Stepped Care for Patients to Optimize Whole Recovery (SC-POWR): An Effectiveness Trial Evaluating a Stepped Care Model for Individuals With Opioid Use Disorder and Chronic Pain.

Many patients who receive treatment for opioid use disorder (OUD) report experiencing chronic pain (CP), which is associated with high levels of ongoing nonmedical opioid use and low retention in OUD treatment. In pilot studies of patients with OUD receiving buprenorphine or methadone who had CP, cognitive behavioral therapy (CBT) attenuated nonmedical opioid use compared with treatment-as-usual (TAU), but patients in both treatment arms exhibited similar pain improvements. Adding exercise and stress reduction to this model may augment pain-related outcomes. With funding from National Institutes of Health, we plan to conduct a randomized clinical trial of 316 patients with OUD and CP to test the effectiveness of TAU compared with Stepped Care for Patients to Optimize Whole Recovery (SC-POWR) to reduce nonmedical opioid use and pain (primary outcomes) (Aim 1) and decrease pain intensity and interference, alcohol use, anxiety, depression and stress, and improve sleep (secondary outcomes) (Aim 2). Eligible participants will be randomized to receive TAU (buprenorphine or methadone and at least once a month individual or group counseling) or SC-POWR (ie, TAU and up to 12 CBT sessions) for 24 weeks. Based on prespecified nonresponse criteria, SC-POWR may be stepped up at week 6 to receive onsite weekly group sessions of exercise (Wii Fit, Tai Chi) and "stepped up" again at week 15 to receive weekly group sessions of stress reduction (relaxation training, auricular acupuncture). They will be followed for another 24 weeks to evaluate durability of treatment response for illicit opioid use, alcohol use, pain, anxiety, depression, stress, sleep, and retention in medications for OUD (Aim 3).

Computer-Assisted Rehabilitation Shows Greater Efficacy Than Traditional in Visuospatial Skills and Cognition in Neglect Patients.

This study is crucial for improving unilateral spatial neglect (USN) treatments, focusing on comparing the effectiveness of computer-assisted cognitive rehabilitation (CACR) against conventional rehabilitation (CR) methods. It aimed to address a significant research gap and improve patient outcomes by evaluating the impact of CACR versus CR on visuospatial perception, visual field and attention, and visual memory in patients with USN. This study was a randomized controlled trial. Forty-five consecutive patients with USN from a university rehabilitation center were divided into two groups: 22 patients received CACR with Rehacom software, focusing on saccadic eye movement, visual field, and visual-motor coordination, while 23 underwent CR that combined hemispheric activation approach, mental imagery training, and vibration therapy. Assessments included the Motor-Free Visual Perception Test (MVPT), Line Bisection Test (LBT), Visual Span Test (VST), and Visual Recognition Test (VRT). The study employed ANCOVA and effect size calculations to evaluate the effectiveness of CACR compared to CR in treating patients with USN. Results indicated that CACR significantly outperformed CR in improving visuospatial perception, visual field, attention, and memory, showcasing its effectiveness in treating USN. These findings demonstrate the superiority of CACR over CR, particularly in enhancing visual memory and attention, as evidenced by the large effect size in VRT and moderate effects in LBT and VST. This suggests CACR's potential as a more effective approach for rehabilitation in patients with USN due to brain injuries.

Basic processes and clinical applications of mental imagery in worry: A systematic review.

BACKGROUND: In this systematic review, we aimed to synthesise existing research on the phenomenology of mental imagery among high worriers compared to healthy individuals, and to characterise the nature and effectiveness of existing imagery-related interventions in treatment of worry. METHODS: PsycInfo, CENTRAL, EMBASE, Medline, Medline Epub, and PubMed were searched for studies examining the relationship between worry/GAD and mental imagery, or interventions using imagery in treatment of worry/GAD. We assessed study quality and used qualitative narrative synthesis to comprehensively map study results. RESULTS: The search yielded 2589 abstracts that were assessed for eligibility independently by two authors. From this, 183 full texts were screened and 50 qualitatively synthesised. Twenty-seven reported an association between worry/GAD and an aspect of mental imagery. Here, overactive negative and worry imagery, and diminished positive future imagining, were associated with worry/GAD. Twenty-three studies reported an intervention. This literature suggested mixed findings regarding efficacy, including for imaginal exposure as an independent technique for GAD. CONCLUSIONS: Findings support dysfunctional negative imagining and diminished positive prospective imagery in GAD. General imagining abilities remain intact, which is promising for efforts to utilise imagery in treatment. Further research is warranted to develop innovative clinical applications of imagery in treatment of GAD.

