Treatment Study of Frontotemporal Dementia
Condition: Frontotemporal Lobar Degeneration
MeSH terms: Dementia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain; Frontotemporal Lobar Degeneration
Study type: Observational

Summary: 
      Objectives. The proposed clinical study has two goals: First, to assess the efficacy of a
      central nervous system stimulant and an atypical antipsychotic in treating the behavioral
      symptoms of FTD and second, to further characterize the biological markers, including
      genetic, imaging, and CSF proteins, of FTD in relation to our existing group of Alzheimer's
      patients.

      Rationale. Frontotemporal dementia (FTD) is increasingly recognized as an important
      neuropsychiatric disorder. Symptoms of FTD include disinhibition, impulsivity, apathy,
      affective lability, and language dysfunction. The clinical syndrome is associated with
      frontal and/or anterior temporal atrophy on imaging and autopsy. Levels of the CSF proteins
      tau and (Beta)-amyloid 1-42, shown to have diagnostic utility in patients with Alzheimer's
      Disease (AD), have also been found to be abnormal in FTD. FTD is less associated with APOE
      genotype than AD, however some familial cases of FTD are associated with specific mutations
      in the gene encoding the tau protein. Currently, no treatments have been proven to be
      effective for altering the course or clinical symptoms of FTD.

      Design. Study subjects will include 50 male and female patients with mild-moderate
      frontotemporal dementia recruited from participants in NINDS protocol 02-N-0001. In a
      double-blinded crossover 11-week study without a placebo control, patients will be treated
      with a stimulant (dextroamphetamine) and an atypical antipsychotic (quetiapine). The primary
      outcome measures will be the Neuropsychiatric Inventory and the Clinical Global Impression of
      Change. Cerebrospinal fluid, cognitive and genetic measures, brain MRIs, and side effects
      scales will also be collected.
    

Detailed description: 
      Objectives. The goal of the proposed clinical study is to assess the efficacy of a central
      nervous system stimulant and an atypical antipsychotic in treating the behavioral symptoms of
      FTD.

      Rationale. Frontotemporal dementia (FTD) is increasingly recognized as an important
      neuropsychiatric disorder. Symptoms of FTD include disinhibition, impulsivity, apathy,
      affective lability, and language dysfunction. The clinical syndrome is associated with
      frontal and/or anterior temporal atrophy on imaging and autopsy. Currently, no treatments
      have been proven to be effective for altering the course or clinical symptoms of FTD.

      Design. Study subjects will include 20 male and female patients with mild-moderate
      frontotemporal dementia recruited from participants in NINDS protocols 02-N-0001 and
      81-N-0010. In a double-blinded crossover 11-week study without a placebo control, patients
      will be treated with a stimulant (dextroamphetamine) and an atypical antipsychotic
      (quetiapine). The primary outcome measures will be the Neuropsychiatric Inventory and the
      Clinical Global Impression of Change. Cognitive measures and side effects scales will also be
      collected.
    

Keywords: Frontotemporal Dementia; Alzheimer's Disease; Atypical Antipsychotic; Stimulant; Apathy; Disinhibition; Antipsychotic; Biomarkers; Dementia; FTD