Blood pressure and haemoglobin A1c are associated with microhaemorrhage in CADASIL: a two-centre cohort study
Abstract
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a hereditary arteriopathy caused by mutations of the Notch3 gene. The risk factors for cerebral microhaemorrhages (CM), their relationship to other MRI lesions in the disease and their potential clinical impact have not been previously defined. Our purpose was to examine the frequency, number and location of microhaemorrhages in a multicentre cohort study, defining predisposing factors and associated radiographic markers in CADASIL patients. We collected clinical data from 147 consecutive patients enrolled in an ongoing prospective cohort study. Degree of neurological disability and cognitive impairment were assessed by standardized scales. T(1)-weighted, FLAIR and T2*-weighted gradient-echo (GE) MRI sequences were performed. Volume and location of lacunar infarcts and white matter hyperintensity (WMH) were assessed. Number and location of CM were recorded. CM were present in 35% patients, most commonly occurring in the thalamus, brainstem and basal ganglia. The location of CM qualitatively differed from areas of lacunar infarction and WMH. There was a significant association between the presence of CM and a history of hypertension (P = 0.005), systolic blood pressure (SBP) (P = 0.014), haemoglobin A1c (HbA1c) (P = 0.004) and the volume of lacunar infarcts (P = 0.010) and WMHs (P = 0.046). The number of CM was independently associated with SBP (P = 0.005), the diagnosis of hypertension (P = 0.0004), volume of WMH (P = 0.0005) and lacunar infarcts (P = 0.004). In contrast, no association was found between blood pressure or HbA1c and the load of WMH or lacunar infarcts. The presence of CM was independently associated with increased modified Rankin scores. CM are independently associated with blood pressure and HbA1c as well as with lacunar infarct and WMH volume in CADASIL. Both the vascular risk factors and regional distribution of CM appear distinct from those associated with other MRI markers, suggesting a distinct pathological process. These lesions have a potential clinical impact in CADASIL. These findings further suggest that modulation of blood pressure and glucose levels might influence the course of the disease.
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Although no treatments have been identified to modify the course of CADASIL, cardiovascular risk factors such as hypertension, elevated hemoglobin A1c, and smoking may be associated with a worse clinical and radiographic phenotype.
“Although no treatments have been identified to modify the course of CADASIL, it is notable that cardiovascular risk factors such as hypertension, elevated hemoglobin A1c, and smoking may be associated with a worse clinical and radiographic phenotype.171,172”
From Vascular Contributions to Cognitive Impairment and Dementia: A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association (2011) · cites this paper as [172]
The Results (Presence of CM and associated factors; Cerebral microhaemorrhages and neurological outcome, pages unavailable) associate hypertension and elevated HbA1c with microhaemorrhages, and systolic blood pressure with poor functional outcome. The Discussion says treatment benefits remain to be tested. But the study does not support including smoking: its tables show no significant association with either microhaemorrhages or poor functional outcome. (LLM, conf=0.90)
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Vasoreactivity in CADASIL: comparison to structural MRI and neuropsychology
Moreton, F. C., Cullen, B., Delles, C., Santosh, C., Gonzalez, R. L., Dani, K., & Muir, K. W. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17710375 · Cited by 37 · see citing works
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Genotype–phenotype correlations of cysteine replacement in CADASIL
Matsushima, T., Conedera, S., Tanaka, R., Li, Y., Yoshino, H., Funayama, M., Ikeda, A., Hosaka, Y., Okuzumi, A., Shimada, Y., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.10.026 · Cited by 19 · see citing works
- Authors
- Viswanathan, A.
- Affiliations
- Harvard University (US)
- Corresponding author
- Viswanathan, A.
- ORCID
- Viswanathan, A.
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-09-01
- Volume
- 129
- Issue
- 9
- Pages
- 2375-2383
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- OpenAlex
- W2148685416
- Cited by
- 205
- References
- 63
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 8 · 2023: 13 · 2022: 7 · 2021: 6 · 2020: 7 · 2019: 4 · 2018: 10 · 2017: 14 · 2016: 12 · 2015: 9 · 2014: 13 · 2013: 11 · 2012: 10
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eisai
- Assistance publique-Hôpitaux de Paris
- Topics
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Health Sciences › Medicine › Psychiatry and Mental health › Neurological Complications and Syndromes
- Keywords
- CADASIL, Notch3, hypertension, systolic blood pressure, HbA1c, lacunar infarction, white matter hyperintensities, vascular risk factors, MRI markers, neurological deficit, cognitive impairment, thalamus, brainstem, basal ganglia, modified Rankin Scale
- MeSH terms
- Adult, Aged, Basal Ganglia, Blood Pressure, Brain, Brain Stem, Cerebral Hemorrhage, Female, Glycated Hemoglobin, Humans, Hypertension, Image Processing, Computer-Assisted, Male, Middle Aged, Risk Factors, Thalamus, Cohort Studies, Magnetic Resonance Angiography, Brain Infarction, CADASIL
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