Kai-Xin-San ameliorates Alzheimer's disease-related neuropathology and cognitive impairment in APP/PS1 mice via the mitochondrial autophagy-NLRP3 inflammasome pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS) is a classic famous prescription that has been utilized for centuries to address dementia. New investigations have shown that the anti-dementia effect of KXS is connected with improved neuroinflammation. Nevertheless, the underlying mechanism is not well elucidated. AIM OF THE STUDY: We propose to discover the ameliorative impact of KXS on Alzheimer's disease (AD) and its regulatory role on the mitochondrial autophagy-nod-like receptor protein 3 (NLRP3) inflammasome pathway. MATERIALS AND METHODS: The Y maze, Morris water maze, and new objection recognition tests were applied to ascertain the spatial learning and memory capacities of amyloid precursor protein/presenilin 1 (APP/PS1) mice after KXS-treatment. Meanwhile, the biochemical indexes of the hippocampus were detected by reagent kits. The pathological alterations and mitochondrial autophagy in the mice' hippocampus were detected utilizing hematoxylin and eosin (H&E), immunohistochemistry, immunofluorescence staining, and transmission electron microscopy. Besides, the PTEN-induced putative kinase 1 (PINK1)/Parkin and NLRP3 inflammasome pathways protein expressions were determined employing the immunoblot analysis. RESULTS: The results of behavioral tests showed that KXS significantly enhanced the AD mice' spatial learning and memory capacities. Furthermore, KXS reversed the biochemical index levels and reduced amyloid-ß protein deposition in AD mice brains. Besides, H&E staining showed that KXS remarkably ameliorated the neuronal damage in AD mice. Concurrently, the results of transmission electron microscopy suggest that KXS ameliorated the mitochondrial damage in microglia and promoted mitochondrial autophagy. Moreover, the immunofluorescence outcomes exhibited that KXS promoted the expression of protein 1 light chain 3B (LC3B) associated with microtubule and the generation of autophagic flux. Notably, the immunofluorescence co-localization results confirmed the presence of mitochondrial autophagy in microglia. Finally, KXS promoted the protein expressions of the PINK1/Parkin pathway and reduced the activation of NLRP3 inflammasome. Most importantly, these beneficial effects of KXS were attenuated by the mitochondrial autophagy inhibitor chloroquine. CONCLUSION: KXS ameliorates AD-related neuropathology and cognitive impairment in APP/PS1 mice by enhancing the mitochondrial autophagy and suppressing the NLRP3 inflammasome pathway.

Not Just a Mood Disorder─Is Depression a Neurodevelopmental, Cognitive Disorder? Focus on Prefronto-Thalamic Circuits.

Depression is one of the most burdensome psychiatric disorders, affecting hundreds of millions of people worldwide. The disease is characterized not only by severe emotional and affective impairments, but also by disturbed vegetative and cognitive functions. Although many candidate mechanisms have been proposed to cause the disease, the pathophysiology of cognitive impairments in depression remains unclear. In this article, we aim to assess the link between cognitive alterations in depression and possible developmental changes in neuronal circuit wiring during critical periods of susceptibility. We review the existing literature and propose a role of serotonin signaling during development in shaping the functional states of prefrontal neuronal circuits and prefronto-thalamic loops. We discuss how early life insults affecting the serotonergic system could be important in the alterations of these local and long-range circuits, thus favoring the emergence of neurodevelopmental disorders, such as depression.

