New onset executive function difficulties at menopause: a possible role for lisdexamfetamine

Abstract

Rationale: Reports of cognitive decline, particularly in the domains of executive functions (EFs), are common among menopausal women.

Objective: This study aims to determine the impact of the psychostimulant lisdexamfetamine (LDX) on subjective and objective cognitive function among menopausal women who report new-onset EF complaints.

Methods: Thirty-two healthy perimenopausal and early postmenopausal women experiencing mid-life-onset executive function difficulties as measured using the Brown Attention Deficit Disorder Scale (BADDS) were administered LDX 40-60 mg/day for 4 weeks in this double-blind, placebo-controlled, cross-over study. Diagnosis of lifetime ADHD was exclusionary. BADDS total and subscale scores and performance on verbal memory and working memory tasks were outcomes of interest.

Results: Analyses revealed a significant effect of LDX treatment over placebo for total BADDS scores (p = 0.0001) and for four out of the five BADDS subscales (all p < 0.004). LDX treatment also resulted in significant improvement in delayed paragraph recall (p = 0.018), but there was no significant effect of treatment on other cognitive measures. Systolic blood pressure (p = 0.017) and heart rate increased significantly (p = 0.006) when women were on LDX but remained, on average, within the normal range.

Conclusions: LDX 40-60 mg/day was well tolerated and improved the subjective measures of executive function as well as objective measures of delayed verbal recall in this sample of healthy menopausal women.

Fig. 1

BADDS scores across the study. Non-parametric mixed models to compare ranks of change-from-baseline scores indicate a significant effect of active treatment on total BADDS scores (numerator degrees of freedom (num df=1, ATS= 15.42, p<0.001). Bars represent standard deviations

Fig. 2

Lisdexamfetamine treatment effects on five domains of executive function as assessed by the BADDS subscale scores. Change from baseline was greater with LDX versus placebo for all BADDS subscales except for managing affective interference (p=0.11). For organization and activation, num df=1, ATS=8.69, p=0.003; for attention and concentration, num df=1, ATS=11.46, p<0.001; for alertness/effort/processing speed, num df=1, ATS=10.89, p=0.001; for working memory/accessing recall, num df=1, ATS=10.89, p=0.001. Bars represent standard deviations

Fig. 3

Delayed verbal recall at baseline and at the end of each treatment arm. Means and standard deviations for the NYU Paragraph Recall Task (delayed). Non-parametric mixed models to compare ranks of change-from-baseline scores indicate a significant effect of active treatment on performance on paragraph A (num df=1, ATS=4.07, p=0.44) and paragraph B (num df=1, ATS=5.59, p=0.018). Bars represent standard deviations. Bars represent standard deviations