Global Cardiovascular Risk Profile and Cerebrovascular Abnormalities in Presymptomatic Individuals with CADASIL or Autosomal Dominant Alzheimer’s Disease

Author:

Schoemaker Dorothee12,Velilla-Jimenez Lina3,Zuluaga Yesica3,Baena Ana3,Ospina Carolina3,Bocanegra Yamile3,Alvarez Sergio4,Ochoa-Escudero Martin4,Guzmán-Vélez Edmarie1,Martinez Jairo1,Lopera Francisco3,Arboleda-Velasquez Joseph F.2,Quiroz Yakeel T.135

Affiliation:

1. Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

2. Department of Ophthalmology, Schepens Eye Research Institute of Mass Eye and Ear, Harvard Medical School, Boston, MA, USA

3. Grupo de Neurociencias, Universidad de Antioquia, Medellín, Colombia

4. Department of Radiology, Hospital Pablo Tobon Uribe, Medellín, Colombia

5. Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Abstract

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.

Publisher

IOS Press

Subject

Psychiatry and Mental health,Geriatrics and Gerontology,Clinical Psychology,General Medicine,General Neuroscience

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