The broad, long-tenn objectives of this proposal are to develop better treatments for frontotemporaldementia (FTD).
The Specific Aims are to:1) Develop an effective therapeutic intervention for the treatment of FTD. To achieve this aim, theproposed project will test the clinical and cognitive effects on FTD patients of a medication that increases the amount of the neurotransmitter dopamine in the brain. This medication acts by inhibiting an enzyme, catechol 0-methyl-transferase (COMT), that degrades dopamine. The proposed project will also use fMRI to determine the effects of COMT inhibition on prefrontal cortex and temporal lobe efficiency while the patients read words that describe animal functions and social attributes.2) Determine the effect of COMT genotype on symptom presentation and disease course in FTD patients.The COMT gene has a common polymorphism that affects its function.The Research Design is a 24-day double-blind, placebo-controlled crossover trial of 28 patients with FTD.The Methods to be used are a comparison of measures of behavioral and cognitive symptoms, and fMRI blood oxygenation level-dependent (BOLD) activation in the prefrontal cortex and temporal lobe, when the patients are taking a COMT inhibitor versus when they are taking a placebo.Frontotemporal dementia Is an illness that results in the degeneration of the frontal aspect of the brain.This study will test whether increasing a brain chemical, called dopamine, that is deficient in the brains of patients with frontotemporal dementia patients improves the symptoms of the illness. It will also use brain imaging and genetics to detemnlne the contribution of dopamine deficiency to the symptoms ofthis illness.

Public Health Relevance

FTD is increasingly recognized as an important cause of morbidity and mortality in the United States. Np treatment has been shown to slow the progression, or improve the cognitive symptoms, associated with this devastating illness. In autopsy, cerebrospinal fluid, and imaging studies, patients with FTD demonstrate deficiencies in the dopamine neurotransmitter system. The proposed study is the first to specifically test dopamine augmentation for- the treatment of FTD. The investigations proposed in this project could provide an entire class of medications, previously unutilized, for the treatment of FTD.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Transition Award (R00)
Project #
5R00NS060766-05
Application #
8197820
Study Section
Special Emphasis Panel (NSS)
Program Officer
Sutherland, Margaret L
Project Start
2009-05-01
Project End
2014-04-30
Budget Start
2011-05-01
Budget End
2014-04-30
Support Year
5
Fiscal Year
2011
Total Cost
$234,108
Indirect Cost
Name
Columbia University (N.Y.)
Department
Psychiatry
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Bertrand, Elodie; Azar, Martina; Rizvi, Batool et al. (2018) Cortical thickness and metacognition in cognitively diverse older adults. Neuropsychology 32:700-710
Fieo, Robert A; Silverman, Hannah; O'Shea, Deirdre et al. (2018) Establishing dimensionality of sexual behaviours in patients with regional brain dysfunction. Brain Inj 32:1455-1464
Huey, Edward D; Lee, Seonjoo; Cheran, Gayathri et al. (2017) Brain Regions Involved in Arousal and Reward Processing are Associated with Apathy in Alzheimer's Disease and Frontotemporal Dementia. J Alzheimers Dis 55:551-558
Devanand, Davangere P; Pelton, Gregory H; D'Antonio, Kristina et al. (2017) Low-dose Lithium Treatment for Agitation and Psychosis in Alzheimer Disease and Frontotemporal Dementia: A Case Series. Alzheimer Dis Assoc Disord 31:73-75
Huey, Edward D; Lee, Seonjoo; Lieberman, Jeffrey A et al. (2016) Brain Regions Associated With Internalizing and Externalizing Psychiatric Symptoms in Patients With Penetrating Traumatic Brain Injury. J Neuropsychiatry Clin Neurosci 28:104-11
Huey, Edward D; Lee, Seonjoo; Brickman, Adam M et al. (2015) Neuropsychiatric effects of neurodegeneration of the medial versus lateral ventral prefrontal cortex in humans. Cortex 73:1-9
Cosentino, Stephanie; Brickman, Adam M; Griffith, Erica et al. (2015) The right insula contributes to memory awareness in cognitively diverse older adults. Neuropsychologia 75:163-9
Floeter, Mary Kay; Katipally, Rohan; Kim, Meredith P et al. (2014) Impaired corticopontocerebellar tracts underlie pseudobulbar affect in motor neuron disorders. Neurology 83:620-7
Boyd, Clara D; Tierney, Michael; Wassermann, Eric M et al. (2014) Visuoperception test predicts pathologic diagnosis of Alzheimer disease in corticobasal syndrome. Neurology 83:510-9
Goldman, Jill S; Quinzii, Catarina; Dunning-Broadbent, Jane et al. (2014) Multiple system atrophy and amyotrophic lateral sclerosis in a family with hexanucleotide repeat expansions in C9orf72. JAMA Neurol 71:771-4

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