Galantamine Improves Gait Performance in Patients With Alzheimer's Disease

To the Editor: Acetylcholine esterase inhibitors (ACEIns) (e.g., donepezil, galantamine, and rivastigmine) are current symptomatic treatments for Alzheimer's disease (AD),1 but they have not been found to prevent or reduce AD-related gait disorders. Recently, it has been shown that impaired executive functions (IEFs) were strongly related to dual-task–related gait changes in patients with dementia.2 Given that ACEIns are known to improve attention and executive function in AD,3 it was hypothesized that ACEIns would also improve dual-task–related gait changes in subjects with AD. Nine subjects with mild to moderate AD (66.7% women, mean age 77.9±2.1, mean Mini-Mental State Examination (MMSE) score 26.4±5.2 at baseline and 22.8±5.3 after 24 weeks of galantamine treatment, mean dose of galantamine after 24 weeks 17.8±3.5 mg/d) according to standard criteria and 18 no-treatment control subjects without dementia (88.9% women, mean age 78.1±1.0, mean MMSE score 29.4±0.8) were included. All subjects underwent neurological examination and neuropsychological testing, and subjects with AD had a magnetic resonance imaging scan. Subjects with extrapyramidal rigidity of the upper limbs; acute medical illness in the previous month; depression; alcoholism; severe orthopedic diagnoses involving the lumber vertebra, pelvis, or lower extremities; using walking aids; anticholinergic medication; or with a contraindication to ACEIns were excluded. The local ethics committee approved the project. Mean values of stride time were determined before and after 6 months of galantamine treatment while single-tasking (only walking) and while dual-tasking (walking while counting backward from 50 aloud). Both walking conditions were measured during steady-state walking on a 10-m walkway using a GAITRite-System (CIR Systems Inc., Havertown, PA) according to the European guidelines for spatiotemporal gait analysis.4 Participants performed the backward-counting task while sitting and walking. Comparisons between the before and after treatment conditions were performed with Wilcoxon matched-pairs signed-ranks tests. Given the directional hypothesis, one-sided P<.05 was considered statistically significant. There was no significant difference between stride time before and after galantamine treatment within walking conditions (P=.09 for single tasking and P=.77 for dual-tasking). Stride time was significantly longer under dual-tasking than walking alone before treatment (P=.01) but not after (P=.09). There were no significant gait changes at all in the no-treatment control group (P=.74). MMSE scores of subjects with AD were significantly lower (P=.02). Mean number of enumerated digits during the backward-counting task did not differ significantly between single- and dual-tasking conditions or between the treatment and no-treatment groups (P=.50 for control group and P=.62 and P=1.00 before and after galantamine, respectively, for the group with AD) (Table 1). These results confirm that subjects with AD and no galantamine treatment showed a significant increase in stride time under dual-task conditions.5 This change in gait parameters is a marker of an inability to appropriately adapt allocation of attention between gait and a walking-associated attention-demanding task with a resulting greater risk of falling.6 In addition, this report is, to our knowledge, the first to demonstrate improvement in gait performance after treatment with galantamine. The absence of a significant increase in stride time while dual-tasking in subjects with AD treated with galantamine suggests a galantamine-associated enhancement of the ability to adapt gait patterns to unexpected situations. If these open-label data can be reproduced and confirmed in a prospective, double-blind, placebo-controlled study design, patients with AD with greater falls risk might benefit from galantamine treatment. We thank Dr. P. McNamara for his helpful revision of the manuscript. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the author and has determined that none of the authors have any financial or any other kind of personal conflicts with this letter. Author Contributions: F. Assal, G. Allali, R.W. Kressig, O. Beauchet: study concept and design. G. Allali, O. Beauchet, F. Assal: acquisition of data. F.R. Hermann, O. Beauchet, G. Allali, R.W. Kressig, F. Assal: analysis and interpretation of data. All authors: preparation of the letter. Sponsor's Role: None.