Infection, inflammation, and poststroke cognitive impairment

Background: Infection and inflammation are dementia risk factors in population‐based cohorts; however, studies in stroke are scarce. We determined the prevalence of infection after stroke and routinely measured inflammatory biomarkers during hospitalization and their associations with acute and 6‐month cognitive impairment. Methods and Results: A prospective stroke cohort completed the Oxford Cognitive Screen at ≤2 weeks and 6 months after stroke. Infection, inflammatory markers (C‐reactive protein, white cell count, and neutrophil/lymphocyte ratio), and systemic inflammatory response syndrome were ascertained throughout admission with electronic patient records supplemented by hand searches. Associations with acute and 6‐month global and domain‐specific cognitive impairment were analyzed using multivariable regression, adjusting for demographic/vascular factors and stroke severity. Among 255 patients (mean age, 73.9 [SD, 12.6] years; 46.3% women; mean education, 12.6 [SD, 3.7] years; median National Institutes of Health Stroke Scale score 5 [range, minimum‐maximum, 0–30]), infection was present in 90 patients (35.3%) at mean 4.4 (SD, 6.9) days after stroke, consisting predominantly of pneumonia (47/90; 52%) and urinary tract infection (39/90; 43%). Admission white cell count was elevated in 25.1% (n=64; mean, 9.5×109/L [SD, 3.2×109/L]), C‐reactive protein in 41.2% (n=105; mean, 27.5 [SD, 50.9 mg/L]), neutrophil/lymphocyte ratio in 55.7% (n=97; mean, 5.5 [SD, 4.5]), and systemic inflammatory response syndrome in 26.6% (n=53 [45.2%] positive during hospitalization). Infection was associated with acute and 6‐month poststroke cognitive impairment (P<0.05adj) with stronger associations acutely for severe infection (infection+systemic inflammatory response syndrome; P=0.03adj). Acute language, executive function and attention domain impairments, and 6‐month number processing impairment were associated with infection (P<0.05adj). No significant relationships were found for any biomarker and cognitive impairment. Conclusions: Infection and elevations in routinely measured inflammatory biomarkers are common following stroke; however, only infection is associated with poststroke cognitive impairment, suggesting that increases in these biomarkers may be nonspecific. Infection may present a tractable target for reducing poststroke cognitive impairment

Domain-specific cognitive impairment 6 months after stroke: The value of early cognitive screening

Background:: Cognitive screening following stroke is widely recommended, yet few studies have considered the prognostic value of acute domain-specific function for longer-term cognitive outcome. Identifying which post-stroke cognitive impairments more commonly occur, recover, and persist, and which impairments hold prognostic value, could inform care planning, and resource allocation. Aims:: This study aimed to determine the prevalence of domain-specific impairment acutely and at 6 months, assess the proportion of change in cognitive performance, and examine the prognostic value of acute domain-specific cognitive screening. Methods:: A prospective stroke cohort completed the Oxford Cognitive Screen acutely (⩽2 weeks) and 6 months post-stroke. We determined the prevalence of acute and 6-month domain-specific impairment and proportion of change in performance from acute to 6 months. Hierarchical multivariable regression was used to predict global and domain-specific cognitive impairment at 6 months adjusted for demographic/vascular factors, stroke severity, and lesion volume. Results:: A total of 430 stroke survivors (mean/SD age 73.9/12.5 years, 46.5% female, median/interquartile range (IQR) National Institute of Health Stroke Scale (NIHSS) 5/2–10) completed 6-month follow-up. Acutely, domain-specific impairments were highly prevalent ranging from 26.7% (n = 112) in praxis to 46.8% (n = 183) in attention. At 6 months, the proportion of domain-specific recovery was highest in praxis (n = 73, 71%) and lowest in language (n = 89, 46%) and memory (n = 82, 48%). Severity of 6-month cognitive impairment was best predicted by the addition of acute cognitive impairment (adj R2 = 0.298, p < 0.0001) over demographic and clinical factors alone (adj R2 = 0.105, p < 0.0001). Acute cognitive function was the strongest predictor of 6-month cognitive performance (p < 0.0001). Acute domain-specific impairments in memory (p < 0.0001), language (p < 0.0001), and praxis (p < 0.0001) significantly predicted overall severity of cognitive impairment at 6 months. Conclusion:: Post-stroke cognitive impairment is highly prevalent across all domains acutely, while impairments in language, memory, and attention predominate at 6 months. Early domain-specific screening can provide valuable prognostic information for longer-term cognitive outcomes

