Affiliations: Psychology Department, University of Pavia, Pavia,
Italy | Center of Cognitive Neuropsychology, Niguarda
Cà Granda Hospital, Milan, Italy | Psychology Department, University of Milano-Bicocca,
Milan, Italy | Neuroradiology Department, Niguarda Cà Granda
Hospital, Milan, Italy | Neurology Unit, Clinic "Santa Maria", Castellanza,
Italy | Neurology Department, Niguarda Cà Granda
Hospital, Milan, Italy | IRCCS Galeazzi, Milan, Italy
Note: [] Corresponding author: Eraldo Paulesu, Dipartimento di
Psicologia, Università degli Studi di Milano-Bicocca, Piazza dell'Ateneo
Nuovo 1, 20122 Milano, Italia. Tel.: +39 2 64483748; Fax: +39 2 64483706;
E-mail: [email protected]
Abstract: 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.
