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

Reading nonsense a journey through the writing of Edward Lear

In this thesis I have addressed some of the problems that have arisen in critical approaches to the nonsense works of Edward Lear from the late nineteenth century. I have entitled it “Reading Nonsense” because my central concern is with how best to apprehend the paradoxes inherent in literary nonsense, which inevitably raises interpretative questions. Because nonsense is a “basic type of communication” whose essence is “unresolved tension between [the] presence and absence of meaning” (Tigges, Anatomy 51), we are called upon either to “make sense of” that which claims to offer up no meaning or to surrender ourselves to meaninglessness. Broadly, critical approaches to nonsense fall into two classes: those that maintain that nonsense is not, in fact, “not sense”, but rather a kind of symbolic language that can be reconciled into meaning; and those which uphold the nonsensicality of nonsense, maintaining that certain ambiguities and paradoxes cannot be accounted for, and it is inappropriate to try to do so. In addition, Lear’s texts are situated in various traditions of writing for children and adults and in the distinctive setting of the Victorian era; and these cultural and literary influences play an important role in the interpretation and misinterpretation of nonsense. My first chapter comprises a mise en scène of the genre of literary nonsense; while in Chapter 2 I turn to the cultural backdrop of Lear’s nonsense in particular, and examine one of the claims frequently made in nonsense criticism: that Lear’s literary nonsense is distinctively “Victorian”. Chapter 3, “How to Read a Learian Limerick”, rests on the exegesis of nonsense that appears in Chapter 1, for here I propose a technique for reading Lear’s limericks that preserves both their “sensical” and nonsensical elements in contrast to critical analyses that attempt to reconcile the nonsense into a code. In Chapter 4 I examine Lear’s songs from the critical perspectives of nonsense and of romanticism. Finally, in conclusion, I consider the role and significance of humour in nonsense, and gesture towards further possible explorations, including in the appendix my essay on the nonsense poetry of South African writer Philip de Vos

Association of neuroimaging markers on clinical CT scans with domain-specific cognitive impairment in the early and later poststroke stages

Background and Objectives: Poststroke cognitive impairment (PSCI) is associated with neuroimaging markers, including cortical atrophy and white matter lesions (WMLs), on clinically acquired CT neuroimaging. The objective was to investigate the association between cortical atrophy/WMLs and PSCI in specific cognitive domains in the acute/subacute and chronic stages after stroke, to provide clarity on the relationship between these neuroimaging markers and the temporal evolution of PSCI. Methods: We visually assessed cortical atrophy using the Global Cortical Atrophy (GCA) scale and WMLs using the Fazekas scale. Oxford Cognitive Screen or Birmingham Cognitive Screen assessed PSCI at 2 time points (acute/subacute and chronic) in 6 domains (language, memory, number processing, executive function, attention, and praxis). We binarized domain-specific performance as impaired/unimpaired using normative cutoffs. Multivariable linear and logistic regression analyses evaluated associations between GCA/Fazekas scores with acute/subacute and chronic global and domain-specific PSCI, and ANCOVAs examined whether these scores were significantly different in patients with recovered vs persistent PSCI. Age, sex, education, NIHSS, lesion volume, and recurrent stroke were covariates in these analyses. Results: Among 411 stroke patients (Mdn/IQR age = 76.16/66.84–83.47; 193 female; 346 ischemic stroke; 107 recurrent stroke), GCA and Fazekas scores were not associated with global cognitive impairment in the acute/subacute stage after stroke, but GCA score was associated with chronic global PSCI (B = 0.01, p < 0.001, 95% CI 0.00–0.01). In domain-specific analyses, GCA score was associated with chronic impairment in the memory (B = 0.06, p < 0.001, 95% CI 0.03–0.10) and attention (B = 0.05, p = 0.003, 95% CI 0.02–0.09) domains, and in patients with persistent PSCI, these domains showed significantly higher GCA scores than patients who had recovered (memory: F(1, 157) = 6.63, p = 0.01, η2G = 0.04; attention: F(1, 268) = 10.66, p = 0.001, η2G = 0.04). Discussion: This study highlights the potential effect of cortical atrophy on the cognitive recovery process after stroke and demonstrates the prognostic utility of CT neuroimaging for poststroke cognitive outcomes. Clinical neuroimaging could help identify patients at long-term risk of PSCI during acute hospitalization

Prevalence and outcomes of frailty in unplanned hospital admissions: a systematic review and meta-analysis of hospital-wide and general (internal) medicine cohorts

Background: Guidelines recommend routine frailty screening for all hospitalised older adults to inform care decisions, based mainly on studies in elective or speciality-specific settings. However, most hospital bed days are accounted for by acute non-elective admissions, in which the prevalence and prognostic value of frailty might differ, and uptake of screening is limited. We therefore did a systematic review and meta-analysis of frailty prevalence and outcomes in unplanned hospital admissions. Methods: We searched MEDLINE, EMBASE and CINAHL up to 31/01/2023 and included observational studies using validated frailty measures in adult hospital-wide or general medicine admissions. Summary data on the prevalence of frailty and associated outcomes, measurement tools, study setting (hospital-wide vs general medicine), and design (prospective vs retrospective) were extracted and risk of bias assessed (modified Joanna Briggs Institute checklists). Unadjusted relative risks (RR; moderate/severe frailty vs no/mild) for mortality (within one year), length of stay (LOS), discharge destination and readmission were calculated and pooled, where appropriate, using random-effects models. PROSPERO CRD42021235663. Findings: Among 45 cohorts (median/SD age = 80/5 years; n = 39,041,266 admissions, n = 22 measurement tools) moderate/severe frailty ranged from 14.3% to 79.6% overall (and in the 26 cohorts with low-moderate risk of bias) with considerable heterogeneity between studies (phet 8 days (RR range = 2.14–3.04; n = 6) and discharge to a location other than home (RR range = 1.97–2.82; n = 4) but was inconsistently related to 30-day readmission (RR range = 0.83–1.94; n = 12). Associations remained clinically significant after adjustment for age, sex and comorbidity where reported. Interpretation: Frailty is common in older patients with acute, non-elective hospital admission and remains predictive of mortality, LOS and discharge home with more severe frailty associated with greater risk, justifying more widespread implementation of screening using clinically administered tools

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

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

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

A human rights-based framework for qualitative dementia research

Background and objectives: People living with dementia have historically been excluded from qualitative research and their voices ignored due to the perception that a person with dementia is not able to express their opinions, preferences and feelings. Research institutions and organizations have contributed by adopting a paternalistic posture of overprotection. Furthermore, traditional research methods have proven to be exclusionary towards this group. The objective of this paper is to address the issue of inclusion of people with dementia in research and provide an evidence-based framework for dementia researchers based on the five principles of human rights: Participation, Accountability, Non-discrimination and equality, Empowerment and Legality (PANEL). Design: This paper adapts the PANEL principles to the research context, and uses evidence from the literature to create a framework for qualitative research in people with dementia. This new framework aims to guide dementia researchers in designing studies around the needs of people with dementia, to improve involvement and participation, facilitate research development and maximize research outcomes. Results: A checklist is presented with questions related to the five PANEL principles. These questions cover ethical, methodological and legal issues that researchers may need to consider while developing qualitative research for people with dementia. Conclusions: The proposed checklist offers a series of questions and considerations to facilitate the development of qualitative research in patients with dementia. It is inspired by current human rights work of recognized dementia researchers and organizations who have been directly involved in policy development. Future studies need to explore its utility in improving participation, facilitating ethics approvals and ensuring that outcomes are relevant to people with dementia