Riluzole in Mild Alzheimer's Disease

A double-blinded, randomized, placebo-controlled study will be performed. Forty-eight
individuals with a diagnosis of mild Alzheimer's disease between 50-95 years old will
complete the study. All forty-eight 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-four mild Alzheimer's disease patients will receive riluzole and another 24 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+)