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Behavioral, cognitive and metabolic responses to cholinesterase
inhibitor therapy in Alzheimer's Disease
Source: 2002;.
Author: Mega MS, Cummings JL, Dinov ID, Masterman DM, Felix J, O'Connor SM, Reback ER, Burzynski MJ, Saxena S, Levy M, Konx A, Small GW, Phelps ME, Toga AW.
Abstract:
Background: Understanding the neurobiologic basis of the spectrum of cognitive and behavioral responses to cholinesterase inhibition therapy in Alzheimer's disease (AD) may help predict which patients could benefit from treatment. Objectives: To identify the cognitive, behavioral and functional imaging characteristics of AD patients who improve when treated with cholinesterase inhibitor therapy. Methods: Nine AD patients were assessed with the Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), and pre- and post-treatment [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) to measure their responses to cholinesterase inhibitor therapy with doneppezil. The PET studies, registered to a probabilistic anatomic atlas, were normalized across the group mean intensity levels and subjected to a voxel by voxel subtraction of the post-treatment minus pre-treatment studies. Sub-Volume Thresholding (SVT) corrected random lobar noise to produce a 3D functional significance map. Results: There was no significant group change in MMSE or total NPI scores after eight weeks of treatment. Substantial heterogeneity in treatment response among patients who observed. The 3D significance map revealed that the left basal forebrain, dorsolateral frontal, perirhinal, posterior insula, inferior temporal, angular gyrus, and right anterior cingulate regions were activated by cholinergic treatment, while motor and thalamic regions were deactivated with treatment. Single subject subtractions supported our a priori hypothesis predicting that individuals who demonstrated a significant behavioral response to therapy also demonstrated a significant metabolic increase in paralimbic cortex as measured by pre- and post-treatment FDG-PET. Conclusion: The general metabolic response to cholinesterase inhibitor therapy may involve cognitive and attentional systems. AD patients who show a behavioral response to cholinesterase inhibitor therapy may have an associated activation of paralimbic regions compared to nonresponders.
Source: 2002;.
Author: Mega MS, Cummings JL, Dinov ID, Masterman DM, Felix J, O'Connor SM, Reback ER, Burzynski MJ, Saxena S, Levy M, Konx A, Small GW, Phelps ME, Toga AW.
Abstract:
Background: Understanding the neurobiologic basis of the spectrum of cognitive and behavioral responses to cholinesterase inhibition therapy in Alzheimer's disease (AD) may help predict which patients could benefit from treatment. Objectives: To identify the cognitive, behavioral and functional imaging characteristics of AD patients who improve when treated with cholinesterase inhibitor therapy. Methods: Nine AD patients were assessed with the Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), and pre- and post-treatment [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) to measure their responses to cholinesterase inhibitor therapy with doneppezil. The PET studies, registered to a probabilistic anatomic atlas, were normalized across the group mean intensity levels and subjected to a voxel by voxel subtraction of the post-treatment minus pre-treatment studies. Sub-Volume Thresholding (SVT) corrected random lobar noise to produce a 3D functional significance map. Results: There was no significant group change in MMSE or total NPI scores after eight weeks of treatment. Substantial heterogeneity in treatment response among patients who observed. The 3D significance map revealed that the left basal forebrain, dorsolateral frontal, perirhinal, posterior insula, inferior temporal, angular gyrus, and right anterior cingulate regions were activated by cholinergic treatment, while motor and thalamic regions were deactivated with treatment. Single subject subtractions supported our a priori hypothesis predicting that individuals who demonstrated a significant behavioral response to therapy also demonstrated a significant metabolic increase in paralimbic cortex as measured by pre- and post-treatment FDG-PET. Conclusion: The general metabolic response to cholinesterase inhibitor therapy may involve cognitive and attentional systems. AD patients who show a behavioral response to cholinesterase inhibitor therapy may have an associated activation of paralimbic regions compared to nonresponders.