Domain-specific cognitive impairments, mood and quality of life 6 months after stroke.

PURPOSE: To identify which acute and 6-month domain-specific cognitive impairments impact mood, participation, and stroke-related quality of life 6 months post-stroke. MATERIALS AND METHODS: A prospective cohort of 430 stroke survivors completed the Oxford Cognitive Screen (OCS) acutely and 6 months post-stroke. Participants completed the Stroke Impact Scale (SIS) and Hospital Depression and Anxiety Scale (HADS) at 6 months. Multivariable regression analyses assessed whether severity of, and domain-specific, cognitive impairment acutely and at 6 months was associated with composite 6-month SIS scores, each SIS subscale, and HADS scores. RESULTS: Increased severity of acute and 6-month cognitive impairment was associated with lower 6-month SIS composite scores independent of age, sex, education years, and stroke severity (both p < 0.001). Domain-specific impairments in memory (p < 0.001) and attention (p = 0.002) acutely, and language (p < 0.001), memory (p = 0.001) and number processing (p = 0.006) at 6 months showed the strongest associations with worse SIS composite scores. Severity of acute and 6-month cognitive impairment was associated with poorer functioning in each SIS subscale, and greater levels of depression (acute p = 0.021, 6-months p < 0.001), but not anxiety (p = 0.174, p = 0.129). CONCLUSIONS: Both acute and 6-month domain-specific cognitive impairments, particularly in memory, were found to negatively impact overall functional and mood outcomes 6 months post-stroke.

At 6 months follow-up, stroke survivors reported the greatest challenges in participation and emotional well-being, suggesting that these specific areas may be worth prioritising.Healthcare professionals involved in post-stroke rehabilitation should prioritize assessing and addressing the severity of post-stroke cognitive impairment as it significantly influences functioning.Implementing targeted interventions particularly for memory deficits could be instrumental in improving overall functional and mood outcomes in stroke survivors.

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.

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, 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.

Reliability of the global cortical atrophy visual rating scale applied to computed tomography versus magnetic resonance imaging scans in acute stroke.

INTRODUCTION: Research using magnetic resonance imaging (MRI) suggests regional cerebral atrophy measures (e.g., frontal lobe, temporal lobe) may predict post-stroke outcomes. Clinical CT scans have excellent potential for use in research but it is unclear whether regional atrophy measures from CT are reliable compared to MRI reference standards. METHODS: We used the Global Cortical Atrophy (GCA) scale to investigate reliability of atrophy measures on CT versus MRI scans from stroke patients originally recruited to the Oxford Cognitive Screening programme. Two raters provided standardised visual ratings at two timepoints. Weighted Kappa statistics assessed the reliability of regional atrophy scores. Spearman's correlation and a two-way repeated measures ANOVA assessed the reliability of the total score. RESULTS: On clinically acquired neuroimaging from 98 stroke patients (mean/SD age = 70.97/11.99, 42 female, 84 ischaemic stroke), regional GCA scores on CT versus MRI showed fair to almost perfect intra-rater agreement (κ = .50-.87), substantial to almost perfect intra-rater agreement on CT (κ = .67-.88), and moderate to almost perfect intra-rater reliability on MRI (κ = .50-.89). Regional GCA scores showed mostly moderate to substantial inter-rater reliability on both CT and MRI (κ = .43-.69), except the temporal horns and parieto-occipital region. There was a strong correlation between total GCA scores on CT and MRI (r (96) = .87-.88, p < .001). CONCLUSIONS: These results support the use of cerebral atrophy measures from CT in clinical research, as visual ratings showed generally good agreement between CT and MRI, between raters, and between timepoints.

Long-term psychological outcomes following stroke: the OX-CHRONIC study.

BACKGROUND: Stroke survivors rate longer-term (> 2 years) psychological recovery as their top priority, but data on how frequently psychological consequences occur is lacking. Prevalence of cognitive impairment, depression/anxiety, fatigue, apathy and related psychological outcomes, and whether rates are stable in long-term stroke, is unknown. METHODS: N = 105 long-term stroke survivors (M [SD] age = 72.92 [13.01]; M [SD] acute NIH Stroke Severity Score = 7.39 [6.25]; 59.0% Male; M [SD] years post-stroke = 4.57 [2.12]) were recruited (potential N = 208). Participants completed 3 remote assessments, including a comprehensive set of standardized cognitive neuropsychological tests comprising domains of memory, attention, language, and executive function, and questionnaires on emotional distress, fatigue, apathy and other psychological outcomes. Ninety participants were re-assessed one year later. Stability of outcomes was assessed by Cohen's d effect size estimates and percent Minimal Clinically Important Difference changes between time points. RESULTS: On the Montreal Cognitive Assessment 65.3% scored < 26. On the Oxford Cognitive Screen 45.9% had at least one cognitive impairment. Attention (27.1%) and executive function (40%) were most frequently impaired. 23.5% and 22.5% had elevated depression/anxiety respectively. Fatigue (51.4%) and apathy (40.5%) rates remained high, comparable to estimates in the first-year post-stroke. Attention (d = -0.12; 85.8% stable) and depression (d = 0.09, 77.1% stable) were the most stable outcomes. Following alpha-adjustments, only perceptuomotor abilities (d = 0.69; 40.4% decline) and fatigue (d = -0.33; 45.3% decline) worsened over one year. Cognitive impairment, depression/anxiety, fatigue and apathy all correlated with worse quality of life. CONCLUSION: Nearly half of participants > 2 years post-event exhibited psychological difficulties including domains of cognition, mood, and fatigue, which impact long-term quality of life. Stroke is a chronic condition with highly prevalent psychological needs, which require monitoring and intervention development.

Poststroke Executive Function in Relation to White Matter Damage on Clinically Acquired CT Brain Imaging.

BACKGROUND: Executive function (EF) impairments are prevalent post stroke and are associated with white matter (WM) damage on MRI. However, less is known about the relationship between poststroke EF and WM damage on CT imaging. OBJECTIVE: To investigate the relationship between poststroke EF and WM damage associated with stroke lesions and WM hypointensities (WMHs) on clinically acquired CT imaging. METHOD: This study analyzed data from the Oxford Cognitive Screening Program, which recruited individuals aged ≥18 years with a confirmed stroke from an acute stroke unit. The individuals completed a follow-up assessment 6 months post stroke. We included individuals with a CT scan showing a visible stroke who completed follow-up EF assessment using the Oxford Cognitive Screen-Plus rule-finding task. We manually delineated stroke lesions and quantified then dichotomized WM damage caused by the stroke using the HCP-842 atlas. We visually rated then dichotomized WMHs using the Age-Related White Matter Changes Scale. RESULTS: Among 87 stroke survivors (Mage = 73.60 ± 11.75; 41 female; 61 ischemic stroke), multivariable linear regression showed that stroke damage to the medial lemniscus (B = -8.86, P < 0.001) and the presence of WMHs (B = -5.42, P = 0.005) were associated with poorer EF 6 months post stroke after adjusting for covariates including age and education. CONCLUSION: Poorer EF was associated with WM damage caused by stroke lesions and WMHs on CT. These results confirm the importance of WM integrity for EF post stroke and demonstrate the prognostic utility of CT-derived imaging markers for poststroke 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.

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, η 2 G = 0.04; attention: F(1, 268) = 10.66, p = 0.001, η 2 G = 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.

Cognitive Impairment After Ischemic and Hemorrhagic Stroke: A Scientific Statement From the American Heart Association/American Stroke Association.