Kai-xin-san improves cognitive impairment in D-gal and Aß25-35 induced ad rats by regulating gut microbiota and reducing neuronal damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS) is a classic herbal formula for the treatment and prevention of AD (Alzheimer's disease) with definite curative effect, but its mechanism, which involves multiple components, pathways, and targets, is not yet fully understood. AIM OF THE STUDY: To verify the effect of KXS on gut microbiota and explore its anti-AD mechanism related with gut microbiota. MATERIALS AND METHODS: AD rat model was established and evaluated by intraperitoneal injection of D-gal and bilateral hippocampal CA1 injections of Aß25-35. The pharmacodynamics of KXS in vivo includes general behavior, Morris water maze test, ELISA, Nissl & HE staining and immunofluorescence. Systematic analysis of gut microbiota was conducted using 16S rRNA gene sequencing technology. The potential role of gut microbiota in the anti-AD effect of KXS was validated with fecal microbiota transplantation (FMT) experiments. RESULTS: KXS could significantly improve cognitive impairment, reduce neuronal damage and attenuate neuroinflammation and colonic inflammation in vivo in AD model rats. Nine differential intestinal bacteria associated with AD were screened, in which four bacteria (Lactobacillus murinus, Ligilactobacillus, Alloprevotella, Prevotellaceae_NK3B31_group) were very significant. CONCLUSION: KXS can maintain the ecological balance of intestinal microbiota and exert its anti-AD effect by regulating the composition and proportion of gut microbiota in AD rats through the microbiota-gut-brain axis.

Hypoparathyroidism: changes in brain structure, cognitive impairment, and reduced quality of life.

Hypoparathyroidism (HypoPT) is a disease with no/or inadequate production/secretion of parathyroid hormone (PTH) from the parathyroid glands. Low levels of PTH result in hypocalcemia, which is often treated with calcium supplementation and active vitamin-D analogs. However, increasing evidence suggests that HypoPT has a profound impact on several organ systems. Quality of life (QOL) is reduced in patients with HypoPT, partly due to symptoms related to the central nervous system-including subjective feelings of confusion, a reduced ability to focus and think clearly (ie, "brain fog"). However, the extent to which these complex symptoms relate to quantifiable changes in patients' cognitive performance as determined by neuropsychological tests remains unclear. The brains of HypoPT patients may reveal tissue calcifications, but the extent to which long-term brain exposure to low PTH levels and/or changing calcium levels affects brain structure is unknown. In a cross-sectional study, we investigated PTH levels, QOL, cognitive impairment, and brain structure in well-treated post-surgical and non-surgical hypoparathyroid patients compared with healthy controls. QOL was quantified by the SF36v2, WHO-5 wellbeing Index, and two disease-specific questionnaires-the HPQ28 and Hypoparathyroidism Symptom Diary. Cognitive functions were tested using comprehensive neuropsychological. Brain structure was quantified by morphological analyses of magnetic resonance imaging images. We found reduced QOL and cognitive functioning in terms of processing speed, executive functions, visual memory, and auditory memory in HypoPT. Furthermore, HypoPT revealed a reduced volume of the hippocampus-and the size of the thalamus in postsurgical patients was associated with the disease duration. Importantly, patients reporting severe brain fog had a smaller hippocampus than those with less brainfog. HypoPT is associated with quantifiable cognitive deficits and changes in brain structure that align with patient symptoms. Our exploratory study warrants further studies of the neurobiological impact of PTH and of the impact of PTH replacements therapy on patients' cognitive functioning.

Hypoparathyroidism (HypoPT) is a disease with insufficient or no production of parathyroid hormone (PTH) from the parathyroid glands resulting in low plasma levels of PTH and calcium. One of the reported symptoms and complications of HypoPT is low quality of life (QOL) and mild impaired cognitive function, often described as "brain fog." We have compared patients with HypoPT and healthy controls in regard to QOL, cognitive function, and brain structure. We have used QOL questionnaires, neuropsychological tests, and magnetic resonance imaging (MRI). We found a reduced QOL and cognitive function in patients with HypoPT. Furthermore, MRI showed a difference in brain structure, with a reduced volume of the hippocampus area, especially in those reporting severe symptoms of "brain fog." Disease duration was found to be associated with the size of the thalamus. Our study suggests that there might be an association between HypoPT patients' symptoms of cognitive deficits and changes in brain structure.

