Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries.

BACKGROUND: We investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation. METHODS: This is an individual patient data study combining two prospective national stroke registries from Switzerland and Norway (2013-2019). We included all consecutive patients with ICH from both registries. The main outcomes were favourable functional outcome (modified Rankin Scale 0-2) and mortality at 3 months. RESULTS: Among 11 349 patients with ICH (mean age 73.6 years; 47.6% women), 1491 (13.1%) were taking VKAs and 1205 (10.6%) DOACs (95.2% factor Xa inhibitors). The median percentage of patients on prior anticoagulation was 23.7 (IQR 22.6-25.1) with VKAs decreasing (from 18.3% to 7.6%) and DOACs increasing (from 3.0% to 18.0%) over time. Prior VKA therapy (n=209 (22.3%); adjusted ORs (aOR), 0.64; 95% CI, 0.49 to 0.84) and prior DOAC therapy (n=184 (25.7%); aOR, 0.64; 95% CI, 0.47 to 0.87) were independently associated with lower odds of favourable outcome compared with patients without anticoagulation (n=2037 (38.8%)). Prior VKA therapy (n=720 (49.4%); aOR, 1.71; 95% CI, 1.41 to 2.08) and prior DOAC therapy (n=460 (39.7%); aOR, 1.28; 95% CI, 1.02 to 1.60) were independently associated with higher odds of mortality compared with patients without anticoagulation (n=2512 (30.2%)). CONCLUSIONS: The spectrum of anticoagulation-associated ICH changed over time. Compared with patients without prior anticoagulation, prior VKA treatment and prior DOAC treatment were independently associated with lower odds of favourable outcome and higher odds of mortality at 3 months. Specific reversal agents unavailable during the study period might improve outcomes of DOAC-associated ICH in the future.

Delirium, neurofilament light chain, and progressive cognitive impairment: analysis of a prospective Norwegian population-based cohort.

BACKGROUND: Previous population-based, longitudinal studies have shown that delirium is associated with an increased risk of dementia and cognitive decline. However, the underlying biological mechanisms are largely unknown. We aimed to assess the effects of delirium on both cognitive trajectories and any neuronal injury, measured via neurofilament light chain (NfL). METHODS: In this analysis of a prospective, 2-year follow-up, cohort study of participants aged 65 years or older living in Sandefjord municipality, Norway, we included cohort participants who were receiving domiciliary care services at least once per week between May 12, 2015, and July 8, 2016. Individuals with a life expectancy of less than 1 week, with Lewy body dementia, with psychiatric illness (except dementia), or for whom substance misuse was the principal indication for domiciliary services were excluded. Participants had a comprehensive assessment at 6-month intervals for 2 years, which included the Montreal Cognitive Assessment (MoCA) and a blood sample for NfL to measure neuronal injury. All information on clinical diagnoses and medications were cross-referenced with medical records. During any acute change in mental status or hospitalisation (ie, admission to hospital), participants were assessed once per day for delirium with Diagnostic and Statistical Manual of Mental Disorders, fifth edition criteria. We also measured NfL from blood samples taken from participants who were acutely hospitalised. FINDINGS: Between May 12, 2015, and July 8, 2016, 210 participants were eligible for inclusion and assessed at baseline (138 [66%] of whom were female and 72 [34%] of whom were male), 203 completed cognitive assessment, and 141 were followed up for 2 years. 160 (76%) of 210 had moderate or severe frailty and 112 (53%) were living with dementia. During the 2-year follow-up, 89 (42%) of 210 participants were diagnosed with one or more episodes of delirium. Incident delirium was independently associated with a decrease in MoCA score at the next 6-month follow-up, even after adjustment for age, sex, education, previous MoCA score, and frailty (adjusted mean difference -1·5, 95% CI -2·9 to -0·1). We found an interaction between previous MoCA score and delirium (ß -0·254, 95% CI -0·441 to -0·066, p=0·010), with the largest decline being observed in people with better baseline cognition. Participants with delirium and good previous cognitive function and participants with a high peak concentration of NfL during any hospitalisation had increased NfL at the next 6-month follow-up. Mediation analyses showed independent pathways from previous MoCA score to follow-up MoCA score with contributions from incident delirium (-1·7, 95% CI -2·8 to -0·6) and from previous NfL to follow-up MoCA score with contributions from acute NfL concentrations (-1·8, -2·5 to -1·1). Delirium was directly linked with a predicted value of 1·2 pg/mL (95% CI 1·02 to 1·40, p=0·029) increase in NfL. INTERPRETATION: In people aged 65 years or older, an episode of delirium was associated with a decline in MoCA score. Greater neuronal injury during acute illness and delirium, measured by NfL, was associated with greater cognitive decline. For clinicians, our finding of delirium associated with both signs of acute neuronal injury, measured via NfL, and cognitive decline is important regarding the risk of long-term cognitive deterioration and to acknowledge that delirium is harmful for the brain. FUNDING: South-Eastern Norway Health Authorities, Old Age Psychiatry Research Network, Telemark Hospital Trust, Vestfold Hospital Trust, and Norwegian National Centre for Ageing and Health. TRANSLATION: For the Norwegian translation of the abstract see Supplementary Materials section.

