Predictors of irritable bowel syndrome-like symptoms in quiescent inflammatory bowel disease.

BACKGROUND: Many patients with quiescent inflammatory bowel disease (IBD) suffer from irritable bowel syndrome (IBS)-like symptoms. Although these symptoms cause significant reductions in quality of life, evidence-based treatments are lacking as risk factors and pathophysiology of these symptoms are not clearly defined. We aimed to identify risk factors for development of IBS-like symptoms in IBD patients with quiescent disease. METHODS: We performed a single-center retrospective cohort study of adults with IBD from 2015 to 2021. Quiescent IBD was defined by a fecal calprotectin level <250 µg/g of stool or endoscopic evidence of quiescent disease. Cox regression was performed to identify variables that were independently associated with the incident development of IBS-like symptoms in IBD patients. KEY RESULTS: A total of 368 IBD patients were included for analysis, including 278 patients with UC and 88 with Crohn's disease. 15.5% of quiescent IBD patients developed IBS symptoms, with an incidence rate of (95% CI 48.0-82.0) 63.3 per 1000 person-years. In the multivariate model, mood disorders (including anxiety and depression) and Crohn's disease were associated with increased risk for developing IBS symptoms. Male sex and higher iron levels conferred lower risk for developing IBS symptoms. Results from the multivariable model were similar in sensitivity analysis with quiescent IBD defined by fecal calprotectin level <150 mcg/g. CONCLUSIONS & INFERENCES: Mood disorder and Crohn's disease were positively associated with IBS-like symptoms in quiescent IBD, whereas male sex and iron levels were protective. Our results were robust to different fecal calprotectin levels, arguing against inflammation as a mechanism for IBS-like symptoms. This data suggests noninflammatory mechanisms may be important in the pathogenesis of IBS-like symptoms in quiescent IBD. Future work may address whether modifying these risk factors may alter disease course.

Motor neurons generate pose-targeted movements via proprioceptive sculpting.

Motor neurons are the final common pathway1 through which the brain controls movement of the body, forming the basic elements from which all movement is composed. Yet how a single motor neuron contributes to control during natural movement remains unclear. Here we anatomically and functionally characterize the individual roles of the motor neurons that control head movement in the fly, Drosophila melanogaster. Counterintuitively, we find that activity in a single motor neuron rotates the head in different directions, depending on the starting posture of the head, such that the head converges towards a pose determined by the identity of the stimulated motor neuron. A feedback model predicts that this convergent behaviour results from motor neuron drive interacting with proprioceptive feedback. We identify and genetically2 suppress a single class of proprioceptive neuron3 that changes the motor neuron-induced convergence as predicted by the feedback model. These data suggest a framework for how the brain controls movements: instead of directly generating movement in a given direction by activating a fixed set of motor neurons, the brain controls movements by adding bias to a continuing proprioceptive-motor loop.

Development and validation of cognitive ageing risk score (CARS) for early detection of subtle cognitive deficits in older people.

BACKGROUND: Early cognitive deficits commonly seen in older people have not been well defined and managed in primary care. The objectives are (1) to develop and validate a new risk score to estimate the risk of dementia in Chinese older population; and (2) to evaluate the use of risk score in conjunction with cognitive screening in detecting early cognitive deficits in community older people. METHODS: A development cohort of 306 cognitive healthy older adults aged 60 or above were followed for 6 years. A CARS was constructed using the estimated coefficients of risk factors associated with dementia at follow up. Validation was carried out in another five-year cohort of 383 older adults. The usefulness of CARS in detecting early cognitive deficits was evaluated. RESULTS: Risk factors include older age, male gender, low level of education, poorly controlled diabetes, prolonged sleep latency, fewer mind body or light exercise, loneliness, and being apolipoprotein e4 carriers. A cutoff of CARS at -1.3 had a sensitivity of 83.9% and a specificity of 75.4% to predict dementia. The area under curve was 82.5% in the development cohort. Early cognitive deficits were characterized by impaired retention (p <.001, 95% CI 0.2-0.9) and attention (p =.012, 95% CI 0.1-0.8). CONCLUSION: The CARS can be used as a standard risk assessment of dementia or in conjunction with a computerized cognitive screening to evaluate a full cognitive profile for detecting early cognitive deficits. The result put forward the integration of risk algorithm into smart healthcare system to provide personalized lifestyle interventions.

