Associations of cognitive impairment with self-isolation and access to health and care during the COVID-19 pandemic in England.

This research explored experiences across three cognitive function groups (no impairment, mild impairment, and dementia) with respect to shielding (either self-isolating or staying at home), COVID-19 infection, and access to health/care services during the COVID-19 pandemic. Analyses were conducted using data from the English Longitudinal Study of Ageing (ELSA) COVID-19 sub-study collected in 2020. We report bivariate estimates across our outcomes of interest by cognitive function group along with multivariate regression results adjusting for demographic, socioeconomic, geographic, and health characteristics. Rates of shielding were high across all cognitive function groups and three measured time points (April, June/July, and Nov/Dec 2020), ranging from 74.6% (95% confidence interval 72.9-76.2) for no impairment in Nov/Dec to 96.7% (92.0-98.7) for dementia in April (bivariate analysis). 44.1% (33.5-55.3) of those with dementia experienced disruption in access to community health services by June/July compared to 34.9% (33.2-36.7) for no impairment. A higher proportion of those with mild impairment reported hospital-based cancellations in June/July (23.1% (20.1-26.4)) and Nov/Dec (16.3% (13.4-19.7)) than those with no impairment (18.0% (16.6-19.4) and 11.7% (10.6-12.9)). Multivariate adjusted models found that those with dementia were 2.4 (1.1-5.0) times more likely than those with no impairment to be shielding in June/July. All other multivariate analyses found no statistically significant differences between cognitive function groups. People with dementia were more likely than people with no impairment to be shielding early in the pandemic, but importantly they were no more likely to experience disruption to services or hospital treatment.

Long term survival after a first transient ischaemic attack in England: A retrospective matched cohort study.

OBJECTIVE: Transient ischaemic attacks (TIA) serve as warning signs for future stroke, and the impact of TIA on long term survival is uncertain. We assessed the long-term hazards of all-cause mortality following a first episode of a transient ischaemic attack (TIA). DESIGN: Retrospective matched cohort study. METHODS: Cohort study using electronic primary health care records from The Health Improvement Network (THIN) database in the United Kingdom. Cases born in or before 1960, resident in England, with a first diagnosis of TIA between January 1986 and January 2017 were matched to three controls on age, sex and general practice. The primary outcome was all-cause mortality. The hazards of all-cause mortality were estimated using a time-varying Double-Cox Weibull survival model with a random frailty effect of general practice, while adjusting for different socio-demographic factors, medical therapies, and comorbidities. RESULTS: 20,633 cases and 58,634 controls were included. During the study period, 24,176 participants died comprising of 7,745 (37.5%) cases and 16,431(28.0%) controls. In terms of hazards of mortality, cases aged 39 to 60 years at the first TIA event had the highest hazard ratio (HR) of mortality compared to their 39-60 years matched controls (HR = 3.04 (2.91 - 3.18)). The HR for cases aged 61-70 years, 71-76 years and 77+ years were 1.98 (1.55 - 2.30), 1.79 (1.20 - 2.07) and 1.52 (1.15 - 1.97) compared to their same-aged matched controls. Cases aged 39-60 at TIA onset who were prescribed aspirin were associated with reduced HR of 0.93 (0.84 - 1.01), 0.90 (0.82 - 0.98) and 0.88 (0.80 - 0.96) at 5, 10 and 15 years respectively, compared to the same aged cases who were not prescribed any antiplatelet. Statistically significant reductions in hazard ratios were observed with aspirin at 10 and 15 years in all age groups. Hazard ratio point estimates for other antiplatelets (dipyridamole or clopidogrel) and dual antiplatelet therapy were very similar to aspirin at 5, 10 and 15 years but with wider confidence intervals that included 1. There was no survival benefit associated with antiplatelet prescription in controls. CONCLUSIONS: The overall risk of death was considerably elevated in all age groups after a first-ever TIA event. Aspirin prescription was associated with a reduced risk. These findings support the use of aspirin in secondary prevention for people with a TIA. The results do not support the use of antiplatelet medication in people without TIA.

Scarred survivors: gate keepers and gate openers to healthcare for migrants in vulnerable circumstances.