Factors Determining Not Returning to Full-Time Work 12 Months After Mild Ischemic Stroke.

Objective: To evaluate prevalence and factors determining not returning to full-time work 1 year after first-ever mild ischemic stroke. Design: Prospective, observational cohort study with 12-month follow-up. Setting: Stroke units and outpatient clinics at 2 Norwegian hospitals. Participants: We included 84 (N=84) full-time working, cognitively healthy patients aged 70 years or younger who suffered an acute first-ever mild ischemic stroke, defined as National Institutes of Health Stroke Scale (NIHSS) score ≤3 points. Interventions: Not applicable. Main Outcome Measures: Vascular risk factors, sociodemographic factors, stroke localization, and etiology were recorded at inclusion. Cognitive impairment, anxiety, depression, fatigue, and apathy 12 months after stroke were assessed with validated instruments. Logistic regression analyses were performed to find correlates of not returning to full-time employment. Results: Of 78 patients assessed 1 year after stroke, 63 (81%) had returned to work, 47 (60%) to full-time employment status. Modified Rankin scale score >1 (adjusted odds ratio, 12.44 [95% confidence interval, 2.37-65.43], P=.003) at follow-up was significantly associated, and diabetes (adjusted odds ratio, 10.56 [95% confidence interval, 0.98-113.47], P=.052) was borderline significantly associated with not returning to full-time work. Female sex, NIHSS at discharge, anxiety per point on the anxiety scale, depression per point on the depression scale, and fatigue per point on the fatigue scale were significantly associated with not returning to full-time work after 1 year, but these associations were only seen in the unadjusted models. Conclusions: Low functional level that persists 12 months after stroke is related to not returning to full-time work. Patients with diabetes mellitus, female patients, and patients with a higher score on fatigue, anxiety, and depression scales may also be at risk of not returning to full-time work post stroke. Working patients should be followed up with a particular focus on factors determining participation in work and social life.

Antithrombotic treatment after intracerebral hemorrhage: Surveys among stroke physicians in Scandinavia and the United Kingdom.

Background and Aims: It is unclear whether patients with previous intracerebral hemorrhage (ICH) should receive antithrombotic treatment to prevent ischemic events. We assessed stroke physicians' opinions about this, and their views on randomizing patients in trials assessing this question. Methods: We conducted three web-based surveys among stroke physicians in Scandinavia and the United Kingdom. Results: Eighty-nine of 205 stroke physicians (43%) responded to the Scandinavian survey, 161 of 180 (89%) to the UK antiplatelet survey, and 153 of 289 (53%) to the UK anticoagulant survey. In Scandinavia, 19 (21%) stroke physicians were uncertain about antiplatelet treatment after ICH for ischemic stroke or transient ischemic attack (TIA) and 21 (24%) for prior myocardial infarction. In the United Kingdom, 116 (77%) were uncertain for ischemic stroke or TIA and 115 (717%) for ischemic heart disease. In Scandinavia, 32 (36%) were uncertain about anticoagulant treatment after ICH for atrial fibrillation, and 26 (29%) for recurrent deep vein thrombosis or pulmonary embolism. In the United Kingdom, 145 (95%) were uncertain about anticoagulants after ICH in at least some cases. In both regions combined, 191 of 250 (76%) would consider randomizing ICH survivors in a trial of starting versus avoiding antiplatelets, and 176 of 242 (73%) in a trial of starting versus avoiding anticoagulants. Conclusion: Considerable proportions of stroke physicians in Scandinavia and the United Kingdom were uncertain about antithrombotic treatment after ICH. A clear majority would consider randomizing patients in trials assessing this question. These findings support the need for such trials.

