Nutraceuticals have been taken as an alternative and add-on treatment for depressive disorders. Direct comparisons between different nutraceuticals and between nutraceuticals and placebo or antidepressants are limited. Thus, it is unclear which nutraceuticals are the most efficacious.

We conducted a network meta-analysis to estimate the comparative efficacy and tolerability of nutraceuticals for the treatment of depressive disorder in adults. The primary outcome was the change in depressive symptoms, as measured by the standard mean difference (SMD). Secondary outcomes included response rate, remission rate, and anxiety. Tolerability was defined as all-cause discontinuation and adverse events. Frequentist random-effect NMA was conducted.

Hundred and ninety-two trials involving 17,437 patients and 44 nutraceuticals were eligible for inclusion. Adjunctive nutraceuticals consistently showed better efficacy than antidepressants (ADT) alone in outcomes including SMD, remission, and response. Notable combinations were Eicosapentaenoic acid + Docosahexaenoic Acid plus ADT (EPA + DHA + ADT) (SMD 1.04, 95% confidence interval 0.64–1.44), S-Adenosyl Methionine (SAMe) + ADT (0.99, 0.31–1.68), curcumin + ADT (1.03, 0.55–1.51), Zinc + ADT (1.59, 0.63–2.55), tryptophan + ADT (1.24, 0.32–2.16), and folate + ADT (0.64, 0.17–1.10). Additionally, four nutraceutical monotherapies demonstrated superior efficacy compared to ADT: EPA + DHA (0.6, 0.32–0.88), SAMe (0.52, 0.18–0.87), curcumin (0.62, −0.17 to 1.40) and saffron (0.69, 0.34–1.04). It is noted that EPA + DHA, SAMe, and curcumin showed strong performance as either monotherapies or adjuncts to ADT. Most nutraceuticals showed comparable tolerability to placebo.

This extensive systematic review and NMA of nutraceuticals for treating depressive disorders indicated a number of nutraceuticals that could offer benefits, either as adjuncts or monotherapies.

The exploration of molecular characteristics has emerged as a prominent trend to advance precision medicine. The utilization of genetic testing to guide therapy is integral to precision medicine. This study aims to investigate the potential patient populations for the reimbursement of next-generation sequencing (NGS) and assess the budget impact from the perspective of Taiwan’s single insurer, the National Health Insurance Administration.

To comprehend the scope for medicines with companion diagnostics (CDx) involved, we analyze the U.S. Food and Drug Administration-approved/cleared diagnostic tests, conduct a literature review to identify medicines approved by the European Medicines Agency that require a CDx, and identify the medicines with CDx involved covered by the National Health Insurance (NHI) in Taiwan. Subsequently, we explore the potential reimbursement indications for NGS testing and conduct a budget impact analysis to evaluate the expected financial impact for the NHI over a five-year period. Furthermore, sensitivity analyses are conducted to deal with uncertainty.

We have compiled 13 cancer types for which NGS can serve as a companion diagnostic. These encompass non-small-cell lung cancer, colorectal cancer, breast cancer, ovarian cancer, biliary tract cancer, acute myeloid leukemia, acute lymphoblastic leukemia, melanoma, cholangiocarcinoma, prostate cancer, pancreatic cancer, gastrointestinal stromal tumor, and thyroid cancer/medullary thyroid cancer. The implementation of NGS reimbursement in NHI will benefit 25,000 to 30,000 patients undergoing targeted therapies. The projected incremental budget impact ranges from TWD570 million to TWD650 million (USD19 million to USD22 million) over five years.

This study focuses on evaluating the financial impact of incorporating NGS testing into NHI reimbursement for relevant cancer drug indications. The findings can serve as references for the planning of reimbursement policies. However, with the advancement of precision medicine, it is foreseeable that there will be a broader range of applications for NGS, and its cost will gradually decrease.

Whether material deprivation-related childhood socio-economic disadvantages (CSD) and care-related adverse childhood experiences (ACE) have different impacts on depressive symptoms in middle-aged and older people is unclear.

In the Guangzhou Biobank Cohort Study, CSD and ACE were assessed by 7 and 5 culturally sensitive questions, respectively, on 8,716 participants aged 50+. Depressive symptoms were measured by 15-item Geriatric Depression Scale (GDS). Multivariable linear regression, stratification analyses, and mediation analyses were done.

Higher CSD and ACE scores were associated with higher GDS score in dose-response manner (P for trend <0.001). Participants with one point increment in CSD and ACE had higher GDS score by 0.11 (95% confidence interval [CI], 0.09–0.14) and 0.41 (95% CI, 0.35–0.47), respectively. The association of CSD with GDS score was significant in women only (P for sex interaction <0.001; women: β (95% CI)=0.14 (0.11–0.17), men: 0.04 (−0.01 to 0.08)). The association between ACE and GDS score was stronger in participants with high social deprivation index (SDI) (P for interaction = 0.01; low SDI: β (95% CI)=0.36 (0.29–0.43), high SDI: 0.64 (0.48–0.80)). The proportion of association of CSD and ACE scores with GDS score mediated via education was 20.11% and 2.28%.