Background: The main barriers to 'vulnerable migrants' receiving good quality primary care are language and administration barriers. Little is known about the experiences of healthcare discrimination faced by migrants from different cultural groups. The aim was to explore vulnerable migrants' perspectives on primary healthcare in a UK city. Methods: Three focus groups and two semi-structured interviews were aided by interpreters. These were analysed against a pre-developed framework based on national standards of care for vulnerable migrants. Recruitment was facilitated via a community organisation. Results: In total, 13 participants took part, six women and seven men. There were five Arabic speakers, four Farsi speakers and four English speakers. Themes included access to primary care, mental health, use of interpreters, post-migration stressors and cultural competency. Conclusion: Vulnerable migrants perceived high levels of discrimination and reported the value of a respectful attitude from health professionals. Appointment booking systems and re-ordering medication are key areas where language barriers cause the most disruption to patient care. Medication-only treatment plans have limitations for mental distress for this population. Community-based therapies which manage post-migration stressors are likely to enhance recovery.

The burden of mental disorders, substance use disorders and self-harm among young people in Europe, 1990-2019: Findings from the Global Burden of Disease Study 2019.

Background: Mental health is a public health issue for European young people, with great heterogeneity in resource allocation. Representative population-based studies are needed. The Global Burden of Disease (GBD) Study 2019 provides internationally comparable information on trends in the health status of populations and changes in the leading causes of disease burden over time. Methods: Prevalence, incidence, Years Lived with Disability (YLDs) and Years of Life Lost (YLLs) from mental disorders (MDs), substance use disorders (SUDs) and self-harm were estimated for young people aged 10-24 years in 31 European countries. Rates per 100,000 population, percentage changes in 1990-2019, 95% Uncertainty Intervals (UIs), and correlations with Sociodemographic Index (SDI), were estimated. Findings: In 2019, rates per 100,000 population were 16,983 (95% UI 12,823 - 21,630) for MDs, 3,891 (3,020 - 4,905) for SUDs, and 89·1 (63·8 - 123·1) for self-harm. In terms of disability, anxiety contributed to 647·3 (432-912·3) YLDs, while in terms of premature death, self-harm contributed to 319·6 (248·9-412·8) YLLs, per 100,000 population. Over the 30 years studied, YLDs increased in eating disorders (14·9%;9·4-20·1) and drug use disorders (16·9%;8·9-26·3), and decreased in idiopathic developmental intellectual disability (-29·1%;23·8-38·5). YLLs decreased in self-harm (-27·9%;38·3-18·7). Variations were found by sex, age-group and country. The burden of SUDs and self-harm was higher in countries with lower SDI, MDs were associated with SUDs. Interpretation: Mental health conditions represent an important burden among young people living in Europe. National policies should strengthen mental health, with a specific focus on young people. Funding: The Bill and Melinda Gates Foundation.

Do statins reduce mortality in older people? Findings from a longitudinal study using primary care records.

OBJECTIVE: Assess whether statins reduce mortality in the general population aged 60 years and above. DESIGN: Retrospective cohort study. SETTING: Primary care practices contributing to The Health Improvement Network database, England and Wales, 1990-2017. PARTICIPANTS: Cohort who turned age 60 between 1990 and 2000 with no previous cardiovascular disease or statin prescription and followed up until 2017. RESULTS: Current statin prescription was associated with a significant reduction in all-cause mortality from age 65 years onward, with greater reductions seen at older ages. The adjusted HRs of mortality associated with statin prescription at ages 65, 70, 75, 80 and 85 years were 0.76 (95% CI 0.71 to 0.81), 0.71 (95% CI 0.68 to 0.75), 0.68 (95% CI 0.65 to 0.72), 0.63 (95% CI 0.53 to 0.73) and 0.54 (95% CI 0.33 to 0.92), respectively. The adjusted HRs did not vary by sex or cardiac risk. CONCLUSIONS: Using regularly updated clinical information on sequential treatment decisions in older people, mortality predictions were updated every 6 months until age 85 years in a combined primary and secondary prevention population. The consistent mortality reduction of statins from age 65 years onward supports their use where clinically indicated at age 75 and older, where there has been particular uncertainty of the benefits.

Inflammation and Depression: A Public Health Perspective.

