Journal of Alzheimer’s Disease 14 (2008) 285–299 285 IOS Press Cerebrovascular Disease and Hippocampal Atrophy Are Differently Linked to Functional Coupling of Brain Areas: An EEG Coherence Study in MCI Subjects Davide Vito Moretti a,* , Giovanni Battista Frisoni a , Michela Pievani a , Sandra Rosini a , Cristina Geroldi a , Giuliano Binetti a and Paolo Maria Rossini a,b,c a IRCCS S. Giovanni di Dio Fatebenefratelli, Brescia, Italy b AFaR., Department of Neuroscience, S. Giovanni Calibita Fatebenefratelli, Rome, Italy c Clinica Neurologica Universit` a ‘Campus Biomedico’, Rome, Italy Abstract. The working hypothesis of paper is that the functional coupling of brain areas is combined with different neuroradio- logical substrates and has different clinical manifestations. 31 normal old subjects and 85 subjects with mild cognitive impairment (MCI) underwent EEG recordings and magnetic resonance imaging (MRI). Intrahemispheric and interhemispheric linear EEG coherences were computed. At first, all normal old and MCI subjects were compared. Subsequently, three subgroups of MCI were obtained based on neuroradiological substrate (subcortical cerebrovascular damage, MCI-CVD; cholinergic pathways vascular damage MCI-CHOL; and hippocampal atrophy, MCI-HIPP) and compared with a normal old sample matched for age, education and Mini-Mental State Examination score. The group of MCI subjects compared to normal old subjects shows: 1) decrease of intrahemispheric coherence in fronto-parietal regions (both right and left hemisphere); 2) increase of interhemispheric coherence on frontal regions in delta frequency; and 3) increase of interhemispheric coherence on temporal regions (from delta to alpha3 frequency bands). In the MCI subgroups, hippocampal atrophy is linked to an increase of interhemispheric coherence seen on frontal and temporal regions whereas subcortical CVD is linked to the largest decrease of coherence in fronto-parietal regions. MCI-CVD patients performed worst on Trail Making Test battery whereas MCI-HIPP patients were impaired on Rey word list delayed recall and Rey figure recall. Keywords: Brain rhythms, cognitive tests, electroencephalography, linear coherence, mild cognitive impairment INTRODUCTION Mild cognitive impairment (MCI) is a clinical state intermediate between normal cognition and dementia, and characterized by memory complaints and cogni- tive impairment, but not by dementia, on neuropsy- chological testing [24,64,66]. MCI is a clinically het- * Corresponding author: Davide Vito Moretti, MD, PhD, IRCCS ‘San Giovanni di Dio – FBF’, 4, Pilastroni road, 25125 Brescia, Italy. Tel.: +39 0303501597; Fax: +39 0303533513; E-mail: davide. moretti@afar.it. erogeneous syndrome comprising a number of condi- tions [66,68]. Among these, amnestic MCI (aMCI), characterized by memory deficit and preserved general cognition, is the most clearly defined. The anatom- ical substrate of aMCI is the degenerative pathology of hippocampus and medial temporal lobe [4,17,61]. Nonetheless, the natural history of a group of subjects at very high-risk for developing dementia due to subcor- tical vascular damage [subcortical vascular MCI (svM- CI)] has recently been described [26,29]. In such stud- ies, MCI patients with cerebrovascular damage (CVD) developed a distinctive clinical phenotype character- ISSN 1387-2877/08/$17.00  2008 – IOS Press and the authors. All rights reserved