Subjective cognitive decline and self-reported sleep problems: The SCIENCe project

We aim to investigate the frequency and type of sleep problems in memory clinic patients with subjective cognitive decline (SCD) and their association with cognition, mental health, brain magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) biomarkers. Three hundred eight subjects (65 ± 8 years, 44% female) were selected from the Subjective Cognitive Impairment Cohort (SCIENCe) project. All subjects answered two sleep questionnaires, Berlin Questionnaire (sleep apnea) and Pittsburgh Sleep Quality Index (sleep quality) and underwent a standardized memory clinic work-up. One hundred ninety-eight (64%) subjects reported sleep problems, based on 107 (35%) positive screenings on sleep apnea and 162 (53%) on poor sleep quality. Subjects with sleep problems reported more severe depressive symptoms, more anxiety, and more severe SCD. Cognitive tests, MRI, and CSF biomarkers did not differ between groups. Our results suggest that improvement of sleep quality and behaviors are potential leads for treatment in many subjects with SCD to relieve the experienced cognitive complaints

Call Characteristics of Patients Suspected of Transient Ischemic Attack (TIA) or Stroke During Out-of-Hours Service: A Comparison Between Men and Women

Background: In the Netherlands, a digital decision support system for telephone triage at out-of-hours services in primary care (OHS-PC) is used. Differences in help-seeking behavior between men and women when transient ischemic attack (TIA) or stroke is suspected could potentially affect telephone triage and allocation of urgency. Aim: To assess patient and call characteristics and allocated urgencies between women and men who contacted OHS-PC with suspected TIA/stroke. Methods: A cross-sectional study of 1,266 telephone triage recordings of subjects with suspected neurological symptoms calling the OHS-PC between 2014 and 2016. The allocated urgencies were derived from the electronic medical records of the OHS-PC and the final diagnosis from the patient's own general practitioner, including diagnoses based on hospital specialist letters. Results: Five hundred forty-six men (mean age = 67.3 ± 17.1) and 720 women (mean age = 69.6 ± 19.5) were included. TIA/stroke was diagnosed in 294 men (54%) (mean age = 72.3 ± 13.6) and 366 women (51%) (mean age = 78.0 ± 13.8). In both genders, FAST (face-arm-speech test) symptoms were common in TIA/stroke (men 78%, women 82%) but also in no TIA/stroke (men 63%, women 62%). Men with TIA/stroke had shorter call durations than men without TIA/stroke (7.10 vs. 8.20 min, p = 0.001), whereas in women this difference was smaller and not significant (7.41 vs. 7.56 min, p = 0.41). Both genders were allocated high urgency in 75% of the final TIA/stroke cases. Conclusion: Overall, patient and call characteristics are mostly comparable between men and women, and these only modestly assist in identifying TIA/stroke. There were no gender differences in allocated urgencies after telephone triage in patients with TIA/stroke

Sex differences in modifiable risk factors for stroke incidence and recurrence: the UCC-SMART study

BACKGROUND AND PURPOSE: Risk factors for stroke differ between women and men in general populations. However, little is known about sex differences in secondary prevention. We investigated if sex interacted with modifiable risk factors for stroke in a large arterial disease cohort. METHODS: Within the prospective UCC-SMART study, 13,898 patients (35% women) with atherosclerotic disease or high-risk factor profile were followed up to 23 years for stroke incidence or recurrence. Hypertension, smoking, diabetes, overweight, dyslipidemia, high alcohol use, and physical inactivity were studied as risk factors. Association between these factors and ischemic and hemorrhagic stroke incidence or recurrence was studied in women and men using Cox proportional hazard models and Poisson regression models. Women-to-men relative hazard ratios (RHR) and rate differences (RD) were estimated for each risk factor. Left-truncated age was used as timescale. RESULTS: The age-adjusted stroke incidence rate was lower in women than men (3.9 vs 4.4 per 1000 person-years), as was the age-adjusted stroke recurrence rate (10.0 vs 11.7). Hypertension and smoking were associated with stroke risk in both sexes. HDL cholesterol was associated with lower stroke incidence in women but not in men (RHR 0.49; CI 0.27-0.88; and RD 1.39; CI - 1.31 to 4.10). Overweight was associated with a lower stroke recurrence in women but not in men (RHR 0.42; CI 0.23-0.80; and RD 9.05; CI 2.78-15.32). CONCLUSIONS: In high-risk population, sex modifies the association of HDL cholesterol on stroke incidence, and the association of overweight on stroke recurrence. Our findings highlight the importance of sex-specific secondary prevention