PURPOSE: Cognitive impairment is a common consequence of stroke and has direct implications for poststroke functioning and quality of life, including the ability to maintain a job, live independently, sustain interpersonal relationships, and drive a vehicle. In this scientific statement, we critically appraise the literature on the prevalence, diagnosis, and management of poststroke cognitive impairment (PSCI) and provide a framework for clinical care while highlighting gaps that merit further study. METHODS: We performed a scoping literature review of randomized controlled clinical trials, prospective and retrospective cohort studies, case-control studies, clinical guidelines, review articles, and editorials on the incidence and prevalence, natural history, diagnosis, and management of PSCI. Scoping reviews determine the scope of a body of literature on a given topic to indicate the volume of literature and the studies currently available and provide an overview of its focus. RESULTS: PSCI is common after stroke, especially in the first year, and ranges from mild to severe. Although cognitive impairment is reversible in some cases early after stroke, up to one-third of individuals with stroke develop dementia within 5 years. The pathophysiology is not yet fully elucidated but is likely attributable to an acute stroke precipitating a series of pathological events, often in the setting of preexisting microvascular and neurodegenerative changes. Screening for associated comorbidities and interdisciplinary management are integral components of the care of individuals with PSCI. There is a need for prospective studies evaluating the individual trajectory of PSCI and the role of the acute vascular event in the predisposition for Alzheimer disease and related dementias, as well as high-quality, randomized clinical trials focused on PSCI management.

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 < 0.001) preventing pooling of results but with rates <25% in only 3 cohorts. Moderate/severe vs no/mild frailty was associated with increased mortality (n = 19 cohorts; RR range = 1.08-3.70), more consistently among cohorts using clinically administered tools (n = 11; RR range = 1.63-3.70; phet = 0.08; pooled RR = 2.53, 95% CI = 2.15-2.97) vs cohorts using (retrospective) administrative coding data (n = 8; RR range = 1.08-3.02; phet < 0.001). Clinically administered tools also predicted increasing mortality across the full range of frailty severity in each of the six cohorts that allowed ordinal analysis (all p < 0.05). Moderate/severe vs no/mild frailty was also associated with a LOS >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. Funding: None.

Associations Between Vascular Risk Factor Levels and Cognitive Decline Among Stroke Survivors.

Importance: Incident stroke is associated with accelerated cognitive decline. Whether poststroke vascular risk factor levels are associated with faster cognitive decline is uncertain. Objective: To evaluate associations of poststroke systolic blood pressure (SBP), glucose, and low-density lipoprotein (LDL) cholesterol levels with cognitive decline. Design, Setting, and Participants: Individual participant data meta-analysis of 4 US cohort studies (conducted 1971-2019). Linear mixed-effects models estimated changes in cognition after incident stroke. Median (IQR) follow-up was 4.7 (2.6-7.9) years. Analysis began August 2021 and was completed March 2023. Exposures: Time-dependent cumulative mean poststroke SBP, glucose, and LDL cholesterol levels. Main Outcomes and Measures: The primary outcome was change in global cognition. Secondary outcomes were change in executive function and memory. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Results: A total of 1120 eligible dementia-free individuals with incident stroke were identified; 982 (87.7%) had available covariate data and 138 (12.3%) were excluded for missing covariate data. Of the 982, 480 (48.9%) were female individuals, and 289 (29.4%) were Black individuals. The median age at incident stroke was 74.6 (IQR, 69.1-79.8; range, 44.1-96.4) years. Cumulative mean poststroke SBP and LDL cholesterol levels were not associated with any cognitive outcome. However, after accounting for cumulative mean poststroke SBP and LDL cholesterol levels, higher cumulative mean poststroke glucose level was associated with faster decline in global cognition (-0.04 points/y faster per each 10-mg/dL increase [95% CI, -0.08 to -0.001 points/y]; P = .046) but not executive function or memory. After restricting to 798 participants with apolipoprotein E4 (APOE4) data and controlling for APOE4 and APOE4 × time, higher cumulative mean poststroke glucose level was associated with a faster decline in global cognition in models without and with adjustment for cumulative mean poststroke SBP and LDL cholesterol levels (-0.05 points/y faster per 10-mg/dL increase [95% CI, -0.09 to -0.01 points/y]; P = .01; -0.07 points/y faster per 10-mg/dL increase [95% CI, -0.11 to -0.03 points/y]; P = .002) but not executive function or memory declines. Conclusions and Relevance: In this cohort study, higher poststroke glucose levels were associated with faster global cognitive decline. We found no evidence that poststroke LDL cholesterol and SBP levels were associated with cognitive decline.

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.

