Objective: To test the hypothesis that depression in patients with Alzheimer disease (AD) is due to specific pathogenesis rather than a reactive phenomenon to cognitive and functional decline. Depression is common in patients with AD and could be a reaction to their frustrations in occupational and social activities. However, autopsy revealed histopathologic differences between AD patients with and without depression, implying a specific pathogenesis. Single-photon emission computed tomography (SPECT) has been widely used for detecting cerebral perfusion in AD. Only few studies discussed the difference in SPECT images of depressed and non-depressed AD patients. These studies used the "region of interest" technique. In statistical parametric mapping (SPM), a voxel-by-voxel analysis is performed, thereby avoiding subjective bias in interpretation. Design: AD patients from the neurological clinic of a teaching hospital. Materials and Methods: AD patients, fulfilling the criteria of the NINCDS-ADRDA for probable AD, gave oral consent for the SPECT study using the technetium-99m hexamethylpropylene amine (99mTc-HMPAO). A psychiatrist diagnosed depression on the basis of patient and primary caregiver interview using a Chinese version of the Structural Clinical Interview for the DSM-III-R. The 17-item Hamilton Depression Rating Scale (HDRS) was used to assess the presence and severity of depressive symptoms for all patients. The SPECT images were reconstructed and analyzed by using SPM (SPM99) in Matlab 5.3. The differences in SPECT images of the depressed and non-depressed patients were tested by the t statistics. Simple regression was used for correlation between variance of cerebral blood flow and HDRS score. Results: Eight of the 43 AD patients (men 9, women 34, 74.7 +/- 7.7 years) were diagnosed to have depressed disorders. There were no significant differences in gender, age, education and cognitive scores between the two groups. The SPECT imaging revealed that the depressed group had significant perfusion reduction over the left frontal gyrus and right cingulate gyrus. There was also an inverse relationship between the HDRS score the cerebral perfusion. The higher the HDRS score, the more pronounced was the reduction of perfusion in the left frontal and right cingulate gyri. The most significant reduction of perfusion occurred in the right cingulate gyrus. Conclusion: The locations we reported have been linked to primary or secondary depression in previous PET and SPECT studies. Therefore, some common pathogenetic process can account for primary depression and depression associated with AD. Although our patient number was small, these differences in SPECT images deserve further investigation.
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