Background Patients with acute ischemic stroke (AIS) may require intensive care unit admission for several reasons, including post-procedural care, management of large hemispheric infarction, and cardiopulmonary instability. The objective of this document is to provide recommendations on the reliability of select individual predictors of outcome, and multivariate prediction models, in the context of counseling critically ill patients with AIS and their surrogates. In addition, broad principles of neuroprognostication in this population were identified. Methods A narrative systematic review was completed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Candidate predictors, including clinical variables and prediction models, were selected on the basis of clinical relevance and the presence of an appropriate body of evidence. The Population/Intervention/Comparator/Outcome/Timing/Setting (PICOTS) question was framed as follows: "When counseling critically ill adults with AIS or their surrogates, should be considered a reliable predictor of poor functional outcome at 3 months or later?" Recommendations were based on quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. Recommendations that met GRADE criteria for good practice statements addressed broad principles of neuroprognostication. Results A total of 518 articles met eligibility criteria to guide recommendations. Good practice recommendations include avoiding premature neuroprognostication, avoiding confounders, the use of multimodal assessment, predicting recovery of swallow function, predicting tracheostomy decannulation, and counseling of patients with large hemispheric infarction and their surrogates prior to neurological decline. Early neurological improvement within 24 h of revascularization was identified as a moderately reliable predictor of good functional outcome. No other individual predictor was considered reliable for the prediction of mortality or functional outcome. Conclusions These guidelines suggest broad principles of neuroprognostication and provide recommendations on the reliability of predictors of functional outcome in the context of counseling critically ill patients with AIS and their surrogates.

Abstract Background and aims Previous studies have proposed an association between BP variability (BPV) and recurrent stroke and major cardiovascular events (MACE) following ischaemic stroke. However, few recent data from large studies exist. We examined the association between mean BP and BPV during follow-up with recurrent vascular events and recurrent stroke in the CONVINCE trial, which randomized participants with recent non-cardioembolic ischaemic stroke to long term colchicine 0.5 mg daily or usual care. Methods Mean BP during follow-up was calculated using all available post-randomization BP readings recorded at six-monthly trial visits. Analysis of BPV was conducted for all participants with ≥3 BP readings during the first year of follow-up. BPV was measured as standard deviation (SD) and coefficient of variation (CV), adjusting for age, qualifying event, time from qualifying event to randomization and treatment group. Results Among 2919 participants with post-randomization BP readings, no association was observed between mean SBP or mean DBP during follow-up and recurrent vascular events or recurrent stroke. In 1629 participants who met pre-specified criteria for BPV analysis, on multivariate analysis of 174 events, each 10-point increase in SD of systolic BPV was associated with a one-fifth increased risk of MACE (adjusted HR 1.22, 95% CI 1.02-1.46, P = 0.032). Similar findings were observed for BPV measured as CV (adjusted HR 1.34, 95% CI 1.02-1.75, P = 0.035). There were no associations with recurrent stroke. Conclusions Significant associations existed between BPV and vascular events in the CONVINCE trial population, highlighting the importance of further investigation into BPV as a target for secondary prevention. Conflict of interest Pádraig Synnott: nothing to disclose.

