Daniel Davis

Background: Presenting features of delirium can be difficult to distinguish from co-existing dementia phenomenology. While the 4 ‘A’s Test (4AT) is a well validated delirium screening tool across multiple patient populations and healthcare settings, how its diagnostic performance varies across different levels of baseline cognition is unclear. Methods: This study harmonises data from two prospective cohorts: the Delirium and Population Health Informatics Cohort (DELPHIC) and Delirium and Cognitive Impact in Dementia (DECIDE). Both cohorts were stratified into tertiles according to baseline cognition. Delirium was defined using DSM-IV (DELPHIC) and DSM-V (DECIDE). 4AT domain scores were operationalised from relevant delirium assessments within each study (MDAS, OSLA, months of the year backwards); item 4 was drawn from assessments of fluctuation. This process yielded an operationalised 4AT. Diagnostic accuracy of the operationalised 4AT was calculated using sensitivity, specificity, and receiver operating characteristics, with pooled estimates for each test domain. Results: Among 396 unique participants and 2468 assessments across both studies, pooled 4AT sensitivity and specificity were 0.73 and 0.89, respectively. Overall 4AT performance was consistent across cognitive tertiles (sensitivity: high 0.82, middle 0.73, low 0.71; specificity: high 0.91; middle 0.92; low 0.86). Conclusions: The operationalised 4AT showed good diagnostic performance in all three levels of baseline cognition. Sensitivity would likely have been higher had clinical information to inform 4AT item 4 been available. Overall, however, the findings support the value of bedside 4AT items in detecting delirium in hospitalised patients across the spectrum of baseline cognition.

Background: Delirium is common in hospitalised older people and is associated with a poor prognosis. It remains poorly characterised at a molecular level. We studied the metabolic signature of delirium using 1H-Magnetic Resonance Spectroscopy (MRS) in a prospective case-control study. Methods: Medical inpatients aged ≥65 with and without delirium (DSM-5) were recruited and assessed for illness severity, frailty and prior cognitive decline. Metabolite concentrations in parietal white matter were obtained using MRS with diffusion MRI used to assess structural changes via the ADC. Results: Out of 38 participants, 25 completed the MRS protocol (13 males and 12 females, mean age 80.5, SD = 6.47). Patients with delirium (n = 13) had greater pre-admission frailty than those without (n = 12) (median Clinical Frailty Scale 5 vs. 4.5; P = .049). There were no significant differences in age, sex, measures of MRS quality, atrophy and white matter disease. In a General Linear Model using the MRS voxel ADC to account for white matter lesion effects, glutamate was higher in delirium patients (P = 0.024). There were no other between-group differences in metabolite concentrations. For patients with and without delirium combined, glutamine increased with age and decreased with cortical atrophy, whilst Myo-inositol decreased with age and increased with median ADC. Conclusions: Our results suggest that delirium is characterised by elevated brain glutamate concentration. This could cause excitotoxic brain injury and contribute to post-delirium cognitive decline and is a potentially modifiable process that merits further investigation.

This commentary proposes a renewed place-based understanding of ageing and social care research, drawing together evidence from an updated review of interventions for social isolation and insights from public engagement in contrasting urban and coastal settings. Despite a longstanding policy emphasis on ‘ageing in place’, structural conditions across England remain uneven, with rural and coastal communities often experiencing shrinking services, limited transport, digital exclusion, and fragile social infrastructures. Our updated umbrella review of 75 recent publications indicates that psychological, social, and hybrid interventions can reduce loneliness, but their impacts are inconsistent, often short-lived, and rarely examined across different geographical settings. We found no study adopted a genuinely place-based framework, leaving questions about how local environments shape both risk factors and intervention effectiveness. Insights from community engagement in London and coastal Lincolnshire further illustrate how place influences everyday experiences of ageing, highlighting shared challenges, such as fragmented services, digital barriers, and rising living costs. Whereas urban location-specific issues included isolation amid density, geographically close inequalities, and limited continuity of services, by contrast, people in coastal communities cited transport deprivation, seasonal and precarious economies and the erosion of community spaces. Taken together, these findings show that spatial inequalities are widening and that research failing to account for these, risks reinforcing them. A strengthened place-based research agenda is needed to ensure interventions are equitable, context-sensitive, and grounded in lived experience.

Background: Hospitals pose a high risk for frailty to develop or accelerate. Still, few community-based cohort studies follow patients before, during, and after hospitalisation. We investigated the degree of immobility during hospitalisation and its impact on subsequent frailty. Methods: In a prospective population-based cohort of individuals aged ≥ 70 from a London UK borough, we performed comprehensive community assessments at baseline and after two years. At each hospitalisation, we measured daily mobility and other clinical variables. Acute immobility burden, a summative level of poor mobility for all hospitalisations, was calculated for each participant and operationalized as low/high based on the population median. A frailty index was calculated for all participants during baseline and follow-up assessments. We estimated the effect of these exposures on follow-up frailty index scores using linear regression. Results: We included 1177 participants. Those admitted ( N = 114) were assessed over 1999 bed-days. The degree of baseline frailty had the largest association with subsequent frailty. However, a high immobility burden during hospitalisation was consistently related to additional increases in frailty (low burden: β = 0.02 per unit increase in FI (95%CI: -0.002-0.04), high burden: β = 0.07, (95%CI: 0.041-0.10)). Immobility burden remained associated with subsequent frailty even when limiting the analysis to: those who were independently mobile; the first seven days of hospitalisation; and accounting for illness severity. High immobility burden was prognostic of subsequent death. Conclusions: The degree of immobility during hospitalisation, a potentially modifiable risk factor, may determine whether hospitalisation contributes to increasing frailty.