Editor's Choice - Effect of Carotid Endarterectomy on 20 Year Incidence of Recorded Dementia: A Randomised Trial.

OBJECTIVE: Stroke and carotid atherosclerosis are associated with dementia. Carotid endarterectomy (CEA) reduces stroke risk, although its effect on later dementia is uncertain. Participants in the Asymptomatic Carotid Surgery Trial (ACST-1), randomly allocated to immediate vs. deferral of CEA (i.e., no intervention unless or until triggered by ipsilateral transient ischaemic attack or stroke), were followed, to study effects on dementia. METHODS: From 1993 to 2003, ACST-1 included 3 120 participants with asymptomatic tight carotid stenosis. All UK and Swedish patients (n = 1 601; 796 immediate vs. 805 deferral) were followed with trial records, national electronic health record linkage, and (UK only) by post and telephone. Cumulative incidence and competing risk analyses were used to measure the effects of risk factors and CEA on dementia risk. Intention to treat analyses yielded hazard ratios (HRs; immediate vs. deferral) of dementia. RESULTS: The median follow up was 19.4 years (interquartile range 16.9 - 21.7). Dementia was recorded in 107 immediate CEA patients and 115 allocated delayed surgery; 1 290 patients died (1 091 [538 vs. 536] before any dementia diagnosis). Dementia incidence rose with age and with female sex (men: 8.3% aged < 70 years at trial entry vs. 15.1% aged ≥ 70; women: 15.1% aged < 70 years at trial entry vs. 22.4% aged ≥ 70 years) and was higher in those with pre-existing cerebral infarction (silent or with prior symptoms; 20.2% vs. 13.6%). Dementia risk was similar in both randomised groups: 6.7% vs. 6.6% at 10 years and 14.3% vs. 15.5% at 20 years, respectively. The dementia HR was 0.98 (95% confidence interval [CI] 0.75 - 1.28; p = .89), with no heterogeneity in the neutral effect of immediate CEA on dementia related to age, carotid stenosis, blood pressure, diabetes, country of residence, or medical treatments at trial entry (heterogeneity values p > .05). CONCLUSION: CEA was not associated with significant reductions in the long term hazards of dementia, but the CI did not exclude a proportional benefit or hazard of about 25%.

Is Frailty Index a better predictor than pre-stroke modified Rankin Scale for neurocognitive outcomes 3-months post-stroke?

BACKGROUND: The prognostic value of frailty measures for post-stroke neurocognitive disorder (NCD) remains to be evaluated. AIMS: The aim of this study was to compare the predictive value of pre-stroke FI with pre-stroke modified Rankin Scale (mRS) for post-stroke cognitive impairment. Further, we explored the added value of including FI in prediction models for cognitive prognosis post-stroke. METHODS: We generated a 36-item Frailty Index (FI), based on the Rockwood FI, to measure frailty based on pre-stroke medical conditions recorded in the Nor-COAST multicentre prospective study baseline assessments. Consecutive participants with a FI score and completed cognitive test battery at three months were included. We generated Odds Ratio (OR) with NCD as the dependent variable. The predictors of primary interest were pre-stroke frailty and mRS. We also measured the predictive values of mRS and FI by the area (AUC) under the receiver operating characteristic curve. RESULTS: 598 participants (43.0% women, mean/SD age = 71.6/11.9, mean/SD education = 12.5/3.8, mean/SD pre-stroke mRS = 0.8/1.0, mean/SD GDS pre-stroke = 1.4/0.8, mean/SD NIHSS day 1 3/4), had a FI mean/SD score = 0.14/0.10. The logistic regression analyses showed that FI (OR 3.09), as well as the mRS (OR 2.21), were strong predictors of major NCD. When FI and mRS were entered as predictors simultaneously, the OR for mRS decreased relatively more than that for FI. AUC for NCD post-stroke was higher for FI than for mRS, both for major NCD (0.762 vs 0.677) and for any NCD (0.681 vs 0.638). CONCLUSIONS: FI is a stronger predictor of post-stroke NCD than pre-stroke mRS and could be a part of the prediction models for cognitive prognosis post-stroke. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02650531 .

