FTD is a significant cause of disability and death with an estimated prevalence of 15 cases per 100,000 persons in the 45- to 64-year-old age range. Despite the magnitude of this problem, there is currently a relative lack of understanding of the causes of, and treatments for, FTD, possibly because criteria for its diagnosis have only recently been developed. As an outcome of the proposed investigations, the investigators expect to determine the effects of cortical dopamine augmentation in FTD, evaluate the effect of dopamine augmentation on processing efficiency with fMRI, and explore the effects of a genetic polymorphism on symptom presentation and disease course. The research proposed in this protocol is significant because it could provide a new class of treatments for FTD, identify the fMRI findings associated with symptom improvement, and determine the contribution of a genetic polymorphism to symptom presentation and disease course.
Inclusion Criteria: - Diagnosis of frontotemporal dementia (FTD) - Age 40 to 85 - Assigned durable power of attorney - Caregiver willing and able to accept the responsibilities involved in the study - Mattis Dementia Rating Scale-2 (MDRS2) score less than 132 Exclusion Criteria: - The diagnosis of any other type of dementia besides FTD including Alzheimer's disease, Lewy body dementia, vascular dementia, dementia associated with Parkinson's disease, corticobasal syndrome, and progressive supranuclear palsy. - Known allergy or serious adverse reaction to tolcapone - Active liver disease - Current alcohol abuse - Active substance abuse - Elevated liver function tests - Patient is taking tolcapone or any other catechol-O-methyltransferase (COMT) inhibitor, benserazide, alpha-methyldopa, dobutamine, apomorphine, isoproterenol, an monoamine oxidase inhibitor (MAO-I), or clozapine - Symptomatic cardiovascular disease (e.g., angina, transient ischemic attack (TIA) , syncope) - Uncontrolled hyper- or hypotension - Any other contraindication to tolcapone - Any medication that significantly affects the dopamine system, including stimulants and antipsychotic medications - Pregnant women