Caffeic acid attenuates memory dysfunction and restores the altered activity of cholinergic, monoaminergic and purinergic in brain of cadmium chloride exposure rats.

OBJECTIVES: This study aims to evaluate the neuroprotective effect of caffeic acid (CAF) against cadmium chloride (CdCl2) in rats via its effect on memory index as well as on altered enzymatic activity in the brain of CdCl2-induced neurotoxicity. METHODS: The experimental rats were divided into seven groups (n=6 rats per group) of healthy rats (group 1), CdCl2 -induced (CD) (3 mg/kg BW) rats (group 2), CD rats + Vitamin C (group 3), CD rats + CAF (10 and 20 mg/kg BW respectively) (group 4 & 5), and healthy rat + CAF (10 and 20 mg/kg BW respectively) (group 6 & 7). Thereafter, CdCl2 and CAF were administered orally to the experimental rats in group 2 to group 5 on daily basis for 14 days. Then, the Y-maze test was performed on the experimental rats to ascertain their memory index. RESULTS: CdCl2 administration significantly altered cognitive function, the activity of cholinesterase, monoamine oxidase, arginase, purinergic enzymes, nitric oxide (NOx), and antioxidant status of Cd rats (untreated) when compared with healthy rats. Thereafter, CD rats treated with vitamin C and CAF (10 and 20 mg/kg BW) respectively exhibited an improved cognitive function, and the observed altered activity of cholinesterase, monoamine oxidase, arginase, purinergic were restored when compared with untreated CD rats. Also, the level of brain NOx and antioxidant status were significantly (p<0.05) enhanced when compared with untreated CD rats. In the same vein, CAF administration offers neuro-protective effect in healthy rats vis-à-vis improved cognitive function, reduction in the activity of some enzymes linked to the progression of cognitive dysfunction, and improved antioxidant status when compared to healthy rats devoid of CAF. CONCLUSIONS: This study demonstrated the neuroprotective effect of CAF against CdCl2 exposure and in healthy rats.

Association between the circulating very long-chain saturated fatty acid and cognitive function in older adults: findings from the NHANES.

BACKGROUND: Age-related cognitive decline has a significant impact on the health and longevity of older adults. Circulating very long-chain saturated fatty acids (VLSFAs) may actively contribute to the improvement of cognitive function. The objective of this study was to investigate the associations between arachidic acid (20:0), docosanoic acid (22:0), tricosanoic acid (23:0), and lignoceric acid (24:0) with cognitive function in older adults. METHODS: This study used a dataset derived from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). A total of 806 adults (≥ 60 years) were included who underwent comprehensive cognitive testing and plasma fatty acid measurements. Multivariable linear regression, restricted cubic spline (RCS), and interaction analyses were used to assess associations between VLSFAs and cognitive function. Partial Spearman' s correlation analysis was used to examine the correlations between VLSFAs and palmitic acid (16:0), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, triglycerides, systemic inflammatory markers, and dietary nutrients. RESULTS: Multivariable linear regression analysis, adjusting for sociodemographic, clinical conditions, and lifestyle factors, showed that 22:0 and 24:0 levels were positively associated with better global cognitive function (ß = 0.37, 95% confidence interval [CI] = 0.01, 0.73; ß = 0.73, 95% CI = 0.29, 1.2, respectively) as well as better CEARD-DR Z-score (ß = 0.82, 95% CI = 0.36, 1.3 and ß = 1.2, 95% CI = 0.63, 1.8, respectively). RCS analysis showed linear associations between higher 22:0 and 24:0 levels and better cognitive performance in both global cognitive function and CERAD-DR tests. CONCLUSIONS: The study suggests that higher levels of 22:0 and 24:0 are associated with better global cognitive function in older adults. 22:0 and 24:0 may be important biomarkers for recognizing cognitive impairment, and supplementation with specific VLSFAs (22:0 and 24:0) may be an important intervention to improve cognitive function. Further studies are needed to elucidate the underlying biological mechanisms between VLSFAs and cognitive function.

