Table 1.

Detailed inclusion and exclusion criteria

Inclusion criteria

1. Age > 84 years

2. No subjective complaint of memory impairment compared to others of their own age

3. Has not sought assessment for memory or cognitive dysfunction

4. Normal memory function defined by an education-adjusted score on the Logical Memory Subscale of the Wechsler Memory Scale-Revised:

a. >8 for 16 or more years of education

b. > or = 4 for 8-15 years of education

c. >2 for 0 -7 years of education

5. Mini-Mental State Examination score >23

6. Blessed Orientation Memory Concentration Test (Telephone Screen) <12

7. Functionally independent (ADL= 0)

8. Clinical Dementia Rating = 0

9. Absence of significant depressive symptoms: CES-D-10 score < 4

10. Sufficient vision and hearing to complete all testing

11. Sufficient English language skills to complete all testing

12. General health status that will not interfere with ability to complete longitudinal study (conditions that will likely lead to this problem are listed below in the study exclusions list)

13. Informant available with frequent (at least 1 hour per day 3 days a week) contact with subject to verify functional status.

Exclusion criteria

1. Diseases associated with dementia such as Alzheimer disease, ischemic vascular dementia, normal pressure hydrocephalus, or Parkinson disease

2. Significant disease of the CNS such as brain tumor, seizure disorder, subdural hematoma, cranial arteritis

3. Current (within the last 2 years) alcohol or substance abuse according to DSM-IV criteria

4. Major depression, schizophrenia, or other major psychiatric disorder defined by DSM-IV criteria

5. Abnormal laboratory values indicating B12 deficiency, thyroid disease, or urinary tract infection (documented chronic bacterial colonization is acceptable)

6. Unstable or significantly symptomatic cardiovascular disease such as coronary artery disease with frequent angina, or congestive heart failure with shortness of breath at rest

7. Insulin dependent diabetes mellitus

8. Active systemic cancer within 5 years of study entry (Gleason Grade <3 prostate cancer, and non-metastatic skin cancers are acceptable)

9. Illness that requires >1 visit per month to a clinician

10. Progressive vision loss (age-related macular degeneration already beginning to significantly degrade vision)

11. Need for oxygen supplementation for adequate function

12. Medications:

a. Frequent use of high doses of analgesics

b. Sedative medications except for those used occasionally for sleep (use limited to no more than twice per week)

c. Subjects taking CNS-active medications that have not been on stable doses for at least 2 months including cimetidine, beta-blockers, and selective serotonin reuptake inhibitors

d. Subjects taking neuroleptics, antiparkinsonian agents, systemic corticosteroids, and narcotic analgesics; in the case where these were used for a self-limited time they must have been discontinued for a period of five half-lives prior to baseline

e. Subjects will not be excluded if they are taking other over-the-counter supplements, but the dose must not be changed during the course of the trial unless medically indicated; the presence and dose of these agents will be recorded

f. Subjects taking cholinesterase inhibitors

g. Use of investigational drugs within five half-lives prior to baseline

ADL = activities of daily living; CES-D = Center for Epidemiologic Studies Depression Scale; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders.