An investigation of neuropsychiatric symptoms, contextual factors, and antidepressant treatment as risk factors for dementia development in people with mild cognitive impairment.

BACKGROUND: While some people with mild cognitive impairment (MCI) progress to dementia, many others show no progression. The aim of this study was to identify factors associated with risk of dementia development in this population. METHOD: A large naturalistic retrospective cohort study was assembled from mental healthcare records in a south London catchment. Patients were selected at first recorded diagnosis of MCI and subsequent dementia diagnosis was ascertained from case notes or death certificate, excluding those with dementia diagnoses and deaths within 6 months of MCI diagnosis. A range of demographic and clinical characteristics were ascertained around MCI diagnosis and Cox proportional hazards models were used to investigate independent predictors of dementia, focussing on neuropsychiatric symptoms, contextual factors, and antidepressant treatment. RESULTS: Of 2250 patients with MCI, 236 (10.5%) developed dementia at least 6 months after MCI diagnosis. Aside from older age, lower cognitive function, and activities of daily living impairment, impaired social relationships and recorded loneliness were associated with a higher risk of developing dementia. Patients of Black (compared to White) ethnicity were at a lower risk. For depression and antidepressant receipt, only tricyclic use compared to no antidepressant use was associated with an increased dementia risk. CONCLUSIONS: No evidence was found for co-morbid affective disorders or different antidepressant classes as risk factors for dementia development following MCI diagnosis, but loneliness and social impairment were independent predictors and would be worth evaluating as targets for interventions to delay progression.

Associations between recorded loneliness and adverse mental health outcomes among patients receiving mental healthcare in South London: a retrospective cohort study.

PURPOSE: Loneliness disproportionately affects people with mental disorders, but associations with mental health outcomes in groups affected remain less well understood. METHOD: A cohort of patients receiving mental healthcare on 30th June 2012 was assembled from a large mental health records database covering a south London catchment area. Recorded loneliness within the preceding 2 years was extracted using natural language processing and outcomes were measured between 30th June 2012 until 30th December 2019, except for survival which applied a censoring point of 6th December 2020 according to data available at the time of extraction. The following mental healthcare outcomes: (i) time to first crisis episode; (ii) time to first emergency presentation; (iii) all-cause mortality; (iv) days active to service per year; and (v) face-to-face contacts per year. RESULTS: Loneliness was recorded in 4,483 (16.7%) patients in the study population and fully adjusted models showed associations with subsequent crisis episode (HR 1.17, 95% CI 1.07-1.29), emergency presentation (HR 1.30, 1.21-1.40), days active per year (IRR 1.04, 1.03-1.05), and face-to-face contacts per year (IRR 1.28, 1.27-1.30). Recorded loneliness in patients with substance misuse problems was particularly strongly associated with adverse outcomes, including risk of emergency presentation (HR 1.68, 1.29-2.18) and mortality (HR 1.29, 1.01-1.65). CONCLUSION: Patients receiving mental healthcare who are recorded as lonely have a higher risk of several adverse outcomes which may require a need for higher service input.

HbA1c recording in patients following a first diagnosis of serious mental illness: the South London and Maudsley Biomedical Research Centre case register.

OBJECTIVES: To investigate factors associated with the recording of glycated haemoglobin (HbA1c) in people with first diagnoses of serious mental illness (SMI) in a large mental healthcare provider, and factors associated with HbA1c levels, when recorded. To our knowledge this is the first such investigation, although attention to dysglycaemia in SMI is an increasing priority in mental healthcare. DESIGN: The study was primarily descriptive in nature, seeking to ascertain the frequency of HbA1c recording in the mental healthcare sector for people following first SMI diagnosis. SETTINGS: A large mental healthcare provider, the South London and Maudsley National Health Service Trust. PARTICIPANTS: Using electronic mental health records data, we ascertained patients with first SMI diagnoses (schizophrenia, schizoaffective disorder, bipolar disorder) from 2008 to 2018. OUTCOME MEASURES: Recording or not of HbA1c level was ascertained from routine local laboratory data and supplemented by a natural language processing (NLP) algorithm for extracting recorded values in text fields (precision 0.89%, recall 0.93%). Age, gender, ethnic group, year of diagnosis, and SMI diagnosis were investigated as covariates in relation to recording or not of HbA1c and first recorded levels. RESULTS: Of 21 462 patients in the sample (6546 bipolar disorder; 14 916 schizophrenia or schizoaffective disorder; mean age 38.8 years, 49% female), 4106 (19.1%) had at least one HbA1c result recorded from laboratory data, increasing to 6901 (32.2%) following NLP. HbA1c recording was independently more likely in non-white ethnic groups (black compared with white: OR 2.45, 95% CI 2.29 to 2.62), and was negatively associated with age (OR per year increase 0.93, 0.92-0.95), female gender (0.83, 0.78-0.88) and bipolar disorder (0.49, 0.45-0.52). CONCLUSIONS: Over a 10-year period, relatively low level of recording of HbA1c was observed, although this has increased over time and ascertainment was increased with text extraction. It remains important to improve the routine monitoring of dysglycaemia in these at-risk disorders.

Antidepressant drug prescription and incidence of COVID-19 in mental health outpatients: a retrospective cohort study.

BACKGROUND: Currently, the main pharmaceutical intervention for COVID-19 is vaccination. While antidepressant (AD) drugs have shown some efficacy in treatment of symptomatic COVID-19, their preventative potential remains largely unexplored. Analysis of association between prescription of ADs and COVID-19 incidence in the population would be beneficial for assessing the utility of ADs in COVID-19 prevention. METHODS: Retrospective study of association between AD prescription and COVID-19 diagnosis was performed in a cohort of community-dwelling adult mental health outpatients during the 1st wave of COVID-19 pandemic in the UK. Clinical record interactive search (CRIS) was performed for mentions of ADs within 3 months preceding admission to inpatient care of the South London and Maudsley (SLaM) NHS Foundation Trust. Incidence of positive COVID-19 tests upon admission and during inpatient treatment was the primary outcome measure. RESULTS: AD mention was associated with approximately 40% lower incidence of positive COVID-19 test results when adjusted for socioeconomic parameters and physical health. This association was also observed for prescription of ADs of the selective serotonin reuptake inhibitor (SSRI) class. CONCLUSIONS: This preliminary study suggests that ADs, and SSRIs in particular, may be of benefit for preventing COVID-19 infection spread in the community. The key limitations of the study are its retrospective nature and the focus on a mental health patient cohort. A more definitive assessment of AD and SSRI preventative potential warrants prospective studies in the wider demographic.

Predictors of hospital readmission for patients diagnosed with delirium: An electronic health record data analysis.

INTRODUCTION: Delirium is an acute and fluctuating change in attention and cognition that increases the risk of functional decline, institutionalisation and death in hospitalised patients. After delirium, patients have a significantly higher risk of readmission to hospital. Our aim was to investigate factors associated with hospital readmission in people with delirium. METHODS: We carried out an observational retrospective cohort study using linked mental health care and hospitalisation records from South London. Logistic regression models were used to predict the odds of 30-day readmission and Cox proportional hazard models to calculate readmission risks when not restricting follow-up time. RESULTS: Of 2814 patients (mean age 78.9 years SD ±11.8) discharged from hospital after an episode of delirium, 823 (29.3%) were readmitted within 30 days. Depressed mood (odds ratio (OR) 1.34 (95% confidence interval (CI) 1.08-1.66)), moderate-to-severe physical health problems (OR 1.67 (95% CI 1.18-2.2.36)) and a history of serious circulatory disease (OR 1.29 (95% CI 1.07-1.55)) were associated with higher odds of hospital readmission, whereas a diagnosis of delirium superimposed on dementia (OR 0.67 (95% CI 0.53-0.84)) and problematic alcohol/substance (OR 0.54 (95% CI 0.33-0.89)) use were associated with lower odds. Cox proportionate hazard models showed similar results. CONCLUSION: Almost one-third of patients with delirium were readmitted within a short period of time, a more detailed understanding of the underlying risk factors could help prevent readmissions. Our findings indicate that the aetiology (as alcohol-related delirium), the recognition that delirium occurred in the context of dementia, as well as potentially modifiable factors, as depressed mood affect readmission risk, and should be assessed in clinical settings.

Body mass index and mortality in patients with schizophrenia spectrum disorders: a cohort study in a South London catchment area.

Background: People with schizophrenia have a high premature mortality risk. Obesity is a key potential underlying risk factor that is relatively unevaluated to date. Aims: In this study, we investigated the associations of routinely recorded body size with all-cause mortality and deaths from common causes in a large cohort of people with schizophrenia spectrum disorders. Methods: We assembled a retrospective observational cohort using data from a large mental health service in South London. We followed all patients over the age of 18 years with a clinical diagnosis of schizophrenia spectrum disorders from the date of their first recorded body mass index (BMI) between 1 January 2007 and 31 March 2018. Results: Of 11 900 patients with a BMI recording, 1566 died. The Cox proportional hazards regression models, after adjusting for sociodemographic, socioeconomic variables and comorbidities, indicated that all-cause mortality was only associated with underweight status compared with healthy weight status (hazard ratio (HR): 1.33, 95% confidence interval (CI): 1.01 to 1.76). Obesity (HR: 1.24, 95% CI: 1.01 to 1.52) and morbid obesity (HR: 1.54, 95% CI: 1.03 to 2.42) were associated with all-cause mortality in the 18-45 years age range, and obesity was associated with lower risk (HR: 0.66, 95% CI: 0.50 to 0.87) in those aged 65+ years. Cancer mortality was raised in underweight individuals (HR: 1.93, 95% CI: 1.03 to 4.10) and respiratory disease mortality raised in those with morbid obesity (HR: 2.17, 95% CI: 1.02 to 5.22). Conclusions: Overall, being underweight was associated with higher mortality in this disorder group; however, this was potentially accounted for by frailty in older age groups, and obesity was a risk factor for premature mortality in younger ages. The impact of obesity on life expectancy for people with schizophrenia spectrum disorders is clear from our findings. A deeper biological understanding of the relationship between these diseases and schizophrenia will help improve clinical practice.

The impact of the first UK COVID-19 lockdown on presentations with psychosis to mental health services for older adults: An electronic health records study in South London.

OBJECTIVES: Social distancing restrictions in the COVID-19 pandemic may have had adverse effects on older adults' mental health. Whereby the impact on mood is well-described, less is known about psychotic symptoms. The aim of this study was to compare characteristics associated with psychotic symptoms during the first UK lockdown and a pre-pandemic comparison period. METHODS: In this retrospective observational study we analysed anonymised records from patients referred to mental health services for older adults in South London in the 16-week period of the UK lockdown starting in March 2020, and in the comparable pre-pandemic period in 2019. We used logistic regression models to compare the associations of different patient characteristics with increased odds of presenting with any psychotic symptom (defined as hallucinations and/or delusion), hallucinations, or delusions, during lockdown and the corresponding pre-pandemic period. RESULTS: 1991 referrals were identified. There were fewer referrals during lockdown but a higher proportion of presentations with any psychotic symptom (48.7% vs. 42.8%, p = 0.018), particularly hallucinations (41.0% vs. 27.8%, p < 0.001). Patients of non-White ethnicity (adjusted odds ratio (OR): 1.83; 95% confidence interval (CI): 1.13-2.99) and patients with dementia (adjusted OR: 3.09; 95% CI: 1.91-4.99) were more likely to be referred with psychotic symptoms during lockdown. While a weaker association between dementia and psychotic symptoms was found in the pre-COVID period (adjusted OR: 1.55; 95% CI: 1.19-2.03), interaction terms indicated higher odds of patients of non-White ethnicity or dementia to present with psychosis during the lockdown period. CONCLUSIONS: During lockdown, referrals to mental health services for adults decreased, but contained a higher proportion with psychotic symptoms. The stronger association with psychotic symptoms in non-White ethnic groups and patients with dementia during lockdown suggests that barriers in accessing care might have increased during the COVID-19 pandemic.

Cardiac surgery receipt and outcomes for people using secondary mental healthcare services: Retrospective cohort study using a large mental healthcare database in South London.

BACKGROUND: Patients diagnosed with mental health problems are more predisposed to cardiovascular disease, including cardiac surgery. Nevertheless, health outcomes after cardiac surgery for patients with mental health problems as a discrete group are unknown. This study examined the association between secondary care mental health service use and postoperative health outcomes following cardiac surgery. METHODS: We conducted a retrospective observational research, utilizing data from a large South London mental healthcare supplier linked to national hospitalization data. OPCS-4 codes were applied to classify cardiac surgery. Health results were compared between those individuals with a mental health disorder diagnosis from secondary care and other local residents, including the length of hospital stay (LOS), inpatient mortality, and 30-day emergency hospital readmission. RESULTS: Twelve thousand three hundred and eighty-four patients received cardiac surgery, including 1,481 with a mental disorder diagnosis. Patients with mental health diagnosis were at greater risk of emergency admissions for cardiac surgery (odds ratio [OR] 1.60; 1.43, 1.79), longer index LOS (incidence rate ratio 1.28; 1.26, 1.30), and at higher risk of 30-day emergency readmission (OR 1.53; 1.31, 1.78). Those who underwent pacemaker insertion and major open surgery had worse postoperative outcomes during index surgery hospital admission while those who had major endovascular surgery had worse health outcomes subsequent 30-day emergency hospital readmission. CONCLUSION: People with a mental health disorder diagnosis undertaking cardiac surgery have significantly worse health outcomes. Personalized guidelines and policies to manage preoperative risk factors require consideration and evaluation.

Unsupervised Machine Learning to Identify Depressive Subtypes.

OBJECTIVES: This study evaluated an unsupervised machine learning method, latent Dirichlet allocation (LDA), as a method for identifying subtypes of depression within symptom data. METHODS: Data from 18,314 depressed patients were used to create LDA models. The outcomes included future emergency presentations, crisis events, and behavioral problems. One model was chosen for further analysis based upon its potential as a clinically meaningful construct. The associations between patient groups created with the final LDA model and outcomes were tested. These steps were repeated with a commonly-used latent variable model to provide additional context to the LDA results. RESULTS: Five subtypes were identified using the final LDA model. Prior to the outcome analysis, the subtypes were labeled based upon the symptom distributions they produced: psychotic, severe, mild, agitated, and anergic-apathetic. The patient groups largely aligned with the outcome data. For example, the psychotic and severe subgroups were more likely to have emergency presentations (odds ratio [OR] = 1.29; 95% confidence interval [CI], 1.17-1.43 and OR = 1.16; 95% CI, 1.05-1.29, respectively), whereas these outcomes were less likely in the mild subgroup (OR = 0.86; 95% CI, 0.78-0.94). We found that the LDA subtypes were characterized by clusters of unique symptoms. This contrasted with the latent variable model subtypes, which were largely stratified by severity. CONCLUSIONS: This study suggests that LDA can surface clinically meaningful, qualitative subtypes. Future work could be incorporated into studies concerning the biological bases of depression, thereby contributing to the development of new psychiatric therapeutics.

The Impact of Dementia on Diabetes Control: An Evaluation of HbA1c Trajectories and Care Outcomes in Linked Primary and Specialist Care Data.

