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

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.