Cognitive recovery after stroke: memory

Memory impairment occurs in over a third of patients after symptomatic stroke. Memory deficits rarely occur in isolation but are an important component of the poststroke cognitive syndrome because of the strong relationship with the risk of poststroke dementia. In this review, we summarize available data on impairment of episodic memory, with a particular emphasis on the natural history of memory impairment after stroke and the factors influencing trajectory informed by an updated systematic review. We next discuss the pathophysiology of memory impairment and mechanisms of both decline and recovery of function. We then turn to the practical issue of measurement of memory deficits after stroke, emerging biomarkers, and therapeutic approaches. Our review identifies critical gaps, particularly in studies of the natural history that properly map the long-term trajectory of memory and the associations with factors that modulate prognosis. Few studies have used advanced neuroimaging and this, in conjunction with other biomarker approaches, has the potential to provide a much richer understanding of the mechanisms at play and promising therapeutic avenues

Decision-making capacity in older medical in-patients: frequency of assessment and rates of incapacity by decision-type and underlying brain/mind impairment

Background: Hospital clinicians find mental capacity assessment challenging and may lack the necessary skills. Given high rates of cognitive impairment, data on mental capacity assessment in real-world hospital cohorts are required to inform the need for staff training and workforce planning. Objectives: In unselected medical inpatients, we determined the rate and outcome of mental capacity assessment by decision type and underlying brain/mind disorder, and recorded the discipline of the assessor. Methods: We included consecutive patients (October–November 2018; November–December 2019) admitted to the complex medicine unit providing acute multidisciplinary care for multi-morbid patients (age ≥ 16 years, average age > 80 years). Audit data were collected at ward multidisciplinary meetings and extracted from electronic patient records. Results: Among 892 patients (mean/SD age = 82.8/8.6, 465 male), 140 (16%) required mental capacity assessment (40/140 (29%) had ≥2 assessments) with 203 assessments in total of which 162 (80%) were done by doctors. Capacity was deemed lacking in 124 (61%) assessments, most commonly in delirium with/without other co-morbid conditions (94/114, 82%) or dementia (9/12, 75%) with lower rates in other disorders (15/27, 56%), and no formal diagnosis of brain/mind disorder (6/50, 12%). Cognitive test scores were overall lower in those lacking capacity (mean/SD abbreviated-mental-test-score = 5.2/2.6, range = 0–10 versus 6.8/2.8, P = 0.001, range = 1–10). Decisions involving discharge planning were most often assessed (48%) followed by treatment (29%), discharge against medical advice (12%) and others (11%). Conclusion: Mental capacity assessments were performed frequently and often repeated, justifying the need for robust training in the practical application of the principles of capacity assessment for staff managing complex older patients

Care pathways in older patients seen in a multidisciplinary same day emergency care (SDEC) unit

Background: Same day emergency care (SDEC) services are being advocated in the UK for frail, older patients in whom hospitalisation may be associated with harm but there are few data on the ‘ambulatory pathway’. We therefore determined the patient pathways pre- and post-first assessment in a SDEC unit focussed on older people. Methods: In consecutive patients, we prospectively recorded follow-up SDEC service reviews (face-to-face, telephone, Hospital-at-Home domiciliary visits), outpatient referrals (e.g. to specialist clinics, imaging, and community/voluntary/social services), and hospital admissions <30 days. In the first 67 patients, we also recorded healthcare interactions (except GP attendances) in the 180 days pre- and post-first assessment. Results: Among 533 patients (mean/SD age = 75.0/17.5 years, 246, 46% deemed frail) assessed in an SDEC unit, 210 were admitted within 30 days (152 immediately). In the 381(71%) remaining initially ambulatory, there were 587 SDEC follow-up reviews and 747 other outpatient referrals (mean = 3.5 per patient) with only 34 (9%) patients being discharged with no further follow-up. In the subset (n = 67), the number of ‘healthcare days’ was greater in the 180 days post- versus pre-SDEC assessment (mean/SD = 26/27 versus 13/22 days, P = 0.003) even after excluding hospital admission days, with greater healthcare days in frail versus non-frail patients. Discussion and Conclusion: SDEC assessment in older, frail patients was associated with a 2-fold increase in frequency of healthcare interactions with complex care pathways involving multiple services. Our findings have implications for the development of admission-avoidance models including cost-effectiveness and optimal delivery of the multi-dimensional aspects of acute geriatric care in the ambulatory setting