OBJECTIVES: Diabetes self-care may become increasingly challenging as cognition declines. We sought to characterize glycated hemoglobin A1c (HbA1c) trajectories, markers of diabetes-related management, health care utilization, and mortality in people with preexisting type 2 diabetes (T2D) with and without dementia and based on the extent of cognitive impairment at the time of dementia diagnosis. DESIGN: Retrospective matched cohort study. SETTING AND PARTICIPANTS: Using a linkage between a primary care (Lambeth DataNet) and a secondary mental healthcare database, up to 5 individuals aged ≥65 y with preexisting T2D without dementia were matched to each individual with dementia based on age, sex, and general practice. METHODS: Comparisons were made for HbA1c trajectories (linear mixed effects models), markers of diabetes-related management and severity at dementia diagnosis (logistic regression), mortality (Cox regression), and health care utilization (multilevel mixed effects binomial regression). RESULTS: In 725 incident dementia and 3154 matched comparators, HbA1c trajectories differed by dementia status; HbA1c increased over time for mild dementia and non-dementia, but the increase was greater in the mild dementia group; for those with moderate-severe dementia, HbA1c decreased over time. Despite individuals with dementia having increased health care utilization around the time of dementia diagnosis, they were less likely to have had routine diabetes-related management. Patients with dementia had a higher prevalence of macrovascular complications and diabetes foot morbidity at dementia diagnosis and a higher mortality risk than those without dementia; these relationships were most marked in those with moderate-severe dementia. CONCLUSIONS AND IMPLICATIONS: Our study has highlighted important differences in the monitoring, management, and control of diabetes in people with dementia. The effects of frailty and the extent of cognitive impairment on the ability to self-manage diabetes and on glycemic control may need to be considered in treatment guidelines and by primary care.

Potentially avoidable causes of hospitalisation in people with dementia: contemporaneous associations by stage of dementia in a South London clinical cohort.

OBJECTIVES: To estimate the frequency of all-cause and ambulatory care sensitive condition (ACSCs)-related hospitalisations among individuals with dementia. In addition, to investigate differences by stage of dementia based on recorded cognitive function. SETTING: Data from a large London dementia care clinical case register, linked to a national hospitalisation database. PARTICIPANTS: Individuals aged ≥65 years with a confirmed dementia diagnosis with recorded cognitive function. OUTCOME MEASURES: Acute general hospital admissions were evaluated within 6 months of a randomly selected cognitive function score in patients with a clinical diagnosis of dementia. To evaluate associations between ACSC-related hospital admissions (overall and individual ACSCs) and stage of dementia, an ordinal regression was performed, modelling stage of dementia as the dependant variable (to facilitate efficient model selection, with no implication concerning the direction of causality). RESULTS: Of the 5294 people with dementia, 2993 (56.5%) had at least one hospitalisation during a 12-month period of evaluation, and 1192 (22.5%) had an ACSC-related admission. Proportions with an all-cause or ACSC-related hospitalisation were greater in the groups with more advanced dementia (all-cause 53.9%, 57.1% and 60.9%, p 0.002; ACSC-related 19.5%, 24.0% and 25.3%, p<0.0001 in the mild, moderate and severe groups, respectively). An ACSC-related admission was associated with 1.3-fold (95% CI 1.1 to 1.5) increased odds of more severe dementia after adjusting for demographic factors. Concerning admissions for individual ACSCs, the most common ACSC was urinary tract infection /pyelonephritis (9.8% of hospitalised patients) followed by pneumonia (7.1%); in an adjusted model, these were each associated with 1.4-fold increased odds of more severe dementia (95% CI 1.2 to 1.7 and 1.1 to 1.7, respectively). CONCLUSIONS: Potentially avoidable hospitalisations were common in people with dementia, particularly in those with greater cognitive impairment. Our results call for greater attention to the extent of cognitive status impairment, and not just dementia diagnosis, when evaluating measures to reduce the risk of potentially avoidable hospitalisations.

Predictors of falls and fractures leading to hospitalisation in 36 101 people with affective disorders: a large representative cohort study.