Effect of PTSD treatment on cardiovascular reactivity during trauma memory recall and correspondence with symptom improvement.

ABSTRACTBackground: Prior research has shown PTSD treatment leads to reductions in cardiovascular reactivity during trauma recall, but the extent to which such reductions are associated with changes in PTSD symptoms is less clear. Moreover, such relationships have not been investigated in a cognitively focused PTSD treatment.Objective: To examine changes in cardiovascular reactivity to the trauma memory in patients receiving cognitive processing therapy (CPT), CPT with a written trauma account, and a written account only condition. We also examined the association of such changes with symptom improvement.Method: 118 women with PTSD secondary to interpersonal violence completed pre- and post-treatment assessments of PTSD symptoms and cardiovascular reactivity during a script-driven imagery task.Results: Results indicated a significant but modest reduction in cardiovascular reactivity in CPT conditions. Changes in cardiovascular reactivity and reexperiencing symptoms were significantly associated among the whole sample. Among individuals with the greatest reactivity to the trauma memory at pretreatment, associations were also seen with changes in total PTSD, numbing, and trauma-related guilt.Conclusions: Results indicate that previous findings on the effect of PTSD treatment on cardiovascular reactivity during trauma recall extend to cognitively oriented treatment. Baseline cardiovascular reactivity may influence the extent to which reductions in PTSD symptoms and reactivity during trauma recall are related.

Cognitive Processing Therapy leads to reduced heart rate reactivity when recalling a trauma memory.Decreases in heart rate reactivity are associated with reduced reexperiencing symptoms.Changes in heart rate reactivity and PTSD symptoms are more closely related among patients with greater pretreatment reactivity.

[Huangpu Tongqiao Capsule improves cognitive impairment in rats with Wilson disease by inhibiting endoplasmic reticulum stress-mediated apoptosis pathway].

OBJECTIVE: To investigate the neuroprotective effect of Huangpu Tongqiao Capsule (HPTQ) in a rat model of Wilson disease (WD) and explore the underlying mechanisms. METHODS: SD rat models of WD were established by feeding of coppersupplemented chow diet and drinking water for 12 weeks, and starting from the 9th week, the rats were treated with low-, moderate- and high-dose HPTQ, penicillamine, or normal saline by gavage on a daily basis for 3 weeks. Copper levels in the liver and 24-h urine of the rats were detected, and their learning and memory abilities were evaluated using Morris water maze test. HE staining was used to observe morphological changes of CA1 region neurons in the hippocampus, and neuronal apoptosis was detected with TUNEL staining. Hippocampal expressions of endoplasmic reticulum stress (ERS)-mediated apoptosis pathway-related proteins GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 at both the mRNA and protein levels were detected using RT-qPCR, immunofluorescence assay or Western blotting. RESULTS: Compared with normal control rats, the rat models with copper overload-induced WD exhibited significantly increased copper levels in both the liver and 24-h urine, impaired learning and memory abilities, obvious hippocampal neuronal damage in the CA1 region and increased TUNEL-positive neurons (P<0.01), with also lowered mRNA and protein expressions of GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 in the hippocampus (all P<0.01). Treatments with HPTQ and penicillamine significantly lowered copper level in the liver but increased urinary copper level, improved learning and memory ability, alleviated neuronal damage and apoptosis in the hippocampus, and decreased hippocampal expressions of GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 in the rat models (P<0.01 or 0.05). CONCLUSION: HPTQ Capsule has neuroprotective effects in rat models of WD possibly by inhibiting ERS-mediated apoptosis pathway.

Art therapies and cognitive function in elderly with subjective cognitive decline: a protocol for a network meta-analysis.