Infection, delirium, and risk of dementia in patients with and without white matter disease on previous brain imaging: a population-based study

Background The increased risk of dementia after delirium and infection might be influenced by cerebral white matter disease (WMD). In patients with transient ischaemic attack (TIA) and minor stroke, we assessed associations between hospital admissions with delirium and 5-year dementia risk and between admissions with infection and dementia risk, stratified by WMD severity (moderate or severe vs absent or mild) on baseline brain imaging. Methods We included patients with TIA and minor stroke (National Institutes of Health Stroke Score <3) from the Oxford Vascular Study (OXVASC), a longitudinal population-based study of the incidence and outcomes of acute vascular events in a population of 94 567 individuals, with no age restrictions, attending eight general practices in Oxfordshire, UK. Hospitalisation data were obtained through linkage to the Oxford Cognitive Comorbidity, Frailty, and Ageing Research Database–Electronic Patient Records (ORCHARD-EPR). Brain imaging was done using CT and MRI, and WMD was prospectively graded according to the age-related white matter changes (ARWMC) scale and categorised into absent, mild, moderate, or severe WMD. Delirium and infection were defined by ICD-10 coding supplemented by hand-searching of hospital records. Dementia was diagnosed using clinical or cognitive assessment, medical records, and death certificates. Associations between hospitalisation with delirium and hospitalisation with infection, and post-event dementia were assessed using time-varying Cox analysis with multivariable adjustment, and all models were stratified by WMD severity. Findings From April 1, 2002, to March 31, 2012, 1369 individuals were prospectively recruited into the study. Of 1369 patients (655 with TIA and 714 with minor stroke, mean age 72 [SD 13] years, 674 female and 695 male, and 364 with moderate or severe WMD), 209 (15%) developed dementia. Hospitalisation during follow-up occurred in 891 (65%) patients of whom 103 (12%) had at least one delirium episode and 236 (26%) had at least one infection episode. Hospitalisation without delirium or infection did not predict subsequent dementia (HR 1·01, 95% CI 0·86–1·20). In contrast, hospitalisation with delirium predicted subsequent dementia independently of infection in patients with and without WMD (2·64, 1·47–4·74; p=0·0013 vs 3·41, 1·91–6·09; p<0·0001) especially in those with unimpaired baseline cognition (cognitive test score above cutoff; 4·01, 2·23–7·19 vs 3·94, 1·95–7·93; both p≤0·0001). However, hospitalisation with infection only predicted dementia in those with moderate or severe WMD (1·75, 1·04–2·94 vs 0·68, 0·39–1·20; pdiff=0·023). Interpretation The increased risk of dementia after delirium is unrelated to the presence of WMD, whereas infection increases risk only in patients with WMD, suggesting differences in underlying mechanisms and in potential preventive strategies. Funding National Institute for Health and Care Research and Wellcome Trust

What is the impact of volunteers providing care and support for people with dementia in acute hospitals? : a meta-synthesis

A quarter of acute hospital beds are occupied by people with dementia, and a hospital stay may impact negatively on their health and wellbeing. The development and implementation of volunteers to provide social, activity-based, one-to-one support for people with dementia in acute hospitals has become routine practice. However, the evidence to support this practice has not been identified or evaluated. This systematic review considers the effect of volunteers on the care and experience of people with co-morbid cognitive impairment/dementia in acute hospitals. The systematic search identified 444 papers, although only three papers included specific analysis relating to the impact of volunteers. The evidence suggests volunteers may have potential to enhance the experiences of people with dementia in acute hospitals; however, there is currently a marked lack of evidence to support the widespread implementation of volunteers. There is therefore an urgent need for multi-site robust research to provide evidence of the impact of volunteers supporting people with cognitive impairment/dementia during an acute hospital stay