The multifaceted role of low-grade systemic inflammation in depression and physical illnesses like cardiovascular disease highlights complex interactions between the body, brain and mind. While current research on inflammation and depression has largely focused on exploring possible disease mechanisms and therapeutic potential, we seek to broaden the current discussion by introducing a public health perspective. In this Viewpoint, we propose that inflammation and its contributing sources could represent important targets for public health strategies aimed at improving both mental and physical health. We discuss potential universal, selective and indicated primary prevention strategies for inflammation-related depression. We consider potential approaches to secondary prevention, including scope for anti-inflammatory treatment and CRP testing for guiding treatment allocation and prognosis. Preventive strategies discussed here could also be relevant for other inflammation-mediated mental health conditions.

Non-benzodiazepine hypnotic use for sleep disturbance in people aged over 55 years living with dementia: a series of cohort studies.

BACKGROUND: Sleep disturbance affects around 60% of people living with dementia and can negatively affect their quality of life and that of their carers. Hypnotic Z-drugs (zolpidem, zopiclone and zaleplon) are commonly used to treat insomnia, but their safety and efficacy have not been evaluated for people living with dementia. OBJECTIVES: To estimate the benefits and harms of Z-drugs in people living with dementia with sleep disturbance. DESIGN: A series of observational cohort studies using existing data from (1) primary care linked to hospital admission data and (2) clinical cohort studies of people living with dementia. DATA SOURCES: Primary care study - Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics mortality data. Clinical cohort studies - the Resource Use and Disease Course in Dementia - Nursing Homes (REDIC) study, National Alzheimer's Coordinating Centre (NACC) clinical data set and the Improving Well-being and Health for People with Dementia (WHELD) in nursing homes randomised controlled trial. SETTING: Primary care study - 371 primary care practices in England. Clinical cohort studies - 47 nursing homes in Norway, 34 Alzheimer's disease centres in the USA and 69 care homes in England. PARTICIPANTS: Primary care study - NHS England primary care patients diagnosed with dementia and aged > 55 years, with sleep disturbance or prescribed Z-drugs or low-dose tricyclic antidepressants, followed over 2 years. Clinical cohort studies - people living with dementia consenting to participate, followed over 3 years, 12 years and 9 months, for REDIC, NACC and WHELD, respectively. INTERVENTIONS: The primary exposure was prescription or use of Z-drugs. Secondary exposures included prescription or use of benzodiazepines, low-dose tricyclic antidepressants and antipsychotics. MAIN OUTCOME MEASURES: Falls, fractures, infection, stroke, venous thromboembolism, mortality, cognitive function and quality of life. There were insufficient data to investigate sleep disturbance. RESULTS: The primary care study and combined clinical cohort studies included 6809 and 18,659 people living with dementia, with 3089 and 914 taking Z-drugs, respectively. New Z-drug use was associated with a greater risk of fractures (hazard ratio 1.40, 95% confidence interval 1.01 to 1.94), with risk increasing with greater cumulative dose (p = 0.002). The hazard ratio for Z-drug use and hip fracture was 1.59 (95% confidence interval 1.00 to 2.53) and for mortality was 1.34 (95% confidence interval 1.10 to 1.64). No excess risks of falls, infections, stroke or venous thromboembolism were detected. Z-drug use also did not have an impact on cognition, neuropsychiatric symptoms, disability or quality of life. LIMITATIONS: Primary care study - possible residual confounding because of difficulties in identifying patients with sleep disturbance and by dementia severity. Clinical cohort studies - the small numbers of people living with dementia taking Z-drugs and outcomes not necessarily being measured before Z-drug initiation restricted analyses. CONCLUSIONS: We observed a dose-dependent increase in fracture risk, but no other harms, with Z-drug use in dementia. However, multiple outcomes were examined, increasing the risk of false-positive findings. The mortality association was unlikely to be causal. Further research is needed to confirm the increased fracture risk. Decisions to prescribe Z-drugs may need to consider the risk of fractures, balanced against the impact of improved sleep for people living with dementia and that of their carers. Our findings suggest that when Z-drugs are prescribed, falls prevention strategies may be needed, and that the prescription should be regularly reviewed. FUTURE WORK: More research is needed on safe and effective management strategies for sleep disturbance in people living with dementia. STUDY REGISTRATION: This study is registered as European Union electronic Register of Post-Authorisation Studies (EU PAS) 18006. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 1. See the NIHR Journals Library website for further project information.

