알츠하이머병 환자에서 콜린에스터라제 억제제의 투여에 의한 대뇌피질 국소혈류의 변화

Abstract

Alzheimer`s Disease(AD) is a progressive, degenerative disease that attacks the brain resulting in impaired memory, thought processing, and behavior. This is associated with a loss in presynaptic cholinergic function. It has been suggested that cholinergic inhibitors could restore this function and improve some symptoms of AD. Previous studies have shown that cholinesterase inhibitors(ChEI) improve cognitive and global functions in patients with mild to moderate AD. This study aims to evaluate regional cerebral blood flow(rCBF) changes and contemporary clinical responses such as cognitive and psychiatric symptoms after ChEI treatment. The subjects were eight at risk AD patients(four males and four females, mean age 69.63 years) recruited from the department of Neurology at Yeungnam University Medical Center between August 2000 and April 2002. The clinical diagnosis of AD was based on DSM-Ⅳ and NINCDS-ADRDA criteria. Huchinski ischemic scores of all the patients were below 1. The mean treatment duration was 30.38 weeks, ranging between 24 to 44 weeks. Four patients received Rivastigmine(ExelonⓇ) 12mg after titration, three patients received Donepezil(AriceptⓇ) 10mg during the whole period, and one patient received Donepezil 10mg after the initial 5mg for three weeks. The base line and follow up Ethylene Cysteine Diethylester Single Photon Emission Computed Tomography(99mTC-ECD SPECT) studies were done within one week prior to ChEI treatment and within one week following the study. Regions of interest(ROIs) were drawn over the left and right frontal lobe, temporal lobe, parietal lobe, and cerebellum. Region to cerebellar ratio(RCR)(each count in the ROIs divided by mean cerebellar ROI count) were calculated as a estimation of rCBF, and base line RCRs were compared with those of the follow up. The results display an overall increase in global cerebral blood flow through K-MMSE(Korean-Mini Mental State Examination), CDR(Clinical Dementia Rating), CDR-SB(Clinical Dementia Rating-Sum of Box), GDS(Global Deterioration Scale), and NPI(Neuropsychiatric Inventory, Cummings). We found that the most significant increase in blood flow occurred in the bilateral parietal lobes(p<0.05). Reduction in the rCBF is more profound on the left hemisphere in the base line(p<0.05) where there is a significant increase of rCBF after ChEI treatment compared with to right hemisphere(p<0.05).