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Randomized Controlled Trial
. 2018 Oct:70:117-124.
doi: 10.1016/j.neurobiolaging.2018.05.033. Epub 2018 May 31.

Guanfacine treatment for prefrontal cognitive dysfunction in older participants: a randomized clinical trial

Nicole M Barcelos  1 , Peter H Van Ness  2 , Allison F Wagner  1 , Martha G MacAvoy  1 , Adam P Mecca  1 , George M Anderson  3 , Mark Trentalange  2 , Keith A Hawkins  4 , Mary Sano  5 , Amy F T Arnsten  6 , Christopher H van Dyck  7
Affiliations
Randomized Controlled Trial

Guanfacine treatment for prefrontal cognitive dysfunction in older participants: a randomized clinical trial

Nicole M Barcelos et al. Neurobiol Aging. 2018 Oct.

Abstract

This study evaluated the effect of the alpha-2A-adrenoceptor agonist guanfacine on prefrontally mediated cognitive functions, as well as quality of life and global function in healthy older participants. One hundred twenty-three participants aged 75 years and older were randomly assigned to guanfacine 0.5 mg, 0.1 mg, or placebo daily for 12 weeks. The primary outcome measure was the change in z-score for 6 prefrontal executive function tasks over 12 weeks (PEF6). Neither dose of guanfacine improved PEF6 z-score relative to placebo. The rate of mean change (95% confidence interval) in PEF6 z-score over 12 weeks was 0.270 (0.159, 0.380) for placebo, compared with 0.121 (0.011, 0.232) for guanfacine 0.1 mg (p = 0.06, compared to placebo) and 0.213 (0.101, 0.324) for 0.5 mg (p = 0.47). Neither dose of guanfacine improved the quality of life or global function relative to placebo. Among common adverse events, only dry mouth was significantly more frequent on guanfacine compared to placebo. Guanfacine failed to ameliorate prefrontal cognitive function in older individuals, who were cognitively normal for age.

Keywords: Brain aging; Cognitive aging; Executive function; Guanfacine; Prefrontal cortex.

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Figures

Figure 1
Figure 1
CONSORT diagram reflecting flow of study participants through the study.
Figure 2
Figure 2. Effect of guanfacine treatment on prefrontal executive function (PEF6 z-score) in cognitively normal older participants.
Least squares means and 95% confidence limits are estimated from linear mixed effects models accounting for serial correlation among repeated PEF6 z-score measurements at three time-points (baseline, 6 weeks, and 12 weeks). Both the observed means (A) and the difference (from baseline) means (B) are shown after multivariable adjustments for age, education, and sex. Abbreviations: PEF6 z-score, mean of z-scores for 6 executive function tasks (CANTAB: Spatial Working Memory, Stockings of Cambridge, Intradimensional/Extradimensional Shift, Paired Associates Learning; Stroop Color Word Score, Trail Making Test B).
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