WHAT WAS THE PROBLEM?: Poor sleep is common in people living with dementia. It can worsen their own and their carer's quality of life. Sleeping tablets called Z-drugs (zolpidem, zopiclone and zaleplon) are often given to people with dementia. Some studies suggest that Z-drugs may be harmful, but no studies have looked into the effects of Z-drugs for people with dementia. Good sleep is important, but we need to understand if Z-drugs cause harm. WHAT DID WE DO?: Using existing medical records, we compared the quality of life, memory and number of falls, infections, strokes, broken bones and deaths for a group of people living with dementia taking a Z-drug, with those for a group not taking any sleep drug. WHAT DID WE FIND?: Z-drug users were no more likely to suffer falls, infection or stroke, but they were more likely to break a bone. We also found that Z-drug users died earlier, but we could not be sure that this was as a result of taking the Z-drug. Using Z-drugs did not appear to affect quality of life or memory. We talked to carers and health-care practitioners, who told us that decisions about Z-drugs need to balance a range of complicated health and social factors. WHAT DOES THIS MEAN?: We found that people living with dementia who take Z-drugs are more likely to break a bone or to die sooner than similar people with dementia who are not taking Z-drugs. However, we cannot be certain that these problems are caused by Z-drugs, as many other factors can also lead to broken bones and death. Further work is needed to clarify the risk of broken bones, but if sleep problems can be managed in other ways then this may be preferable. Patients and family carers should be involved in decisions about Z-drugs, so that they can balance the possible harms against the benefits.

Cognitive decline associated with anticholinergics, benzodiazepines and Z-drugs: Findings from The Irish Longitudinal Study on Ageing (TILDA).

AIMS: To estimate the association between patterns of anticholinergic, benzodiazepine and Z-drug medication use and change in cognitive function in middle-aged and older adults. METHODS: This prospective cohort study used data from the first three waves of The Irish Longitudinal Study on Ageing (TILDA), including community-dwelling adults aged ≥50 years followed for up to 4 years (n = 7027). Cognitive function was assessed using the Mini Mental State Examination, animal naming test and word recall tests. Regular medication use was self-reported at baseline and follow-up interviews at 2 and 4 years. Pharmacy dispensing claims for a subset (n = 2905) allowed assessment of medication use between interviews and cumulative dosage. Medication use at consecutive waves of TILDA was analysed in relation to change in cognitive function between waves. RESULTS: Strongly anticholinergic medications (Anticholinergic Cognitive Burden scale 3), benzodiazepines and Z-drugs were reported by 7.3%, 5.8% and 5.1% of participants, respectively, at any time during the study. Adjusting for potential confounders, new anticholinergic use between interviews was associated with change in recall score (-1.09, 95% confidence interval -1.64, -0.53) over 2 years compared to non-use, but not with MMSE (0.07; 95% CI -0.21, 0.34) or animal naming (-0.70; 95% CI -1.43, 0.03). The pharmacy claims analysis was consistent with this finding. Other hypothesised associations were not supported. CONCLUSIONS: Except for new use of anticholinergic medications, no other findings supported a risk of cognitive decline over 2-year periods in this middle-aged and older cohort. Patients and prescribers should weigh this potential risk against potential benefits of commencing anticholinergic medications.

Adverse effects of Z-drugs for sleep disturbance in people living with dementia: a population-based cohort study.

BACKGROUND: Sleep disturbance is common in dementia and often treated with Z-drugs (zopiclone, zaleplon, and zolpidem). While some observational studies suggest that Z-drugs are associated with adverse events such as falls and fracture risks in older people, this has not been studied in dementia. METHODS: We used data from 27,090 patients diagnosed with dementia between January 2000 and March 2016 from the Clinical Practice Research Datalink linked to Hospital Episodes Statistics data in England. We compared adverse events for 3532 patients newly prescribed Z-drugs by time-varying dosage to (1) 1833 non-sedative-users with sleep disturbance; (2) 10,214 non-sedative-users with proximal GP consultation matched on age, sex, and antipsychotic use; and (3) 5172 patients newly prescribed benzodiazepines. We defined higher dose Z-drugs and benzodiazepines as prescriptions equivalent to ≥ 7.5 mg zopiclone or > 5 mg diazepam daily. Cox regression was used to estimate hazard ratios (HRs) for incident fracture, hip fracture, fall, mortality, acute bacterial infection, ischaemic stroke/transient ischaemic attack, and venous thromboembolism over a 2-year follow-up, adjusted for demographic- and health-related covariates. RESULTS: The mean (SD) age of patients was 83 (7.7) years, and 16,802 (62%) were women. Of 3532 patients prescribed Z-drugs, 584 (17%) were initiated at higher doses. For patients prescribed higher dose Z-drugs relative to non-users with sleep disturbance, the HRs (95% confidence interval) for fractures, hip fractures, falls, and ischaemic stroke were 1.67 (1.13-2.46), 1.96 (1.16-3.31), 1.33 (1.06-1.66), and 1.88 (1.14-3.10), respectively. We observed similar associations when compared to non-sedative-users with proximal GP consultation. Minimal or inconsistent excess risks were observed at ≤ 3.75 mg zopiclone or equivalent daily, and for mortality, infection, and venous thromboembolism. We observed no differences in adverse events for Z-drugs compared to benzodiazepines, except lower mortality rates with Z-drugs (HR [95% confidence interval] of 0.73 [0.64-0.83]). CONCLUSIONS: Higher dose Z-drug use in dementia is associated with increased fracture and stroke risks, similar or greater to that for higher dose benzodiazepines. Higher dose Z-drugs should be avoided, if possible, in people living with dementia, and non-pharmacological alternatives preferentially considered. Prescriptions for higher dose Z-drugs in dementia should be regularly reviewed. TRIAL REGISTRATION: ENCePP e-register of studies, EUPAS18006.

Increasing prevalence of anticholinergic medication use in older people in England over 20 years: cognitive function and ageing study I and II.

BACKGROUND: Anticholinergic medication use is linked with increased cognitive decline, dementia, falls and mortality, and their use should be limited in older people. Here we estimate the prevalence of anticholinergic use in England's older population in 1991 and 2011, and describe changes in use by participant's age, sex, cognition and disability. METHODS: We compared data from participants aged 65+ years from the Cognitive Function and Ageing Studies (CFAS I and II), collected during 1990-1993 (N = 7635) and 2008-2011 (N = 7762). We estimated the prevalence of potent anticholinergic use (Anticholinergic Cognitive Burden [ACB] score = 3) and average anticholinergic burden (sum of ACB scores), using inverse probability weights standardised to the 2011 UK population. These were stratified by age, sex, Mini-Mental State Examination score, and activities of daily living (ADL) or instrumental ADL (IADL) disability. RESULTS: Prevalence of potent anticholinergic use increased from 5.7% (95% Confidence Interval [CI] 5.2-6.3%) of the older population in 1990-93 to 9.9% (9.3-10.7%) in 2008-11, adjusted odds ratio of 1.90 (95% CI 1.67-2.16). People with clinically significant cognitive impairment (MMSE [Mini Mental State Examination] 21 or less) were the heaviest users of potent anticholinergics in CFAS II (16.5% [95% CI 12.0-22.3%]). Large increases in the prevalence of the use medication with 'any' anticholinergic activity were seen in older people with clinically significant cognitive impairment (53.3% in CFAS I to 71.5% in CFAS II). CONCLUSIONS: Use of potent anticholinergic medications nearly doubled in England's older population over 20 years with some of the greatest increases amongst those particularly vulnerable to anticholinergic side-effects.

Evaluating a specialist primary care service for patients experiencing homelessness: a qualitative study.

BACKGROUND: People experiencing homelessness (PEH) often experience poor health, multimorbidity, and early mortality and experience barriers to accessing high quality health care. Little is known about how best to provide specialist primary care for these patients. AIM: To evaluate the health care provided to patients experiencing homelessness who were seen in a specialist primary care service. DESIGN & SETTING: A qualitative evaluation of a city centre primary healthcare service for excluded and vulnerable people, such as rough sleepers, who find it difficult to visit mainstream GP services. METHOD: Data on patient characteristics and service use were extracted from primary care records using electronic and free-text searches to provide context to the evaluation. Semi-structured interviews with 11 patients and four staff were used to explore attitudes and experiences. RESULTS: Patients had high needs compared with the general population. Patients valued continuity of care, ease of access, multidisciplinary care, and person-centred care. Staff were concerned that they lacked opportunities for reflection and learning, and that low clinical capacity affected service safety and quality. Staff also wanted more patient involvement in service planning. CONCLUSION: PEH's complex health and social problems benefited from a specialist primary care service, which is thought to reduce barriers to access, treat potentially challenging patients in a non-judgmental way, and provide personal continuity of care in order to develop trust.