Abstract Background and aims It is uncertain whether benefit from anti-inflammatory therapies after stroke is confined to patients with atherosclerosis. Methods We performed a post-hoc analysis of the CONVINCE trial (comparing colchicine+usual care vs. usual care) in patients stratified according to the presence/absence of atherosclerosis (cervico-cranial artery plaque, coronary disease, peripheral arterial disease, or carotid revascularisation). The primary outcome was MACE (composite of fatal/non-fatal recurrent ischemic stroke or coronary event). Results The trial included 3,144 participants (1,875 with atherosclerosis, median follow-up 33.6 months, 338 MACE events). On intention-to-treat analysis, there were numerically fewer MACE events in the atherosclerosis group assigned to colchicine (105 [11.1%], 3.88 [95% CI 3.21-4.70] per 100 person-years) vs.usual care (132 [14.2%], 4.83 [4.07-5.73]/100 person-years), which was not statistically significant (HR 0.83, 0.64-1.07). There was no difference in the rate of the primary outcome according to treatment allocation in the non-atherosclerosis subgroup (HR 0.94, 0.64-1.39) (Pinteraction 0.60). There was a non-significant reduced risk of recurrent ischemic stroke in the colchicine arm (HR 0.76, 0.56-1.05) in the atherosclerosis group only. In the pre-specified on-treatment analysis, colchicine reduced the risk of MACE in patients with atherosclerosis (HR 0.76, 0.58-0.99), but not without (HR 0.95, 0.63-1.42). Conclusions There was no significant between-group interactions for colchicine and atherosclerosis for MACE. However, outcome events were numerically fewer in patients with atherosclerosis assigned to colchicine and significant benefit was observed in the on-treatment analysis in this group. Data suggest the presence of atherosclerosis should be an inclusion criteria in future trials of anti-inflammatory therapies. Conflict of interest Figure 1 - belongs to Conclusions

INTRODUCTION:The Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke (CONVINCE) trial showed that recurrent events were significantly reduced among colchicine-adherent non-cardioembolic stroke patients in the on-treatment analysis. This study aimed to validate the SMART-REACH risk score in stroke patients, and to determine whether colchicine's efficacy varies by baseline atherosclerotic cardiovascular disease (ASCVD) risk. PATIENTS AND METHODS:Patients with non-severe non-cardioembolic ischaemic stroke/transient ischaemic attack (TIA) were randomised to colchicine 0.5 mg plus usual care or usual care alone. Participants were stratified into moderate (10%-19%), high (20%-30%) and very high (≥30%) 10-year ASCVD risk categories using the SMART-REACH model. Model performance was assessed using the C-statistic and calibration plots. The primary endpoint (major adverse cardiovascular events [MACE]) was a composite of fatal or non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest or hospitalisation for unstable angina. RESULTS:Among 3144 patients, MACE incidence significantly increased with ASCVD risk levels: 7.2% (moderate), 8.8% (high) and 13.8% (very high) (P < .01). The C-statistic for 3-year risk of MACE was 0.59 (95% CI, 0.56-0.63). While no statistically significant treatment interaction was found (P = .88), absolute risk reductions (ARRs) were more pronounced in higher-risk groups: moderate risk 7.2% (colchicine) vs 7.2% (usual care) (hazard ratio [HR] 1.01; 95% CI, 0.55-1.83); high risk 7.7% vs 9.8% (ARR 2.1%; HR 0.79; 95% CI, 0.53-1.18); very high risk 12.5% vs 15.2% (ARR 2.7%; HR 0.85; 95% CI, 0.64-1.12). DISCUSSION AND CONCLUSION:We identified an association between very high baseline ASCVD risk (≥30%) assigned by the SMART-REACH score and increased recurrent MACE. Although no significant treatment interaction was observed, patients in higher risk categories may represent a more promising target population for secondary prevention with colchicine. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT02898610.