Effect of increasing cognitive activity participation on default mode network in older adults with subjective cognitive decline: a randomised controlled trial.

BACKGROUND: Having more cognitive activities may prevent dementia, but its evidence of modulating the functional brain network is limited. This randomised controlled trial (RCT) investigated the effect of increased cognitive activity participation on the default mode network (DMN) in older adults who had already been having regular cognitive activity participation and experiencing subjective cognitive decline (SCD). METHODS: Community-living Chinese individuals aged 55-75 years with regular practice of Chinese calligraphy and screened positive for SCD (but negative for mild cognitive impairment or dementia) were randomly allocated to either the intervention or control group. Over 6 months, the intervention group doubled their weekly calligraphy practice time, while the control group maintained their usual amount of practice. The primary outcome was functional connectivities (FCs) of DMN, with pre-specified regions of interest including medial prefrontal cortex (mPFC), inferior parietal lobe (IPL), hippocampal formation (HF), posterior cingulate cortex (PCC), and lateral temporal cortex (LTC). FC changes were compared using repeated measures multivariate analysis of variance (MANOVA). This study is registered at the Chinese Clinical Trial Registry, ChiCTR1900024433. FINDINGS: Between 15 January 2020 and 31 December 2021, 112 individuals consented and completed the baseline assessment. The participants, who had a mean age of 66.3 (SD 4.3) years, with 83 (74%) being women, had been practising calligraphy for an average duration of 9.7 years before enrolment and, in the preceding six months, for an average of 3.1 hours per week. 96 (86%) completed the post-intervention fMRI scan. Significant between-group differences were observed in the FCs between mPFC and right LTC (group difference = 0.25 [95% CI = 0.06-0.44], p = 0.009), mPFC and right IPL (0.23 [0.06-0.39]; p = 0.007), left HF and right LTC (0.28 [0.002-0.57]; p = 0.04), and left HF and right IPL (0.34 [0.09-0.60]; p = 0.009). INTERPRETATION: Our findings, which reveal positive neuromodulatory effects with increased calligraphy practice, highlight the importance of engaging more in cognitive activities in late life for better brain health. FUNDING: Research Grants Council, Hong Kong (grant number 24114519).

Psychotic Symptoms in Patients With Major Neurological Diseases.

Neurological diseases often manifest with neuropsychiatric symptoms such as depression, emotional incontinence, anger, apathy and fatigue. In addition, affected patients may also experience psychotic symptoms such as hallucinations and delusions. Various factors contribute to the development of psychotic symptoms, and the mechanisms of psychosis are similar, but still differ among various neurological diseases. Although psychotic symptoms are uncommon, and have been less well investigated, they may annoy patients and their families as well as impair the patients' quality of life and increase the caregiver burden. Therefore, we need to appropriately identify and treat these psychotic symptoms in patients with neurological diseases.

Percutaneous electrical nerve field stimulation for adolescents with irritable bowel syndrome: Cost-benefit and cost-minimization analysis.

Abdominal pain drives significant cost for adolescents with irritable bowel syndrome (IBS). We performed an economic analysis to estimate cost-savings for patients' families and healthcare insurance, and health outcomes, based on abdominal pain improvement with percutaneous electrical nerve field stimulation (PENFS) with IB-Stim® (Neuraxis). We constructed a Markov model with a 1-year time horizon comparing outcomes and costs with PENFS versus usual care without PENFS. Clinical outcomes were derived from a sham-controlled double-blind trial of PENFS for adolescents with IBS. Costs/work-productivity impact for parents were derived from appropriate observational cohorts. PENFS was associated with 18 added healthy days over 1 year of follow-up, increased annual parental wages of $5,802 due to fewer missed work days to care for the child, and $4744 in cost-savings to insurance. Percutaneous electrical field nerve stimulation for adolescents with IBS appears to yield significant cost-savings to patients' families and insurance.

Benefits of Prokinetics, Gastroparesis Diet, or Neuromodulators Alone or in Combination for Symptoms of Gastroparesis.