Anticholinergic drugs and incident dementia, mild cognitive impairment and cognitive decline: a meta-analysis.

BACKGROUND: the long-term effect of the use of drugs with anticholinergic activity on cognitive function remains unclear. METHODS: we conducted a systematic review and meta-analysis of the relationship between anticholinergic drugs and risk of dementia, mild cognitive impairment (MCI) and cognitive decline in the older population. We identified studies published between January 2002 and April 2018 with ≥12 weeks follow-up between strongly anticholinergic drug exposure and the study outcome measurement. We pooled adjusted odds ratios (OR) for studies reporting any, and at least short-term (90+ days) or long-term (365+ days) anticholinergic use for dementia and MCI outcomes, and standardised mean differences (SMD) in global cognition test scores for cognitive decline outcomes. Statistical heterogeneity was measured using the I2 statistic and risk of bias using ROBINS-I. RESULTS: twenty-six studies (including 621,548 participants) met our inclusion criteria. 'Any' anticholinergic use was associated with incident dementia (OR 1.20, 95% confidence interval [CI] 1.09-1.32, I2 = 86%). Short-term and long-term use were also associated with incident dementia (OR 1.23, 95% CI 1.17-1.29, I2 = 2%; and OR 1.50, 95% CI 1.22-1.85, I2 = 90%). 'Any' anticholinergic use was associated with cognitive decline (SMD 0.15; 95% CI 0.09-0.21, I2 = 3%) but showed no statistically significant difference for MCI (OR 1.24, 95% CI 0.97-1.59, I2 = 0%). CONCLUSIONS: anticholinergic drug use is associated with increased dementia incidence and cognitive decline in observational studies. However, a causal link cannot yet be inferred, as studies were observational with considerable risk of bias. Stronger evidence from high-quality studies is needed to guide the management of long-term use.

The "unknown territory" of goal-setting: Negotiating a novel interactional activity within primary care doctor-patient consultations for patients with multiple chronic conditions.

Goal-setting is widely recommended for supporting patients with multiple long-term conditions. It involves a proactive approach to a clinical consultation, requiring doctors and patients to work together to identify patient's priorities, values and desired outcomes as a basis for setting goals for the patient to work towards. Importantly it comprises a set of activities that, for many doctors and patients, represents a distinct departure from a conventional consultation, including goal elicitation, goal-setting and action planning. This indicates that goal-setting is an uncertain interactional space subject to inequalities in understanding and expectations about what type of conversation is taking place, the roles of patient and doctor, and how patient priorities may be configured as goals. Analysing such spaces therefore has the potential for revealing how the principles of goal-setting are realised in practice. In this paper, we draw on Goffman's concept of 'frames' to present an examination of how doctors' and patients' sense making of goal-setting was consequential for the interactions that followed. Informed by Interactional Sociolinguistics, we used conversation analysis methods to analyse 22 video-recorded goal-setting consultations with patients with multiple long-term conditions. Data were collected between 2016 and 2018 in three UK general practices as part of a feasibility study. We analysed verbal and non-verbal actions for evidence of GP and patient framings of consultation activities and how this was consequential for setting goals. We identified three interactional patterns: GPs checking and reframing patients' understanding of the goal-setting consultation, GPs actively aligning with patients' framing of their goal, and patients passively and actively resisting GP framing of the patient goals. These reframing practices provided "telling cases" of goal-setting interactions, where doctors and patients need to negotiate each other's perspectives but also conflicting discourses of patient-centredness, population-based evidence for treating different chronic illnesses and conventional doctor-patient relations.

Neuropathological Correlates of Cumulative Benzodiazepine and Anticholinergic Drug Use.