Predictors of cognitive and emotional symptoms 12 months after first-ever mild stroke.

Even mild strokes may affect the patients' everyday life by impairing cognitive and emotional functions. Our aim was to study predictors of such impairments one year after first-ever mild stroke. We included cognitively healthy patients ≤ 70 years with acute mild stroke. Vascular risk factors, sociodemographic factors and stroke classifications were recorded. At one-year post-stroke, different domains related to cognitive and emotional function were assessed with validated instruments. Logistic regression analyses were performed to identify predictors of cognitive and emotional outcome. Of 117 patient assessed at follow-up, only 21 patients (18%) scored within the reference range on all cognitive and emotional assessments. Younger age, multiple infarcts, and being outside working life at stroke onset were independent predictors of cognitive impairments (psychomotor speed, attention, executive and visuospatial function, memory). Female gender and a higher National Institutes of Health Stroke Scale (NIHSS) score at discharge were significantly associated with emotional impairments (anxiety, depressive symptoms, fatigue, apathy, emotional lability) after one year, but these associations were only seen in the unadjusted models. In conclusion, patients in working age may profit from a follow-up during the post-stroke period, with extra focus on cognitive and emotional functions.

Primary progressive aphasia. / Primær progressiv afasi.

Neurodegenerative dementia may, in rare cases, initially manifest as isolated language impairments in the absence of other cognitive symptoms. These impairments are often somewhat imprecisely referred to as difficulties with 'word finding'. There are several variants of this form of dementia, each caused by different underlying neuropathologies. Occasionally problems with speech rather than language predominate. Patients may have exclusively language or speech-related symptoms for several years, but eventually all will progress to generalised dementia. This clinical review describes primary progressive aphasia: a collective term for forms of dementia that begin with language impairments.

Cognitive impairment in people with physical frailty using the phenotype model: A systematic review and meta analysis.

OBJECTIVE: We performed a systematic review and meta-analysis to study the relationship between cognitive functioning and phenotypic frailty status. METHODS: We searched Pubmed, Cochrane Library and Epistemonikos from 2000 until March 2022, and used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Samples included both sexes, age ≥55 years, assessed with standardized measures of the different cognitive domains and the frailty phenotype model and analyzing the relationship between the frailty subtypes pre-frail, frail and robust and specific cognitive function. RESULTS: Eleven studies published from 2008 until March 2022 fulfilled the inclusion criteria, and 10 were included in our meta-analyses. Sample sizes varied from 104 to 4649 individuals. Mean Mini-Mental State Examination (MMSE) scores ranged from 17.0 to 27.6, with mean difference (MD) of -2.55 (95% confidence interval [CI] -3.32, -1.78) in frail compared to robust, MD -1.64 (95% CI -2.21, -1.06) in frail compared to prefrail and MD -0.68 (95% CI -0.94, -0.43) in prefrail compared to robust. In subgroup analyses, frail persons had lower scores in the memory domain with standardized mean difference (SMD) -1.01 (95% CI -1.42, -0.59). CONCLUSION: MMSE scores were significantly lower in frail compared to robust and prefrail persons and in prefrail compared to robust persons. Subgroup analysis of memory revealed significantly poorer scores in frail compared to robust. The results indicate a strong relationship between physical frailty and cognitive impairment suggesting incorporation of cognitive function in frailty assessments.

Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial.

