Light therapy for sleep disturbances in older adults with dementia: a systematic review, meta-analysis and meta-regression.

BACKGROUND: Sleep disturbances in older adults with dementia are common. Light therapy may help in regulating their sleep or wake cycle. However, data in the literature on the effectiveness of light therapy for the people with the said condition remain inconclusive. Thus, further research is warranted. OBJECTIVES: This review aims to synthesize the best available evidence on the effectiveness of light therapy in reducing sleep disturbances among older adults with dementia. METHODS: PubMed, Embase, Scopus, CINAHL, Cochrane Library, ALOIS, PsycInfo, Web of Science, ProQuest, OpenGrey, various trial registries and different journals specializing on sleep were searched without limitations on the year of publication. Cochrane's Risk of Bias Tool version 1 and GRADE criteria were used to assess risk of bias and certainty of evidence, respectively. Meta-analysis and meta-regression analyses were conducted using Stata software. RESULTS: A total of 18 randomized controlled trials (RCTs) involving 1012 older persons with dementia were included. The meta-analysis revealed that light therapy significantly reduced night-time awakenings (p = 0.04), enhanced sleep quality (p = 0.01) and increased relative amplitude (p = 0.01) with a small to medium effect (g = 0.26-0.43). Subgroup analyses showed that studies conducted in the Western Pacific region had a larger effect size on sleep duration and efficiency than those conducted in other regions. Univariate random-effects meta-regression revealed that sample size was a significant covariate for the effect size of sleep duration and sleep efficiency. CONCLUSION: This study found that the majority of outcomes had a low level of certainty. Therefore, additional well-designed and large-scale trials must be conducted to achieve a more definitive conclusion.

CED-4 CARD domain residues can modulate non-apoptotic neuronal regeneration functions independently from apoptosis.

A major challenge in regenerative medicine is the repair of injured neurons. Regeneration of laser-cut C. elegans neurons requires early action of core apoptosis activator CED-4/Apaf1 and CED-3/caspase. While testing models for CED-4 as a candidate calcium-sensitive activator of repair, we unexpectedly discovered that amino acid substitutions affecting alpha-helix-6 within the CED-4 caspase recruitment domain (CARD) confer a CED-4 gain-of-function (gf) activity that increases axonal regrowth without disrupting CED-4 apoptosis activity. The in vivo caspase reporter CA-GFP reveals a rapid localized increase in caspase activity upon axotomy, which is absent in ced-4 and ced-3 loss-of-function mutants but present in the ced-4(gf) mutant. The ced-3 loss-of-function mutation can significantly suppress the axonal regrowth of the ced-4(gf) mutant, indicating that CED-4(gf) regeneration depends on CED-3 caspase. Thus, we identified a subdomain within the CED-4 CARD that regulates the dynamic and controlled caspase activity required for efficient regeneration.