Impact of educational level and lesion volume on cognitive performance in subcortical ischaemic vascular dementia: a study in CADASIL

Background and purpose: Vascular dementia is the second most common form of dementia following Alzheimer's Disease (AD), with subcortical ischemic vascular dementia (SIVD) being an important variant. Current research underlines the importance of vascular factors in AD and the high amount of comorbidity. CADASIL, a monogenic variant of small vessel disease, can be regarded as a model of “pure“ SIVD and is characterized by a specific pattern of cognitive deficits with impairment in processing speed and executive functions. Cerebral lacunar lesion volume has been shown to be an important substrate of cognitive deficits in CADASIL.

The cognitive reserve hypothesis states that premorbid cognitive ability, usually measured by educational level, has a protective influence on cognitive decline. Our aim was to explore the impact of educational level on cognition and its relation to lesion volume in CADASIL patients as a model for SIVD.

Methods: A cohort of 232 CADASIL patients (104m/128f, mean age 50.1+-11.2 y) from an ongoing prospective two-center cohort study were cross-sectionally studied and divided into 2 matched groups with ≤10 years and >10 years of education. Based on the distribution of lacunar lesion volume the two groups were divided into tertiles: low (M=0.146+-0.147ml), medium (M=0.727+-0.149ml) and high lesion volume (M=2.518+-1.325ml). We conducted a 2 (educational level) x 3 (lesion volume) multivariate analysis of variance using age and education corrected Z scores of neuropsychological tests addressing cognitive deficits associated with SIVD.

Results: Significant effects of impaired performance with increasing lesion volume were found for processing speed (F=8.121, p<0.001), memory (F=8.299, p<0.001), and executive function (F=13.752, p<0.001). Higher educated patients showed no impairment at low lesion volume in processing speed and executive function, but performance was impaired regardless of education at higher lesion volume (interaction effects for processing speed, F=3.380, p<0.05; executive function F=4.872, p<0.01).

Conclusions: Our data suggest that in pure SIVD cognitive reserve is an active compensation mechanism, leading to better cognitive performance in patients with low lacunar lesion volume, while there is decline once pathology accumulates. This effect is specific for processing speed and executive function, the two domains typically affected in SIVD.