Dement Neurocogn Disord.  2015 Sep;14(3):106-113. 10.12779/dnd.2015.14.3.106.

Single Photon Emission Computerized Tomography and Neuropsychological Tests That Predict a Good Response to Donepezil Therapy for Alzheimer's Disease

  • 1Department of Neurology, Chonnam National University Medical School, Gwangju, Korea.
  • 2Department of Nuclear Medicine, Chosun University Hospital, Gwangju, Korea.
  • 3Department of Nuclear Medicine, Chonnam National University Medical School, Gwangju, Korea.
  • 4Department of Radiology, Chonnam National University Medical School, Gwangju, Korea.
  • 5Department of Neurology, Dong-A University College of Medicine, Busan, Korea.
  • 6Department of Psychiatry, New York University Medical Center, New York, NY, USA.


Cholinesterase inhibitors (ChEIs) are effective in Alzheimer's disease (AD) treatment. The aim of this study is 1) to find neuropsychological factors that affect the functional response to ChEI therapy and 2) to determine whether regional cerebral blood flow (rCBF) pretreatment predicts a cognitive change in response to ChEI.
We prospectively recruited 32 patients diagnosed with probable AD and treated them with donepezil, a ChEI, over one year. The patients were divided into stable (s-AD) and declined (d-AD) AD groups, based on changes in Korean version of Mini-Mental State Examination (K-MMSE) scores. Patients were assessed using the Alzheimer's Disease Co-operative Study-Activities of Daily Living (ADCS-ADL) and Seoul Neuropsychologic Screening Battery, as well as brain single photon emission computerized tomography (SPECT) at baseline and last medical evaluations. The predictors of therapeutic responses were analyzed using general linear models.
Based on their cognitive function changes, AD patients were classified into two groups: s-AD (n=14, annual change in K-MMSE score <0.9), or d-AD (n=18, annual change in K-MMSE score > or =0.9). The s-AD at baseline showed significantly better ADCS-ADL function (p=0.04) and had a tendency to preserve frontal function compared to the d-AD group. Global Statistical Parametric Mapping analysis revealed no significant decrease of rCBF between baseline and follow-up SPECT, in either the s-AD or the d-AD groups. However, on regional perfusion analysis of baseline SPECT, the d-AD group demonstrated perfusion deficits in the supramarginal gyrus, inferior occipital gyrus, and rolandic operculum compared with the s-AD group.
Highly preserved ADCS-ADLs predicted a better improvement in MMSE scores in response to ChEI therapy and a more positive functional response in the group with preserved frontal function. rCBF provided hints to the variable response to donepezil therapy with ChEI treatment.


Alzheimer's disease; acetylcholinesterase inhibitor; regional cerebral blood flow; single photon emission computerized tomography; Korean version of Mini-Mental State Examination

MeSH Terms

Alzheimer Disease*
Cholinesterase Inhibitors
Follow-Up Studies
Linear Models
Mass Screening
Neuropsychological Tests*
Prospective Studies
Tomography, Emission-Computed, Single-Photon*
Cholinesterase Inhibitors


  • Fig. 1 The change from baseline of the K-MMSE score per year for AD patients (n=32). Patients with at least a 0.9 score decrease in K-MMSE score per year are categorized in the AD decline group (d-AD, n=18), whereas the others are categorized in the stable AD group (s-AD, n=14). AD: Alzheimer's disease, K-MMSE: Korean version of Mini-Mental State Examination.

  • Fig. 2 Global Statistical Parametric Mapping software analysis showing a relative decrease in the regional cerebral blood flow of brain single photon emission computerized tomography in the stable Alzheimer's disease (AD) group (s-AD) at baseline (A) and follow up (B); and in the declined AD group (d-AD) at baseline (C) and follow up (D) compared to elderly healthy controls (n=12). We used a threshold Z-score ≥2.33 (which corresponding to a p-value ≤0.01). The color of the outer contour corresponds to a Z score of 0-10.


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