable contributor to component 1. The stable contributors go in the same direction as the IRI scores, indicating a positive correlation between them. EC, empathic concern; IRI, Interpersonal Reactivity Index; PT, perspective taking

**Fig. 4**
Relationship between diagnosis, IRI, and contributors using partial least squares correlation. IRI, Interpersonal Reactivity Index; FS, FreeSurfer cortical thickness (68 regions); WMH, lobar white matter hyperintensities (10 regions); MoCA, Montreal Cognitive Assessment; AD, Alzheimer’s disease; ALS, amyotrophic lateral sclerosis; CVD, cerebrovascular disease; FTD, frontotemporal disease; MCI, mild cognitive impairment; PD, Parkinson’s disease

See this image and copyright information in PMC

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Investigating the contribution of white matter hyperintensities and cortical thickness to empathy in neurodegenerative and cerebrovascular diseases

Collaborators

Affiliations

Investigating the contribution of white matter hyperintensities and cortical thickness to empathy in neurodegenerative and cerebrovascular diseases

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

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LinkOut - more resources

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