Status epilepticus (SE) is a heterogeneous disorder with significant morbidity and mortality. This guideline provides broad principles of neuroprognostication and recommendations on the reliability of clinical predictors of outcome that clinicians may consider when counseling surrogate decision-makers of patients with SE. This narrative systematic review used Grading of Recommendations Assessment, Development and Evaluation methodology. Good practice recommendations addressed essential principles of neuroprognostication. Candidate predictors, including clinical variables and prediction models, were selected based on clinical relevance and the availability of appropriate evidence. The question was: “When counseling surrogates of patients with SE, should [predictor, with time of assessment if appropriate] be considered a reliable predictor of [outcome] assessed at [time point]?” Outcomes were selected and rated by the panel. Screening criteria were used to exclude smaller and lower-quality studies. Following construction of the evidence profile and summary of findings, recommendations were based on four Grading of Recommendations Assessment, Development and Evaluation criteria: quality of evidence, balance of desirable and undesirable consequences, values and preferences, and resource use. Good practice recommendations include establishing appropriate long-term goals with surrogates of patients with SE that may extend beyond seizure control alone, setting expectations for recovery in patients with refractory/super-refractory SE, using predictors specific to underlying pathologies as a basis for neuroprognostication, considering potential confounders, and deferring neuroprognostication in cases of unclear etiology until appropriate diagnostic evaluation is performed. Nine clinical variables and two prediction models were selected. A sufficient body of evidence was available only for the prediction of mortality. Forty-two articles met the eligibility criteria for guiding recommendations. None of the variables and models selected were identified as reliable predictors of mortality in patients with SE. This guideline provides broad principles for neuroprognostication and recommendations on the reliability of predictors of in-hospital mortality in the context of counseling surrogates of patients with SE.

BACKGROUND:Anti-inflammatory therapies reduce the risk of major adverse cardiovascular events (MACEs) in coronary disease, but efficacy has not been shown after stroke. It is uncertain if patients with atherosclerosis are more likely to benefit from anti-inflammatory prevention. METHODS:We performed a post hoc analysis of the CONVINCE trial (randomized, open-label, blinded-end point assessed; Colchicine for Prevention of Vascular Inflammation in Non-Cardioembolic Stroke), comparing colchicine 0.5 mg plus usual care versus usual care. We performed a subgroup analysis in patients stratified according to the presence/absence of atherosclerosis (defined as cervico-cranial/aortic artery plaque, coronary disease, peripheral arterial disease, and carotid revascularization). The primary outcome was MACE. Analyses were adjusted for age, qualifying event, time from event to randomization, and coronary disease. RESULTS:Three thousand one hundred forty-four participants were included. There were 338 MACE events during follow-up (median, 33.6 months). On intention-to-treat analysis, there were numerically fewer MACE events in the atherosclerosis group assigned to colchicine (105 [11.1%], 3.88 [95% CI, 3.21-4.70] per 100 person-years) versus usual care (132 [14.2%], 4.83 [4.07-5.73] per 100 person-years), which was not statistically significant (hazard ratio [HR], 0.83 [95% CI, 0.64-1.07]). There was no difference in the rate of the primary outcome according to treatment allocation in the nonatherosclerosis subgroup (HR, 0.94 [95% CI, 0.64-1.39]; Pinteraction=0.60). There was a nonsignificant reduced risk of recurrent ischemic stroke in the colchicine arm (HR, 0.76 [95% CI, 0.56-1.05]) in the atherosclerosis group, but no difference in events was observed in the nonatherosclerotic group (HR, 0.92 [95% CI, 0.60-1.42]; Pinteraction=0.48). In the prespecified on-treatment analysis, colchicine reduced the risk of MACE in patients with atherosclerosis (HR, 0.76 [95% CI, 0.58-0.99]) but not without (HR, 0.95 [95% CI, 0.63-1.42]; Pinteraction=0.37). CONCLUSIONS:There were no significant between-group interactions for colchicine and atherosclerosis for MACE in intention-to-treat or on-treatment populations. However, outcome events were numerically fewer in patients with atherosclerosis assigned to colchicine, and significant benefit was observed in the on-treatment analysis in this group. Data suggest that the presence of atherosclerosis should be an inclusion criterion in future anti-inflammatory therapy trials. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT02898610.

