Changes in cerebral glucose metabolism in patients with Parkinson’s disease with dementia after cholinesterase inhibitor therapy

Abstract

OBJECTIVE: To evaluate changes in cerebral glucose metabolism in Parkinson’s disease dementia (PDD) patients after cholinesterase inhibitor therapy. BACKGROUND: Cholinesterase inhibitors (ChEI) are now widely used with proven efficacy in patients with PDD. There have been several reports describing how the drugs are benefiting the PDD patients in terms of clinical and neuropsychological scales. But there has never been a study on how the drug effect is represented on brain images. We performed serial 18FFDG PET studies in patients with PDD before and after ChEI therapy. METHOD: We investigated 11 patients with clinical diagnosis of PDD. Patients were treated with either donepezil or galantamine. End point was when patients were treated for at least 3 months and when the patient or family members reported improved cognition. 18F-FDG PET scan was done before initiation of treatment and after completion drug trial. SPM images were created by comparisons between groups on a voxel-by-voxel basis using paired tstatistics. RESULTS: Patients were treated for mean duration of 8.4±4.5 months. Cognitive testes done by MMSE showed improvement after ChEI therapy in 10 patients, especially on memory and serial 7 tasks. Mean improvement in MMSE score was 5.5 points. SPM analysis showed increased glucose metabolism in left superior / middle frontal gyrus and left inferior parietal gyrus, mainly angular gyrus. There was also a region of decreased glucose metabolism in right medial temporal cortex, including fusiform, parrahippocampal gyrus and hippocampus. The degree of improvement in MMSE score only correlated with degree of decreased glucose metabolism on right medial temporal cortex. DISCUSSION: Our study has shown that PDD patients treated with ChEI have increased glucose metabolism in left superior / middle frontal and inferior parietal cortices, and decreased metabolism in right medial temporal cortex. It would be interpreted as that it shows poor correlation with changes in cognitive domains in these patients, and bears little similarities with prior resting FDG-PET studies involving PDD patients. Similar pattern of metabolic changes have been demonstrated before in similarly designed studies with patients with Alzheimer’s disease. The authors conclude that ChEI therapy in PDD patients restores cognitive function by enhancing cholinergic neurotransmission in certain common areas regardless of the underlying pathologic process.

파킨슨병치매는 파킨슨병 환자의 약 40%에서 나타나며, 주로 주의집중력의 장애, 기억력 장애, 집행기능 장애를 보인다. 알츠하이머병에서 사용되는 콜린분해효소억제제가 파킨슨병치매 환자에서도 인지 기능을 호전시키는 효능이 있는 것으로 알려져 있으나, 이러한 치료 효과를 기능적인 두뇌 영상에서 분석하고자 한 시도는 거의 없었다. 이에 저자는 11 명의 파킨슨병치매 환자를 대상으로 donepezil 혹은 galantamine 으로 치료를 하기 전과 치료를 한 뒤의 MMSE 와 F18-FDG PET 영상을 분석하였다. 결과적으로 환자들은 MMSE 점수에서 평균 5.5 점의 향상을 보였고, 특히 기억력, 계산력 검사에서 호전 소견이 두드러졌다. PET 영상을 SPM 을 사용하여 비교한 결과 치료를 받은 후의 영상에서 좌뇌의 상/중간전두고랑(superior / middle frontal gyrus)과 각이랑/모서리위이랑(angular / supramarginal gyrus)의 포도당대사 증가소견과, 우뇌의 내측 측두엽(medial temporal bobe)의 포도당대사 감소소견을 관찰할 수 있었다. 특히 MMSE 의 호전정도와 우뇌의 내측 측두엽의 포도당대사 저하 정도에서 유의한 상관관계를 나타내었다. 이러한 포도당대사의 변화 소견은 알츠하이머병에서 보이는 소견과 비슷하며, 따라서 두 개의 병이 서로 다른 증상과 병리를 보임에도 불구하고, 콜린분해효소억제제의 치료 효과는 두 개의 병에서 비슷한 기전을 갖고 있다고 생각된다.