SPECT follow-up study of cerebral blood flow changes during Donepezil therapy in patients with Alzheimer's disease.
OBJECTIVE
Treatment with acetylcholinesterase inhibitors (AchEIs) is beneficial for patients with Alzheimer's disease (AD). But the clinical response varies. Functional neuroimaging techniques might allow objective evaluation of the topographic correlates of the effect of therapy on brain functioning. We attempted to evaluate the possible correlation between regional cerebral blood flow (rCBF) differences in patients with AD and response to donepezil hydrochloride (Donepezil) therapy.


METHODS
The subjects of this study were 51 consecutive patients with AD receiving Donepezil who underwent SPECT at baseline and 10-14 months later. We divided the patients into stabilized (n = 19) and nonstabilized (n = 32) subgroups based on changes in the Mini Mental State Examination (MMSE) score. Analysis of single-photon emission computed tomography (SPECT) data was done using 3-dimensional stereotactic surface projections (3D-SSP) and the stereotactic extraction estimation (SEE) method. We compared differences in rCBF between the two subgroups at baseline and follow-up, and between the baseline and follow-up in each subgroup.


RESULTS
Significant correlation was recognized between the mean Z score changes of the left frontal lobe, left limbic lobe, and MMSE change. There were no significant baseline differences in rCBF in any region of the brain between the two subgroups. At the study endpoint, the nonstabilized subgroup showed lower rCBF in the lateral and medial frontal lobes, limbic lobe, lower lateral temporal lobe, and cingulate gyrus compared to the stabilized subgroup. Both patient groups showed a significant post-treatment increase over baseline values in the frontal lobe, and the stabilized group had more extensive and intense increases in the lateral and medial frontal lobes and orbital surface.


CONCLUSIONS
Our study suggests that the diversity of clinical responses to Donepezil therapy in patients with AD is associated with rCBF changes, mainly in the frontal lobe. SPECT may be a promising tool to assess the impact of AchEI therapy on the brain function of patients with AD.
Shimizu
Soichiro
S
Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan. soichiro_s@hotmail.com
Hanyu
Haruo
H
Iwamoto
Toshihiko
T
Koizumi
Kiyoshi
K
Abe
Kimihiko
K
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D016009:Chi-Square Distribution; D000077265:Donepezil; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000627:therapeutic use*; D010880:Piperidines / Q000627:therapeutic use*; D018709:Statistics, Nonparametric; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil