Polypharmacy in people with dementia: Associations with adverse health outcomes
Polypharmacy has been linked to higher risks of hospitalisation and death in community samples. It is commonly present in people with dementia but these risks have rarely been studied in this population. We aimed to investigate associations between polypharmacy and emergency department attendance, any and unplanned hospitalisation, and mortality in patients with dementia. Using a large mental health care database in South London, linked to hospitalisation and mortality data, we assembled a retrospective cohort of patients diagnosed with dementia. We ascertained number of medications prescribed at the time of dementia diagnosis and conducted multivariate Cox regression analyses. Of 4668 pati…
Aspirin and incident depressive symptoms: A longitudinal cohort study over 8 years
Objective: Aspirin exhibits anti-atherosclerotic and anti-inflammatory properties—two potential risk factors for depression. The relationship between aspirin use and depression, however, remains unclear. We investigated whether the aspirin use is associated with a decreased incidence of depressive symptoms in a large North American cohort. Methods: Data from the Osteoarthritis Initiative dataset, a multicenter, longitudinal study on community-dwelling adults was analyzed. Aspirin use was defined through self-report in the past 30 days and confirmed by a trained interviewer. Incident depressive symptoms were defined as a score of ≥16 in the 20-item Center for Epidemiologic Studies-Depression…
Risk of Hospitalized Falls and Hip Fractures in 22,103 Older Adults Receiving Mental Health Care vs 161,603 Controls: A Large Cohort Study.
Abstract: Objectives: To investigate the risk of hospitalized fall or hip fracture among older adults using mental health services. Design: Retrospective cohort study. Setting and Participants: Residents of a South London catchment aged >60 years receiving specialist mental health care between 2008 and 2016. Measures: Falls and/or a hip fracture leading to hospitalization were ascertained from linked national records. Incidence rates and incidence rate ratios (IRRs) were age- and gender-standardized to the catchment population. Multivariable survival analyses were applied investigating falls and/or hip fractures as outcomes. Results: In 22,103 older adults, incidence rates were 60.1 per 100…
The transcription factor IFN regulatory factor–4 controls experimental colitis in mice via T cell–derived IL-6
The proinflammatory cytokine IL-6 seems to have an important role in the intestinal inflammation that characterizes inflammatory bowel diseases (IBDs) such as Crohn disease and ulcerative colitis. However, little is known about the molecular mechanisms regulating IL-6 production in IBD. Here, we assessed the role of the transcriptional regulator IFN regulatory factor-4 (IRF4) in this process. Patients with either Crohn disease or ulcerative colitis exhibited increased IRF4 expression in lamina propria CD3+ T cells as compared with control patients. Consistent with IRF4 having a regulatory function in T cells, in a mouse model of IBD whereby colitis is induced in RAG-deficient mice by transp…
The relationship between Polypharmacy and Trajectories of Cognitive Decline in People with Dementia: a large representative cohort study
Polypharmacy, defined through the number of medications prescribed, has been linked to a range of adverse health outcomes in people with dementia. It is however unclear whether a numerical threshold of concurrently prescribed drugs is a suitable predictor for cognitive decline. We aimed to test associations between polypharmacy and both short-term (six months) and long-term (three years) cognitive trajectories in patients with incident dementia. Using data from a large mental health and dementia care database in South London, a cohort of 12,148 patients (mean age = 80.7 years, 61.1% female, mean MMSE = 18.6) clinically diagnosed with dementia was identified. We determined the number of medi…
IRF4 regulates IL-17A promoter activity and controls RORγt-dependent Th17 colitis in vivo
The transcription factor IRF4 is involved in several T-cell-dependent chronic inflammatory diseases. To elucidate the mechanisms for pathological cytokine production in colitis, we addressed the role of the IRF transcription factors in human inflammatory bowel disease (IBD) and experimental colitis.IRF levels and cytokine production in IBD patients were studied as well as the effects of IRF4 deficiency in experimental colitis.In contrast to IRF1, IRF5, and IRF8, IRF4 expression in IBD was augmented in the presence of active inflammation. Furthermore, IRF4 levels significantly correlated with IL-6 and IL-17 mRNA expression and to a lesser extent with IL-22 mRNA expression in IBD. To further …
Associations of neuropsychiatric symptoms and antidepressant prescription with survival in Alzheimer's disease
Objective Depression is associated with increased mortality in community samples. The use of antidepressant medication may also increase mortality, however, it is still unclear whether taking antidepressants before or after a diagnosis of dementia influences survival. Design Retrospective. Setting A cohort with a diagnosis of Alzheimer disease (AD) from a large mental health and dementia care database in South London, linked to hospitalization and mortality data. Participants Mild dementia (Mini-Mental State Examination ≥18/30) at the point of diagnosis. Measurements We ascertained antidepressant prescription, either in the 6 months before or after dementia diagnosis, and used the HoNOS65+,…
Weight loss in Alzheimer’s disease, vascular dementia and dementia with Lewy bodies: Impact on mortality and hospitalization by dementia subtype
Objectives Loss of weight is associated with cognitive decline as well as several adverse outcomes in dementia. The aim of this study was to assess whether weight loss is associated with mortality and hospitalization in dementia subtypes. Methods A cohort of 11,607 patients with dementia in Alzheimer's disease (AD), vascular dementia (VD), or dementia with Lewy bodies (DLB) was assembled from a large dementia care health records database in Southeast London. A natural language processing algorithm was developed to established whether loss of weight was recorded around the time of dementia diagnosis. Cox proportional hazard models were applied to examine the associations of reported weight l…
Polypharmacy Is Associated With Higher Frailty Risk in Older People: An 8-Year Longitudinal Cohort Study
Objective To investigate whether polypharmacy is associated with a higher incidence of frailty in a large cohort of North Americans during 8 years of follow-up. Design Longitudinal study, follow-up of 8 years. Participants A total of 4402 individuals at high risk or having knee osteoarthritis free from frailty at baseline. Measurements Details regarding medication prescription were captured and categorized as 0–3, 4–6, and ≥7. Frailty was defined using the Study of Osteoporotic Fracture index as the presence of ≥2 out of (1) weight loss ≥5% between baseline and the subsequent follow-up visit; (2) inability to do 5 chair stands; and (3) low energy level according to the Study of Osteoporotic…
Predictors of Falls and Fractures Leading to Hospitalization in People With Dementia: A Representative Cohort Study.
OBJECTIVES: Investigate predictors of falls and fractures leading to hospitalization in a large cohort of people with dementia. DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: People with diagnosed dementia between January 2007 and March 2013, aged >65 years, were assembled using data from the Maudsley Biomedical Research Centre Case Register, from 4 boroughs in London serving a population of 1.3 million people. MEASURES: Falls and/or fractures leading to hospitalization were ascertained from linked national records. Demographic data, cognitive test scores, medications, and symptom and functioning scores from Health of the Nation Outcome Scales (HoNOS65+) were modeled in mul…
Survival time and differences between dementia with Lewy bodies and Alzheimer’s disease following diagnosis: a meta-analysis of longitudinal studies.
Objective: To synthesize the evidence across longitudinal studies comparing survival in dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Methods: We conducted a systematic review and meta-analysis of studies comparing survival in clinically diagnosed DLB to AD. Longitudinal cohort studies were identified through a systematic search of major electronic databases from inception to May 2018. A random effects meta-analysis was performed to calculate survival time and relative risk of death. Results: Overall, 11 studies were identified including 22,952 patients with dementia: 2029 with DLB (mean diagnosis age 76.3; 47% female) compared with 20,923 with AD (mean diagnosis age 77.2; 6…
Pain is not associated with cognitive decline in older adults: A four-year longitudinal study.
The finding of a potential association between pain and cognitive decline is limited to a few cross-sectional studies with relatively samples. We therefore aimed to investigate whether the presence and severity of pain at baseline could predict a decline in cognitive function over four years of follow-up in the English Longitudinal Study of Ageing. At baseline, participants with no dementia who were “often troubled by pain” were considered to have pain. Pain severity was categorized as mild, moderate, or severe. Cognitive function was explored through verbal fluency (assessed by asking how many different animals the participants could name in 60 s), memory (sum of immediate and delayed verb…
Low-Dose Aspirin Use and Cognitive Function in Older Age: A Systematic Review and Meta-analysis
Objectives:\ud \ud To investigate whether low-dose aspirin (<300 mg/d) can influence the onset of cognitive impairment or dementia in observational studies and improve cognitive test scores in randomized controlled trials (RCTs) in participants without dementia.\ud \ud Design:\ud \ud Systematic review and meta-analysis.\ud \ud Setting:\ud \ud Observational and interventional studies.\ud \ud Participants:\ud \ud Individuals with no dementia or cognitive impairment initially.\ud \ud Measurements:\ud \ud Odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for the maximum number of covariates from each study, were used to summarize data on the incidence of dementia and cognitive impa…