Bright Light Therapy for Parkinson Disease: A Literature Review and Meta-Analysis of Randomized Controlled Trials.

Sleep disorders and depression are significant nonmotor symptoms (NMSs) of Parkinson disease (PD). However, few effective, evidence-proven medical treatments are available for alleviating these symptoms. Bright light therapy (BLT) is a well-established treatment for circadian rhythm sleep disorders and seasonal affective disorder. The present study conducted a literature review for the effect of BLT on PD, especially a meta-analysis of randomized controlled trials (RCTs). We searched for studies using the PubMed and Cochrane Library databases. The major outcomes were the effects on sleep and depression. The effect on motor symptoms was also analyzed as a secondary outcome. This study was registered with PROSPERO (CRD42020204454). Six studies were included in the literature review only, and the other five RCTs were included in the meta-analysis. Despite the positive effects of BLT on PD patients, which were demonstrated in noncontrolled studies, in the meta-analysis of the RCTs, BLT did not significantly improve the depressive symptoms (standardized mean difference (SMD): -0.15, 95% confidence interval (CI): -0.48 to 0.17, p = 0.36) and excessive daytime sleepiness (EDS) (SMD: -0.12, 95% CI: -0.49 to 0.25, p = 0.53) in PD patients. Regarding motor symptoms, no significant beneficial effects were conferred (SMD: -0.11, 95% CI: -0.44 to 0.21, p = 0.49). In conclusion, BLT did not significantly alleviate depression and sleepiness. The inconsistency between BLT protocols, such as the varied timing, dosages, and treatment durations, may render BLT's efficacy difficult to demonstrate. The small effect size obtained from the present meta-analysis indicates that future RCTs are necessary, for which BLT protocols are standardized and more patients are enrolled to determine whether a significant therapeutic benefit was conferred.

Coffee consumption and the risk of cerebrovascular disease: a meta-analysis of prospective cohort studies.

BACKGROUND: Stroke is a crucial health threat to adults worldwide. Despite extensive knowledge of risk-factor mitigation, no primary prevention exists for healthy people. Coffee is a widely consumed beverage globally. Health benefit of coffee for several neurological diseases has been identified; however, the association between stroke risk and coffee consumption in healthy people has not been determined. We investigated the effect of coffee on stroke risk by conducting a meta-analysis of prospective cohort studies. METHODS: Electronic databases, namely PubMed, BioMed Central, Medline, and Google Scholar, were searched using terms related to stroke and coffee. Articles that described clear diagnostic criteria for stroke and details on coffee consumption were included. The reference lists of relevant articles were reviewed to identify eligible studies not shortlisted using these terms. Enrolled studies were grouped into three outcome categories: overall stroke, hemorrhagic stroke, and ischemic stroke. RESULTS: Seven studies were included and all of them were large-scale, long-term, follow-up cohort studies of a healthy population. Upon comparing the least-coffee-consuming groups from each study, the meta-analysis revealed a reduction in the risk of overall stroke during follow-up (hazard ratio [HR] for overall stroke = 0.922, 95% confidence interval [CI] = 0.855-0.994, P = 0.035). In studies with a clear definition of hemorrhagic and ischemic stroke, coffee consumption reduced the risk of ischemic stroke more robustly than that of hemorrhagic stroke (hemorrhagic, HR = 0.895, 95% CI = 0.824-0.972, P = .008; ischemic, HR = 0.834, 95% CI = 0.739-0.876, P < .001). No obvious dose-dependent or U-shaped effect was observed. CONCLUSIONS: Coffee consumption reduces the risk of overall stroke, especially ischemic stroke. Further investigation is required to identify beneficial components in coffee, including caffeine and phenolic acids, to develop preventive medication for stroke.

Effects of concomitant use of hydrogen water and photobiomodulation on Parkinson disease: A pilot study.

BACKGROUND: Parkinson disease (PD), the second most common neurodegenerative disease, has no cure or applicable disease-modifying approach, only symptomatic therapy. Oxidative stress and mitochondrial dysfunction play key roles in PD pathophysiology. Animal studies have demonstrated that photobiomodulation (PBM) may enhance mitochondrial function and boost adenosine triphosphate production, thus alleviating PD symptoms; however, this process can cause increased reactive oxygen species (ROS) production. Molecular hydrogen (H2) is a potent and possibly therapeutic antioxidant that can mitigate the effect of ROS. PBM targeting the brainstem may facilitate neuronal activity, and the concomitant H2 may clear additional ROS produced by PBM. Therefore, this study aimed to determine the safety and effectiveness of PBM + H2 in patients with PD. METHODS: We included 18 patients with PD (age 30-80 years) who were at Hoehn and Yahr stages II-III. All the participants received daily PBM + H2 therapy for 2 weeks. The adverse event and the Unified Parkinson Disease Rating Scale (UPDRS) scores were recorded. RESULTS: We noted that the UPDRS scores began significantly decreasing from the first week, and this improvement persisted until the end of therapy. Moreover, no adverse event was recorded. After 1 week of therapy cessation, UPDRS scores slightly increased but the improvement remained significant compared with the baseline. CONCLUSION: This novel, proof-of-concept study demonstrated that PBM+H2 therapy is safe and reduces disease severity. A larger-scaled clinical trial is warranted to completely investigate the effects of PBM + H2 therapy on PD.

The Effect of Caffeine on the Risk and Progression of Parkinson's Disease: A Meta-Analysis.

