Cognitive and Metabolic Responses to Metrifonate Therapy in Alzheimer Disease
作者:
Michael Mega,
Jeffrey Cummings,
Susan O'Connor,
Ivo Dinov,
Erin Reback,
Jenaro Felix,
Donna Masterman,
Michael Phelps,
Gary Small,
Arthur Toga,
期刊:
Neuropsychiatry, Neuropsychology & Behavioral Neurology
(OVID Available online 2001)
卷期:
Volume 14,
issue 1
页码: 63-68
ISSN:0894-878X
年代: 2001
出版商: OVID
数据来源: OVID
摘要:
ObjectiveThe objective of this study was to identify the relation between the cognitive benefit seen with the cholinesterase inhibitor metrifonate and changes in brain metabolism as visualized with [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET).BackgroundThe regional metabolic correlates of treatment with cholinesterase inhibitors are poorly understood.MethodsSix patients with mild to moderate Alzheimer disease (AD) were evaluated before and after treatment with the long-lasting cholinesterase inhibitor metrifonate. Patients were given 60 or 80 mg of metrifonate per day (based on weight) for 6 to 12 weeks. Clinical evaluations included the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog), the Mini-Mental State Examination (MMSE), and the Neuropsychiatric Inventory. Imaging was carried out using FDG-PET. The PET studies, registered to a probabilistic anatomic atlas, were normalized across the group's mean intensity levels and subjected to voxel-by-voxel subtraction of the posttreatment minus pretreatment studies. Subvolume thresholding corrected random lobar noise to produce a three-dimensional functional significance map.ResultsThe criteria for cognitive improvement with treatment were met for the MMSE (>2 points improvement from baseline), and the drawing subscale of the ADAS-cog was significantly improved with treatment. The three-dimensional significance map revealed a significant metabolic increase of the dorsolateral frontoparietal network on the left and bilateral temporal cortex with metrifonate treatment.ConclusionThe clinical benefits observed in AD with cholinesterase inhibitor therapy are associated with a metabolic increase of heteromodal cognitive and medial temporal networks.
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