BACKGROUND & AIMS: Prokinetics have limited effectiveness for treating symptoms of gastroparesis. Thus, alternative or adjunct therapies, such as gastroparesis diets or neuromodulators, are often prescribed. Their therapeutic benefits alone or in combination remain unclear. METHODS: One hundred and twenty-nine patients with symptoms of gastroparesis underwent wireless motility capsule gastric emptying time and gastric emptying scintigraphy. Based on test results, changes in therapy were recommended. Changes in Gastroparesis Cardinal Symptom Index (GCSI) and individual symptom scores over 6 months were related to recommendations for prokinetics, gastroparesis diet, or neuromodulators given as solo new therapies or in dual combinations. Multivariate analyses were performed to adjust for gastric emptying and other variables. RESULTS: In the whole group regardless of therapy, GCSI scores decreased by 0.53 points (interquartile range, -1.25 to 0.05; P < .0001) over 6 months. GCSI did not decrease for prokinetics as solo new therapy (P = .95). Conversely, neuromodulators as solo therapy decreased GCSI scores (P = .04) and all individual symptoms except nausea/vomiting (P = .86). Prokinetics combined with gastroparesis diets or neuromodulators improved GCSI scores (P ≤ .04) and most individual symptoms. Adjusting for gastric emptying time on multivariate analyses showed greater GCSI decreases for nondelayed emptying for neuromodulators as solo new therapy (P = .01). Gastric emptying scintigraphy, gender, diabetes, and functional dyspepsia did not influence responses to any treatment. CONCLUSIONS: Initiating prokinetics as solo new therapy had little benefit for patients with symptoms of gastroparesis. Neuromodulators as the only new therapy decreased symptoms other than nausea and vomiting, especially with nondelayed gastric emptying. Adding gastroparesis diets or neuromodulators to prokinetics offered relief, suggesting that combination therapies may be more useful in managing these patients. (ClinicalTrials.gov NCT02022826.).

The Fecal Microbiome in Quiescent Crohn's Disease with Persistent Gastrointestinal Symptoms Show Enrichment of Oral Microbes But Depletion of Butyrate and Indole Producers.

Background and Aims: Even in the absence of inflammation, persistent symptoms in Crohn's disease (CD) are prevalent and negatively impact quality of life. We aimed to determine whether quiescent CD patients with persistent symptoms ( qCD+symptoms ) have changes in microbial structure and functional potential compared to those without symptoms ( qCD-symptoms ). Methods: We performed a prospective multi-center observational study nested within the SPARC IBD study. CD patients were included if they had evidence of quiescent disease as defined by fecal calprotectin level < 150 mcg/g. Persistent symptoms were defined by the CD-PRO2 questionnaire. Active CD ( aCD ), diarrhea-predominant irritable bowel syndrome ( IBS-D ), and healthy controls ( HC ) were included as controls. Stool samples underwent whole genome shotgun metagenomic sequencing. Results: A total of 424 patients were analyzed, including 39 qCD+symptoms, 274 qCD-symptoms, 21 aCD, 40 IBS-D, and 50 HC. Patients with qCD+symptoms had a less diverse microbiome, including significant reductions in Shannon diversity ( P <.001) and significant differences in microbial community structure ( P <.0001), compared with qCD-symptoms, IBS-D, and HC. Further, patients with qCD+symptoms showed significant enrichment of bacterial species that are normal inhabitants of the oral microbiome, including Klebsiella pneumoniae (q=.003) as well as depletion of important butyrate and indole producers, such as Eubacterium rectale (q=.001), Lachnospiraceae spp . (q<.0001), and Faecalibacterium prausnitzii (q<.0001), compared with qCD-symptoms. Finally, qCD+symptoms showed significant reductions in bacterial tnaA genes, which mediate tryptophan metabolism, as well as significant tnaA allelic variation, compared with qCD-symptoms. Conclusion: The microbiome in patients with qCD+symptoms show significant changes in diversity, community profile, and composition compared with qCD-symptoms. Future studies will focus on the functional significance of these changes. What You Need to Know: Background: Persistent symptoms in quiescent Crohn's disease (CD) are prevalent and lead to worse outcomes. While changes in the microbial community have been implicated, the mechanisms by which altered microbiota may lead to qCD+symptoms remain unclear.Findings: Quiescent CD patients with persistent symptoms demonstrated significant differences in microbial diversity and composition compared to those without persistent symptoms. Specifically, quiescent CD patients with persistent symptoms were enriched in bacterial species that are normal inhabitants of the oral microbiome but depleted in important butyrate and indole producers compared to those without persistent symptoms.Implications for Patient Care: Alterations in the gut microbiome may be a potential mediator of persistent symptoms in quiescent CD. Future studies will determine whether targeting these microbial changes may improve symptoms in quiescent CD.

