TY - JOUR
T1 - GOOD or BAD responder? Behavioural and neuroanatomical markers of clinical response to donepezil in dementia
AU - Bottini, Gabriella
AU - Berlingeri, Manuela
AU - Basilico, Stefania
AU - Passoni, Serena
AU - Danelli, Laura
AU - Colombo, Nadia
AU - Sberna, Maurizio
AU - Franceschi, Massimo
AU - Sterzi, Roberto
AU - Paulesu, Eraldo
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Acetilcholinesterase inhibitors
KW - Alzheimer's disease
KW - donepezil
KW - MRI
KW - voxel-based morphometry
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U2 - 10.3233/BEN-2011-0359
DO - 10.3233/BEN-2011-0359
M3 - Article
C2 - 22530263
AN - SCOPUS:84858654338
VL - 25
SP - 61
EP - 72
JO - Behavioural Neurology
JF - Behavioural Neurology
SN - 0953-4180
IS - 2
ER -