Memantine (10mg BID) for the Frontal and Temporal Subtypes of Frontotemporal Dementia

Inclusion Criteria

A subject must meet ALL of the following criteria to be considered for enrollment in this study:

• Signed and dated written informed consent obtained from the subject and the subject's caregiver in accordance with local IRB regulations.
• Must meet criteria Neary et al. criteria for frontotemporal dementia (FTD) or semantic dementia (SD)
• Age: 40-80
• CT or MRI of brain within 12 months consistent with a diagnosis of FTD or SD.
• MMSE ≥ 15 at screening visit.
• Judged by investigator to be able to comply with neuropsychological evaluation at baseline.
• Must have reliable caregiver accompany subject to all study visits. Caregiver must read, understand and speak English fluently in order to ensure comprehension of informed consent form and informant-based assessments of subject. Caregiver must also have frequent contact with subject (at least 3 times per week for one hour) and be willing to monitor study medication compliance and the subject's health and concomitant medications throughout the study.
• In the opinion of the investigator, the patient and the caregiver will be compliant with the protocol and have a high probability of completing the study.

Exclusion Criteria

Any one of the following will exclude a subject from being enrolled into the study:

• Insufficient fluency in English to complete neuropsychological and functional assessments.
• Concurrent Motor Neuron Disease judged by investigator to have bulbar or upper extremity impairments at baseline that would interfere with neuropsychological assessment, or that are expected to lead to such impairments within one month.
• Exclusion criteria as listed in Neary criteria. Diagnosis of progressive nonfluent aphasia by Neary criteria.
• Use of memantine within 4 weeks prior to randomization.
• 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, seizure disorder, or head injury with loss of consciousness) within the past year.
• Concurrent treatment with acetylcholinesterase inhibitors, antipsychotic agents, mood stabilizers (valproate or lithium) or benzodiazepines (other than temazepam or zolpidem), or use of any of these agents within 4 weeks prior to randomization. Atypical antipsychotic agents may be started after the baseline visit if felt to be medically necessary by the investigator and will be recorded as a secondary outcome measure.
• History of alcohol or substance abuse within 1 year prior to screening, if deemed clinically significant by investigator.
• Any current malignancy, or any clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal or neurological disease. If the condition has been stable for at least the past year and is judged by the investigator not to interfere with the patient's participation in the study, the patient may be included.
• Clinically significant lab abnormalities at screening, including Creatinine ≥ 1.7, B12 below laboratory normal reference range or TSH above site's laboratory normal reference range. Subjects with abnormal B12 or TSH levels at screening may be included per investigator's discretion.
• CT or MRI evidence of any of the following: hydrocephalus, stroke, space-occupying lesion, cerebral infection or any clinically significant CNS disease other than FTD.

10.Systolic blood pressure greater than 180 or less than 90 mm Hg. Diastolic blood pressure greater than 105 or less than 50 mm Hg.

• Abnormal ECG at screening judged to be clinically significant by the investigator.
• Use of investigational drugs or participation in investigational drug study within 60 days of screening.