A Predictive Model to Identify Complicated Clostridiodes difficile Infection.

Background: Clostridioides difficile infection (CDI) is a leading cause of health care-associated infection and may result in organ dysfunction, colectomy, and death. Published risk scores to predict severe complications from CDI demonstrate poor performance upon external validation. We hypothesized that building and validating a model using geographically and temporally distinct cohorts would more accurately predict risk for complications from CDI. Methods: We conducted a multicenter retrospective cohort study of adults diagnosed with CDI. After randomly partitioning the data into training and validation sets, we developed and compared 3 machine learning algorithms (lasso regression, random forest, stacked ensemble) with 10-fold cross-validation to predict disease-related complications (intensive care unit admission, colectomy, or death attributable to CDI) within 30 days of diagnosis. Model performance was assessed using the area under the receiver operating curve (AUC). Results: A total of 3646 patients with CDI were included, of whom 217 (6%) had complications. All 3 models performed well (AUC, 0.88-0.89). Variables of importance were similar across models, including albumin, bicarbonate, change in creatinine, non-CDI-related intensive care unit admission, and concomitant non-CDI antibiotics. Sensitivity analyses indicated that model performance was robust even when varying derivation cohort inclusion and CDI testing approach. However, race was an important modifier, with models showing worse performance in non-White patients. Conclusions: Using a large heterogeneous population of patients, we developed and validated a prediction model that estimates risk for complications from CDI with good accuracy. Future studies should aim to reduce the disparity in model accuracy between White and non-White patients and to improve performance overall.

Dementia literacy in an ageing world.

AIMS: This discursive article aims to capture and explore the most pertinent nursing aspects of dementia literacy (DL). BACKGROUND: Older people constitute a rapidly increasing proportion of the global population, experiencing higher risk of developing chronic disease, including dementia. It is important that older adults receive and understand reliable health-related information, as age-related changes may affect the level of health literacy in an older person. It has been suggested that older adults may have poorer health literacy than younger adults, associated with poorer health outcomes. Health literacy, how people receive, interpret and act on health information, play a significant role in dementia-related disorders, both as a possible predicter of onset of dementia and as a potential modifier of cognitive decline. Dementia literacy constitutes one aspect of health literacy in relation to nursing care, related to knowledge of dementia-related disorders and approaches towards older people with dementia. DESIGN: This discursive article explores the importance of DL for the nursing profession, including dementia-related assessment, education and interventions. METHOD: This article is informed by analysis of relevant descriptive and empirical literature and policy documents related to DL, an increasingly important aspect of dementia-related nursing care. Valid assessment tools that can accurately assess aspects an individuals' DL are examined; these have the potential to help nurses detect dementia-related symptoms. With early detection and prevention of dementia, older people may have better chance of benefiting from evolving treatment options. CONCLUSION: Greater attention needs to be given to the issue of DL in older people, especially in terms of nursing assessment and care. Globally, increased DL-related education is urgently required to improve knowledge of this concept; this includes public awareness initiatives to better understanding this chronic condition. IMPLICATION NURSING PRACTICE: Enhancing DL has the potential to empower older people to have greater access to healthcare services and to make more informed decisions about their health care. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution, as this is a discursive article.

Effect of computerized cognitive training on mood, cognition, and serum brain-derived neurotrophic factor level in late-life depression - a pilot randomized controlled trial.

