Left frontal lobe hypoperfusion and depressive symptoms in Alzheimer׳s disease patients taking cholinesterase inhibitors

• Dorsolateral prefrontal hypoperfusion was reported in depressive AD patients.
• It is not clear whether a similar condition is present on AChEI medication.
• AD patients with depressive symptoms showed similar hypoperfusion on AChEI medication.
• Dorsolateral prefrontal area is involved in depressive symptoms in AD with AChEI.

Depressive symptoms are common in patients with Alzheimer׳s disease (AD) and increase the caregiver burden. Many studies have reported dorsolateral prefrontal hypometabolism or hypoperfusion in AD patients with depressive symptoms, most of whom did not take acetylcholinesterase inhibitors (AChEI). It is not clear, however, whether a similar condition is present in patients taking AChEI medication. Fifty-seven consecutive AD patients taking AChEI were recruited at a memory clinic. Objective depressive symptoms were evaluated using the depression domain of the Neuropsychiatric Inventory (NPI-dep). All patients underwent brain single photon emission computed tomography (SPECT) with 99mTc-ethylcysteinate dimer, and the SPECT images were analyzed using the Statistical Parametric Mapping 8 program. No significant differences between groups with positive and negative NPI-dep scores were found with respect to age, sex, years of education, and cognitive function. Compared with patients with negative NPI-dep scores, patients with NPI-dep scores ≥1 showed significant hypoperfusion in the left middle frontal region. Our results indicate that the dorsolateral prefrontal area is significantly involved in the pathogenesis of depressive symptoms in AD patients being treated with AChEI. The area on the left side especially may be closely related to the depressive symptoms evaluated using the NPI.