INTRODUCTION: Postoperative delirium is common in older cardiac surgery patients and associated with negative short-term and long-term outcomes. The alpha-2-adrenergic receptor agonist dexmedetomidine shows promise as prophylaxis and treatment for delirium in intensive care units (ICU) and postoperative settings. Clonidine has similar pharmacological properties and can be administered both parenterally and orally. We aim to study whether repurposing of clonidine can represent a novel treatment option for delirium, and the possible effects of dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns and biomarkers of neuronal injury, and whether these effects are associated with frailty status. METHODS AND ANALYSIS: This five-centre, double-blind randomised controlled trial will include 900 cardiac surgery patients aged 70+ years. Participants will be randomised 1:1:1 to dexmedetomidine or clonidine or placebo. The study drug will be given as a continuous intravenous infusion from the start of cardiopulmonary bypass, at a rate of 0.4 µg/kg/hour. The infusion rate will be decreased to 0.2 µg/kg/hour postoperatively and be continued until discharge from the ICU or 24 hours postoperatively, whichever happens first.Primary end point is the 7-day cumulative incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Secondary end points include the composite end point of coma, delirium or death, in addition to delirium severity and motor activity patterns, levels of circulating biomarkers of neuronal injury, cognitive function and frailty status 1 and 6 months after surgery. ETHICS AND DISSEMINATION: This trial is approved by the Regional Committee for Ethics in Medical Research in Norway (South-East Norway) and by the Norwegian Medicines Agency. Dissemination plans include publication in peer-reviewed medical journals and presentation at scientific meetings. TRIAL REGISTRATION NUMBER: NCT05029050.

Association between statin use and physical performance in home-dwelling older patients receiving polypharmacy: cross-sectional study.

BACKGROUND: In older patients with polypharmacy and multiple comorbidities, even low grades of statin-associated muscle symptoms may have clinical implications. The aim of this study was therefore to investigate the potential associations between statin use and measures of physical performance and muscle function. METHODS: Participants were aged 70+, treated with at least seven regular systemic medications, and not expected to die or become institutionalized within 6 months. Physical performance measured as gait speed and Short Physical Performance Battery (SPPB) score, and muscle function measured as grip strength, were compared between users and non-users of statins. In the subgroup of statin users, the dose-response relationship was assessed using harmonized simvastatin equivalents adjusted for statin potency, pharmacokinetic interactions and SLCO1B1 c.521 T > C genotype. Multiple linear regression analyses were applied to investigate potential associations between stain use and exposure as independent variables, and physical performance and muscle function as outcomes, adjusted for age, gender, body mass, comorbidity, disability and dementia. RESULTS: 174 patients (87 users and 87 non-users of statins) with a mean (SD) age of 83.3 (7.3) years were included. In analyses adjusted only for gender, grip strength was significantly higher in users than in non-users of statins [regression coefficient (B) 2.7, 95% confidence interval (CI) 1.0 to 4.4]. When adjusted for confounders, the association was no longer statistically significant (B 1.1, 95% CI - 0.5 to 2.7). SPPB and gait speed was also better in statin users than in non-users, but the differences were not statistically significant. In dose-response analyses adjusted for confounders, we found a statistically significant increase in SPPB score (B 0.01, 95% CI 0.00 to 0.02) and gait speed (B 0.001, 95% CI 0.000 to 0.002) per mg increase in simvastatin equivalents. CONCLUSIONS: In contrast to our hypothesis, statin use and exposure was associated with better measures of physical performance and muscle function in older patients with complex drug treatment. The unexpected findings of this cross-sectional, observational study should be further investigated by comparing physical performance before and after statin initiation or statin withdrawal in prospective studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02379455 , registered March 5, 2015.

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 .

The association between geriatric treatment and 30-day readmission risk among medical inpatients aged ≥75 years with multimorbidity.

BACKGROUND: Readmission to hospital is frequent among older patients and reported as a post-discharge adverse outcome. The effect of treatment in a geriatric ward for acutely admitted older patients on mortality and function is well established, but less is known about the possible influence of such treatment on the risk of readmission, particularly in the oldest and most vulnerable patients. Our aim was to assess the risk for early readmission for multimorbid patients > 75 years treated in a geriatric ward compared to medical wards and to identify risk factors for 30-day readmissions. METHODS: Prospective cohort study of patients acutely admitted to a medical department at a Norwegian regional hospital. Eligible patients were community-dwelling, multimorbid, receiving home care services, and aged 75+. Patients were consecutively included in the period from 1 April to 31 October 2012. Clinical data were retrieved from the referral letter and medical records. RESULTS: We included 227 patients with a mean (SD) age of 86.0 (5.7) years, 134 (59%) were female and 59 (26%) were readmitted within 30 days after discharge. We found no statistically significant difference in readmission rate between patients treated in a geriatric ward versus other medical wards. In adjusted Cox proportional hazards regression analyses, lower age (hazard ratio (95% confidence interval) 0.95 (0.91-0.99) per year), female gender (2.17 (1.15-4.00)) and higher MMSE score (1.03 (1.00-1.06) per point) were significant risk factors for readmission. CONCLUSIONS: Lower age, female gender and higher cognitive function were the main risk factors for 30-day readmission to hospital among old patients with multimorbidity. We found no impact of geriatric care on the readmission rate.

Association between clinical frailty, illness severity and post-discharge survival: a prospective cohort study of older medical inpatients in Norway.

PURPOSE: Study associations between frailty, illness severity and post-discharge survival in older adults admitted to medical wards with acute clinical conditions. METHODS: Prospective cohort study of 195 individuals (mean age 86; 63% females) admitted to two medical wards with acute illness, followed up for all-cause mortality for 20 months after discharge. Ward physicians screened for frailty and quantified its degree from one to eight using Clinical Frailty Scale (CFS), while clinical illness severity was estimated by New Early Warning Score 2 (NEWS2) and laboratory illness severity was calculated by a frailty index (FI-lab) using routine blood tests. RESULTS: CFS, NEWS2 and FI-lab scores were independently associated with post-discharge survival in an adjusted Cox proportional hazards model with age, ward category (acute geriatric and general medical) and comorbidity as covariates. Adjusted hazard ratios and 95% confidence intervals were 1.54 (1.24-1.91) for CFS, 1.12 (1.03-1.23) for NEWS2, and 1.02 (1.00-1.05) for FI-lab. A frailty × illness severity category interaction effect (p = 0.003), suggested that the impact of frailty on survival was greater in those experiencing higher levels of illness severity. Among patients with at least moderate frailty (CFS six to eight) and high illness severity according to both NEWS2 and FI-lab, two (13%) were alive at follow-up. CONCLUSION: Frailty screening aided prognostication of survival following discharge in older acutely ill persons admitted to medical wards. The prognostic value of frailty increased when combined with readily available illness severity markers acquired during admission.

Cerebrospinal fluid catecholamines in delirium and dementia.

Dopamine and noradrenaline are functionally connected to delirium and have been targets for pharmacological interventions but the biochemical evidence to support this notion is limited. To study the CSF levels of dopamine, noradrenaline and the third catecholamine adrenaline in delirium and dementia, these were quantified in three patient cohorts: (i) cognitively normal elderly patients (n = 122); (ii) hip fracture patients with or without delirium and dementia (n = 118); and (iii) patients with delirium precipitated by another medical condition (medical delirium, n = 26). Delirium was assessed by the Confusion Assessment Method. The hip fracture cohort had higher CSF levels of noradrenaline and adrenaline than the two other cohorts (both P < 0.001). Within the hip fracture cohort those with delirium (n = 65) had lower CSF adrenaline and dopamine levels than those without delirium (n = 52, P = 0.03, P = 0.002). Similarly, the medical delirium patients had lower CSF dopamine levels than the cognitively normal elderly (P < 0.001). Age did not correlate with the CSF catecholamine levels. These findings with lower CSF dopamine levels in hip fracture- and medical delirium patients challenge the theory of dopamine excess in delirium and question use of antipsychotics in delirium. The use of alpha-2 agonists with the potential to reduce noradrenaline release needs further examination.

