Guanfacine Treatment for Prefrontal Cognitive Dysfunction in Elderly Subjects

Not Applicable

Completed

Brief Summary: This proposal aims to determine whether low does of the alpha-2A-adrenoceptor agonist guanfacine can improve deficits in prefrontally-mediated cognitive functions in healthy elderly subjects.

Detailed Description: 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.

Recruitment & Eligibility

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

Arm && Interventions

Primary Outcome Measures

Name	Time	Method
Mean in the Prefrontal Executive Function Z-score (PEF6_6)	12 weeks	The primary outcome measure (PEF6_Z) is the mean of z-scores for 6 executive function tasks (CANTAB: Spatial Working Memory, Stockings of Cambridge, Intradimensiona/Extradimensional Shift, Paired Associates Learning; Stroop Color Word Score, Trail Making Test - B). The score is composed of six component scales coded as z scores that measures cognitive functioning in which higher scores represent better cognitive functioning; therefore, the least squares means listed here represent mean outcome changes from baseline

Secondary Outcome Measures

Name	Time	Method
Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC)	12 weeks	The seven-point scale was collapsed into 3 groups and coded as a three-level ordinal scale of global status, representing ordered levels of worse (including minimally, moderately and markedly worse), unchanged, and improved (including minimally, moderately, and markedly improved) global status.
Quality of Life (SF-36 MCS)	12 weeks	Quality of Life (QOL) was assessed using the SF-36 (36-Item Short-Form Health Survey; QualityMetric, Lincoln, RI), MCS subscale. The SF-36 is a self-administered general health-related quality of life scale with 36 items. The MCS subscale has been shown to be responsive in psychoactive drug trials. The score range is 0-100. Higher scores represent better mental health; therefore, the least squares means listed here represent mean outcome changes from baseline.