Amyloid senile plaques (SPs) and neurofibrillary tangles (NFTs) are neuropathological hallmarks of Alzheimer's disease (AD) that also accumulate in key brain regions in association with normal aging. This project will expand an established program in early detection and prevention of AD designed (1) to identify presymptomatic persons most likely to benefit from early intervention and (2) to provide an objective, noninvasive means to monitor therapeutic trials.

A total of 194 volunteers will be recruited for this 2-year study. Participants will receive a baseline clinical and imaging evaluation and one follow-up evaluation two years later. These evaluations will include clinical and neuropsychological assessments, structural MRI and/or PET scans. Additional scans and scanning procedures will be performed on a subset of participants and participant visits, including serotonin density levels.

• Memory Disorders
• Alzheimer's Disease

• Controls
• Mild Cognitive Impairment
• Alzheimer's disease
• FTD

• Ercoli L, Siddarth P, Huang SC, Miller K, Bookheimer SY, Wright BC, Phelps ME, Small G. Perceived loss of memory ability and cerebral metabolic decline in persons with the apolipoprotein E-IV genetic risk for Alzheimer disease. Arch Gen Psychiatry. 2006 Apr;63(4):442-8.
• Kepe V, Barrio JR, Huang SC, Ercoli L, Siddarth P, Shoghi-Jadid K, Cole GM, Satyamurthy N, Cummings JL, Small GW, Phelps ME. Serotonin 1A receptors in the living brain of Alzheimer's disease patients. Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):702-7. Epub 2006 Jan 9.
• Small GW, Silverman DH, Siddarth P, Ercoli LM, Miller KJ, Lavretsky H, Wright BC, Bookheimer SY, Barrio JR, Phelps ME. Effects of a 14-day healthy longevity lifestyle program on cognition and brain function. Am J Geriatr Psychiatry. 2006 Jun;14(6):538-45.

Inclusion Criteria:

• Agreement to participate in a clinical and brain imaging study
• Age 30 years or older
• No significant cerebrovascular disease - modified Ischemic Score of ≤ 4
• For volunteers with MCI or dementia, there must be a family member or potential caregiver available
• Adequate visual and auditory acuity to allow neuropsychological testing
• Screening laboratory tests and ECG without significant abnormalities that might interfere with the study.

Exclusion Criteria:

• Evidence of neurologic or other physical illness that could produce cognitive deterioration; in addition to a physical and neurological examination, volunteers will be screened for Parkinson's disease
• History of myocardial infarction within the previous year or unstable cardiac disease
• Uncontrolled hypertension (systolic BP>170 or diastolic BP>100), history of significant liver disease, clinically significant pulmonary disease, diabetes, or cancer
• Major psychiatric disorders, such as bipolar disorder or schizophrenia
• Because medications can affect cognitive functioning, volunteers needing medicines that could influence psychometric test results will be excluded; use of any of the following drugs will also exclude volunteers: centrally active beta-blockers, narcotics, clonidine, anti-Parkinsonian medications, benzodiazepines, systemic corticosteroids, and medications with significant cholinergic or anticholinergic effects, anti-convulsants, or warfarin
• Current diagnosis or history of alcoholism or drug dependence
• Evidence of untreated depression as determined by a HAM-D (Hamilton, 1960) score of ≥ 12 (17-item version) or untreated anxiety by a score of ≥ 8 on the Hamilton Anxiety Scale (HAM-A; Hamilton, 1959)
• Use of any investigational drugs within the previous month or longer, depending on drug half-life
• Contraindication for MRI scan (e.g., metal in body, claustrophobia)