Objective: To evaluate the efficacy of psychosocial and healthcare interventions on reducing hospitalisation in people with dementia (PwD). Design: Umbrella review of existing systematic reviews and meta-analyses. Search strategy: MEDLINE, Embase, Cochrane, and CINAHL were searched until September 2025 for relevant keywords and medical subject headings. Inclusion criteria: Peer-reviewed systematic reviews with or without meta-analyses examining the effect of any psychosocial or healthcare intervention compared to a suitable control group on any measure of hospitalisation in people with dementia. Methods: Two reviewers assessed eligibility, and eligible papers were grouped into categories and appraised by two reviewers using AMSTAR (A MeaSurement Tool to Assess systematic Reviews) version 2. We assessed certainty of evidence for each intervention type using GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Results: The search identified 25 systematic reviews, comprising 77 unique primary studies (47 randomised control trials, 30 non-randomised studies of interventions), totalling 1,483,077 participants. There was high-certainty evidence that case management and exercise programmes had no effect on hospitalisation of PwD. There was low certainty evidence that advance care planning (ACP) reduced hospital admissions. Moderate certainty evidence from one study suggested that including clinical pharmacists in multidisciplinary teams (MDTs) reduced medication-related hospital admissions. Conclusions: The current evidence for psychosocial and healthcare interventions in reducing hospitalisation in dementia is insufficient to make strong recommendations. ACPs show promise in reducing hospitalisations, and clinical pharmacists in MDTs may reduce medication-related readmissions. As evidence-based recommendations are needed to reduce the burden of dementia-related hospitalisations, more robust research is needed, especially high-quality randomised control trials with greater detail and standardised checklists for interventions and outcomes to reduce heterogeneity and establish more confident clinical recommendations. Registration: PROSPERO 2024 CRD42024604296

Background Delirium is strongly associated with subsequent dementia, but this is often assumed to reflect underlying associations of baseline health with dementia. We examined the associations of delirium on admission with incident dementia across the spectrum of multimorbidity. Methods Retrospective population-based cohort study using linked primary care and hospital data for emergency admissions aged ≥65 years in Lothian, Scotland, from 1 Apr 2017 to 1 Apr 2020. Delirium on admission was assessed at the bedside for all patients using the 4AT (www.the4AT.com). Associations of delirium, multimorbidity, and their interaction with incident dementia and mortality were examined using Fine-Gray competing-risks regression and Cox proportional hazards models. Results Of 23,558 people without pre-existing dementia (mean age 78.9 years, 54% female), 4135 (18%) had an admission with delirium. Delirium was associated with higher incident dementia risk. The relative risk was highest in those without multimorbidity (adjusted Hazard Ratio (aHR) 3.38, 95% CI 2.46–4.63) and decreased with an increasing number of long-term conditions. Delirium was also associated with increased mortality, regardless of multimorbidity. In those without multimorbidity, delirium was associated with higher early mortality (≤90 days: aHR 4.23, 95% CI 3.27 to 5.49) and late mortality (>90 days: aHR 1.64, 95% CI 1.33 to 2.03). Conclusion Delirium is strongly associated with incident dementia in older adults across the multimorbidity spectrum, with the highest relative risk in people without multimorbidity. Findings support routine delirium assessment on hospital admission for all older adults and highlight need to further investigate neurodegenerative mechanisms in delirium.

Background and objectives: Lipid-lowering agents are effective in reducing cardiovascular risk, but their effect on cognitive impairment and dementia is uncertain. The aim of this meta-analysis was to determine whether lipid-lowering therapy, compared to control, was associated with a reduction in risk of dementia or cognitive impairment. Methods: We performed a systematic review and meta-analysis of randomised controlled trials comparing lipid-lowering therapy to control that reported dementia or change in cognitive scores, adhering to the Cochrane Collaboration Guidelines. A random effects meta-analysis was used to estimate a pooled treatment-effect. The primary outcome measure was incident cognitive impairment or dementia. Results: Twenty randomised controlled trials were eligible for inclusion, 15 trials (n = 139 169 participants) reported dementia or cognitive impairment on follow-up (primary outcome) and nine trials (n = 32 370) reported on change in cognitive score. The mean (SD) age of trial participants was 65.4 (5.06) years in the intervention arm and 65.4 (5.03) in the control arm. Lipid-lowering therapy compared with control was not associated with a significant reduction in dementia or cognitive impairment (1.33% vs 1.36% over a mean trial follow-up of 34.5 months; Odds Ratio, 0.96; 95% CI, 0.74–1.26). Heterogeneity was moderate (I2 = 37.6%). There was no significant association amongst drug classes (Statin; OR 0.90; 95% CI, 0.67–1.21, PCSK9 inhibitor: OR 1.77; 95% CI, 0.46–6.83, Other: OR 0.85; 0.61–1.17). Discussion: In this meta-analysis of over 100 000 participants, lipid-lowering therapy was not significantly associated with a lower risk of incident cognitive impairment or dementia. This meta-analysis provides evidence to support the safety of lipid-lowering therapy on cognitive health, however, does not provide evidence of risk reduction of incident cognitive impairment or dementia.