CSD and ACE were associated with late-life depressive symptoms with dose-response patterns, especially in women and those with low adulthood socio-economic status. Education was a major mediator for CSD but not ACE. Eliminating ACE should be a top priority.

tDCS application to the DLPFC is associated with the improvements of executive function, memory enhancement, language, processing speed, global cognitive symptoms and apathy over time after treatment. DLB is the second most common form of degenerative dementia. There is no FDA-approved medications that can slow, stop or improve the progression of cognitive declines in DLB. Identifying effective treatments is a critical issue for DLB. In neuropathology, extracelluar α-syn oligomers interfere with the expression of long-term potentiation(LTP), and influence memory and learning. tDCS has been proposed to affect long-term synaptic plasticity through LTP and long-term depression, thereby improving cognitive ability. So far, only two studies have evaluated the effect of tDCS in DLB. In this pilot study, we investigate the effect of tDCS on left DLPFC in DLB.

Fourteen DLB aged 55-90 years (mean age 76.4, with 4 males and 10 females) were included in a double-blind, randomized, sham-controlled cross over design study. DLB diagnostics is according to DSM-5 criteria. CDR ratings for DLB participants ranged from 0.5 to 2. The active tDCS (or sham) process consists of daily sessions of active tDCS (or sham) for 10 consecutive days. The anodal electrode was placed over the left DLPFC and the cathodal electrode was placed over the right supraorbital area, with a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min in a session. Before and after these treatment sessions, all subjects received a series of neuropsychological tests, including CDR, MMSE, CASI, NPI and WCST. Chi-square test, Wilcoxon signed ranks test and Mann-Whitney U test were used to assess differences in participant demographic characteristics and to compare differences among groups.

The active tDCS group showed significant improvements on the three items of CASI, ‘language ability’, ‘concentration and calculation’, ‘categorical verbal fluency’, after active stimulations. There is no improvement in MMSE, CASI, NPI and WCST scores in the sham groups.

These results suggest that left DLPFC anodal, and right deltoid cathodal tDCS, may have some cognitive benefits in DLB. Larger-scale trials are needed to confirm the effect of tDCS in DLB.

Key words: Transcranial Direct Current Stimulation, Dementia with Lewy Bodies, cognitive function, Wisconsin Card Sorting Test, left DLPFC

Transcranial direct current stimulation (tDCS) has been proposed to affect long-term synaptic plasticity through LTP and LTD, thereby improving cognitive ability. In pathology, the amyloid deposits in AD disrupts the balance between long-term potentiation (LTP) and long-term depression (LTD) of neuronal cells and synaptic plasticity. An increasing number of studies have been concluded a positive therapeutic effect on cognition in AD. In brain stimulation, dorsolateral prefrontal cortex (DLPFC) was associated with improvements in memory enhancement, language, processing speed, global cognitive symptoms, and apathy over a period of treatment. Theoretically, the aftereffect of tDCS would need to be re-stimulated by tDCS to maintain its delayed plastic response benefits. In this pilot study, we investigate the maintenance effects of continuing tDCS at three different times, weekly, every two weeks, and every four weeks, for 12 weeks.

Twenty-eight AD participants aged 55-90 years were enrolled (mean age 72.7, 77.3, and 76.2 in the three groups - maintained weekly (7 cases), biweekly (9 cases) and every 4 weeks (12 cases)). The anodal electrode was placed over the left dorsal lateral prefrontal cortex and the cathodal electrode was placed over the right supraorbital area. In each active session, we applied a current intensity of 2 mA and an electrode size of 25 cm2 for 30 min. All subjects received a series of neuropsychological assessments including CDR, MMSE, CASI and WCST at (1) baseline, (2) post-10sessions of tDCS (in 2weeks), and (3) post-maintenance phase (total of 12 weeks). Chi-square tests, Wilcoxon signed rank tests and Mann-Whitney U tests were used to assess differences in participant demographic characteristics and to compare differences in test scores between groups.

After 10 sessions of tDCS stimulations, the total CASI scores in the 1-week group improved significantly from baseline to 2 weeks. However, there are no significant difference in MMSE, CASI or WCST between baseline and after maintain phase stimulations in each group.

Although tDCS has a positive effect in AD, it is recommended to prolong the number of tDCS stimulations, such as 20 sessions in 4 weeks.