BACKGROUND: Benzodiazepines and anticholinergic drugs have been implicated in causing cognitive decline and potentially increasing dementia risk. However, evidence for an association with neuropathology is limited. OBJECTIVE: To estimate the correlation between neuropathology at death and prior use of benzodiazepines and anticholinergic drugs. METHODS: We categorized 298 brain donors from the population-based Medical Research Council Cognitive Function and Ageing Study, according to their history of benzodiazepine (including Z-drugs) or anticholinergic medication (drugs scoring 3 on the Anticholinergic Cognitive Burden scale) use. We used logistic regression to compare dichotomized neuropathological features for those with and without history of benzodiazepine and anticholinergic drug use before dementia, adjusted for confounders. RESULTS: Forty-nine (16%) and 51 (17%) participants reported benzodiazepine and anticholinergic drug use. Alzheimer's disease neuropathologic change was similar whether or not exposed to either drug, for example 46% and 57% had intermediate/high levels among those with and without anticholinergic drug use. Although not significant after multiple testing adjustments, we estimated an odds ratio (OR) of 0.40 (95% confidence interval [95% CI] 0.18-0.87) for anticholinergic use and cortical atrophy. For benzodiazepine use, we estimated ORs of 4.63 (1.11-19.24) and 3.30 (1.02-10.68) for neuronal loss in the nucleus basalis and substantial nigra. There was evidence of neuronal loss in the nucleus basalis with anticholinergic drug use, but the association reduced when adjusted for confounders. CONCLUSIONS: We found no evidence that benzodiazepine or anticholinergic drug use is associated with typical pathological features of Alzheimer's disease; however, we cannot rule out effects owing to small numbers.

Anticholinergic and benzodiazepine medication use and risk of incident dementia: a UK cohort study.

BACKGROUND: Studies suggest that anticholinergic medication or benzodiazepine use could increase dementia risk. We tested this hypothesis using data from a UK cohort study. METHODS: We used data from the baseline (Y0), 2-year (Y2) and 10-year (Y10) waves of the Medical Research Council Cognitive Function and Ageing Study. Participants without dementia at Y2 were included (n = 8216). Use of benzodiazepines (including nonbenzodiazepine Z-drugs), anticholinergics with score 3 (ACB3) and anticholinergics with score 1 or 2 (ACB12) according to the Anticholinergic Cognitive Burden scale were coded as ever use (use at Y0 or Y2), recurrent use (Y0 and Y2), new use (Y2, but not Y0) or discontinued use (Y0, but not Y2). The outcome was incident dementia by Y10. Incidence rate ratios (IRR) were estimated using Poisson regression adjusted for potential confounders. Pre-planned subgroup analyses were conducted by age, sex and Y2 Mini-Mental State Examination (MMSE) score. RESULTS: Dementia incidence was 9.3% (N = 220 cases) between Y2 and Y10. The adjusted IRRs (95%CI) of developing dementia were 1.06 (0.72, 1.60), 1.28 (0.82, 2.00) and 0.89 (0.68, 1.17) for benzodiazepines, ACB3 and ACB12 ever-users compared with non-users. For recurrent users the respective IRRs were 1.30 (0.79, 2.14), 1.68 (1.00, 2.82) and 0.95 (0.71, 1.28). ACB3 ever-use was associated with dementia among those with Y2 MMSE> 25 (IRR = 2.28 [1.32-3.92]), but not if Y2 MMSE≤25 (IRR = 0.94 [0.51-1.73]). CONCLUSIONS: Neither benzodiazepines nor ACB12 medications were associated with dementia. Recurrent use of ACB3 anticholinergics was associated with dementia, particularly in those with good baseline cognitive function. The long-term prescribing of anticholinergics should be avoided in older people.

Can goal-setting for patients with multimorbidity improve outcomes in primary care? Cluster randomised feasibility trial.