OBJECTIVES: To investigate predictors of falls and fractures leading to hospitalisation in people with affective disorders. DESIGN: Cohort study. SETTING: The South London and Maudsley National Health Service (NHS) Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register. PARTICIPANTS: A large cohort of people with affective disorders (International Classification of Diseases- 10th version [ICD-10] codes F30-F34) diagnosed between January 2008 and March 2016 was assembled using data from the SLaM BRC Case Register. PRIMARY AND SECONDARY OUTCOME MEASURES: Falls and fractures leading to hospitalisation were ascertained from linked national hospitalisation data. Multivariable Cox proportional hazards analyses were administrated to identify predictors of first falls and fractures. RESULTS: Of 36 101 people with affective disorders (mean age 44.4 years, 60.2% female), 816 (incidence rate 9.91 per 1000 person-years) and 1117 (incidence rate 11.92 per 1000 person-years) experienced either a fall or fracture, respectively. In multivariable analyses, older age, analgesic use, increased physical illness burden, previous hospital admission due to certain comorbid physical illnesses and increase in attendances to accident and emergency services following diagnosis were significant risk factors for both falls and fractures. Having a history of falls was a strong risk factor for recurrent falls, and a previous fracture was also associated with future fractures. CONCLUSIONS: Over a mean 5 years' follow-up, approximately 8% of people with affective disorders were hospitalised with a fall or fracture. Several similar factors were found to predict risk of falls and fracture, for example, older age, comorbid physical disorders and analgesic use. Routine screening for bone mineral density and fall prevention programmes should be considered for this clinical group.

Sedation-Associated Medications at Dementia Diagnosis, Their Receptor Activity, and Associations With Adverse Outcomes in a Large Clinical Cohort.

OBJECTIVES: We aimed to investigate whether sedative medications are associated with adverse outcomes in people with dementia, and whether specific characteristics of these medications predict a higher risk of harm. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: 15,210 patients diagnosed with dementia between 2008 and 2017 in South London. METHODS: From recorded medications at dementia diagnosis, we ascertained those with drowsiness listed as a side effect (termed "sedative" hereafter) and subdivided them by frequency and strength of sedation, receptor profile, half-life, and whether they were psychotropics. Multivariable Cox regression models were applied to determine risk of mortality and emergency hospitalization, and generalized estimating equations to investigate cognitive decline. Final models were adjusted for 19 potential confounders, including measures of physical and mental health, functioning, and central anticholinergic burden. RESULTS: At diagnosis, 70.4% of patients with dementia were receiving at least 1 sedative medication. Median survival time was 4.0 years and median time to first hospitalization 1.4 years. After controlling for potential confounders, receipt of any sedative medication at dementia diagnosis was associated with accelerated cognitive decline and a higher hospitalization risk, but only medications with a cautionary warning yielded an increased mortality hazard. Medications acting through γ-aminobutyric acid agonism, psychotropic sedatives, and those with a short half-life were associated with a higher risk of mortality. γ-aminobutyric acid agonists, N-methyl-d-aspartate receptor antagonists, and nonpsychotropic sedatives were associated with an increased hospitalization risk. α1 antagonist, antihistamines, N-methyl-d-aspartate receptor antagonists, psychotropic sedatives, and those with the shortest or longest half-life were associated with accelerated cognitive decline. CONCLUSIONS AND IMPLICATIONS: Receipt of any sedative agent was associated with hospitalization and accelerated cognitive decline. Differences in hazard appear to exist between frequency and strength of sedation, receptor profiles, half-life, and prescribing indication. These differences should be taken into consideration in medication reviews at the time of dementia diagnosis.

Associations between loneliness and acute hospitalisation outcomes among patients receiving mental healthcare in South London: a retrospective cohort study.