INTRODUCTION: Subjective cognitive decline means a decline in the subjective perception of self-cognitive function, which is likely to evolve into mild cognitive impairment and dementia. The number of elderly with subjective cognitive decline has increased, bringing huge burdens and challenges to caregivers and society. With the increase in research on art therapies, some of them have gradually been proven to be effective for cognitive function. Therefore, this study aims to summarise the evidence and identify the best art therapy for elderly with subjective cognitive decline. METHODS AND ANALYSIS: We will include published randomised controlled trials written in English and Chinese if the intervention is one of the art therapies and applied in people aged 60 and above with subjective cognitive decline. Eight electronic databases, including the Cochrane Central Register of Controlled Trials, PubMed, Web of Science, Elsevier, China BioMedical Literature Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database, will be searched from January 2013 to December 2023. Art therapies will mainly include music therapy, reminiscence therapy, painting therapy, dance therapy, reading therapy, horticultural therapy, museum therapy, calligraphy therapy and so on. The outcome will be cognitive function. Study selection, data extraction and quality assessment will be performed by two reviewers. The risk of bias will be evaluated according to the Cochrane Collaboration's risk-of-bias tool, and the evidence quality will be assessed with the Grading of Recommendations Assessment, Development and Evaluation. Standard pairwise meta-analysis and Bayesian network meta-analysis will be conducted. The probabilities of each art therapy will be ranked based on the surface under the cumulative ranking curve. ETHICS AND DISSEMINATION: Ethical approval is not required for reviewing published studies. To provide important evidence for clinicians and guideline developers, the findings of this study will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023443773.

Co-administration of probiotic and vitamin D significantly improves cognitive function in schizophrenic patients: A double-blinded randomized controlled trial.

AIM: Manipulation of the intestinal microbiome and supplying vitamin D can attenuate psychiatric symptoms in schizophrenic patients. The current study tried to evaluate the effects of probiotic/vitamin D supplementation on the cognitive function and disease severity of schizophrenic patients. METHODS: In the present study, 70 patients (aged 18-65) with schizophrenia were recruited. Participants were randomly allocated to the placebo (n = 35) and intervention (probiotic supplements+400 IU vitamin D, n = 35) groups. Severity of disease and cognitive function (primary outcomes) were evaluated by Positive and Negative Syndrome Scale (PANSS) and Montreal Cognitive Assessment (MoCA) tests, respectively. Moreover, lipid profile, body mass index (BMI), gastrointestinal (GI) problems, serum C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were evaluated as secondary outcomes. RESULTS: A total of 69 patients completed the study. The MoCA score was increased by 1.96 units in the probiotic-containing supplement group compared to the placebo (p = 0.004). Also, the percentage of subjects with MoCA score ≥ 26 rose significantly in the intervention group (p = 0.031). Moreover, TC (p = 0.011), FBS (p = 0.009), and CRP (p < 0.001) significantly decreased in the supplement group compared to the placebo. Although the probiotic supplement reduced PANSS score by 2.82 units, the difference between the study groups was not statistically significant (p = 0.247). CONCLUSION: Co-administration of probiotics and vitamin D has beneficial effects on the improvement of cognitive function in schizophrenic patients.

Non-Pharmacological Interventions for Depression and Anxiety in Parkinson's Disease.

Non-pharmacological interventions, including cognitive-behavioral therapy (CBT), non-invasive brain stimulation (NIBS), electroconvulsive therapy (ECT), light therapy (LT), and physical rehabilitation/exercise, have shown promise as effective approaches to treat symptoms of depression and anxiety in individuals with Parkinson's disease (PD). In this narrative literature overview, we discuss the state-of-the-art regarding these treatment options and address future perspectives for clinical practice and research. Non-pharmacological interventions hold promise to treat depression and anxiety in PD. There is meta-analytic evidence for the efficacy of CBT, NIBS, ECT, LT, and exercise on improving depressive symptoms. For the treatment of anxiety symptoms, CBT shows large effects but scientific evidence of other non-pharmacological interventions is limited. Importantly, these treatments are safe interventions with no or mild side-effects. More research is needed to tailor treatment to the individuals' needs and combined interventions may provide synergistic effects.We conclude that non-pharmacological interventions should be considered as alternative or augmentative treatments to pharmacological and neurosurgical approaches for the treatment of depression and anxiety in individuals with PD.

Predictors of post stroke cognitive impairment: VITATOPS cognition substudy.