INTRODUCTION: Goal-setting is recommended for patients with multimorbidity, but there is little evidence to support its use in general practice. OBJECTIVE: To assess the feasibility of goal-setting for patients with multimorbidity, before undertaking a definitive trial. DESIGN AND SETTING: Cluster-randomised controlled feasibility trial of goal-setting compared with control in six general practices. PARTICIPANTS: Adults with two or more long term health conditions and at risk of unplanned hospital admission. INTERVENTIONS: General practitioners (GPs) underwent training and patients were asked to consider goals before an initial goal-setting consultation and a follow-up consultation 6 months later. The control group received usual care planning. OUTCOME MEASURES: Health-related quality of life (EQ-5D-5L), capability (ICEpop CAPability measure for Older people), Patient Assessment of Chronic Illness Care and healthcare use. All consultations were video-recorded or audio-recorded, and focus groups were held with participating GPs and patients. RESULTS: Fifty-two participants were recruited with a response rate of 12%. Full follow-up data were available for 41. In the goal-setting group, mean age was 80.4 years, 54% were female and the median number of prescribed medications was 13, compared with 77.2 years, 39% female and 11.5 medications in the control group. The mean initial consultation time was 23.0 min in the goal-setting group and 19.2 in the control group. Overall 28% of patient participants had no cognitive impairment. Participants set between one and three goals on a wide range of subjects, such as chronic disease management, walking, maintaining social and leisure interests, and weight management. Patient participants found goal-setting acceptable and would have liked more frequent follow-up. GPs unanimously liked goal-setting and felt it delivered more patient-centred care, and they highlighted the importance of training. CONCLUSIONS: This goal-setting intervention was feasible to deliver in general practice. A larger, definitive study is needed to test its effectiveness. TRIAL REGISTRATION NUMBER: ISRCTN13248305; Post-results.

History of Benzodiazepine Prescriptions and Risk of Dementia: Possible Bias Due to Prevalent Users and Covariate Measurement Timing in a Nested Case-Control Study.

Previous estimates of whether long-term exposure to benzodiazepines increases dementia risk are conflicting and are compromised by the difficulty of controlling for confounders and by reverse causation. We investigated how estimates for the association between benzodiazepine use and later dementia incidence varied based on study design choices, using a case-control study nested within the United Kingdom's Clinical Practice Research Datalink. A total of 40,770 dementia cases diagnosed between April 2006 and July 2015 were matched on age, sex, available data history, and deprivation to 283,933 control subjects. Benzodiazepines and Z-drug prescriptions were ascertained in a drug-exposure period 4-20 years before dementia diagnosis. Estimates varied with the inclusion of new or prevalent users, with the timing of covariate ascertainment, and with varying time between exposure and outcome. There was no association between any new prescription of benzodiazepines and dementia (adjusted odds ratio (OR) = 1.03, 95% confidence interval (CI): 1.00, 1.07), whereas an inverse association was observed among prevalent users (adjusted OR = 0.91, 95% CI: 0.87, 0.95), although this was likely induced by unintentional adjustment for colliders. By considering the choice of confounders and timing of exposure and covariate measurement, our findings overall are consistent with no causal effect of benzodiazepines or Z-drugs on dementia incidence.

Optimal SBP targets in routine clinical care.

OBJECTIVE: Compare outcomes of intensive treatment of SBP to less than 120 mmHg versus standard treatment to less than 140 mmHg in the US clinical Systolic Blood Pressure Intervention Trial (SPRINT) with similar hypertensive patients managed in routine primary care in the United Kingdom. METHODS: Hypertensive patients aged 50-90 without diabetes or chronic kidney disease (CKD) were selected in SPRINT and The Health Improvement Network (THIN) database. Patients were enrolled in 2010-2013 and followed-up to 2015 (SPRINT N = 4112; THIN N = 8631). Cox's proportional hazards regressions were fitted to estimate the hazard of all-cause mortality or CKD (main adverse effect) associated with intensive treatment, adjusted for sex, age, ethnicity, smoking, blood pressure, cardiovascular disease, aspirin, statin, number of antihypertensive drugs at baseline, change in number of antihypertensive drugs at trial entry, and clinical site. RESULTS: Almost half of the patients had intensive treatment (43-45%). In SPRINT, intensive treatment was associated with a decreased hazard of mortality of 0.63 (0.43-0.92), while in THIN with an increased hazard of 1.66 (1.28-2.15). In THIN, this effect was time-dependent. Intensive treatment was associated with an increased hazard of CKD of 2.67 (1.74-4.11) in SPRINT and 1.35 (1.08-1.70) in THIN. In THIN, this effect differed by the number of antihypertensive drugs prescribed at baseline. CONCLUSION: It appears that intensive treatment of SBP may be harmful in the general population where all have access to routine healthcare as with the UK National Health Services, but could be beneficial in high-risk patients who are closely monitored.