Pharmacological and Non-Pharmacological Interventions to Improve Sleep in People with Cognitive Impairment: A Systematic Review and Meta-Analysis

Sleep disturbance is common among people with cognitive impairment and, when present, is an important target for intervention because it potentially leads to negative outcomes and cognitive decline. Given this association, sleep represents a potential public health target, although evidence for efficacy is lacking. For this study, a systematic review and meta-analysis was undertaken of controlled clinical trials of pharmacological and non-pharmacological interventions to improve sleep in mild cognitive impairment and dementia. A total of 144 trials involving 13,471 participants (median 50 per trial) were included. To measure sleep, 68 trials used subjective measures exclusively, and 41 used only objective measures, while 35 used a combination. In all, 287 discrete sleep outcome measures were reported. Bright light therapy was the most frequently examined non-pharmacological intervention, but results were equivocal. Other non-pharmacological interventions (such as physical activity, cognitive behavioural therapy for insomnia, music, and continuous positive airway pressure) showed promise but require further evidence. Results for melatonin, the most frequently examined pharmacological intervention, were inconclusive, but lower doses may be more effective. Other pharmacological interventions (such as trazadone and orexin-receptor antagonists) demonstrated effectiveness in a small number of trials but require further evidence. Overall, there is insufficient evidence upon which to base clinical decisions regarding the treatment of sleep disturbance in this population. Existing research is marked by wide heterogeneity, which limits opportunities for data synthesis. A core outcome set is urgently required to ensure that future research provides more coherent and reliable evidence to improve outcomes for people with cognitive impairment and sleep disturbance.