Coffee and caffeine are speculated to be associated with the reduced risk of Parkinson's disease (PD). The present study aimed to investigate the disease-modifying potential of caffeine on PD, either for healthy people or patients, through a meta-analysis. The electronic databases were searched using terms related to PD and coffee and caffeinated food products. Articles were included only upon fulfillment of clear diagnostic criteria for PD and details regarding their caffeine content. Reference lists of relevant articles were reviewed to identify eligible studies not shortlisted using these terms. In total, the present study enrolled 13 studies, nine were categorized into a healthy cohort and the rest into a PD cohort. The individuals in the healthy cohort with regular caffeine consumption had a significantly lower risk of PD during follow-up evaluation (hazard ratio (HR) = 0.797, 95% CI = 0.748-0.849, p < 0.001). The outcomes of disease progression in PD cohorts included dyskinesia, motor fluctuation, symptom onset, and levodopa initiation. Individuals consuming caffeine presented a significantly lower rate of PD progression (HR = 0.834, 95% CI = 0.707-0.984, p = 0.03). In conclusion, caffeine modified disease risk and progression in PD, among both healthy individuals or those with PD. Potential biological benefits, such as those obtained from adenosine 2A receptor antagonism, may require further investigation for designing new drugs.

Association Between Anemia and Dementia: A Nationwide, Populationbased Cohort Study in Taiwan.

BACKGROUND: In addition to the traditional risk predictors, whether anemia is an early biomarker of dementia, needs to be confirmed. OBJECTIVE: This population-based cohort study aimed to investigate the dementia risk in patients with newly diagnosed anemia using data from the Taiwan National Health Insurance Research Database. METHODS: All newly diagnosed anemia patients (n = 26,343) with no history of stroke hospitalization, central nervous disease other than dementia, psychiatric disorders, traumatic brain injury, major operations, or blood loss diseases, were enrolled. A group of non-anemic controls, 1:4 matched with anemic patients on the basis of demographics and comorbidities, was also included. A competing risk analysis was used to evaluate the dementia risk in anemic patients compared to that of their matched controls. RESULTS: The adjusted subdistribution hazard ratio (SHR) of dementia risk in anemic patients was 1.14 (95% confidence interval [CI]: 1.08~1.21, p<0.001). Patients with iron supplements tended to exhibit a lower dementia risk (adjusted SHR: 0.84; 95% CI: 0.75~0.94, p=0.002) compared to patients without iron supplement. A subgroup analysis showed that a positive association between dementia and anemia existed in females, those aged 70 years and older, and patients without hypertension, diabetes, or hyperlipidemia. CONCLUSION: The present population-based cohort study identified that newly diagnosed anemia is a risk factor for dementia and also that iron supplementation was able to reduce the risk of dementia in people with iron deficiency anemia.

Suboptimal Baseline Serum Vitamin B12 Is Associated With Cognitive Decline in People With Alzheimer's Disease Undergoing Cholinesterase Inhibitor Treatment.

OBJECTIVES: Cholinesterase inhibitors (ChEIs) are the mainstream treatment for delaying cognitive decline in Alzheimer's disease (AD). Low vitamin B12 is associated with cognitive dysfunction, and its supplementation has been applied as the treatment for certain types of reversible dementia. The present study hypothesized that baseline serum vitamin B12 is associated with the deterioration of cognitive function in people with AD undergoing ChEI treatment. MATERIALS AND METHODS: Between 2009 and 2016, medical records from 165 Taiwanese with mild to moderate AD who underwent ChEI treatment for at least 2 years were reviewed. Their baseline serum vitamin B12 levels were measured before treatment initiation. Their cognitive function was assessed using the Mini-Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI). Student's t test and multivariable logistic regression were used to analyze the association between cognitive decline and vitamin B12 level. Statistical analyses were performed using SPSS 19.0. RESULTS: Overall, 122 participants were women. Their median age was 76 years (ranging from 54 to 91). For people with optimal baseline vitamin B12 (above the median level of 436 ng/L), the rates of MMSE and CASI decline were 0.78 ± 1.28 and 2.84 ± 4.21 per year, respectively, which were significantly slower than those with suboptimal vitamin B12 (1.42 ± 1.67 and 4.94 ± 5.88 per year; p = 0.007 and 0.009, respectively). After adjustment for age, sex, education level, hypertension, diabetes, history of stroke, and baseline cognitive function, the baseline serum vitamin B12 level was negatively associated with MMSE and CASI decline. CONCLUSION: Suboptimal baseline serum vitamin B12 level is associated with cognitive decline in people with AD undergoing ChEI treatment.

Newly Diagnosed Anemia Increases Risk of Parkinson's disease: A Population-Based Cohort Study.

Anemia and low hemoglobin have been identified to increase Parkinson's disease (PD) risk. This population-based cohort study investigated PD risk in newly diagnosed anemic patients by using data from the Taiwan National Health Insurance Research Database. All newly diagnosed anemic patients (n = 86,334) without a history of stroke, neurodegenerative diseases, traumatic brain injury, major operations, or blood loss diseases were enrolled. A cohort of nonanemic controls, 1:1 matched with anemic patients on the basis of the demographics and pre-existing medical conditions, was also included. Competing risk analysis was used to evaluate PD risk in anemic patients compared with that in their matched controls. The adjusted hazard ratio (aHR) of PD risk in the anemic patients was 1.36 (95% confidence interval [CI]: 1.22-1.52, p < 0.001). Iron deficiency anemia (IDA) patients tended to exhibit a higher PD risk (aHR: 1.49; 95% CI: 1.24-1.79, p < 0.001). Furthermore, Iron supplement did not significantly affect the PD risk: the aHRs for PD risk were 1.32 (95% CI: 1.07-1.63, p < 0.01) and 1.86 (95% CI: 1.46-2.35, p < 0.001) in IDA patients with and without iron supplementation, respectively. The population-based cohort study indicated newly diagnosed anemia increases PD risk.