Cognitive aging is a major source of disability in an increasingly aging population. The paucity of effective treatments for cognitive aging disorders, and most importantly in Alzheimer's disease instigates a need for further research into novel therapeutic possibilities. Alzheimer's disease is the most common neurodegenerative disorder and its prevalence steeply increases. Glutamate-mediated excitotoxicity in neuropsychiatric disorders and in particular in Alzheimer's disease has been shown to cause significant cerebral damage. Early effective therapeutic intervention in Alzheimer's disease is critical in order to prevent or at least slow down neuropathological progression that will lead to widespread irreversible neuronal loss and significant cognitive dysfunction. Riluzole, a glutamate modulator agent, will be tested in mild Alzheimer's disease patients. Cognitive functional changes along with two established in vivo biomarkers, namely, Magnetic Resonance Spectroscopy (MRS) and Fluorodeoxyglucose (18F) positron emission tomography (FDG-PET) will be evaluated.

A double-blinded, randomized, placebo-controlled study will be performed. Forty-two individuals with a diagnosis of mild Alzheimer's disease between 50-95 years old will complete the study. All forty-two individuals will have been on an acetylcholinesterase inhibitor, which is FDA approved for the treatment of Alzheimer's disease, for at least 2 months prior to initiating the study, unless the medication was not previously tolerated. Twenty to twenty-two mild Alzheimer's disease patients will receive riluzole and another 20-22 will receive a placebo. All patients will have a neurological evaluation and neuropsychological tests performed to confirm that they meet criteria for probable Alzheimer's disease set out by the National Institute on Aging - Alzheimer's disease Association that recently revisited the NINCDS-ADRDA criteria along with FDG-PET biomarker consistent with Alzheimer's disease.

Inclusion Criteria:

• Male or female; 50 - 95 years old with mild Alzheimer's disease determined after neurological and neuropsychological evaluation following the National Institute on Aging - Alzheimer's disease Association criteria that recently revisited the NINCDS-ADRDA criteria. For mild Alzheimer's disease, Clinical Dementia Ratings Scale (CDR) should be 0.5 or 1 and Mini Mental State Examination (MMSS) between 19 and 27.
• Must be on donepezil (Aricept®) or rivastigmine (Exelon®) or galantamine (Razadyne®) at a consistent dose for at least 2 months. Patients will be considered for inclusion if they were previously unable to tolerate acetylcholinesterase inhibitors and as a result, are no longer on the medication for at least 2 months.
• Must be fluent in English
• The subject will appoint or have previously appointed a health care proxy specifically designated for research consent and that this be documented.

Exclusion Criteria:

• Severe Alzheimer's disease and other dementias as determined by neuropsychological testing and neurological evaluation.
• Previous riluzole treatment.
• MRI contraindication (severe claustrophobia, metal implants, shunts, pacemaker, joint implants, metal valves).
• Currently taking medications that either have evidence of glutamatergic activity or has previous MRS evidence of effects on brain glutamate levels at the discretion of the PI such as memantine, lamotrigine, lithium, opiates, bupropion, psychostimulants such as amphetamines and methylphenidate, tricyclic antidepressants, benzodiazepines and any other drug that the investigators judge might interfere with the study. (subjects on those medications may still be included in the study however only the values of NAA from MRS will be utilized and not the glutamate measurements).
• Currently a user of the following illicit drugs: cocaine, methylenedioxymethamphetamine (MDMA) ("ecstasy"), heroin and other opioids or has a history of drug or alcohol abuse within the past 5 years.
• Serum creatinine >1.5 times the upper limit of normal.
• Abnormal liver function test (greater than 2 times the upper limit of normal for alanine aminotransferase (ALT) or aspartate aminotransferase (AST); or bilirubin >1.5 times the upper limit of normal.
• History of brain disease including Parkinson's Disease, severe brain trauma, seizures, history of stroke, clinically significant lacunar infarct in a region important for cognition or multiple lacunes or a cortical infarct or focal lesions of clinical significance, multiple sclerosis, mental retardation, normal pressure hydrocephalus, central nervous system (CNS) tumor, Huntington's disease, subdural hematoma or other serious neurological disorder.
• Uncontrolled diabetes mellitus (Hba1c higher than 7) or chronically uncontrolled hypertension.
• Subject must not be taking Namenda® (memantine) for 6-weeks prior to study entrance.
• Currently taking any concomitant hepatotoxic drugs such as allopurinol, methyldopa and sulfasalazine.
• Any unstable serious co-existing medical condition(s) including but not limited to myocardial infarction, coronary artery disease requiring coronary bypass surgery, unstable angina, clinically evident congestive heart failure within 6 months prior to the screening visit.
• Current smoker or user of nicotine-containing products, such as chewing tobacco, nicotine patch or gum for the past 2 months.
• Current untreated major depression defined by Geriatric Depression Scale > 20.
• Participation in any investigational or marketed drug or device trial within 30 days prior to the screening visit.
• Significant neuropsychiatric illnesses such as bipolar disorder, schizophrenia, moderate-severe anxiety, vascular dementia, Creutzfeldt-Jakob dementia, HIV dementia, and dementia in other specified diseases.
• Subjects who have been on donepezil for longer than 5 years.
• Weight> 300 pounds.
• Lactose intolerance.
• Any medical or social condition that, in the opinion of the Investigator, might pose additional risk to the participant or confound the results of the study.
• Positive Hepatitis Serology (Hep. B antigen+ or Hep. C antibody+)

6 months

1.Sample size was relatively small, and results require replication in larger-sample studies. 2.lack of amyloid characterization. 3.MRS is unable to differentiate neurotransmitter or vesicular and metabolic pools of glutamate. Longitudinal MRS measurements can be subject to technical variability and head motion. 4. the study was not powered for neuropsychological outcome and clinical changes must be viewed only as directional/exploratory.