Open Label Pilot Study of the Effects of Memantine on FDG-PET in Frontotemporal Dementia

Memantine has been approved for use in Alzheimer's disease. Its mechanism of action raises questions of whether it can also be effective for non-Alzheimer's dementias such as frontotemporal dementia (FTD), which currently has no disease-modifying treatment.

This is an open-label study to probe the effects of memantine in 15 outpatients diagnosed with FTD, as shown objectively by comparing PET scans performed before and after use of the medication. The specific type of PET scan, FDG-PET, allows the investigators to gauge the effects of memantine on cortical activity levels. The investigators hypothesize that subjects on memantine will show normalization of cortical metabolic activity.


Eligibility Criteria:
Inclusion Criteria:

* Must meet criteria for frontotemporal lobar degeneration (FTD) by Neary et al. criteria. 28 Subjects may have either the behavioural or the aphasic variant of FTD.
* Able to undergo psychometric testing.
* Must have reliable informant with daily contact with patient
* May be taking concurrent psychotropic medications, but must be on stable dosing regimen for 3 months prior to trial enrollment
* On the basis of a physical examination, medical history (including psychiatric and neurological), and results of blood chemistry carried out at screening visit, the patient in the investigator's opinion is considered healthy.
* Signed Informed Consent must be obtained from the patient or legally responsible representative and the informant prior to initiating any study specific procedures.

Exclusion Criteria:

* Complaint of recurrent or persistent dizziness or constipation
* Abnormal chemistry panel particular with respect to ruling out renal insufficiency or failure. We will exclude those patients with creatinine clearance (CLcr) \< 50ml/min, per the Sakana equations for men and women.
* Angina, myocardial infarction, severe hypertension, severe cardiac arrhythmia, unstable diabetes mellitus, or new abnormalities on EKG within the past year.
* Any current malignancy, or any clinically significant hematological, endocrine, renal, hepatic, gastrointestinal or non-dementia neurological disease. If the condition has been stable for at least the past year and is judged by the investigators not to interfere with the patient's participation in the study, the patient may be included. Basal cell carcinoma is an exception.
* Non-English speaking, as cognitive tests will be in English.
* Evidence of other neurological or psychiatric disorders which preclude diagnosis of FTD (including, but not limited to, stroke, Parkinson's disease, any psychotic disorder, severe bipolar or unipolar depression) within the past year
* Current or prior history of uncontrolled seizure disorder, due to seizures reported as adverse events with memantine.
* Patients with suspected alcohol or substance abuse within last 1 year. If past history of abuse or dependence must have been abstinent for 1 year with continuing progression of dementia despite abstinence.
* Patients with active delusions or hallucinations at the time of screening.
* Female patients who are not at least two years post-menopausal or surgically sterile. Pre-menopausal women will be excluded; because almost all women are post-menopausal at the age of onset of FTD, we do not anticipate having to exclude more than one potential subject on the basis of this one exclusion criterion.
* Use of investigational drugs or participation in another investigational drug study within 3 months of screening.
* Patients who have previously been treated with memantine or have participated in an investigational study with memantine.
* Patients with history of severe drug allergy or hypersensitivity or known hypersensitivity to amantadine or memantine.