Association between vascular risk factors burden and neurodegenerative diseases: results from ONDRI

Manuel Montero-Odasso^#^{1

2

3}, Frederico Pieruccini-Faria^#^{4

5}, Sandra E Black^{6

7}, Malcolm A Binns^{8

9

10}, Morris Freedman^{8

11

12}, David A Grimes¹³, Robert A Hegele¹⁴, Seyyed Hassan Haddad¹⁴, Anthony E Lang¹⁵, Mario Masellis¹¹, Jennifer Mandzia^{16

17}, Derek Beaton¹⁸, Joel Ramirez⁷, Angela C Roberts^{19

20

21

22}, William McIlroy²³, Stephen H Pasternak^{5

14

16}, Lorne Zinman^{24

25}, Agessandro Abrahao^{24

25}, Rick H Swartz^{7

25}, Sean Symons²⁶, Brian Tan⁸, Carmela Tartaglia²⁷, Surim Son^{28

5}, Ryota Sakurai²⁹, Allison Dilliott³⁰, Benjamin F Cornish²³, Areej Hezam⁵, Michael J Strong^{14

16}; ONDRI Investigators; Robert Bartha^{31

14}

Affiliations

¹ Department of Medicine, Division of Geriatric Medicine, Parkwood Hospital, Western University, London, ON, Canada. mmontero@uwo.ca.
² Department of Epidemiology and Biostatistics, Western University, London, ON, Canada. mmontero@uwo.ca.
³ Lawson Health Research Institute, London, ON, Canada. mmontero@uwo.ca.
⁴ Department of Medicine, Division of Geriatric Medicine, Parkwood Hospital, Western University, London, ON, Canada.
⁵ Lawson Health Research Institute, London, ON, Canada.
⁶ Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
⁷ Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
⁸ Rotman Research Institute, Baycrest Health Sciences, Toronto, ON, Canada.
⁹ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
¹⁰ St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
¹¹ Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹² Department of Medicine, Mt. Sinai Hospital, Toronto, ON, Canada.
¹³ Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹⁴ Robarts Research Institute, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.
¹⁵ Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, The Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁶ Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
¹⁷ Southwestern Ontario Stroke Network, LHSC Stroke Program, London, ON, Canada.
¹⁸ Data Science & Advanced Analytics, Unity Health Toronto, University of Toronto, Toronto, ON, Canada.
¹⁹ Department of Computer Science, University of Western Ontario, London, ON, Canada.
²⁰ School of Communication Sciences and Disorders, Western University, London, ON, Canada.
²¹ Canadian Centre for Activity and Aging, Western University, London, ON, Canada.
²² Western Institute for Neuroscience, Western University, London, ON, Canada.
²³ Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, ON, Canada.
²⁴ Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²⁵ Division of Neurology and Department of Medicine, University of Toronto, Toronto, ON, Canada.
²⁶ Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²⁷ Division of Neurology, Department of Medicine, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
²⁸ Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
²⁹ Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.
³⁰ Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Quebec, Canada.
³¹ Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.

^# Contributed equally.

PMID: 40413670
DOI: 10.1007/s00415-025-13152-7

Association between vascular risk factors burden and neurodegenerative diseases: results from ONDRI

Manuel Montero-Odasso et al. J Neurol. 2025.

. 2025 May 25;272(6):418.

doi: 10.1007/s00415-025-13152-7.

Authors

Affiliations

¹ Department of Medicine, Division of Geriatric Medicine, Parkwood Hospital, Western University, London, ON, Canada. mmontero@uwo.ca.
² Department of Epidemiology and Biostatistics, Western University, London, ON, Canada. mmontero@uwo.ca.
³ Lawson Health Research Institute, London, ON, Canada. mmontero@uwo.ca.
⁴ Department of Medicine, Division of Geriatric Medicine, Parkwood Hospital, Western University, London, ON, Canada.
⁵ Lawson Health Research Institute, London, ON, Canada.
⁶ Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada.
⁷ Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
⁸ Rotman Research Institute, Baycrest Health Sciences, Toronto, ON, Canada.
⁹ Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
¹⁰ St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
¹¹ Division of Neurology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹² Department of Medicine, Mt. Sinai Hospital, Toronto, ON, Canada.
¹³ Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
¹⁴ Robarts Research Institute, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.
¹⁵ Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Toronto Western Hospital, The Department of Medicine, University of Toronto, Toronto, ON, Canada.
¹⁶ Department of Clinical Neurological Sciences, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
¹⁷ Southwestern Ontario Stroke Network, LHSC Stroke Program, London, ON, Canada.
¹⁸ Data Science & Advanced Analytics, Unity Health Toronto, University of Toronto, Toronto, ON, Canada.
¹⁹ Department of Computer Science, University of Western Ontario, London, ON, Canada.
²⁰ School of Communication Sciences and Disorders, Western University, London, ON, Canada.
²¹ Canadian Centre for Activity and Aging, Western University, London, ON, Canada.
²² Western Institute for Neuroscience, Western University, London, ON, Canada.
²³ Department of Kinesiology and Health Sciences, University of Waterloo, Waterloo, ON, Canada.
²⁴ Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²⁵ Division of Neurology and Department of Medicine, University of Toronto, Toronto, ON, Canada.
²⁶ Department of Medical Imaging, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
²⁷ Division of Neurology, Department of Medicine, Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada.
²⁸ Department of Epidemiology and Biostatistics, Western University, London, ON, Canada.
²⁹ Research Team for Social Participation and Community Health, Tokyo Metropolitan Institute for Geriatrics and Gerontology, Tokyo, Japan.
³⁰ Department of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Quebec, Canada.
³¹ Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.