White Matter Imaging Correlates of Early Cognitive Impairment Detected by the Montreal Cognitive Assessment after Transient Ischemic Attack and Minor Stroke

BACKGROUND AND PURPOSE:&nbsp; Among screening tools for cognitive impairment in large cohorts, the Montreal Cognitive assessment (MoCA) appears to be more sensitive to early cognitive impairment than the Mini-Mental State Examination (MMSE), particularly after transient ischemic attack (TIA) or minor stroke. We reasoned that if MoCA-detected early cognitive impairment is pathologically significant, then it should be specifically associated with the presence of white matter hyperintensities (WMH) and reduced fractional anisotropy (FA) on MRI. METHODS:&nbsp;Consecutive eligible patients with TIA or minor stroke (Oxford Vascular Study) underwent MRI and cognitive assessment. We correlated MoCA and MMSE scores with WMH and FA, then specifically studied patients with low MoCA and normal MMSE. RESULTS: Among 400 patients, MoCA and MMSE scores were significantly correlated (all p&lt;0.001) with WMH volumes (rMoCA=-0.336, rMMSE=-0.297) and FA (rMoCA=0.409, rMMSE=0.369), and -on voxel-wise analyses- with WMH in frontal white matter and reduced FA in almost all white matter tracts. However, only the MoCA was independently correlated with WMH volumes (r=-0.183, p&lt;0.001), average FA values (r=0.218, p&lt;0.001), and voxel-wise reduced FA in anterior tracts after controlling for the MMSE. In addition, patients with low MoCA but normal MMSE (N=57) had higher WMH volumes (t=3.1,p=0.002), lower average FA (t=-4.0,p&lt;0.001), and lower voxel-wise FA in almost all white matter tracts than those with normal MoCA and MMSE (N=238). CONCLUSIONS:&nbsp;In patients with TIA or minor stroke, early cognitive impairment detected with the MoCA but not with the MMSE was independently associated with white matter damage on MRI, particularly reduced FA

Sepsis recognition tools in acute ambulatory care::associations with process of care and clinical outcomes in a service evaluation of an Emergency Multidisciplinary Unit in Oxfordshire

To assess the performance of currently available sepsis recognition tools in patients referred to a community-based acute ambulatory care unit.Service evaluation of consecutive patients over a 4-month period.Community-based acute ambulatory care unit.Observations, blood results and outcome data were analysed from patients with a suspected infection. Clinical features at first assessment were used to populate sepsis recognition tools including: systemic inflammatory response syndrome (SIRS) criteria, National Early Warning Score (NEWS), quick Sequential Organ Failure Assessment (qSOFA) and National Institute for Health and Care Excellence (NICE) criteria. Scores were assessed against the clinical need for escalated care (use of intravenous antibiotics, fluids, ongoing ambulatory care or hospital treatment) and poor clinical outcome (all-cause mortality and readmission at 30 days after index assessment).Of 533 patients (median age 81 years), 316 had suspected infection with 120 patients requiring care escalated beyond simple community care. SIRS had the highest positive predictive value (50.9%, 95% CI 41.6% to 60.3%) and negative predictive value (68.9%, 95% CI 62.6% to 75.3%) for the need for escalated care. Both NEWS and SIRS were better at predicting the need for escalated care than qSOFA and NICE criteria in patients with suspected infection (all P<0.001). While new-onset confusion predicted the need for escalated care for infection in patients ≥85 years old (n=114), 23.7% of patients ≥85 years had new-onset confusion without evidence for infection.Acute ambulatory care clinicians should use caution in applying the new NICE endorsed criteria for determining the need for intravenous therapy and hospital-based location of care. NICE criteria have poorer performance when compared against NEWS and SIRS and new-onset confusion was prevalent in patients aged ≥85 years without infection