PURPOSE: It is well known that loneliness can worsen physical and mental health outcomes, but there is a dearth of research on the impact of loneliness in populations receiving mental healthcare. This study aimed to investigate cross-sectional correlates of loneliness among such patients and longitudinal risk for acute general hospitalisations. METHOD: A retrospective observational study was conducted on the data from patients aged 18 + receiving assessment/care at a large mental healthcare provider in South London. Recorded loneliness status was ascertained among active patients on the index date, 30th Jun 2012. Acute general hospitalisation (emergency/elective) outcomes were obtained until 31st Mar 2018. Length of stay was modelled using Poisson regression models and time-to hospitalisation and time-to mortality were modelled using Cox proportional hazards regression models. RESULTS: The data from 26,745 patients were analysed. The prevalence of patients with recorded loneliness was 16.4% at the index date. In the fully adjusted model, patients with recorded loneliness had higher hazards of emergency (HR 1.15, 95% CI 1.09-1.22) and elective (1.05, 1.01-1.12) hospitalisation than patients who were not recorded as lonely, and a longer duration of both emergency (IRR 1.06, 95% CI 1.05-1.07) and elective (1.02, 1.01-1.03) general hospitalisations. There was no association between loneliness and mortality. Correlates of loneliness included having an eating disorder (OR 1.67, 95% CI 1.29-2.25) and serious mental illnesses (OR 1.44, 1.29-1.62). CONCLUSION: Loneliness in patients receiving mental healthcare is associated with higher use of general hospital services. Increased attention to the physical healthcare of this patient group is therefore warranted.

Centrally-acting anticholinergic drugs- associations with mortality, hospitalisation and cognitive decline following dementia diagnosis in people receiving antidepressant and antipsychotic drugs.

OBJECTIVES: Long-term use of anticholinergic medication in older people is associated with increased risk of cognitive decline and mortality, but this relationship could be confounded by the underlying illness the drugs are treating. To investigate associations between central anticholinergic antidepressants or antipsychotics and mortality, hospitalisation and cognitive decline in people with dementia. METHOD: In cohorts of patients with a dementia diagnosis receiving antidepressant and/or antipsychotic medication (N = 4,380 and N = 2,335 respectively), assembled from a large healthcare database, central anticholinergic burden scores were estimated using the Anticholinergic Effect on Cognition (AEC) scale. Data were linked to national mortality and hospitalisation data sources, and Mini-Mental State Examination (MMSE) scores were used to investigate cognitive decline. RESULTS: There was a reduced mortality risk in people receiving agents with high central anticholinergic burden compared to those with no or low burden which was statistically significant in the antidepressant cohort (Hazard ratio (HR): 0.88; 95% confidence interval (CI): 0.79-0.98; p = 0.023) but not the antipsychotic one (HR: 0.91; 95% CI: 0.82-1.02; p = 0.105). Patients on antidepressants with no central anticholinergic burden had accelerated cognitive decline compared with other groups, whereas no differences were found in the antipsychotic cohort. No significant associations were detected between antidepressant or antipsychotic-related central anticholinergic burden and hospitalisation. CONCLUSION: These counter-intuitive findings may reflect factors underlying the choice of psychotropics rather than the agents themselves, although do not support a strong role for central anticholinergic drug actions on dementia outcomes. Further studies, including randomized switching of agents are needed to clarify this relationship.

Identifying subtypes of depression in clinician-annotated text: a retrospective cohort study.

Current criteria for depression are imprecise and do not accurately characterize its distinct clinical presentations. As a result, its diagnosis lacks clinical utility in both treatment and research settings. Data-driven efforts to refine criteria have typically focused on a limited set of symptoms that do not reflect the disorder's heterogeneity. By contrast, clinicians often write about patients in depth, creating descriptions that may better characterize depression. However, clinical text is not commonly used to this end. Here we show that clinically relevant depressive subtypes can be derived from unstructured electronic health records. Five subtypes were identified amongst 18,314 patients with depression treated at a large mental healthcare provider by using unsupervised machine learning: severe-typical, psychotic, mild-typical, agitated, and anergic-apathetic. Subtypes were used to place patients in groups for validation; groups were found to be associated with future outcomes and characteristics that were consistent with the subtypes. These associations suggest that these categorizations are actionable due to their validity with respect to disease prognosis. Moreover, they were derived with automated techniques that might theoretically be widely implemented, allowing for future analyses in more varied populations and settings. Additional research, especially with respect to treatment response, may prove useful in further evaluation.