INTRODUCTION:Hypertension is a major modifiable risk factor for stroke. Studies between 1996 and 2013 reported high rates of non-achievement of guideline recommended blood pressure (BP) targets following stroke/TIA. Few recent large studies of long-term post-stroke BP management exist, and no studies have reported findings since the introduction of new guideline recommendations (systolic blood pressure [SBP] < 130 mmHg) in 2022. PATIENTS AND METHODS:We analysed BP control in the CONVINCE trial, which randomised 3154 recent ischaemic stroke/high-risk TIA patients to colchicine 0.5 mg daily or usual care. Clinic BP was measured at 6-monthly trial visits from 2017 to 2024. We calculated mean follow-up BP using all available follow-up BP measurements, and examined factors associated with non-achievement of pre-2022 guideline BP targets by multivariable logistic regression. RESULTS:Of 3144 randomised consenting patients, at least 1 follow-up BP reading was available for 2920. There were high rates of antiplatelet medication (97.6%) and statin (94.1%) usage. Mean SBP during follow-up was 136.6 mmHg (SD 12.8), mean diastolic BP was 79.3 mmHg (SD 7.8). A total of 36% of participants had mean SBP ≥ 140 mmHg and failed to meet pre-2022 guideline targets, while 70% had mean SBP ≥ 130 mmHg, not achieving current guideline targets. On multivariable logistic regression, increased age (OR: 1.026 per year increase; 95% CI, 1.018-1.034), history of hypertension (OR: 1.47; 95% CI, 1.24-1.74) and lacunar stroke subtype (OR: 1.26; 95% CI, 1.06-1.49) were independently associated with guideline non-achievement. DISCUSSION AND CONCLUSION:In a large contemporary secondary stroke prevention trial, over one-third of participants did not achieve less-stringent pre-2022 BP guideline targets, and 70% did not achieve current ESO guideline targets. New approaches are needed to improve guideline implementation in practice.Trial Registration: ClinicalTrials.gov (NCT02898610).

During a migraine attack, patients with migraine experience non-persistent cognitive impairment. However, some studies discuss migraine also as a risk factor for dementia in later life. The evidence, particularly with regard to mild cognitive impairment (MCI) as a precursor to dementia, is controversial. The aim of this study is to investigate the risk of incident MCI after five years in initially cognitively healthy participants with vs. without migraine. 2476 participants of the second (t1) and third (t2) examination of the prospective, population-based Heinz Nixdorf Recall Study (t1: 2005-2009, Ø62.9 years; t2: 2010-2015, Ø68.1 years) with complete data on migraine status (t1), cognitive performance (T1&T2) and age-appropriate cognition (t1) were included. MCI (at t2) was defined according to Winblad et al. (2004); migraine (at t1) was defined as self-reported diagnosis. Log-linear regression analyses with Poisson distribution were used to calculate the relative risk (RR) for incident MCI with 95% confidence interval (CI) for migraine vs. no migraine (unadjusted; adjusted for age, sex, education, alcohol consumption, smoking status, body mass index, depression according to directed acylic graph). 328 (13.2%) of the 2476 participants reported a migraine. Overall, 28 (8.5%) participants with migraine vs. 239 (11.1%) without migraine met the criteria for MCI at t2. There was no increased risk of incident MCI (unadjusted: RR 0.77, 95% CI 0.52-1.14; adjusted: RR 0.77, 95% CI 0.52-1.16) in participants with migraine. Even though migraine attacks impair cognitive performance, our data show no longitudinal association between migraine and MCI as a precursor to dementia. In further analyses, a distinction should be made between migraine with and without aura.

After successful resuscitation, cases of persisting neurological deficits or prolonged intensive care usually require inpatient neurological rehabilitation treatment. Depending on the severity this is either early neurological and neurosurgical rehabilitation in phase B as a continuation of acute hospital treatment or neurological rehabilitation in phase C or D. To relieve the burden on intensive care and monitoring wards in acute care hospitals, phase B often initially involves intensive care with weaning from ventilation and decannulation. In this phase, quantitative and qualitative disturbances of consciousness often occur, along with disorientation and behavioral disorders in the sense of organic psychosis or delirium. After reorientation and sufficient independence in activities of daily living, rehabilitation with a focus on the remaining individual neurological and neuropsychological deficits is then possible, which can individually be very different. This requires regular monitoring of progress and adjustment of therapy goals. Residual emotional, memory or cognitive problems after discharge from inpatient rehabilitation can often prevent return to work and can pose major challenges to home life.