Carotid Atherosclerosis and Longitudinal Changes of MRI Visual Rating Measures in Stroke Survivors: A Seven-Year Follow-Up Study.

OBJECTIVES: We aimed to assess longitudinal changes in MRI measures of brain atrophy and white matter lesions in stroke and transient ischemic attack (TIA) survivors, and explore whether carotid stenosis predicts progression of these changes, assessed by visual rating scales. MATERIALS AND METHODS: All patients with a first-ever stroke or TIA admitted to Bærum Hospital, Norway, in 2007/2008, were invited in the acute phase and followed for seven years. Carotid ultrasound was performed during the hospital stay. Carotid stenosis was defined as ≥50% narrowing of lumen. MRI was performed one and seven years after the index event and analyzed according to the visual rating scales Fazekas scale (0-3), Medial Temporal Lobe Atrophy (MTLA) (0-4) score, and Global Cortical Atrophy (GCA) scale (0-3). Patients with MRI scans at both time points were included in this sub-study. RESULTS: Of 227 patients recruited, 76 had both MRI examinations. Mean age 73.9±10.6, 41% women, and 9% had ≥50% carotid stenosis. Mean Fazekas scale was 1.7±0.9 and 1.8±1.0, mean MTLA score 1.0 ±1.0 and 1.7±1.0, and mean GCA scale score 1.4±0.7 and 1.4±0.6 after one and seven years, respectively. 71% retained the same Fazekas scale score, while 21% showed progression. Deterioration in GCA scale was seen in 20% and increasing MTLA score in 57%. Carotid stenosis was not associated with progression on Fazekas score, MTLA score or GCA scale. CONCLUSIONS: Three out of five showed progression on the MTLA score. Carotid stenosis was not associated with longitudinal change of visual rating scales.

Pre-stroke cognitive impairment is associated with vascular imaging pathology: a prospective observational study.

BACKGROUND: Chronic brain pathology and pre-stroke cognitive impairment (PCI) is predictive of post-stroke dementia. The aim of the current study was to measure pre-stroke neurodegenerative and vascular disease burden found on brain MRI and to assess the association between pre-stroke imaging pathology and PCI, whilst also looking for potential sex differences. METHODS: This prospective brain MRI cohort is part of the multicentre Norwegian cognitive impairment after stroke (Nor-COAST) study. Patients hospitalized with acute ischemic or hemorrhagic stroke were included from five participating stroke units. Visual rating scales were used to categorize baseline MRIs (N = 410) as vascular, neurodegenerative, mixed, or normal, based on the presence of pathological imaging findings. Pre-stroke cognition was assessed by interviews of patients or caregivers using the Global Deterioration Scale (GDS). Stroke severity was assessed with the National Institute of Health Stroke Scale (NIHSS). Univariate and multiple logistic regression analyses were performed to investigate the association between imaging markers, PCI, and sex. RESULTS: Patients' (N = 410) mean (SD) age was 73.6 (±11) years; 182 (44%) participants were female, the mean (SD) NIHSS at admittance was 4.1 (±5). In 68% of the participants, at least one pathological imaging marker was found. Medial temporal lobe atrophy (MTA) was present in 30% of patients, white matter hyperintensities (WMH) in 38% of patients and lacunes in 35% of patients. PCI was found in 30% of the patients. PCI was associated with cerebrovascular pathology (OR 2.5; CI = 1.4 to 4.5, p = 0.001) and mixed pathology (OR 3.4; CI = 1.9 to 6.1, p = 0.001) but was not associated with neurodegeneration (OR 1.0; CI = 0.5 to 2.2; p = 0.973). Pathological MRI markers, including MTA and lacunes, were more prevalent among men, as was a history of clinical stroke prior to the index stroke. The OR of PCI for women was not significantly increased (OR 1.2; CI = 0.8 to 1.9; p = 0.3). CONCLUSIONS: Pre-stroke chronic brain pathology is common in stroke patients, with a higher prevalence in men. Vascular pathology and mixed pathology are associated with PCI. There were no significant sex differences for the risk of PCI. TRIAL REGISTRATION: NCT02650531 , date of registration: 08.01.2016.