Global Cardiovascular Risk Profile and Cerebrovascular Abnormalities in Presymptomatic Individuals with CADASIL or
Dorothee Schoemaker1,2, Lina Velilla-Jimenez3, Yesica Zuluaga3
1Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Insights
Cardiovascular risk factors impact brain health. In cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), higher cardiovascular risk correlated with brain changes, suggesting benefits from risk factor management.
Area of Science:
- Neurology
- Cardiology
- Neuroimaging
- Genetics
Background:
- Cardiovascular risk factors are known to increase the likelihood of developing dementia, including Alzheimer's disease and vascular dementia.
- Autosomal dominant mutations can lead to the early onset of dementia, providing a model to study disease mechanisms.
Purpose of the Study:
- To investigate the influence of the global cardiovascular risk profile on early cognitive and neuroimaging features in individuals with autosomal dominant mutations causing early-onset dementia.
- To compare these effects in autosomal dominant Alzheimer's disease (ADAD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).
Main Methods:
- Study included 85 participants: 20 with PSEN1 E280A mutation (ADAD), 20 with NOTCH3 mutations (CADASIL), and 45 non-carriers.
- All subjects underwent clinical, neuropsychological, and MRI evaluations.
- Global cardiovascular risk was assessed using the Framingham Cardiovascular Risk Profile (FCRP) score.
Main Results:
- In CADASIL patients, a higher FCRP score was linked to reduced hippocampal volume and increased severity of cerebral microbleeds, lacunes, and basal ganglia perivascular space enlargement.
- No significant association between FCRP score and neuroimaging measures was found in ADAD or non-carrier subjects.
- FCRP score correlated with executive function in non-carriers but not in CADASIL or ADAD patients.
Conclusions:
- Individuals with CADASIL and other forms of vascular cognitive impairment may particularly benefit from interventions targeting cardiovascular risk factors.
- Early management of cardiovascular health is crucial for mitigating neuroimaging changes associated with vascular dementia subtypes.
Background:
Cardiovascular risk factors increase the risk of developing dementia, including Alzheimer's disease and vascular dementia.
Objective:
Studying individuals with autosomal dominant mutations leading to the early onset of dementia, this study examines the effect of the global cardiovascular risk profile on early cognitive and neuroimaging features of Alzheimer's disease and vascular dementia.
Methods:
We studied 85 non-demented and stroke-free individuals, including 20 subjects with Presenilin1 (PSEN1) E280A mutation leading to the early onset of autosomal dominant Alzheimer's disease (ADAD), 20 subjects with NOTCH3 mutations leading to cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to the early onset of vascular dementia, and 45 non-affected family members (non-carriers). All subjects underwent clinical and neuropsychological evaluations and an MRI. The global cardiovascular risk profile was estimated using the office-based Framingham Cardiovascular Risk Profile (FCRP) score.
Results:
In individuals with CADASIL, a higher FCRP score was associated with a reduced hippocampal volume (B = -0.06, p < 0.05) and an increased severity of cerebral microbleeds (B = 0.13, p < 0.001), lacunes (B = 0.30, p < 0.001), and perivascular space enlargement in the basal ganglia (B = 0.50, p < 0.05). There was no significant association between the FCRP score and neuroimaging measures in ADAD or non-carrier subjects. While the FCRP score was related to performance in executive function in non-carrier subjects (B = 0.06, p < 0.05), it was not significantly associated with cognitive performance in individuals with CADASIL or ADAD.
Conclusion:
Our results suggest that individuals with CADASIL and other forms of vascular cognitive impairment might particularly benefit from early interventions aimed at controlling cardiovascular risks.
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