Memory and Mental Health in Aging

Inclusion Criteria:

• Mini-Mental Exam score between 24 and 30
• Hamilton Depression Score of 12 or less on 17-item scale
• Visual and auditory acuity adequate for neuropsychological testing
• General good health (no additional diseases expected to interfere with the study)
• Normal B12, Rapid Plasma Reagin (RPR), and Thyroid Function Tests
• Normal general clinical chemistry, complete blood count, and electrocardiogram (ECG)
• Female participants must be 2 years postmenopausal or surgically sterile

Exclusion Criteria:

• Significant neurologic disease
• Possible or probable Alzheimer's Disease (AD)
• Parkinson's disease
• Multi-infarct dementia
• Huntington's disease
• Normal pressure hydrocephalus
• Brain tumor
• Progressive supranuclear palsy
• Seizure disorder
• Subdural hematoma
• Multiple sclerosis
• History of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities
• Major depression or other major psychiatric disorder as described in DSM IV within the past 2 years
• Psychotic features, agitation, or behavioral problems within the last 3 months
• History of alcohol or substance abuse or dependence within the past 2 years
• Significant systemic illness or unstable medical condition including: a) history of systemic cancer within the last 5 years (nonmetastatic skin cancers are acceptable); b) history of myocardial infarction within the past year or unstable or severe cardiovascular disease, including angina or CHF with symptoms at rest; c) clinically significant obstructive pulmonary disease or asthma; d) clinically significant and unstable gastrointestinal disorder such as ulcer disease or a history of active or occult gastrointestinal bleeding within 2 years; e) clinically significant laboratory test abnormalities on the battery of screening tests (hematology, prothrombin time, chemistry, urinalysis, ECG); f) insulin-requiring diabetes or uncontrolled diabetes mellitus; g) uncontrolled hypertension (systolic BP greater than 170 or diastolic greater than 100); h) history of clinically significant liver disease, coagulopathy, or vitamin K deficiency within the past 2 years
• Use of centrally active beta-blockers, narcotics, methyldopa, and clonidine within 4 weeks prior to screening
• Use of anti-Parkinsonian medications (e.g. Sinemet, amantadine, bromocriptine, pergolide, and selegiline) within 2 months prior to screening
• Use of neuroleptics or narcotic analgesics within 4 weeks prior to screening
• Use of long-acting benzodiazepines or barbiturates within 4 weeks prior to screening
• Use of short-acting anxiolytics or sedative hypnotics more frequently than 2 times per week within 4 weeks prior to screening (note: sedative agents should not be used within 72 hours of screening)
• Initiation or change in dose of an antidepressant lacking significant cholinergic side effects within the 4 weeks prior to screening (use of stable doses of antidepressants for at least 4 weeks prior to screening is acceptable)
• Use of systemic corticosteroids within 3 months prior to screening
• Medications with significant cholinergic or anticholinergic side effects (e.g. pyridostigmine, tricyclic antidepressants, meclizine, and oxybutynin) within 4 weeks prior to screening
• Use of anti-convulsants (e.g. Phenytoin, Phenobarbital, Carbamazepine) within 2 months prior to screening
• Use of warfarin (Coumadin) within 4 weeks prior to screening
• Prior use of any FDA approved medications for the treatment of AD (e.g. tacrine, donepezil, or other newly approved medications)