Hippocampal volume is an independent predictor of cognitive performance in CADASIL

Recent evidence suggests that hippocampal changes are present in vascular cognitive impairment but their importance and relationship with ischaemic mechanisms remain controversial. To investigate these issues we performed MRI and cognitive assessment in a large cohort (n = 144) of patients with CADASIL, a hereditary small vessel disease and model of pure vascular cognitive impairment. Dementia status was ascribed according to DSM-IV and global cognitive function assessed with the Minimental State Examination (MMSE) and Mattis Dementia Rating Scale (MDRS). Hippocampal volume (HV) correlated with age (r = −0.33, p < 0.001), brain volume (r = 0.39, p < 0.001) and lacunar lesion volume (r = −0.23, p = 0.008), but not white matter lesions or microhaemorrhages. HV was reduced in dementia (2272 ± 333 mm3 versus 2642 ± 349 mm3, p < 0.001) in the whole cohort and the subgroup progressing to dementia before age 60. HV correlated with MMSE (r = 0.30, p < 0.001), MDRS (r = 0.40, p < 0.001) and in a multivariate model predicted cognition independent of typical vascular lesions and whole brain atrophy. These findings strengthen the view that hippocampal atrophy is an important pathway of cognitive impairment in vascular as well as degenerative disease.