Loneliness in older adult mental health services during the COVID-19 pandemic and before: Associations with disability, functioning and pharmacotherapy.

OBJECTIVES: Loneliness is associated with psychiatric morbidity. Restrictions placed on the population during the first COVID-19 lockdown may have disproportionately affected older adults, possibly through increasing loneliness. We sought to investigate this by examining loneliness in referrals to mental health of older adults (MHOA) services during the first UK COVID-19 lockdown. METHODS: Referrals to MHOA services from a large South London catchment area were identified for the 16-week period of the UK lockdown starting in March 2020 and for the corresponding period in 2019. A natural language processing algorithm identified loneliness in the patients' records. We applied logistic regression models adjusted for age, gender, ethnicity and diagnosis, to examine associations of loneliness in the study population. RESULTS: 1991 referrals were identified, 56.9% of whom were female, with a mean age of 77.9 years. Only 26.9% occurred during the 2020 lockdown, but with a higher prevalence of loneliness (22.0 vs. 17.7%, p = 0.028). In the whole sample, loneliness was associated with non-accidental self-injury (Odds ratio [OR]: 1.65), depressed mood (OR: 1.73), psychotic symptoms (OR: 1.65), relationship problems (OR: 1.49), problems with daytime activities (OR: 1.36), and antidepressant use (OR: 2.11). During lockdown, loneliness was associated with non-accidental self-injury (OR: 2.52), problem drinking or drug-taking (OR 2.33), and antidepressant use (OR 2.10). CONCLUSIONS: Loneliness is associated with more severe symptoms of affective illness, worse functional problems and increased use of antidepressant medication in older adults. During lockdown, loneliness in referrals to MHOA services increased and was associated with increased risk-taking behaviour. Loneliness is a potential modifiable risk factor for mental illness, and efforts to minimise it in older adults should be prioritised as we emerge from the pandemic.

Effect of trazodone on cognitive decline in people with dementia: Cohort study using UK routinely collected data.

OBJECTIVES: Evidence in mouse models has found that the antidepressant trazodone may be protective against neurodegeneration. We therefore aimed to compare cognitive decline of people with dementia taking trazodone with those taking other antidepressants. METHODS: Three identical naturalistic cohort studies using UK clinical registers. We included all people with dementia assessed during 2008-16 who were recorded taking trazodone, citalopram or mirtazapine for at least 6 weeks. Linear mixed models examined age, time and sex-adjusted Mini-mental state examination (MMSE) change in people with all-cause dementia taking trazodone compared with those taking citalopram and mirtazapine. In secondary analyses, we examined those with non-vascular dementia; mild dementia; and adjusted results for neuropsychiatric symptoms. We combined results from the three study sites using random-effects meta-analysis. RESULTS: We included 2,199 people with dementia, including 406 taking trazodone, with mean 2.2 years follow-up. There was no difference in adjusted cognitive decline in people with all-cause or non-vascular dementia taking trazodone, citalopram or mirtazapine in any of the three study sites. When data from the three sites were combined in meta-analysis, we found greater mean MMSE decline in people with all-cause dementia taking trazodone compared to those taking citalopram (0·26 points per successive MMSE measurement, 95% CI 0·03-0·49; p = 0·03). Results in sensitivity analyses were consistent with primary analyses. CONCLUSIONS: There was no evidence of cognitive benefit from trazodone compared to other antidepressants in people with dementia in three naturalistic cohort studies. Despite preclinical evidence, trazodone should not be advocated for cognition in dementia.