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Behavioural Neurology
Volume 25, Issue 2, Pages 61-72

GOOD or BAD Responder? Behavioural and Neuroanatomical Markers of Clinical Response to Donepezil in Dementia

Gabriella Bottini,1,2 Manuela Berlingeri,3 Stefania Basilico,2 Serena Passoni,2 Laura Danelli,3 Nadia Colombo,4 Maurizio Sberna,4 Massimo Franceschi,5 Roberto Sterzi,6 and Eraldo Paulesu3,7

1Psychology Department, University of Pavia, Pavia, Italy
2Center of Cognitive Neuropsychology, Niguarda Cà Granda Hospital, Milan, Italy
3Psychology Department, University of Milano-Bicocca, Milan, Italy
4Neuroradiology Department, Niguarda Cà Granda Hospital, Milan, Italy
5Neurology Unit, Clinic "Santa Maria", Castellanza, Italy
6Neurology Department, Niguarda Cà Granda Hospital, Milan, Italy
7IRCCS Galeazzi, Milan, Italy

Received 19 January 2012; Accepted 19 January 2012

Copyright © 2012 Hindawi Publishing Corporation and the authors. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


We explored the neuropsychological and neuromorphometrical differences between probable Alzheimer's disease patients showing a good or a bad response to nine months treatment with donepezil. Before treatment, the neuropsychological profile of the two patient groups was perfectly matched. By the ninth month after treatment, the BAD-responders showed a decline of the MMSE score together with a progressive impairment of executive functions. A voxel-based morphometry investigation (VBM), at the time of the second neuropsychological assessment, showed that the BAD-responders had larger grey and white matter atrophies involving the substantia innominata of Meynert bilaterally, the ventral part of caudate nuclei and the left uncinate fasciculus, brain areas belonging to the cholinergic pathways. A more widespread degeneration of the central cholinergic pathways may explain the lack of donepezil efficacy in those patients not responding to a treatment that operates on the grounds that some degree of endogeneous release of acetylcholine is still available.