Background: A crucial part of delirium care is assessing for recovery, yet there are no validated methods for this. The 4AT is a widely used delirium assessment tool, but its performance in assessing recovery remains unstudied. This study evaluated the 4AT’s performance in assessing recovery from delirium. Materials and methods: In this prospective diagnostic accuracy study, older hospitalised patients (≥70 years) with reference standard delirium on enrolment were assessed 2–4 times over ≤9 days. Paired researchers independently conducted blinded assessments of (i) a reference standard (Diagnostic and Statistical Manual for Mental Disorders, 5th edition), including the Delirium Rating Scale-Revised-98 and neuropsychological tests and (ii) the 4AT (index test, score ≥ 4 positive) plus brief measures of distress and psychotic symptoms. Results: A total of 120 people with delirium participated [median age 86.3, range 70–99, 67 (55.8%) female and 55 (45.8%) with dementia]. All of them completed the first two assessments, 103 (85.8%) completed three and 69 (57.5%) four. Reference standard delirium was present in 102/120 (85%), 72/103 (69.9%) and 53/69 (76.8%) cases at assessments two to four, respectively. In Receiver Operating Characteristic analyses, the 4AT’s sensitivity for detecting delirium was 0.95 (confidence interval 0.91–0.99), 0.96 (0.91–1) and 0.94 (0.88–1), and specificity was 0.67 (0.13–1), 0.88 (0.71–1) and 1 (1–1) at assessments two to four. In total 18 (15%) participants recovered from delirium. Distress was common in delirium and decreased with recovery. Conclusion: The 4AT maintains diagnostic accuracy on repeated admissions and may effectively assess delirium recovery in acute hospital settings. Fewer patients than expected recovered within 9 days, suggesting more studies on the natural history of delirium in different settings would be informative.

This study examines the accuracy of CTseg segmentation software to diagnose Alzheimer's disease dementia and other dementias using routine CT scans from a New Zealand memory service. Analyzing 168 scans (89 with dementia and 79 without dementia) the software segmented the brain to produce total brain volume and hippocampal volume. CTseg-derived total brain volume (sensitivity 72%, specificity 58%) and hippocampal volume (sensitivity 71%, specificity 62%) were reasonably effective at differentiating dementia from non-dementia at time of diagnosis. Our findings suggest that CTseg automated volumetric analysis has some potential to aid dementia diagnosis in real-world clinical settings.

Background: Antidepressants are associated with postural hypotension (PH), but it is not typically recognised as a common adverse effect. PH is linked with serious complications in older adults, for example, falls, stroke, and cognitive decline. Randomised controlled trials (RCTs) examining antidepressants often exclude older people and do not focus on adverse effects.Aim: To examine the risk of PH associated with antidepressant use in adults aged ≥60 years in UK primary care.Design and setting: A self-controlled case series using routinely collected primary care data from the IQVIA Medical Research Database (IMRD) from 1 January 2000 to 31 December 2018.Method: Data from >41 000 adults aged ≥60 years in IMRD between 1 January 2000 to 31 December 2018 were obtained. Antidepressant prescriptions were determined using code lists based on British National Formulary classification. Risk of PH was examined during four exposure risk periods (90-days pre-prescription; day 1–28; 29–56; and ≥57) compared with periods outside these risk windows.Results: Among 41 005 people with incident PH in the study period, 8899 (22%) were prescribed a selective serotonin reuptake inhibitor (SSRI); 8313 (20%) were prescribed a tricyclic antidepressant (TCA); and 4656 (11%) were prescribed an ‘other antidepressant’. The authors observed a consistent increased risk of PH in day 1–28 inallantidepressant exposure, which reduced thereafter. Risk of PH was highest with SSRIs (incidence rate ratio [IRR] 4.22, 95% confidence interval [CI] = 3.76 to 4.74), followed by ‘other antidepressants’ (IRR 2.17, 95% CI = 1.76 to 2.68), and then TCAs (IRR 2.12, 95% CI = 1.79 to 2.50). Risk of PH reduced from day ≥28 for all antidepressants.Conclusion: A statistically substantial increased risk of PH was observed with all antidepressants in the first month, particularly SSRIs. Prescribers should be aware of this risk and may consider monitoring PH when initiating antidepressants in older adults.