Background: The aim of this pilot randomized controlled trial was to test the feasibility of a computerized cognitive training targeting executive dysfunction in late-life depression and to investigate its impact on mood, cognition, and brain-derived neurotrophic factor (BDNF) levels. Methods: A total of 28 community-living Chinese individuals aged 55-75 with moderate-to-severe depression and cognitive symptoms (but without mild cognitive impairment or dementia) were recruited from a community centre in Hong Kong. Participants were randomly allocated to either the experimental (receiving computerized cognitive training) or the control group (receiving computer-based health education). Both programs lasted for one hour and were conducted twice a week for 6 weeks at the community centre. We assessed mood using the Hamilton Rating Scale for Depression (HAM-D) and Patient Health Questionaire-9 (PHQ-9), cognition using the Montreal Cognitive Assessment (MoCA), and serum BDNF levels at baseline and follow-up. We performed repeated measures analysis of variance to compare the differences in outcome changes between groups and correlation analysis to test if changes in mood and cognition correlated with changes in BDNF level. Results: Our sample had a mean age of 66.8 (SD = 5.3) years, a mean HAM-D score of 19.4 (SD = 7.5), and a mean PHQ-9 score of 18.0 (SD = 6.3). No adverse effects were reported. Significant differences were observed between the experimental and control groups in changes in HAM-D (-8.4 vs. -2.9; group difference = -5.5; p = 0.01), PHQ-9 (-6.6 vs. -0.6; -6.0; p < 0.001), MoCA (1.4 vs. -1.3; 2.7; p = 0.001), and serum BDNF levels (in pg/ml; 2088.3 vs. -3277.4; 5365.6; p = 0.02). Additionally, changes in HAM-D, PHQ-9, and MoCA scores correlated significantly with changes in BDNF level. Conclusion: With computerized cognitive training improving mood and cognition and increasing serum BDNF levels in 6 weeks, it may serve as a safe and effective evidence-based alternative or adjuvant treatment for late-life depression. Clinical trial registration: https://www.chictr.org.cn/indexEN.html, identifier ChiCTR1900027029.

Dementia and risk of visual impairment in Chinese older adults.

We had previously identified visual impairment increasing risk of incident dementia. While a bi-directional vision-cognition association has subsequently been proposed, no study has specifically examined the longitudinal association between dementia and incidence of clinically defined visual impairment. In this territory-wide community cohort study of 10,806 visually unimpaired older adults, we examined their visual acuity annually for 6 years and tested if dementia at baseline was independently associated with higher risk of incident visual impairment (LogMAR ≥ 0.50 in the better eye despite best correction, which is equivalent to moderate visual impairment according to the World Health Organization definition). By the end of Year 6, a total of 3151 (29.2%) participants developed visual impairment. However, we did not find baseline dementia associating with higher risk of incident visual impairment, after controlling for baseline visual acuity, cataract, glaucoma, diabetes, hypertension, hypercholesterolemia, heart diseases, stroke, Parkinson's disease, depression, hearing and physical impairments, physical, intellectual and social activities, diet, smoking, age, sex, educational level, and socioeconomic status. Among different covariables, baseline visual acuity appears to be more important than dementia in contributing to the development of visual impairment. Our present findings highlight the need for re-evaluating whether dementia is indeed a risk factor for visual impairment.

Common mental disorders during the COVID-19 pandemic in Hong Kong: Age-related differences and implications for dementia risk.

Background: The COVID-19 pandemic has imposed a profound negative impact on the mental health and wellbeing of societies and individuals worldwide. Older adults may be more vulnerable to the mental health effects of the pandemic, either directly from the infection itself or indirectly through the preventive measures. However, the existing literature on mental health in the older age groups has not been consistent so far. The aim of this study was therefore to assess the prevalence of common mental disorders (CMD; including depression and anxiety disorders) given their association with dementia risk, and to further examine age-related differences between older (≥60 years old) and younger (18-59 years old) adult's psychological status during the COVID-19 pandemic. Method: This was a secondary analysis of a cross-sectional survey-study conducted during the second wave of COVID-19 pandemic in Hong Kong. The survey was disseminated through different social media platforms to the general population and included sociodemographic questions, self-reported physical health, and previous encounter with SARS or COVID-19. CMD was the primary outcome and was assessed using the 6-item Kessler Scale. A total of 1030 adults fulfilled inclusion criteria. Results: The prevalence of CMD during the pandemic was 16.1%. Compared to younger adults, older adults were significantly less likely to have a CMD (unadjusted OR = 0.07, 95% CI = 0.02-0.30, p < 0.001), with 18.1% of younger adults having CMD compared to 1.6% in the older cohort. Age differences remained significant after controlling for sociodemographic factors, physical health, and previous encounter with SARS or COVID-19 (adjusted OR = 0.12, 95% CI = 0.02-0.57, p = 0.008). Conclusion: Common mental disorders are highly prevalent during the COVID-19 pandemic in Hong Kong, though older adults appeared to be less affected mentally. Present findings highlight the urgent need to implement measures and strategies to mitigate the mental health problems, with particular attention to the younger cohort. Given their association with higher dementia risk, early detection and treatment of depression and anxiety disorders will be of critical importance in providing some relief to the already pressurized dementia burden in the longer term.