Sexual dimorphism in peripheral blood cell characteristics linked to recanalization success of endovascular thrombectomy in acute ischemic stroke

Endovascular thrombectomy (EVT) success to treat acute ischemic stroke varies with factors like stroke etiology and clot composition, which can differ between sexes. We studied if sex-specific blood cell characteristics (BCCs) are related to recanalization success. We analyzed electronic health records of 333 EVT patients from a single intervention center, and extracted 71 BCCs from the Sapphire flow cytometry analyzer. Through Sparse Partial Least Squares Discriminant Analysis, incorporating cross-validation and stability selection, we identified BCCs associated with successful recanalization (TICI 3) in both sexes. Stroke etiology was considered, while controlling for cardiovascular risk factors. Of the patients, successful recanalization was achieved in 51% of women and 49% of men. 21 of the 71 BCCs showed significant differences between sexes (pFDR-corrected < 0.05). The female-focused recanalization model had lower error rates than both combined [t(192.4) = 5.9, p < 0.001] and male-only models [t(182.6) = - 15.6, p < 0.001]. In women, successful recanalization and cardioembolism were associated with a higher number of reticulocytes, while unsuccessful recanalization and large artery atherosclerosis (LAA) as cause of stroke were associated with a higher mean corpuscular hemoglobin concentration. In men, unsuccessful recanalization and LAA as cause of stroke were associated with a higher coefficient of variance of lymphocyte complexity of the intracellular structure. Sex-specific BCCs related to recanalization success varied and were linked to stroke etiology. This enhanced understanding may facilitate personalized treatment for acute ischemic stroke

Spatial distributions of white matter hyperintensities on brain MRI: A pooled analysis of individual participant data from 11 memory clinic cohorts

Introduction: The spatial distribution of white matter hyperintensities (WMH) on MRI is often considered in the diagnostic evaluation of patients with cognitive problems. In some patients, clinicians may classify WMH patterns as unusual, but this is largely based on expert opinion, because detailed quantitative information about WMH distribution frequencies in a memory clinic setting is lacking. Here we report voxel wise 3D WMH distribution frequencies in a large multicenter dataset and also aimed to identify individuals with unusual WMH patterns. Methods: Individual participant data (N = 3525, including 777 participants with subjective cognitive decline, 1389 participants with mild cognitive impairment and 1359 patients with dementia) from eleven memory clinic cohorts, recruited through the Meta VCI Map Consortium, were used. WMH segmentations were provided by participating centers or performed in Utrecht and registered to the Montreal Neurological Institute (MNI)-152 brain template for spatial normalization. To determine WMH distribution frequencies, we calculated WMH probability maps at voxel level. To identify individuals with unusual WMH patterns, region-of-interest (ROI) based WMH probability maps, rule-based scores, and a machine learning method (Local Outlier Factor (LOF)), were implemented. Results: WMH occurred in 82% of voxels from the white matter template with large variation between subjects. Only a small proportion of the white matter (1.7%), mainly in the periventricular areas, was affected by WMH in at least 20% of participants. A large portion of the total white matter was affected infrequently. Nevertheless, 93.8% of individual participants had lesions in voxels that were affected in less than 2% of the population, mainly located in subcortical areas. Only the machine learning method effectively identified individuals with unusual patterns, in particular subjects with asymmetric WMH distribution or with WMH at relatively rarely affected locations despite common locations not being affected. Discussion: Aggregating data from several memory clinic cohorts, we provide a detailed 3D map of WMH lesion distribution frequencies, that informs on common as well as rare localizations. The use of data-driven analysis with LOF can be used to identify unusual patterns, which might serve as an alert that rare causes of WMH should be considered