Importance After a transient ischemic attack (TIA) or minor stroke, the long-term risk of stroke is not well-known. Objective To determine the annual incidence rates and cumulative incidences of stroke up to 10 years after TIA or minor stroke. Data Sources MEDLINE, Embase, and Web of Science were searched from inception through June 26, 2024. Study Selection Prospective or retrospective cohort studies reporting stroke risk during a minimum follow-up of 1 year in patients with TIA or minor stroke. Data Extraction and Synthesis Two reviewers independently performed data extraction and assessed study quality. Unpublished aggregate-level data on number of events and person-years during discrete follow-up intervals were obtained directly from the authors of the included studies to calculate incidence rates in individual studies. Data across studies were pooled using random-effects meta-analysis. Main Outcomes and Measures The primary outcome was any stroke. Study-level characteristics were investigated as potential sources of variability in stroke rates across studies. Results The analysis involved 171 068 patients (median age, 69 years [IQR, 65-71]; median proportion of male patients, 57% [IQR, 52%-60%]) from 38 included studies. The pooled rate of stroke per 100 person-years was 5.94 events (95% CI, 5.18-6.76; 38 studies; I-2 = 97%) in the first year, 1.80 events (95% CI, 1.58-2.04; 25 studies; I-2 = 90%) annually in the second through fifth years, and 1.72 events (95% CI, 1.31-2.18; 12 studies; I-2 = 84%) annually in the sixth through tenth years. The 5- and 10-year cumulative incidence of stroke was 12.5% (95% CI, 11.0%-14.1%) and 19.8% (95% CI, 16.7%-23.1%), respectively. Stroke rates were higher in studies conducted in North America (rate ratio [RR], 1.43 [95% CI, 1.36-1.50]) and Asia (RR, 1.62 [95% CI, 1.52-1.73]), compared with Europe, in cohorts recruited in or after 2007 (RR, 1.42 [95% CI, 1.23-1.64]), and in studies that used active vs passive outcome ascertainment methods (RR, 1.11 [95% CI, 1.07-1.17]). Studies focusing solely on patients with TIA (RR, 0.68 [95% CI, 0.65-0.71) or first-ever index events (RR, 0.45 [95% CI, 0.42-0.49]) had lower stroke rates than studies with an unselected patient population. Conclusions and Relevance Patients who have had a TIA or minor stroke are at a persistently high risk of subsequent stroke. Findings from this study underscore the need for improving long-term stroke prevention measures in this patient group.

Background Oral anticoagulation is highly effective in preventing ischemic events in patients with atrial fibrillation. Still, a considerable number of patients have an acute ischemic stroke or transient ischemic attack despite anticoagulation. In this study, we investigated the association of prior antithrombotic regimens with stroke severity, volume, and hemorrhagic transformation. Methods and Results This is a post hoc analysis of the prospective, multicenter, observational PRODAST (Prospective Record of the Use of Dabigatran in Patients With Acute Stroke or TIA) study, which was conducted in 86 stroke units in Germany between July 2015 and November 2020. In 9030 patients with atrial fibrillation who had an acute ischemic stroke or transient ischemic attack within 7 days before enrollment, we analyzed the association of anticoagulants in comparison to lack of prevalent antithrombotic treatment with clinical stroke severity, infarct size, and risk for hemorrhagic transformation. A total of 4479 patients had prior anticoagulation at the time of index event. After adjustment for confounders (arterial hypertension, diabetes, heart failure, age, and sex), patients with prior anticoagulation had less severe strokes (−2.5 National Institutes of Health Stroke Scale points [95% CI, −2.8 to −2.2]), smaller infarct sizes (−23 mL [95% CI, −44 mL to −2 mL], n=4041), and reduced odds for hemorrhagic transformation (5% versus 10%; odds ratio, 0.48 [95% CI, 0.40–0.57]) compared with patients without antithrombotic treatment. These findings were confirmed using sensitivity analyses accounting for thrombolysis and mechanical thrombectomy, as well as timing of brain imaging. Antiplatelet therapy had hardly any association with the end points compared with no antithrombotic pretreatment. Conclusions Prior anticoagulation was not only associated with less severe stroke and smaller infarct size but also with a reduced risk of hemorrhagic transformation compared with no antithrombotic pretreatment. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02507856.