Secondary bile acids mediate high-fat diet-induced upregulation of R-spondin 3 and intestinal epithelial proliferation.

A high-fat diet (HFD) contributes to the increased incidence of colorectal cancer, but the mechanisms are unclear. We found that R-spondin 3 (Rspo3), a ligand for leucine-rich, repeat-containing GPCR 4 and 5 (LGR4 and LGR5), was the main subtype of R-spondins and was produced by myofibroblasts beneath the crypts in the intestine. HFD upregulated colonic Rspo3, LGR4, LGR5, and ß-catenin gene expression in specific pathogen-free rodents, but not in germ-free mice, and the upregulations were prevented by the bile acid (BA) binder cholestyramine or antibiotic treatment, indicating mediation by both BA and gut microbiota. Cholestyramine or antibiotic treatments prevented HFD-induced enrichment of members of the Lachnospiraceae and Rumincoccaceae, which can transform primary BA into secondary BA. Oral administration of deoxycholic acid (DCA), or inoculation of a combination of the BA deconjugator Lactobacillus plantarum and 7α-dehydroxylase-containing Clostridium scindens with an HFD to germ-free mice increased serum DCA and colonic Rspo3 mRNA levels, indicating that formation of secondary BA by gut microbiota is responsible for HFD-induced upregulation of Rspo3. In primary myofibroblasts, DCA increased Rspo3 mRNA via TGR5. Finally, we showed that cholestyramine or conditional deletion of Rspo3 prevented HFD- or DCA-induced intestinal proliferation. We conclude that secondary BA is responsible for HFD-induced upregulation of Rspo3, which, in turn, mediates HFD-induced intestinal epithelial proliferation.

Is sleep quality a potential predictor of neurocognitive disorders? A 6-year follow-up study in Chinese older adults.

OBJECTIVE: To investigate the longitudinal association of sleep quality with incidence of neurocognitive disorders in 6 years. METHODS: This was a 6-year follow-up study of community-living older adults who scored a Clinical Dementia Rating (CDR) of 0 at baseline. Sleep quality was assessed by the self-rated Pittsburgh Sleep Quality Index (PSQI) questionnaire, where higher scores indicated poorer sleep quality, and a cutoff score of 5 or above was suggestive of sleep disorder. The study outcome was incident neurocognitive disorders in 6 years, as identified by a CDR of 0.5 or above. Poisson regression analysis was conducted to test if baseline sleep quality was independently associated with risk of incident neurocognitive disorders in 6 years. RESULTS: Of the 290 participants in this study, 166 (57.2%) developed neurocognitive disorders in 6 years. They had poorer sleep quality (mean [SD] total PSQI score: 6.2 [3.8] vs. 4.9 [3.2], p = 0.001) and higher prevalence of sleep disorder (100 [60.2%] vs. 56 [45.2%], p = 0.01) at baseline than those who remained free of neurocognitive disorder. After controlling for age, gender, education, and physical and psychiatric morbidities, the risk ratios (RRs) for incident neurocognitive disorders were 1.05 (95% confidence interval (CI) = 1.00-1.11, p < 0.05) for PSQI total score and 1.50 (95% CI = 1.05-2.14, p = 0.03) for sleep disorder at baseline. CONCLUSIONS: Sleep quality might predict the development of neurocognitive disorders. From a clinical perspective, enquiry of sleep quality and screening for sleep disorder should be promoted as part of the neurocognitive disorder risk assessment in older adults.

Increasing participation in habitual intellectual activities on modulating functional connectivity of default mode network among older adults at risk of dementia: study protocol of a randomized controlled trial.

BACKGROUND: Active participation in intellectual leisure activities such as calligraphy helps prevent cognitive decline and dementia, but the underlying mechanisms are not fully understood. With disrupted functional connectivity (FC) of default mode network (DMN) associated with cognitive decline, we speculate that intellectual activities might optimize cognitive function through modulating FC of DMN. This two-arm single-blind randomized controlled trial aims to identify the effects of increasing practice of calligraphy on cognitive function and FC of DMN in people with subjective cognitive decline (SCD). METHODS: One hundred twelve community-living Chinese aged 55 to 75 years old with SCD but without mild cognitive impairment or dementia and with prior practice of calligraphy as defined by 1 h of calligraphy per week will be recruited through elderly social centres in Hong Kong and randomized into either control or intervention group. The control group will continue with their usual practice of calligraphy, whereas the intervention group will double their practice of calligraphy. Measurement of cognitive outcomes and neuroimaging on resting-state FC will be performed at baseline and in 6 months. Repeated measures analysis of variance will be used to assess cognitive and FC changes, with time being the within-group factor, control/intervention as the between-group measure, and important covariates (age, sex, educational and occupational attainment, health, and other lifestyle factors) controlled for. DISCUSSION: This study will shed light on the underlying neurocognitive mechanisms of how intellectual activities promotes cognitive maintenance. Our anticipated findings will provide evidence that reversing or slowing FC disruption by actively participating in intellectual activities is still possible for the at-risk individuals. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900024433 . Registered on 11 July 2019.

Late-life longitudinal blood pressure trajectories as predictor of dementia.

While hypertension is widely recognized as a risk factor for dementia, few observational studies and clinical trials fully accounted for the effect of age on blood pressure (BP) changes prior to dementia onset. In this territory-wide population-based longitudinal study of 16,591 community-living dementia-free older adults, we followed their BP and cognitive status and tested if loss of longitudinal increase in BP in late life was associated with higher dementia risk in 6 years, with consideration of the confounding effects of hypertension, hypotension, BP variability, and other health problems and behaviours and, in the data analysis, exclusion of individuals who developed dementia within 3 years after baseline to minimize risk of reverse causality. Over 72,997 person-years of follow-up, 1429 participants developed dementia. We found that loss of longitudinal increase in systolic BP (defined as SBP increased by either < 10 mmHg or 10%) from baseline to Year 3 was independently associated with higher risk of incident dementia at Years 4 to 6 (adjusted OR 1.22, 95% CI 1.02-1.45, p = 0.03; adjusted OR 1.24, 95% CI 1.03-1.50, p = 0.02; respectively). Our findings suggest that late-life SBP trajectory changes might independently predict dementia onset and highlight the importance of including longitudinal BP monitoring in dementia risk assessment.

A Randomized Pilot Study to Compare the Effectiveness of a Low FODMAP Diet vs Psyllium in Patients With Fecal Incontinence and Loose Stools.

INTRODUCTION: The aim of the study was to compare the effectiveness of a low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol diet (LFD) vs psyllium on the frequency and severity of fecal incontinence (FI) episodes in patients with loose stools. METHODS: This was a single-center, randomized pilot trial of adult patients with FI (Rome III) with at least 1 weekly FI episode associated with loose stool. Eligible patients were randomized to 4 weeks of either a dietitian-led LFD or 6 g/d psyllium treatment. RESULTS: Forty-three subjects were randomized from October 2014 to May 2019. Thirty-seven patients completed the study (19 LFD and 18 psyllium). There was no statistically significant difference in the proportion of treatment responders (>50% reduction in FI episodes compared with baseline) for treatment weeks 1-4 (LFD 38.9%, psyllium 50%, P = .33). Compared with baseline, mean fecal incontinence severity index score significantly improved with LFD (39.4 vs 32.6, P = .02) but not with psyllium (35.4 vs 32.1, P = .29). Compared with baseline values, the LFD group reported improvements in fecal incontinence quality of life coping/behavior, depression/self-perception, and embarrassment subscales. The psyllium group reported improvement in incontinence quality of life coping/behavior. DISCUSSION: In this pilot study, there was no difference in the proportion of patients who reported a 50% reduction of FI episodes with the LFD or psyllium. Subjects in the psyllium group reported a greater reduction in overall FI episodes, whereas the LFD group reported consistent improvements in FI severity and quality of life. Further work to understand these apparently discrepant results are warranted but the LFD and psyllium seem to provide viable treatment options for patients with FI and loose stools.