Brain Advance Access published online on February 9, 2007
Brain, doi:10.1093/brain/awl377
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The topography of grey matter involvement in early and late onset Alzheimer's disease
1Laboratory of Epidemiology Neuroimaging and Telemedicine, 2Psychogeriatric Ward, IRCCS Centro San Giovanni di Dio FBF, The National Centre for Research and Care of Alzheimer's and Mental Diseases, 3Service of Neuroradiology, Istituto Clinico Città di Brescia, Brescia, 4Service of Neuroradiology, Ospedale Maggiore, Borgo Trento, Verona, Italy and 5Laboratory of Neuroimaging, Department of Neurology, UCLA School of Medicine, Los Angeles, CA, USA
Correspondence to:
Giovanni B. Frisoni, MD, Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS Centro San Giovanni di Dio FBF, The National Centre for Research and Care of Alzheimer's and Mental Diseases, via Pilastroni 4, 25125 Brescia, Italy E-mail: papers{at}centroAlzheimer.it
Clinical observations have suggested that the neuropsychological profile of early and late onset forms of Alzheimer's disease (EOAD and LOAD) differ in that neocortical functions are more affected in the former and learning in the latter, suggesting that they might be different diseases. The aim of this study is to assess the brain structural basis of these observations, and test whether neocortical areas are more heavily affected in EOAD and medial temporal areas in LOAD. Fifteen patients with EOAD and 15 with LOAD (onset before and after age 65; Mini Mental State Examination 19.8, SD 4.0 and 20.7, SD 4.2) were assessed with a neuropsychological battery and high-resolution MRI together with 1:1 age- and sex-matched controls. Cortical atrophy was assessed with cortical pattern matching, and hippocampal atrophy with region-of-interest-based analysis. EOAD patients performed more poorly than LOAD on visuospatial, frontal-executive and learning tests. EOAD patients had the largest atrophy in the occipital [25% grey matter (GM) loss in the left and 24% in the right hemisphere] and parietal lobes (23% loss on both sides), while LOAD patients were remarkably atrophic in the hippocampus (21 and 22% loss). Hippocampal GM loss of EOAD (9 and 16% to the left and right) and occipital (12 and 14%) and parietal (13 and 12%) loss of LOAD patients were less marked. In EOAD, GM loss of 25% or more was mapped to large neocortical areas and affected all lobes, with relative sparing of primary sensory, motor, and visual cortex, and anterior cingulate and orbital cortex. In LOAD, GM loss was diffusely milder (below 15%); losses of 15–20% were confined to temporoparietal and retrosplenial cortex, and reached 25% in restricted areas of the medial temporal lobe and right superior temporal gyrus. These findings indicate that EOAD and LOAD differ in their typical topographic patterns of brain atrophy, suggesting different predisposing or aetiological factors.
Key Words: Alzheimer's disease; age at onset; magnetic resonance; hippocampus; computational neuroanatomy
Abbreviations: EOAD, early onset Alzheimer's disease; LOAD, late onset Alzheimer's disease; GM, grey matter; GMD, grey matter density
Received August 31, 2006. Revised October 26, 2006. Accepted December 15, 2006.
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