Guanfacine Treatment for Prefrontal Cognitive Dysfunction in Elderly Subjects

Primary:

- To determine whether low does of the α2A-adrenoceptor agonist guanfacine can improve
deficits in prefrontally-mediated working memory and executive control functions, in
healthy elderly subjects. Subjects will be randomly assigned to receive placebo or
guanfacine at one of two dose levels: 0.1 mg, or 0.5 mg daily at bedtime in
double-blind fashion for twelve weeks.

Secondary:

- To determine whether guanfacine can favorably influence global status and quality of
life (QOL) in healthy elderly subjects.

- To determine whether low-dose guanfacine is safe and well-tolerated in healthy elderly
subjects.

Inclusion Criteria:

Subjects enrolled will be nondemented, male and female individuals who meet the following
inclusion criteria:

- 75 years of age or older

- Fluent in English

- Stable medical condition for at least 4 weeks prior to Screening visit

- Stable dose of non-excluded medications for at least 4 weeks prior to Screening visit

Exclusion Criteria:

- Dementia

- Mild Cognitive Impairment (Amnestic MCI)

- Clinically significant neurologic disease

- Clinically significant or unstable medical conditions that would interfere with
participation in the trial

- Known hypersensitivity to guanfacine

- History of alcohol or substance abuse or dependence within the past 5 years

- Active major psychiatric disorders, including major depression

- History of mental retardation

- Significant abnormalities on clinical laboratories, ECG, or physical examination

- Impairment of visual or auditory acuity sufficient to interfere with completion of
study procedures

- Education level < 6 years