Sex Differences in Poststroke Cognitive Impairment : A Multicenter Study in 2343 Patients With Acute Ischemic Stroke

Funding Information: Dr Exalto is supported by Alzheimer Nederland WE.03-2019-15 and Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation (CVON 2018-28 & 2012-06). The Meta-VCI Map consortium is supported by Vici Grant 918.16.616 from The Netherlands Organisation for Health Research and Development (ZonMw) to Dr Biessels. Harmonization analyses were supported by a Rudolf Magnus Young Talent Fellowship from the University Medical Center Utrecht Brain Center to Dr Biesbroek. The CASPER cohort was supported by Maastricht University, Health Foundation Limburg, and Stichting Adriana van Rinsum-Ponsen. The CROMIS-2 cohort was funded by the UK Stroke Association and the British Heart Foundation (grant number TSA BHF 2009/01). The CU-STRIDE cohort was supported by the Health and Health Services Research Fund of the Food and Health Bureau of the Government of Hong Kong (grant number 0708041), the Lui Che Woo Institute of Innovative Medicine, and Therese Pei Fong Chow Research Center for Prevention of Dementia. The GRECogVASC cohort was funded by Amiens University Hospital and by a grant from the French Ministry of Health (grant number DGOS R1/2013/144). The MSS-2 cohort is funded by the Wellcome Trust (grant number WT088134/Z/09/A to Dr Wardlaw) and the Row Fogo Charitable Trust. The PROCRAS cohort was funded via ZonMW as part of the TopZorg project in 2015 (grant number 842003011). The CODECS cohort (ongoing) is supported by a grant from Stichting Coolsingel (grant number 514). The Bundang VCI and Hallym VCI cohort groups do not wish to report any relevant funding sources. At the time of contribution, Dr Hamilton was funded by the College of Medicine and Veterinary Medicine at the University of Edinburgh and was supported by the Wellcome Trust through the Translational Neuroscience PhD program at the University of Edinburgh. Publisher Copyright: © 2023 Lippincott Williams and Wilkins. All rights reserved.Peer reviewedPublisher PD

Sex Differences in Poststroke Cognitive Impairment: A Multicenter Study in 2343 Patients With Acute Ischemic Stroke

BACKGROUND: Poststroke cognitive impairment (PSCI) occurs in about half of stroke survivors. Cumulative evidence indicates that functional outcomes of stroke are worse in women than men. Yet it is unknown whether the occurrence and characteristics of PSCI differ between men and women. METHODS: Individual patient data from 9 cohorts of patients with ischemic stroke were harmonized and pooled through the Meta-VCI-Map consortium (n=2343, 38% women). We included patients with visible symptomatic infarcts on computed tomography/magnetic resonance imaging and cognitive assessment within 15 months after stroke. PSCI was defined as impairment in ≥1 cognitive domains on neuropsychological assessment. Logistic regression analyses were performed to compare men to women, adjusted for study cohort, to obtain odds ratios for PSCI and individual cognitive domains. We also explored sensitivity and specificity of cognitive screening tools for detecting PSCI, according to sex (Mini-Mental State Examination, 4 cohorts, n=1814; Montreal Cognitive Assessment, 3 cohorts, n=278). RESULTS: PSCI was found in 51% of both women and men. Men had a lower risk of impairment of attention and executive functioning (men: odds ratio, 0.76 [95% CI, 0.61-0.96]), and language (men: odds ratio, 0.67 [95% CI, 0.45-0.85]), but a higher risk of verbal memory impairment (men: odds ratio, 1.43 [95% CI, 1.17-1.75]). The sensitivity of Mini-Mental State Examination (<25) for PSCI was higher for women (0.53) than for men (0.27; P=0.02), with a lower specificity for women (0.80) than men (0.96; P=0.01). Sensitivity and specificity of Montreal Cognitive Assessment (<26.) for PSCI was comparable between women and men (0.91 versus 0.86; P=0.62 and 0.29 versus 0.28; P=0.86, respectively). CONCLUSIONS: Sex was not associated with PSCI occurrence but affected domains differed between men and women. The latter may explain why sensitivity of the Mini-Mental State Examination for detecting PSCI was higher in women with a lower specificity compared with men. These sex differences need to be considered when screening for and diagnosing PSCI in clinical practice

Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities:A multicenter study in 3132 memory clinic patients

INTRODUCTION: White matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-β1-42 (Aβ42)-positive status. METHODS: Individual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume.RESULTS: VRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p &lt; 0.001), external capsule (B = 0.052, p &lt; 0.001), and middle cerebellar peduncle (B = 0.067, p &lt; 0.001), and Aß42-positive status with WMH in posterior thalamic radiation (B = 0.097, p &lt; 0.001) and splenium (B = 0.103, p &lt; 0.001). DISCUSSION: Vascular risk factors and Aß42 pathology have distinct signature WMH patterns. This regional vulnerability may incite future studies into how arteriolosclerosis and Aß42 pathology affect the brain's white matter. Highlights: Key dementia etiologies may be associated with specific patterns of white matter hyperintensities (WMH). We related WMH locations to vascular risk and cerebral Aβ42 status in 11 memory clinic cohorts. Aβ42 positive status was associated with posterior WMH in splenium and posterior thalamic radiation. Vascular risk was associated with anterior and infratentorial WMH. Amyloid pathology and vascular risk have distinct signature WMH patterns.</p

Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study

INTRODUCTION: Progress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. METHODS: We used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. RESULTS: Six survey rounds comprising 65-79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders-Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. DISCUSSION: The VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders-Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration

Alzheimer's Disease and Cognitive Decline in Patients with Cardiovascular Diseases Along the Heart-Brain Axis

Background: We hypothesize that Alzheimer's disease (AD)-related pathology may accelerate cognitive decline in patients with cardiovascular diseases. Objective: To investigate the association between blood-based biomarkers of AD, astrocyte activation, and neurodegeneration and cognitive decline. Methods: From the multi-center Heart-Brain study, we included 412 patients with heart failure, carotid occlusive disease or vascular cognitive impairment (age:68.6±9.0) and 128 reference participants (65.7±7.5). Baseline amyloid-β42/40 (Aβ42/40), phosphorylated-tau181 (pTau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) were determined using SiMoA (Quanterix). Memory, attention, language, and executive functioning were evaluated (follow-up:2.1±0.3 years). We applied linear mixed models with terms for biomarker, time and biomarker*time interactions, adjusted for age, sex, education, and site, to assess associations between biomarkers and cognitive decline. Results: Among patients, Aβ42/40 was not associated with cognitive performance at baseline. However, lower Aβ42/40 was associated with steeper decline in global cognition (β±SE:0.04±0.02). Higher pTau181 was associated with worse baseline performance on global cognition (-0.14±0.04) and memory (-0.31±0.09) and with steeper decline in global cognition (-0.07±0.02), memory (-0.09±0.04), attention (-0.05±0.02), and language (-0.10±0.03). Higher GFAP was associated with worse baseline performance on global cognition (-0.22±0.05), memory (-0.43±0.10), attention (-0.14±0.06), language (-0.15±0.05), and executive functioning (-0.15±0.05) and steeper decline in global cognition (-0.05±0.01). Higher NfL was associated with worse baseline performance on global cognition (-0.16±0.04), memory (-0.28±0.09), attention (-0.20±0.06), and executive functioning (-0.10±0.04), but was not associated with performance over time. In reference participants, no associations were found. Conclusions: Our findings suggest that blood-based biomarkers of AD-related pathology predict cognitive decline in patients with cardiovascular diseases