Cognitive decline and diabetes: a systematic review of the neuropathological correlates accounting for cognition at death.

Given conflicting findings in epidemiologic studies, we determined the relative contributions of different neuropathologies to the excess risk of cognitive decline in diabetes mellitus (DM) through a systematic review of the literature. Included studies compared subjects with and without DM and reported neuropathological outcomes accounting for cognition at death. Data on Alzheimer's disease (AD) pathology, cerebrovascular disease and non-vascular, non-AD pathology were extracted from each study. Eleven studies (n=6 prospective cohorts, n=5 retrospective post-mortem series, total n=6330) met inclusion criteria. All 11 studies quantified AD changes and 10/11 measured cerebrovascular disease: macroscopic lesions (n=9), microinfarcts (n=8), cerebral amyloid angiopathy (CAA, n=7), lacunes (n=6), white matter disease (n=5), haemorrhages (n=4), microbleeds (n=1), hippocampal microvasculature (n=1). Other pathology was infrequently examined. No study reported increased AD pathology in DM, three studies showed a decrease (n=872) and four (n= 4018) showed no difference, after adjustment for cognition at death. No study reported reduced cerebrovascular pathology in DM. Three studies (n=2345) reported an increase in large infarcts, lacunes and microinfarcts. One study found lower cognitive scores in DM compared to non-DM subjects despite similar cerebrovascular and AD-pathology load suggesting contributions from other neuropathological processes. In conclusion, lack of an association between DM and AD-related neuropathology was consistent across studies, irrespective of methodology. In contrast to AD, DM was associated with increased large and small vessel disease. Data on other pathologies such as non-AD neurodegeneration, and blood-brain-barrier breakdown were lacking. Further studies evaluating relative contributions of different neuropathologies to the excess risk of DM are needed.

Associations of Chronic Kidney Disease With Dementia Before and After TIA and Stroke: Population-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Individuals with chronic kidney disease (CKD) appear to be at increased risk of cognitive impairment, with both vascular and neurodegenerative mechanisms postulated. To explore the vascular hypothesis, we studied the association between CKD and dementia before and after TIA and stroke. METHODS: In a prospective, population-based cohort study of TIA and stroke (Oxford Vascular Study; 2002-2012), pre-event and new postevent dementia were ascertained through direct patient assessment and follow-up for 5 years, supplemented by review of hospital/primary care records. Associations between pre-event dementia and CKD (defined as an estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2) were examined using logistic regression and between postevent dementia and CKD using Cox and competing risk regression models, adjusted for age, sex, education, stroke severity, prior stroke, white matter disease, diabetes mellitus, and dysphasia. RESULTS: Among 2,305 patients with TIA/stroke (median [interquartile range] age, 77 [67-84] years, 1,133 [49%] male, 688 [30%] TIA), 1,174 (50.9%) had CKD. CKD was associated with both pre-event (odds ratio [OR] 2.04 [95% confidence interval (CI) 1.52-2.72]; p < 0.001) and postevent dementia (hazard ratio [HR] 2.01 [95% CI 1.65-2.44]; p < 0.001), but these associations attenuated after adjustment for covariates (OR 0.92 [0.65-1.31]; p = 0.65 and HR 1.09 [0.85-1.39]; p = 0.50). The results were similar when a competing risk model was used (subdistribution HR [SHR] 1.74 [1.43-2.12]; p < 0.001, attenuating to 1.01 [0.78-1.33]; p = 0.92 with adjustment). CKD was more strongly associated with late (>1 year) postevent dementia (SHR 2.32 [1.70-3.17]; p < 0.001), particularly after TIA and minor stroke (SHR 3.08 [2.05-4.64]; p < 0.001), but not significantly so after adjustment (SHR 1.53 [0.90-2.60]; p = 0.12). DISCUSSION: In patients with TIA and stroke, CKD was not independently associated with either pre- or postevent dementia, suggesting that renal-specific mechanisms are unlikely to play an important role in aetiology.

Utility of white matter disease and atrophy on routinely acquired brain imaging for prediction of long-term delirium risk: population-based cohort study.

