Experimental Improvement of Attention / Cognitive Speed Does Not Improve Memory in Multiple Sclerosis
Emily Dvorak1, Ilana Katz Sand1, James Sumowski1
1Neurology, Icahn School of Medicine At Mount Sinai
Objective:
To investigate whether atomoxetine (FDA-approved to improve attention) versus placebo improves memory in persons with MS.
Background:
Correlational studies link memory performance with attention and cognitive speed in persons with MS, which has led to the belief that inattention or slowed cognitive speed underlie MS memory deficits. This assumption has shaped memory rehabilitation approaches, which have been ineffective. Herein we used data from a pilot cross-over trial of atomoxetine in persons with MS to examine whether experimentally improving attention and cognitive speed improves memory.
Design/Methods:
Ten persons with MS with objective memory impairment (mean[sd] normative z: -1.86[0.55]) completed a double-blind randomized controlled crossover trial of atomoxetine (80mg daily) versus placebo for 14 weeks (two counterbalanced six-week phases separated by two-week washout). Primary memory outcome (MEMORY) was a composite of the Selective Reminding Test and Brief Visuospatial Memory Test, Revised. Patients also completed CANTAB Rapid Visual Information Processing (RVP) assessing sustained attention and cognitive speed during a six-minute continuous performance task requiring persons to monitor single-digit numbers rapidly presented onscreen to identify target three-digit sequences (e.g., 3-5-7). Paired two-tailed t-tests compared outcomes (norm-referenced z-scores) between placebo and drug after adjusting for counterbalanced order.
Results:
Improvement on RVP (attention / cognitive speed) from baseline was better on atomoxetine (mean[sd] z change: +0.57[0.48]) than placebo (+0.25[0.29]; t[9]=3.96, p=0.003, d=0.72). In contrast, change from baseline on MEMORY did not differ between atomoxetine (+0.32[0.76]) and placebo (+0.24[0.70]; t[9]=0.40, p=0.700, d=0.10).
Conclusions:
Experimental improvement of attention / cognitive speed with atomoxetine did not improve memory in persons with MS, which refutes correlational evidence linking these functions. We lack validated memory rehabilitation approaches, perhaps in part because attention / cognitive speed have been treatment targets. Renewed investigation of underlying mechanisms of MS memory impairment is necessary to develop strategies for memory rehabilitation.