Introduction:As studies on the association between type 2 diabetes mellitus (T2DM) and mild cognitive impairment (MCI), including amnestic (aMCI) and non-amnestic (naMCI) subtypes, vary by sex and age, we investigated the sex- and age-specific effects of T2DM on incident MCI after five years in a population-based sample. Methods:A total of 145 participants with T2DM and 1322 without T2DM were included. MCI was defined using established criteria excluding subjective cognitive decline. Adjusted relative risks (aRRs) were calculated considering age, education, body mass index, smoking, and alcohol intake, and stratified by sex and age (middle-aged: 50-65 years; old-aged: 66-80 years). Results:MCI occurred in 39.3% (n = 57) of participants with T2DM versus 27.5% (n = 363) without (aRR: 1.29, 95% confidence interval [CI]: 0.97-1.73). Middle-aged men showed an association with naMCI (aRR: 2.35, 95% CI: 1.26-4.39) and middle-aged women with aMCI (aRR: 2.05, 95% CI: 0.58-7.21). Discussion:T2DM increases MCI risk, particularly in middle-aged individuals with poorly controlled T2DM, emphasizing the need for prevention strategies. Highlights:Longitudinal results from the population-based Heinz Nixdorf Recall study in Germany.Incident mild cognitie impairment (MCI) was more common in type 2 diabetes mellitus (T2DM; 39% vs 28%).T2DM affects incident MCI and subtypes in middle-aged, not old-aged; stronger in men with poorly controlled T2DM.Importance of enhancing age- and sex-specific prevention at the population level.

Background: The Colchicine for prevention of vascular inflammation in Non-CardioEmbolic stroke (CONVINCE) trial evaluated long-term treatment with colchicine for the prevention of major adverse cardiovascular events (MACE) in a stroke population. Although the intention-to-treat analysis did not demonstrate a significant reduction in the primary endpoint, fewer outcome events were observed in the colchicine-treated group. It is unknown if a potential treatment effect is modified by ischemic stroke etiology. Aims: In this pre-specified secondary analysis, we aimed to evaluate the efficacy of colchicine for prevention of MACE in patients with minor stroke or high-risk transient ischemic attack (TIA) according to index event stroke etiology. Methods: A total of 3154 patients with recent non-cardioembolic stroke or TIA were randomly assigned to receive colchicine, 0.5 mg daily in addition to guideline-based usual care or usual care alone. The primary endpoint was a composite of first fatal or non-fatal recurrent ischemic stroke, myocardial infarction, cardiac arrest, or hospitalization for unstable angina. Subgroups of patients with large-artery atherosclerosis, small-vessel disease, and cryptogenic stroke were evaluated. Results: A total of 3100 patients were included in the current analysis. The treatment effect did not vary across stroke subtype subgroups (p = 0.64 for interaction). In patients allocated to colchicine versus usual care alone, the primary endpoint occurred in 32 of 260 (12.3%) versus 42 of 263 (16%) patients with large-artery atherosclerosis (hazard ratio (HR), 0.77 (95% CI, 0.48–1.22)); 39 of 419 (9.3%) versus 47 of 435 (10.8%) patients with small-vessel occlusion (HR, 0.87 (95% CI, 0.57–1.34)); and 82 of 877 (9.4%) versus 92 of 846 (10.5%) patients with cryptogenic stroke (HR, 0.89 (95% CI, 0.66–1.12)). Conclusions: The direction of effect for prevention of recurrent MACE favored colchicine, consistent with randomized trials in coronary disease, regardless of stroke subtype. Future stroke trials should consider selecting patients with evidence of atherosclerosis irrespective of stroke subtype. Trial Registration: ClinicalTrials.gov Identifier: NCT02898610