Cognitive impairment is a growing problem with increasing burden in ageing global population. Older adults with major depressive disorder (MDD) have higher risk of dementia during ageing. Neurofilament light chain (NfL) has been proven as a potential biomarker related to dementia. The present study aims to assess the cognitive deficits in older adults with MDD and investigate their association with peripheral blood levels of NfL.

We enrolled 39 individuals with MDD and 15 individuals with mild neurocognitive disorder or major neurocognitive disorder, Alzheimer’s type. Both groups were over age 65 and with restricted Mini-Mental State Examination (MMSE) score. Demographic data, clinical variables, and plasma NfL levels were obtained. We used cluster analysis according to their cognitive profile and estimated the correlation between plasma NfL levels and cognitive impairment in each domain.

In the MDD group, participants have higher rate of family psychiatry history and higher rate of current alcohol use habit compared with patients with neurocognitive disorders. In the neurocognitive disorders group, participants showed significantly lower score in total MMSE and higher plasma NfL levels. Part of the MDD patients presented cognitive deficits similar to that of neurocognitive disorders (cluster A). In cluster A, the total MMSE score (r=-0.58277, p=0.0287) and the comprehension domain (r=-0.71717, p=0.0039) were negatively correlated to NfL levels after adjusting for age, while the associations had not been observed in the other cluster.

We noted the negative correlation between NfL levels and cognitive performance in MDD patients whose cognitive manifestation were more similar to that of degenerative neurocognitive disorders. NfL might be a potential marker to predict patients with MDD to develop cognitive decline especially in domains typically found in Alzheimer’s disease. Further longitudinal studies are required to validate our findings for clinical implications.

Despite mounting evidence demonstrates circulating endothelial progenitor cells (cEPCs) quantitative changes in depression, no study has investigated cEPC functions in major depressive disorder (MDD). We investigated the role of cEPC adhesive and apoptotic functions in MDD.

We recruited 68 patients with MDD and 56 healthy controls (HCs). The depression symptoms, anxiety, psychosomatic symptoms, subjective cognitive dysfunction, quality of life, and functional disability were evaluated using the Hamilton Depression Rating Scale and Montgomery–Åsberg Depression Rating Scale, Hamilton Anxiety Rating Scale, Depression and Somatic Symptoms Scale (DSSS), Perceived Deficits Questionnaire-Depression, 12-Item Short Form Health Survey (SF-12), and Sheehan Disability Scale (SDS), respectively. Working memory and executive function were assessed using a 2-back task and Wisconsin Card Sorting Test (WCST). Inflammatory marker (soluble interleukin-6 receptor, C-reactive protein, and tumor necrosis factor-α receptor-1), cEPC adhesive, and apoptotic levels were measured using in vitro assays.

The MDD patients showed significantly lower cEPC adhesive levels than the HCs, and this difference in adhesive function remained statistically significant even after adjusting for inflammatory marker levels. The cEPC adhesion levels were in inverse correlations with commission and omission errors in 2-back task, the percent perseverative response and percent perseverative errors in WCST, and the DSSS and SDS scores, but in positive correlations with SF-12 physical and mental component scores. cEPC apoptotic levels did not differ significantly between the groups.

The findings indicate that cEPC adhesive function is diminished in MDD and impacts various aspects of cognitive and psychosocial functions associated with the disorder.

National health insurance (NHI) Taiwan has provided additional markups on dental service fees for people with specific disabilities, and the expenditure has increased significantly from TWD473 million (USD15 million) in 2016 to TWD722 million (USD24 million) in 2022. The purpose of this study was to determine oral health risk and to develop a risk assessment model for capitation outpatient dental payments in children with Autism.

Based on the literature and expert opinion, we developed a level of oral health risk model from the claim records of 2019. The model uses oral outpatient claim data to analyze: (i) the degree of caries disease; (ii) the level of dental fear or cooperation; and (iii) the level of tooth structure. Each factor was given a score from zero to four and a total score was calculated. Low-, medium-, and high-risk groups were formed based on the total points. The oral health risk capitation models are estimated by ordinary least squares using an individual’s annual outpatient dental expenditure in 2019 as the dependent variable. For subgroups based on age group and level of disability, expenditures predicted by the models are compared with actual outpatient dental expenditures. Predictive R-squared and predictive ratios were used to evaluate the model’s predictability.

The demographic variables, level of oral health risk, preventive dental care, and the type of dental health care predicted 30 percent of subsequent outpatient dental expenditure in children with autism. For subgroups (age group and disability level) of high-risk patients, the model substantially overpredicted the expenditure, whereas underprediction occurred in the low-risk group.

The risk-adjusted model based on principal oral health was more accurate in predicting an individual’s future expenditure than the relevant study in Taiwan. The finding provides insight into the important risk factor in the outpatient dental expenditure of children with autism and the fund planning of dental services for people with specific disabilities.