OBJECTIVE: The 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). BACKGROUND: The regional metabolic correlates of treatment with cholinesterase inhibitors are poorly understood. METHODS: Six 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. RESULTS: The 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. CONCLUSION: The clinical benefits observed in AD with cholinesterase inhibitor therapy are associated with a metabolic increase of heteromodal cognitive and medial temporal networks.
OBJECTIVE: The 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). BACKGROUND: The regional metabolic correlates of treatment with cholinesterase inhibitors are poorly understood. METHODS: Six 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. RESULTS: The 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. CONCLUSION: The clinical benefits observed in AD with cholinesterase inhibitor therapy are associated with a metabolic increase of heteromodal cognitive and medial temporal networks.
Authors: Constantine G Lyketsos; Maria C Carrillo; J Michael Ryan; Ara S Khachaturian; Paula Trzepacz; Joan Amatniek; Jesse Cedarbaum; Robert Brashear; David S Miller Journal: Alzheimers Dement Date: 2011-09 Impact factor: 21.566
Authors: E Stefanova; A Wall; O Almkvist; A Nilsson; A Forsberg; B Långström; A Nordberg Journal: J Neural Transm (Vienna) Date: 2005-07-29 Impact factor: 3.575
Authors: Stefan J Teipel; Alexander Drzezga; Peter Bartenstein; Hans-Jürgen Möller; Markus Schwaiger; Harald Hampel Journal: Psychopharmacology (Berl) Date: 2006-06-01 Impact factor: 4.530
Authors: Gary W Small; Susan Y Bookheimer; Paul M Thompson; Greg M Cole; S-C Huang; Vladimir Kepe; Jorge R Barrio Journal: Lancet Neurol Date: 2008-02 Impact factor: 44.182