INTRODUCTION: Post stroke cognitive impairment (PSCI) is a common complication of ischemic stroke. PSCI can involve different depending on clinical and stroke related characteristics. The aim of this study is to determine the factors associated with impairments in specific cognitive domains. METHODS: The Vitamins to Prevent Stroke (VITATOPS) trial is a large, multinational randomised controlled trial. In this substudy, consecutive patients admitted for ischaemic stroke or transient ischaemic attack (TIA) at a tertiary hospital in Singapore were included. PSCI was defined as impairment of any of the six cognitive subgroups - visuoconstruction, attention, verbal memory, language, visual memory and visuomotor function - that were assessed annually for up to five years. Univariate and multivariate Cox proportional hazard models were used to determine factors associated with impairments in each of these cognitive domains. RESULTS: A total of 736 patients were included in this study, of which 173 (23.5 %) developed cognitive impairment. Out of the six cognitive domains, the greatest proportion of patients had an impairment in visuoconstruction (26.4 %) followed by attention (19.8 %), verbal memory (18.3 %), language (17.5 %), visual memory (17.3 %) and visuomotor function (14.8 %). Patients with posterior circulation cerebral infarction (POCI) as the index stroke subtype had higher rates of cognitive impairment. Further subgroup analyses show that Indian race and advanced age were predictive of language impairment, whilst fewer years of education and POCI were predictive of verbal memory impairment. POCI was predictive of visual memory impairment, and advanced age and POCI were predictive of visuomotor function impairment. CONCLUSION: We identified visuoconstruction and attention domains to be the most affected in our Asian cohort of PSCI. Advanced age, lower levels of education, posterior circulation strokes and concomitant comorbidities such as peripheral artery disease are independent predictors of PSCI.

Mechanistic insights and emerging therapeutic stratagems for Alzheimer's disease.

Alzheimer's disease (AD), a multi-factorial neurodegenerative disorder has affected over 30 million individuals globally and these numbers are expected to increase in the coming decades. Current therapeutic interventions are largely ineffective as they focus on a single target. Development of an effective drug therapy requires a deep understanding of the various factors influencing the onset and progression of the disease. Aging and genetic factors exert a major influence on the development of AD. Other factors like post-viral infections, iron overload, gut dysbiosis, and vascular dysfunction also exacerbate the onset and progression of AD. Further, post-translational modifications in tau, DRP1, CREB, and p65 proteins increase the disease severity through triggering mitochondrial dysfunction, synaptic loss, and differential interaction of amyloid beta with different receptors leading to impaired intracellular signalling. With advancements in neuroscience tools, new inter-relations that aggravate AD are being discovered including pre-existing diseases and exposure to other pathogens. Simultaneously, new therapeutic strategies involving modulation of gene expression through targeted delivery or modulation with light, harnessing the immune response to promote clearance of amyloid deposits, introduction of stem cells and extracellular vesicles to replace the destroyed neurons, exploring new therapeutic molecules from plant, marine and biological sources delivered in the free state or through nanoparticles and use of non-pharmacological interventions like music, transcranial stimulation and yoga. Polypharmacology approaches involving combination of therapeutic agents are also under active investigation for superior therapeutic outcomes. This review elaborates on various disease-causing factors, their underlying mechanisms, the inter-play between different disease-causing players, and emerging therapeutic options including those under clinical trials, for treatment of AD. The challenges involved in AD therapy and the way forward have also been discussed.

Multicomponent Intervention on Improving the Cognitive Ability of Older Adults with Mild Cognitive Impairment: A Pilot Randomized Controlled Trial.

This pilot randomized controlled trial aimed to evaluate the feasibility and potential outcomes of an innovative 16-session multicomponent intervention model to improve cognitive abilities in older adults with mild cognitive impairment (MCI) by promoting healthy lifestyle, cognitive skills, tai chi and mindfulness practices. This study was a multicentre, randomized controlled, two-arm, parallel-group, unblinded trial in Hong Kong. 57 Chinese older adults with MCI recruited from three local elderly centers were randomly assigned to either the control or intervention group. The study results support the feasibility and efficacy of the multicomponent intervention, and recommend future larger-scale randomized control trials.

The infant gut microbiome and cognitive development in malnutrition.