^# Contributed equally.

PMID: 40413670
DOI: 10.1007/s00415-025-13152-7

Abstract

Background: Vascular risk factors are common in older adults and contribute to brain damage, can manifest as increased white matter hyperintensities (WMH), and associated with future risk of stroke and dementia. However, their prevalence, effect across different neurodegenerative diseases, and association with WMH remains underexplored.

Objective: To investigate the association between vascular risk burden, and brain white matter integrity, across five neurodegenerative conditions.

Methods: Cross-sectional study including 520 participants from the Ontario Neurodegenerative Disease Research Initiative (ONDRI) cohorts: 126 with amnestic Mild Cognitive Impairment/Alzheimer's Disease (MCI/AD), 53 with Frontotemporal Dementia (FTD), 161 with Cerebrovascular Disease (CVD), 140 with Parkinson's Disease (PD), and 40 with Amyotrophic Lateral Sclerosis (ALS), along with 41 cognitively healthy controls. A vascular risk index (VRI, range 0-5) assessed hypertension, diabetes, dyslipidemia, obesity (BMI ≥ 30), and smoking history. Macro (WMH volume) and micro (Diffusion tensor imaging) white matter integrity were evaluated using 3-Tesla MRI. Associations were analyzed using multinomial logistic regression and ANCOVA, adjusting for age, sex, education, and APOE ε4 allele status.

Results: Vascular risk factors, particularly hypertension and hypercholesterolemia, were more prevalent in the disease cohorts than controls. A higher VRI was significantly associated with MCI/AD (1.5-fold, p = 0.05), FTD (1.7-fold, p =0 .02), and CVD (2.6-fold, p < 0.005) cohorts. High VRI was associated with reduced macro and microstructural white matter integrity in the pooled sample (macro: p = 0.005; micro: p = 0.003), and separately in CVD (macro: p = 0.04; micro: p = 0.002). APOE ε4 status only mildly attenuated these associations.

Conclusion: Vascular risk burden is prevalent in neurocognitive syndromes including MCI/AD, FTD and CVD, and impacts white matter integrity. Future studies are needed to explore if vascular risk management may mitigate the consequences of neurodegeneration in these clinical groups.

Keywords: Aged; Cardiovascular factors; Cohort study; Dementia; Neurodegeneration; Vascular risk; White matter hyperintensity.

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Conflict of interest statement

Declarations. Conflicts of interest: MMO is President and member of the executive of the Canadian Geriatrics Society and of the World Falls Prevention Society, member of the Advisory Board of the CIHR Institute of Aging, Member of the Research Executive Committee of the Canadian Consortium on Neurodegeneration in Aging (CCNA) and Associate Editor of the Journal of Alzheimer’s Disease, the Journal Gerontology Medical Sciences and Geriatrics, and holds the Wolfe Research Professorship in Aging.

References

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1. Matej R, Tesar A, Rusina R (2019) Alzheimer’s disease and other neurodegenerative dementias in comorbidity: a clinical and neuropathological overview. Clin Biochem 73:26–31 - PubMed - DOI
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1. Hachinski V, Munoz DG (1997) Cerebrovascular pathology in Alzheimer’s disease: cause, effect or epiphenomenon? Ann N Y Acad Sci 826:1–6 - PubMed - DOI
1. Carvalho de Abreu DC, Pieruccini-Faria F, Sarquis-Adamson Y, Black A, Fraser J, Van Ooteghem K et al (2023) White matter hyperintensity burden predicts cognitive but not motor decline in Parkinson’s disease: results from the Ontario Neurodegenerative Diseases Research Initiative. Eur J Neurol. 30(4):920–33 - PubMed - DOI

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Association between vascular risk factors burden and neurodegenerative diseases: results from ONDRI

Affiliations

Association between vascular risk factors burden and neurodegenerative diseases: results from ONDRI

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous