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Evidence suggests the crucial role of dysfunctional default mode (DMN), salience and frontoparietal (FPN) networks, collectively termed the triple network model, in the pathophysiology of treatment-resistant depression (TRD).
Aims
Using the graph theory- and seed-based functional connectivity analyses, we attempted to elucidate the role of low-dose ketamine in the triple networks, namely the DMN, salience and FPN.
Method
Resting-state functional connectivity magnetic resonance imaging (rs–fcMRI) data derived from two previous clinical trials of a single, low-dose ketamine infusion were analysed. In clinical trial 1 (Trial 1), patients with TRD were randomised to either a ketamine or normal saline group, while in clinical trial 2 (Trial 2) those patients with TRD and pronounced suicidal symptoms received a single infusion of either 0.05 mg/kg ketamine or 0.045 mg/kg midazolam. All participants underwent rs–fcMRI pre and post infusion at Day 3. Both graph theory- and seed-based functional connectivity analyses were performed independently.
Results
Trial 1 demonstrated significant group-by-time effects on the degree centrality and cluster coefficient in the right posterior cingulate cortex (PCC) cortex ventral 23a and b (DMN) and the cluster coefficient in the right supramarginal gyrus perisylvian language (salience). Trial 2 found a significant group-by-time effect on the characteristic path length in the left PCC 7Am (DMN). In addition, both ketamine and normal saline infusions exerted a time effect on the cluster coefficient in the right dorsolateral prefrontal cortex a9-46v (FPN) in Trial 1.
Conclusions
These findings may support the utility of the triple-network model in elucidating ketamine’s antidepressant effect. Alterations in DMN, salience and FPN function may underlie this effect.
To investigate the associations between dietary patterns and biological ageing, identify the most recommended dietary pattern for ageing and explore the potential mediating role of gut microbiota in less-developed ethnic minority regions (LEMRs). This prospective cohort study included 8288 participants aged 30–79 years from the China Multi-Ethnic Cohort study. Anthropometric measurements and clinical biomarkers were utilised to construct biological age based on Klemera and Doubal’s method (KDM-BA) and KDM-BA acceleration (KDM-AA). Dietary information was obtained through the baseline FFQ. Six dietary patterns were constructed: plant-based diet index, healthful plant-based diet index, unhealthful plant-based diet index, healthy diet score, Dietary Approaches to Stop Hypertension (DASH), and alternative Mediterranean diets. Follow-up adjusted for baseline analysis assessed the associations between dietary patterns and KDM-AA. Additionally, quantile G-computation identified significant beneficial and harmful food groups. In the subsample of 764 participants, we used causal mediation model to explore the mediating role of gut microbiota in these associations. The results showed that all dietary patterns were associated with KDM-AA, with DASH exhibiting the strongest negative association (β = −0·91, 95 % CI (–1·19, −0·63)). The component analyses revealed that beneficial food groups primarily included tea and soy products, whereas harmful groups mainly comprised salt and processed vegetables. In mediation analysis, the Synergistetes and Pyramidobacter possibly mediated the negative associations between plant-based diets and KDM-AA (5·61–9·19 %). Overall, healthy dietary patterns, especially DASH, are negatively associated with biological ageing in LEMRs, indicating that Synergistetes and Pyramidobacter may be potential mediators. Developing appropriate strategies may promote healthy ageing in LEMRs.
The right inferior frontal gyrus (RIFG) is a potential beneficial brain stimulation target for autism. This randomized, double-blind, two-arm, parallel-group, sham-controlled clinical trial assessed the efficacy of intermittent theta burst stimulation (iTBS) over the RIFG in reducing autistic symptoms (NCT04987749).
Methods
Conducted at a single medical center, the trial enrolled 60 intellectually able autistic individuals (aged 8–30 years; 30 active iTBS). The intervention comprised 16 sessions (two stimulations per week for eight weeks) of neuro-navigated iTBS or sham over the RIFG. Fifty-seven participants (28 active) completed the intervention and assessments at Week 8 (the primary endpoint) and follow-up at Week 12.
Results
Autistic symptoms (primary outcome) based on the Social Responsiveness Scale decreased in both groups (significant time effect), but there was no significant difference between groups (null time-by-treatment interaction). Likewise, there was no significant between-group difference in changes in repetitive behaviors and exploratory outcomes of adaptive function and emotion dysregulation. Changes in social cognition (secondary outcome) differed between groups in feeling scores on the Frith-Happe Animations (Week 8, p = 0.026; Week 12, p = 0.025). Post-hoc analysis showed that the active group improved better on this social cognition than the sham group. Dropout rates did not vary between groups; the most common adverse event in both groups was local pain. Notably, our findings would not survive stringent multiple comparison corrections.
Conclusions
Our findings suggest that iTBS over the RIFG is not different from sham in reducing autistic symptoms and emotion dysregulation. Nonetheless, RIFG iTBS may improve social cognition of mentalizing others' feelings in autistic individuals.
Treatment-resistant depression (TRD) is not uncommon in older people. Brain stimulation, such as 4-6 weeks of repetitive transcranial magnetic stimulation (rTMS) or theta burst stimulation (TBS) targeting the left dorsolateral prefrontal cortex, has been evidenced as an essential intervention for adult TRD and also documented in the current international treatment guideline. In 2018, Taiwan Food and Drug Administration cleared the rTMS as a treatment option for TRD and now rTMS is still a treatment at their own expense in Taiwan. Additionally, prolonged intermittent TBS (piTBS) protocol has been proven its similar antidepressant efficacy as standard 4-6 weeks rTMS/iTBS in adult TRD, but in a shorter treatment course of 2 weeks. For older adults with depression, 4-6 weeks of treatment course may burden their caregiver due to their limited ambulation and transportation ability. However, hitherto there was no study to investigate the antidepressant efficacy of left-sided prefrontal piTBS in treating older TRD.
Methods:
A chart review was performed at a single Taiwan hospital from 2018 to 2020. 17-items Hamilton Depression Rating Scale (HDRS-17) was measured before and after the piTBS intervention. Maudsley Staging Method was used for the depression treatment refractoriness.
Results:
We identified 23 old adults with TRD (mean [SD] age, 66.0[5.2]; 78% female) who underwent 10-20 sessions of daily piTBS (1800 pulses/session; 10sessions, n=18, 15sessions,n=4, 20session,n=1). On continuous outcomes, mean(SD) HDRS-17 total scores improved from 20.5(6.62) to 11.8(7.7) after receiving piTBS intervention. The mean percent improvement of HDRS-17 was 46.0%±29.4%. Dichotomous outcomes showed response rate of 43.5% and remission rate of 34.8%. No seizures or other serious adverse events were noted, and no premature discontinuation was noted.
Conclusion:
This study is the largest study demonstrating the piTBS protocol provides a comparable reduction in depression symptoms in older adults with TRD, similar to the effectiveness in adult TRD and the efficacy of standard sequential bilateral rTMS/iTBS in older TRD in the FOUR-D trial. Regarding desirable efficiency and effectiveness, piTBS may be an optimal form of rTMS in treating older adults with TRD. Further large comparative effectiveness trials with standard iTBS or high-frequency rTMS in this population are warranted.
To evaluate the mental health of paediatric cochlear implant users and analyse the relationship between six dimensions (movements, cognitive ability, emotion and will, sociality, living habits and language) and hearing and speech rehabilitation.
Methods
Eighty-two cochlear implant users were assessed using the Mental Health Survey Questionnaire. Age at implantation, time of implant use and listening modes were investigated. Categories of Auditory Performance and the Speech Intelligibility Rating Scale were used to score hearing and speech abilities.
Results
More recipients scored lower in cognitive ability and language. Age at implantation was statistically significant (p < 0.05) for movements, cognitive ability, emotion and will, and language. The time of implant usage and listening mode indicated statistical significance (p < 0.05) in cognitive ability, sociality and language.
Conclusion
Timely attention should be paid to the mental health of paediatric cochlear implant users, and corresponding psychological interventions should be implemented to make personalised rehabilitation plans.
There was no previous meta-analysis investigating the efficacy/tolerability of psychostimulants for symptoms of attention-deficit hyperactivity disorder (ADHD) in preschool children.
Methods
Databases including PubMed, the Cochrane Library, EMBASE, ScienceDirect, and ClinicalTrials.gov were searched from inception to March 2022 for randomized controlled trials (RCTs) on therapeutic efficacy of psychostimulants against ADHD symptoms in preschool children (age ≤6 years) compared with placebos. Primary outcomes were (a) changes in ADHD symptoms evaluated by validated rating scales from parents’/teacher’s observation, or (b) post-intervention improvements in neuropsychological performance. Secondary outcomes were risks of adverse events.
Results
Meta-analysis of nine eligible trials including 544 preschool children (mean age=4.86 years, female=11.98%, median treatment duration=4.33 weeks) supported the efficacy of psychostimulants against global symptoms from observations of parents (Hedges’ g=0.6152, p<0.0001) and teachers (Hedges’ g=0.6563, p=0.0039). Efficacy of psychostimulants was also noted against symptoms of inattention and hyperactivity/impulsivity, especially the latter (i.e., main symptoms in preschool children). Moreover, male gender, older age, and longer treatment duration were associated with better efficacy. Regarding adverse events, only the risk of poor appetite was higher in the psychostimulant group (odds ratio [OR]=2.39). However, the qualities of evidence were low to very low, indicating potential discrepancy between the true and estimated effect.
Conclusions
Our results showed that psychostimulants might be beneficial for preschool children with ADHD, especially hyperactivity/impulsivity from teachers’ observation, with tolerable side effects. Nevertheless, the true magnitude of the effect needs to be confirmed with more research due to low to very low certainty of the evidence.
High-molecular-weight glutenin subunits (HMW-GS) contribute to dough elasticity and bread baking quality in wheat. In this study, wheat varieties were classified based on their HMW-GS composition into three groups: 1Dx5 (5 + 10, Gaoyou 8901, Xinmai 28, Xinmai 19, Xinmai 26 and Jinbaoyin), 1Dx2 (2 + 12, Zhoumai 24, Xinmai 9 and Yumai) and 1Dx4 (4 + 12, Aikang 58). Sequence analysis showed that 1Dx-GY8901, 1Dx-XM28, 1Dx-XM19 and 1Dx-XM26 were similar to the 1Dx5 gene and clustered on the same branch, while 1Dx-AK58, 1Dx-ZM24, 1Dx-JBY, 1Dx-YM, 1Dx-XM9 and 1Dx-JBY were more similar to the 1Dx2 gene and clustered on the same branch with 1Dx.2.2. There was a mutation of Ser to Cys at position S2, for an extra Cys in the repeat regions of 1Dx-XM19, 1Dx-XM26, 1Dx-XM28 and 1Dx-GY8901. The wheat HMW-GS genes exhibited similar percentages of α-helix, extended strand, β-turn and random coil structure, with ranges of 13.33–13.59, 4.77–5.78, 7.08–9.18 and 72.3–73.94%, respectively. Sequence conservation and the composition of HMW-GS subunits were also analysed for a series of strong gluten wheat varieties, Xinmai 9 (1, 7 + 8, 2 + 12), Xinmai 19 (1, 7 + 9, 5 + 10), Xinmai 26 (1, 7 + 8, 5 + 10) and Xinmai 28 (1, 7 + 9, 5 + 10). The results of this work should facilitate future breeding efforts and provide the theoretical basis for wheat quality improvement.
The aim of our study was to determine the distribution of hepatitis B virus (HBV) genotypes and subgenotypes in ethnic minorities in Yunnan province to provide evidence supporting the theoretical basis for hepatitis B prevention and control. We obtained serum samples and demographic data from 765 individuals reported by Yunnan province who had either acute or chronic HBV infection and were from one of 20 ethnic minority populations: Achang, Bai, Brown, Tibetan, Dai, Deang, Dulong, Hani, Hui, Jingpo, Lahu, Yi, Lisu Miao, Naxi, Nu, Pumi, Wa, Yao, or Zhuang people. We sequenced the HBV DNA and determined the genotypes and subgenotypes of the isolated HBVs. We mapped the genotype and subgenotype distribution by ethnic minority population and conducted descriptive analyses. There were four genotypes among the 20 ethnic groups: genotype B (21.3% of samples), C (76.6%), D (1.8%) and I (0.3%). The most common subgenotype was C1. There were no genotype differences by gender (P = 0.954) or age (P = 0.274), but there were differences by region (P < 0.001). There were differences in genotype distribution (P < 0.001) and subgenotype distribution (P = 0.011) by ethnic group. Genotype D was most prominent in Tibet and most HBV isolates were C/D recombinant viruses. The only two genotype I virus isolates were in Zhuang people. Susceptibility and geographic patterns may influence HBV prevalence in different ethnic populations, but additional research is needed for such a determination.
Chronic inflammation exerts pleiotropic effects in the aetiology and progression of chronic obstructive pulmonary disease (COPD). Glucosamine is widely used in many countries and may have anti-inflammatory properties. We aimed to prospectively evaluate the association of regular glucosamine use with incident COPD risk and explore whether such association could be modified by smoking in the UK Biobank cohort, which recruited more than half a million participants aged 40–69 years from across the UK between 2006 and 2010. Cox proportional hazards models with adjustment for potential confounding factors were used to calculate hazard ratios (HR) as well as 95 % CI for the risk of incident COPD. During a median follow-up of 8·96 years (interquartile range 8·29–9·53 years), 9016 new-onset events of COPD were documented. We found that the regular use of glucosamine was associated with a significantly lower risk of incident COPD with multivariable adjusted HR of 0·80 (95 % CI, 0·75, 0·85; P < 0·001). When subgroup analyses were performed by smoking status, the adjusted HR for the association of regular glucosamine use with incident COPD were 0·84 (0·73, 0·96), 0·84 (0·77, 0·92) and 0·71 (0·62, 0·80) among never smokers, former smokers and current smokers, respectively. No significant interaction was observed between glucosamine use and smoking status (Pfor interaction = 0·078). Incident COPD could be reduced by 14 % to 84 % through a combination of regular glucosamine use and smoking cessation.
Inflammation is a central mechanism in metabolic disorders associated with morbidity and mortality and dietary factors can modulate inflammation. We aimed to prospectively investigate the association between an empirically developed, food-based dietary inflammatory pattern (EDIP) score and the risk of overall and cause-specific mortality, using data from the US National Health and Nutrition Examination Survey from 1999 to 2014. EDIP score was derived by entering thirty-nine predefined commonly consumed food groups into the reduced rank regression models followed by stepwise linear regression, which was most predictive of two plasma inflammation biomarkers including C-reactive protein and leucocyte count among 25 500 US adults. This score was further validated in a testing set of 9466 adults. Deaths from baseline until 31 December 2015 were identified through record linkage to the National Death Index. During a median follow-up of 7·8 years among 40 074 participants, we documented 4904 deaths. Compared with participants in the lowest quintile of EDIP score, those in the highest quintile had a higher risk of overall death (hazard ratio (HR) = 1·19, 95 % CI 1·08, 1·32, Ptrend = 0·002), and deaths from cancer (HR = 1·41, 95 % CI 1·14, 1·74, Ptrend = 0·017) and CVD (HR = 1·22, 95 % CI 0·98, 1·53, Ptrend = 0·211). When stratified by age, the association of EDIP with overall mortality was stronger among individuals under 65 years of age (Pinteraction = 0·001). Diets with a higher inflammatory potential were associated with increased risk of overall and cancer-specific mortality. Interventions to reduce the adverse effect of pro-inflammatory diets may potentially promote health and longevity.
The coexistence of underweight (UW) and overweight (OW)/obese (OB) at the population level is known to affect iron deficiency (ID) anaemia (IDA), but how the weight status affects erythropoiesis during pregnancy is less clear at a population scale. This study investigated associations between the pre-pregnancy BMI (pBMI) and erythropoiesis-related nutritional deficiencies.
Design:
Anthropometry, blood biochemistry and 24-h dietary recall data were collected during prenatal care visits. The weight status was defined based on the pBMI. Mild nutrition deficiency-related erythropoiesis was defined if individuals had an ID, folate depletion or a vitamin B12 deficiency.
Setting:
The Nationwide Nutrition and Health Survey in Taiwan (Pregnant NAHSIT 2017–2019).
Participants:
We included 1456 women aged 20 to 45 years with singleton pregnancies.
Results:
Among these pregnant women, 9·6 % were UW, and 29·2 % were either OW (15·8 %) or OB (13·4 %). A U-shaped association between the pBMI and IDA was observed, with decreased odds (OR; 95 % CI) for OW subjects (0·6; 95 % CI (0·4, 0·9)) but increased odds for UW (1·2; 95 % CI (0·8, 2·0)) and OB subjects (1·2; 95 % CI (0·8, 1·8)). The pBMI was positively correlated with the prevalence of a mild nutritional deficiency. Compared to normal weight, OB pregnant women had 3·4-fold (3·4; 95 % CI (1·4, 8·1)) higher odds for multiple mild nutritional deficiencies, while UW individuals had lowest odds (0·3; 95 % CI (0·1, 1·2)). A dietary analysis showed negative relationships of pBMI with energy, carbohydrates, protein, Fe and folate intakes, but positive relationship with fat intakes.
Conclusion:
The pre-pregnancy weight status can possibly serve as a good nutritional screening tool for preventing IDA during pregnancy.
To investigate potential risk factors for mild behavioral impairment (MBI) among non-demented geriatrics.
Design:
Population-based, cross-sectional survey.
Setting:
Taiwan Alzheimer Disease Association (TADA) Database.
Participants:
Participants were selected by multistage random sampling of all Taiwan counties. They received in-person interviews between December 2011 and March 2013.
Measurements:
Demographic data, lifestyle and habits, medical comorbidities, cognitive status measured by the Taiwanese Mini-Mental Status Examination (TMSE) and presence of MCI of the participants were collected. Subjects were distributed to the MBI and non-MBI groups. These factors had been evaluated for their effects on MBI in the univariate and multivariable logistic regression models.
Results:
In total, 6,196 non-demented participants aged 65 years or older, including 409 MBI and 5,787 non-MBI participants, were recruited. After adjustment for age, sex, education, body mass index, lifestyle and habits, medical comorbidities, and MCI, good sleep was associated with lower risk of MBI (OR 0.09, 95% CI 0.07 – 0.12). Low body weight (OR 2.01, 95% CI 1.21–3.33), low-to-medium education (OR 1.40, 95%CI 1.06–1.85; OR 2.32, 95% CI 1.67–3.21), medical comorbidities of hypertension (OR 1.56, 95% CI 1.25–1.95), hyperlipidemia (OR 1.29, 95% CI 1.00–1.67), cancer (OR 2.05, 95% CI 1.37–3.06) were significantly associated with increased MBI risk. MCI neither increased nor decreased risk of MBI (OR 1.00, 95% CI 0.76–1.32).
Conclusions:
Good sleep was associated with lower MBI risk. Underweight, lower education, medical comorbidities of cancer, hypertension, hyperlipidemia were predictive of MBI.
Dietary salt intake may vary depending on different lifestyles. We aimed to estimate the different salt intakes and evaluate the knowledge and self-awareness about salt among people speaking the Teochew, Teochew–Hakka and Hakka dialects in the Chaoshan region of southern China.
Design:
The study followed a cluster sampling of residents in Chaoshan region. General characteristics, lifestyles, health status as well as knowledge and self-awareness related to salt intake were investigated using a questionnaire. Anthropometric variables as well as Na and K excretion in a 24-h urine collection were measured.
Setting:
Chaoshan region of China.
Participants:
Four hundred fifteen adults who spoke only one of these three dialects.
Results:
The salt intake of adults who spoke the Teochew, Teochew–Hakka and Hakka dialects was 7·19 (interquartile range (IQR) 5·29–10·17), 9·03 (IQR 6·62–11·54) and 10·12 (IQR 7·61–12·82) g/d, respectively, with significant differences between Teochew and Teochew–Hakka speakers and between Teochew and Hakka speakers (both P < 0·05). The Na:K ratio for adults who spoke the three dialects was 3·00 (IQR 2·00–4·11), 3·50 (IQR 2·64–4·82) and 4·52 (IQR 3·35–5·97), respectively, and differed significantly among the groups (all P < 0·05). Multiple linear regression analysis showed increased Na:K ratio associated with hypertension (β = 0·71, P = 0·043) in Hakka speakers. Knowledge and self-awareness about salt intake were poor in this population.
Conclusions:
Salt intake was closely related to lifestyles and was higher than the upper limit (5 g/d) recommended by the WHO in adults of Chaoshan, especially those speaking the Hakka dialect.
Primary liver cancer is the third leading cause of cancer-related death worldwide. Most patients are diagnosed at late stages with poor prognosis; thus, identification of modifiable risk factors for primary prevention of liver cancer is urgently needed. The well-established risk factors of liver cancer include chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), heavy alcohol consumption, metabolic diseases such as obesity and diabetes, and aflatoxin exposure. However, a large proportion of cancer cases worldwide cannot be explained by current known risk factors. Dietary factors have been suspected as important, but dietary aetiology of liver cancer remains poorly understood. In this review, we summarised and evaluated the observational studies of diet including single nutrients, food and food groups, as well as dietary patterns with the risk of developing liver cancer. Although there are large knowledge gaps between diet and liver cancer risk, current epidemiological evidence supports an important role of diet in liver cancer development. For example, exposure to aflatoxin, heavy alcohol drinking and possibly dairy product (not including yogurt) intake increase, while intake of coffee, fish and tea, light-to-moderate alcohol drinking and several healthy dietary patterns (e.g. Alternative Healthy Eating Index) may decrease liver cancer risk. Future studies with large sample size and accurate diet measurement are warranted and need to consider issues such as the possible aetiological heterogeneity between liver cancer subtypes, the influence of chronic HBV or HCV infection, the high-risk populations (e.g. cirrhosis) and a potential interplay with host gut microbiota or genetic variations.
Synaptotagmin 1 (Syt1) is an abundant and important presynaptic vesicle protein that binds Ca2+ for the regulation of synaptic vesicle exocytosis. Our previous study reported its localization and function on spindle assembly in mouse oocyte meiotic maturation. The present study was designed to investigate the function of Syt1 during mouse oocyte activation and subsequent cortical granule exocytosis (CGE) using confocal microscopy, morpholinol-based knockdown and time-lapse live cell imaging. By employing live cell imaging, we first studied the dynamic process of CGE and calculated the time interval between [Ca2+]i rise and CGE after oocyte activation. We further showed that Syt1 was co-localized to cortical granules (CGs) at the oocyte cortex. After oocyte activation with SrCl2, the Syt1 distribution pattern was altered significantly, similar to the changes seen for the CGs. Knockdown of Syt1 inhibited [Ca2+]i oscillations, disrupted the F-actin distribution pattern and delayed the time of cortical reaction. In summary, as a synaptic vesicle protein and calcium sensor for exocytosis, Syt1 acts as an essential regulator in mouse oocyte activation events including the generation of Ca2+ signals and CGE.
The objectives of this study were to investigate the primary diagnoses and outcomes of emergency department visits in older people with dementia and to compare these parameters with those in older adults without dementia.
Design and Setting:
This hospital-based retrospective study retrieved patient records from a hospital research database, which included the outpatient and inpatient claims of two hospitals.
Participants:
The patient records were retrieved from the two hospitals in an urban setting. The inclusion criteria were all patients aged 65 and older who had attended the two hospitals as an outpatient or inpatient between January 1, 2009, and December 31, 2016. Patients with dementia were identified to have at least three reports of diagnostic codes, either during outpatient visits, during emergency department visits, or in hospitalized database records. The other patients were categorized as patients without dementia.
Measurements:
The primary diagnosis during the emergency department visit, cost of emergency department treatment, cost of hospital admission, length of hospital stay, and diagnosis of death were collected.
Results:
A total of 149,203 outpatients and inpatients aged 65 and older who were admitted to the two hospitals were retrieved. The rate of emergency department visits in patients with dementia (23.2%) was lower than that in those without dementia (48.6%). The most frequent primary reason for emergency department visits and the main cause of patient death was pneumonia. Patients with dementia in the emergency department had higher hospital admission rates and longer hospital stays; however, the cost of treatment did not show a significant difference between the two groups.
Conclusions:
Future large and prospective studies should explore the severity of disease in older people with dementia and compare results with older adults without dementia in the emergency department.
The extent to which schizophrenia is associated with the risk of all-cause dementia is controversial. This study investigated the risk of dementia by type in patients with schizophrenia.
Methods:
Data were collected from the Taiwanese National Health Insurance Database 2005 and analyzed using multivariate Cox proportional hazard regression models to determine the effect of schizophrenia on the dementia risk after adjusting for demographic characteristics, comorbidities, and medications. Fine and Gray's competing risk analysis was used to determine the risk of dementia, as death can act as a competing risk factor for dementia.
Results:
We assessed 6040 schizophrenia patients and 24,160 propensity scale-matched control patients. Schizophrenia patients exhibited a 1.80-fold risk of dementia compared to controls (adjusted hazard ratio [aHR] = 1.80, 95% confidence interval [CI] = 1.36 ∼ 2.21, p < 0.001) after adjusting for covariates. Cardiovascular disease (aHR = 5.26; 95% CI = 4.50 ∼ 6.72; p < 0.001), hypertension (aHR = 1.83; 95% CI = 1.77 ∼ 2.04; p = 0.002), traumatic head injury (aHR = 1.35; 95% CI = 1.24 ∼ 1.78; p < 0.001), chronic lung diseases (aHR = 1.64; 95% CI = 1.13 ∼ 2.56; p < 0.001), alcohol-related disorders (aHR = 3.67; 95% CI = 2.68 ∼ 4.92; p < 0.001), and Parkinson’s disease (aHR = 1.72; 95% CI = 1.25 ∼ 2.40; p < 0.001) were significantly associated with dementia risk. Notably, first-generation antipsychotics (aHR = 0.80; 95% CI = 0.56 ∼ 0.95; p= 0.044) and second-generation antipsychotics (aHR = 0.24; 95% CI = 0.11 ∼ 0.60; p < 0.001) were associated with a lower dementia risk. Sensitivity tests yielded consistent findings after excluding the first year and first 3 years of observation. Patients with schizophrenia had the highest risk of developing Alzheimer’s [dementia/disease?] among dementia subtypes (aHR = 2.10; 95% CI = 1.88 ∼ 3.86; p < 0.001), followed by vascular dementia (aHR = 1.67; 95% CI = 1.27 ∼ 2.12; p < 0.001) and unspecified dementia (aHR = 1.30; 95% CI = 1.04 ∼ 2.01; p < 0.001).
Conclusions:
Schizophrenia was significantly associated with the risk of all-cause dementia. Data are scarce on the mechanisms through which antipsychotic agents protect persons with schizophrenia from developing dementia. Further research is recommended to elucidate the neurobiological mechanisms underlying the association between schizophrenia and dementia, and whether antipsychotics protect against the development of dementia in schizophrenia.