Malnutrition affects 195 million children under the age of five worldwide with long term effects that include impaired cognitive development. Brain development occurs rapidly over the first 36 months of life. Whilst seemingly independent, changes to the brain and gut microbiome are linked by metabolites, hormones, and neurotransmitters as part of the gut-brain axis. In the context of severe malnutrition, the composition of the gut microbiome and the repertoire of biochemicals exchanged via the gut-brain axis vary when compared to healthy individuals. These effects are primarily due to the recognized interacting determinants, macro- and micronutrient deficiencies, infection, infestations and toxins related to poor sanitation, and a dearth of psycho-social stimulation. The standard of care for the treatment of severe acute malnutrition is focused on nutritional repletion and weight restoration through the provision of macro- and micronutrients, the latter usually in excess of recommended dietary allowances (RDA). However, existing formulations and supplements have not been designed to specifically address key recovery requirements for brain and gut microbiome development. Animal model studies indicate that treatments targeting the gut microbiome could improve brain development. Despite this, research on humans targeting the gut microbiome with the aim of restoring brain functionality are scarce. We conclude that there is a need for assessment of cognition and the use of various tools that permit visualization of the brain anatomy and function (e.g., Magnetic resonance imaging (MRI), functional near-infrared spectroscopy (fNIRS), electroencephalogram (EEG)) to understand how interventions targeting the gut microbiome impact brain development.

Skills training followed by either EMDR or narrative therapy for posttraumatic stress disorder in adult survivors of childhood abuse: a randomized controlled trial.

Background: Individuals suffering from PTSD following childhood abuse represent a large subgroup of patients attending mental health services. The aim of phase-based treatment is to tailor treatment to the specific needs to childhood abuse survivors with PTSD with a Skills Training in Affective and Interpersonal Regulation (STAIR) phase, in which emotion dysregulation and interpersonal problems are targeted, and a trauma-focused phase.Objective: The purpose of this study was to compare STAIR + Eye Movement Desensitization and Reprocessing (EMDR) vs. STAIR + Narrative Therapy (NT) as treatments for PTSD following childhood-onset trauma in a routine clinical setting.Method: Sixty-eight adults were randomly assigned to STAIR/EMDR (8 STAIR-sessions followed by 12 EMDR-sessions) or STAIR/NT (8 STAIR-sessions followed by 12 NT-sessions). Assessments took place at pre-treatment, after each treatment phase and at 3 and 12 months post-intervention follow-up. Primary outcomes were interviewer-rated and self-reported symptom levels of PTSD. Secondary outcomes included symptom levels of depression and disturbances in emotion regulation and interpersonal skills.Results: Multilevel analyses in the intent-to-treat sample indicated that patients in both treatments improved substantially on PTSD symptom severity (CAPS: d = 0.81 to 1.29; PDS: d = 1.68 to 2.15), as well as on symptom levels of depression, anxiety, emotion regulation, dissociation and interpersonal skills. Effects increased or were maintained until 12-month follow-up. At mid-treatment, after STAIR, patients in both treatments improved moderately on PTSD symptom severity (PDS: d = 1.68 to 2.15), as well as on symptom levels of depression (BDI: d = .32 to .31). Symptoms of anxiety, emotion dysregulation, interpersonal problems and dissociation were not decreased after STAIR. There were no significant differences between the two conditions on any outcome.Conclusion: PTSD in adult survivors of childhood interpersonal trauma can effectively be treated by phase-based interventions using either EMDR or NT in the trauma-processing phase.Trial registration: ClinicalTrials.gov identifier: NCT01443182..

The study directly compares Skills Training in Affective and Interpersonal Regulation (STAIR) followed by either EMDR or Narrative Therapy in the trauma-processing phase in routine clinical setting.The brief phase-based treatment was found to be effective in reducing both symptoms of PTSD as well as emotion regulation and interpersonal problems in survivors of childhood abuse.Posttraumatic Stress Disorder in adult survivors of childhood interpersonal trauma can effectively be treated by phase-based interventions using either EMDR or Narrative Therapy in the trauma-processing phase.