BACKGROUND: brain imaging done as part of standard care may have clinical utility beyond its immediate indication. Using delirium as an exemplar, we determined the predictive value of baseline brain imaging variables [white matter changes (WMC) and atrophy] for delirium risk on long-term follow-up after transient ischemic attack (TIA)/stroke in a population-based cohort study. METHODS: surviving TIA/stroke participants in the Oxford Vascular Study (OXVASC) were assessed prospectively for delirium during all hospitalisations over 6 months (2013-14). Using logistic regression, independent associations were determined between baseline OXVASC computed tomography or magnetic resonance brain imaging measures of WMC and cerebral atrophy (none/mild versus moderate/severe) and delirium adjusted for age, sex, baseline stroke severity, depression, illness severity and pre-admission cognition. RESULTS: among 1,565 TIA/stroke survivors with 194 hospital admissions (158 patients, mean/standard deviation age at admission = 79.2/11.5 years), delirium occurred in 59 (37%). WMC and atrophy on baseline imaging were associated with delirium [odds ratio (OR) = 3.41, 1.21-5.85, P = 0.001 and OR = 2.50, 1.23-5.08, P = 0.01 (unadjusted) and OR = 2.67, 1.21-5.85, P = 0.02 and OR = 2.18, 1.00-4.73, P = 0.05 (adjusted age and sex)]. Associations were strengthened when analyses were restricted to patients hospitalised within 5 years of baseline brain imaging [OR = 6.04, 2.39-15.24, P < 0.0001 and OR = 4.64, 1.46-14.82, P = 0.009 (unadjusted)] but only WMC remained significant after adjustment for all covariates including pre-admission cognition (OR = 4.83, 1.29-18.13, P = 0.02 for Mini-Mental State Examination and OR = 5.15, 1.26-21.09, P = 0.02 for Montreal Cognitive Assessment). CONCLUSIONS: WMC and atrophy on brain imaging done up to 5 years earlier predicted delirium and may have clinical utility in risk stratification. Associations with WMC but not atrophy were independent of pre-admission cognitive impairment.

Cognitive Predictors of Delirium on Long-Term Follow-Up after TIA and Stroke: Population-Based Cohort Study.

INTRODUCTION: TIA and stroke cause cognitive impairment with a typical "vascular" pattern, including prominent frontal/executive deficits. Cognitive impairment is associated with increased delirium risk and the few available data suggest that executive dysfunction is important. We therefore determined the predictive value of both severity and pattern of cognitive deficits for delirium on long-term follow-up after TIA/stroke. METHODS: Surviving TIA/stroke participants on October 1, 2013, in the Oxford Vascular Study (OXVASC) were assessed prospectively for delirium during all hospitalizations over the subsequent 6 months. Associations between OXVASC pre-admission mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores, and delirium during hospitalizations on follow-up were determined using logistic regression adjusted for covariates, including demographic factors, history of depression, baseline stroke severity, and admission illness severity. RESULTS: Among 1,565 TIA/stroke survivors, 158 patients (mean/SD age = 79.2/11.5 years) had ≥1 admission and 59 (37%) had ≥1 delirium episode. Mean/SD time between baseline TIA/stroke and admission was 4.7/3.6 years and between most recent OXVASC cognitive testing and admission was 1.7/1.8 years. MMSE and MoCA scores were associated with delirium: odds ratio (OR) = 1.16 (95% CI 1.07-1.27, p < 0.0001 per point decrease in MMSE) and OR = 1.20 (1.11-1.30, p < 0.0001 MoCA) and associations were robust to adjustment for all covariates, including stroke severity: OR = 1.11 (1.01-1.22, p = 0.03, MMSE) and OR = 1.15 (1.05-1.25, p = 0.003, MoCA). All 10 subtests on the MoCA and 4/11 on the MMSE were significantly associated with delirium with highest predictive value for frontal/executive and recall domains. CONCLUSIONS: Cognitive impairment of increasing severity after TIA/stroke predisposed to delirium particularly deficits in frontal/executive domains and recall. Long-term risk of delirium should be considered as part of the overall cerebrovascular disease burden.