Nach erfolgreicher Reanimation erfolgt im Falle persistierender neurologischer Ausfälle oder prolongierter Intensivbehandlung in der Regel eine stationäre neurologische Rehabilitationsbehandlung. Je nach Schweregrad ist dies entweder eine neurologisch-neurochirurgische Frührehabilitation der Phase B als Fortsetzung der Akutkrankenhausbehandlung oder eine neurologische Rehabilitation der Phase C oder D. Zur Entlastung von Intensiv- und Überwachungsstationen der Akutkrankenhäuser erfolgt in Phase B initial oft eine Intensivbehandlung mit Entwöhnung von der Beatmung sowie Dekanülierung. In dieser Phase bestehen neben quantitativen häufig auch qualitative Bewusstseinsstörungen mit Desorientierung und Verhaltensstörung im Sinne einer organischen Psychose bzw. eines Delirs. Nach Reorientierung und bei ausreichender Selbstständigkeit in den Aktivitäten des täglichen Lebens ist dann eine Rehabilitation mit Schwerpunkt auf den verbleibenden neurologischen und neuropsychologischen Defiziten möglich, die individuell sehr verschieden sein können. Dementsprechend sind eine regelmäßige Verlaufskontrolle und Anpassung der Therapieziele erforderlich. Auch nach Entlassung aus der stationären Rehabilitation bestehen oft noch emotionale, mnestische oder kognitive Probleme, die einen beruflichen Wiedereinstieg verhindern und das häusliche Leben vor große Herausforderungen stellen können.

BACKGROUND:Modifiable physical and social environments are believed to influence cognitive health in older age. OBJECTIVES:To employ cutting-edge methods to analyze the impact of correlated environmental and socioeconomic neighborhood factors on cognitive function in German older participants. METHODS:In the German Heinz Nixdorf Recall cohort study, participants underwent neuropsychological testing at the first follow-up examination (2006-2008) to derive a global cognitive score (GCS). Long-term exposure to air pollution was estimated by the land-use regression and chemistry transport models. Road traffic noise was assessed as outdoor weighted 24h and nighttime means. Seven neighborhood-level socioeconomic position (nSEP) characteristics were linked from administrative data. The joint effects of exposure combinations on GCS were estimated using two dimensionality reduction techniques: principal component (PC) analysis (PCA) and self-organizing maps (SOM). RESULTS:Overall, 3748 individuals were included (median age 65 years; 50.7 % female). In single-exposure linear regression analysis, higher particle matter with aerodynamic diameter ≤2.5 μm (PM2.5) and nitrogen oxides exposure, higher proportion of welfare recipients, and lower living area per resident were negatively associated with GCS. In the PCA, the first principal component (PC), the direction of maximum variance, was positively correlated with all disadvantageous nSEP factors and higher concentrations of all environmental exposures except ozone. This PC was associated with lower GCS. SOM revealed associations with lower GCS for 3 of 6 exposure clusters. These clusters were characterized by low nSEP (Cluster 1), high environmental exposure (Cluster 4) and high concentration of accumulation mode particle number concentration (Cluster 5). DISCUSSION:We identified associations between distinct combinations of intercorrelated air pollution, road traffic noise, and nSEP disadvantages with poorer cognitive function, using two different dimensionality reduction methods. Our findings highlight the importance of considering combined environmental and social exposures to systematically assess the potential benefits of multimodal urban interventions aimed at mitigating these risk factors.