Associations Between Age at Menopause, Vascular Risk, and 3-Year Cognitive Change in the Canadian Longitudinal Study on Aging

Annals of Neurology

Objective This study was undertaken to determine whether assessing learning over days reveals Alzheimer disease (AD) biomarker‐related declines in memory consolidation that are otherwise undetectable with single time point assessments. Methods Thirty‐six (21.9%) cognitively unimpaired older adults (aged 60–91 years) were classified with elevated β‐amyloid (Aβ+) and 128 (78%) were Aβ− using positron emission tomography with 11CPittsburgh compound B. Participants completed the multiday Boston Remote Assessment for Neurocognitive Health (BRANCH) for 12 min/day on personal devices (ie, smartphones, laptops), which captures the trajectory of daily learning of the same content on 3 repeated tests (Digit Signs, Groceries‐Prices, Face‐Name). Learning is computed as a composite of accuracy across all 3 measures. Participants also completed standard in‐clinic cognitive tests as part of the …

Interventional Neuroradiology

ObjectiveCarotid artery webs are an underappreciated cause of recurrent ischemic stroke, and may represent a significant portion of cryptogenic stroke. Evidence-based guidelines for the management of symptomatic carotid webs do not exist. The goal of this study is to audit our local experience for patients with symptomatic carotid artery webs undergoing carotid stenting as a treatment option, along with describing the hypothesized dynamic physiology of carotid webs.MethodsAll patients undergoing stenting for symptomatic carotid artery web at two comprehensive regional stroke centers with high endovascular thrombectomy volume from January 1, 2012 to March 1, 2021 were included. The modified Rankin Scale (mRS) score was used to define functional outcome at 3 months after stenting.ResultsFourteen consecutive patients with symptomatic carotid artery webs underwent stenting. Twelve patients were …

Alzheimer's & Dementia

INTRODUCTION Hypertension and diabetes are common cardiovascular risk factors that increase Alzheimer's disease (AD) risk. However, it is unclear whether AD risk differs in hypertensive individuals with and without diabetes. METHODS Cognitively normal individuals (N = 11,074) from the National Alzheimer's Coordinating Center (NACC) were categorized as having (1) hypertension with diabetes (HTN+/DM+), (2) hypertension without diabetes (HTN+/DM‐), or (3) neither (HTN‐/DM‐). AD risk in HTN+/DM+ and HTN+/DM‐ was compared to HTN‐/DM‐. This risk was then investigated in those with AD neuropathology (ADNP), cerebral amyloid angiopathy (CAA), cerebrovascular neuropathology (CVNP), arteriolosclerosis, and atherosclerosis. Finally, AD risk in HTN‐/DM+ was compared to HTN‐/DM‐. RESULTS Seven percent (N = 830) of individuals developed AD. HTN+/DM+ (hazard ratio [HR] = 1.31 [1.19 …

Focused ultrasound (FUS) is an incisionless surgical procedure that uses nonionizing energy to precisely ablate tissue for disconnecting circuits or to perform neuromodulation in treatment-resistant psychiatric disorders. Preliminary open-label studies in obsessive-compulsive disorder (OCD) and major depressive disorder (MDD) demonstrate favorable efficacy and safety profiles. This chapter provides an overview of the FUS technique and its applications in psychiatric disorders.

Alzheimer's & Dementia

INTRODUCTION Apolipoprotein E E4 allele (APOE E4) and slow gait are independently associated with cognitive impairment and dementia. However, it is unknown whether their coexistence is associated with poorer cognitive performance and its underlying mechanism in neurodegenerative diseases. METHODS Gait speed, APOE E4, cognition, and neuroimaging were assessed in 480 older adults with neurodegeneration. Participants were grouped by APOE E4 presence and slow gait. Mediation analyses were conducted to determine if brain structures could explain the link between these factors and cognitive performance. RESULTS APOE E4 carriers with slow gait had the lowest global cognitive performance and smaller gray matter volumes compared to non‐APOE E4 carriers with normal gait. Coexistence of APOE E4 and slow gait best predicted global and domain‐specific poorer cognitive performances …

Alzheimer's & Dementia

INTRODUCTION We investigated whether novel plasma biomarkers are associated with cognition, cognitive decline, and functional independence in activities of daily living across and within neurodegenerative diseases. METHODS Glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), phosphorylated tau (p‐tau)181 and amyloid beta (Aβ)42/40 were measured using ultra‐sensitive Simoa immunoassays in 44 healthy controls and 480 participants diagnosed with Alzheimer's disease/mild cognitive impairment (AD/MCI), Parkinson's disease (PD), frontotemporal dementia (FTD) spectrum disorders, or cerebrovascular disease (CVD). RESULTS GFAP, NfL, and/or p‐tau181 were elevated among all diseases compared to controls, and were broadly associated with worse baseline cognitive performance, greater cognitive decline, and/or lower functional independence. While GFAP, NfL, and p‐tau181 …

Psychoneuroendocrinology

BackgroundThe relationship between insulin-like growth factor-1 (IGF-1) and cognition has been studied in healthy individuals, but not extensively with regards to insulin resistance and type 2 diabetes mellitus (T2DM). In this retrospective observational study, we investigated relationships of IGF-1 with memory and executive function across people with normoglycemia, prediabetes, and T2DM.MethodsData from the Midlife in the United States (MIDUS) study were used. Episodic memory and executive function were assessed using the Brief Test of Adult Cognition by Telephone approximately 21.42 ± 12.10 months prior to measuring IGF-1 levels from a fasting blood sample. Normoglycemia was identified as individuals without a physician diagnosis of diabetes and glycated hemoglobin (HbA1c) ≤5.6%. Prediabetes was identified as those without a physician diagnosis of diabetes and HbA1c between 5.7%−6.4 …

The Lancet Neurology

BackgroundPick's disease is a rare and predominantly sporadic form of frontotemporal dementia that is classified as a primary tauopathy. Pick's disease is pathologically defined by the presence in the frontal and temporal lobes of Pick bodies, composed of hyperphosphorylated, three-repeat tau protein, encoded by the MAPT gene. MAPT has two distinct haplotypes, H1 and H2; the MAPT H1 haplotype is the major genetic risk factor for four-repeat tauopathies (eg, progressive supranuclear palsy and corticobasal degeneration), and the MAPT H2 haplotype is protective for these disorders. The primary aim of this study was to evaluate the association of MAPT H2 with Pick's disease risk, age at onset, and disease duration.MethodsIn this genetic association study, we used data from the Pick's disease International Consortium, which we established to enable collection of data from individuals with pathologically …

Brain

Vascular dysfunction is increasingly recognized as an important contributor to the pathogenesis of Alzheimer’s disease. Alterations in vascular endothelial growth factor (VEGF) pathways have been implicated as potential mechanisms. However, the specific impact of VEGF proteins in preclinical Alzheimer’s disease and their relationships with other Alzheimer’s disease and vascular pathologies during this critical early period remain to be elucidated. We included 317 older adults from the Harvard Aging Brain Study, a cohort of individuals who were cognitively unimpaired at baseline and followed longitudinally for up to 12 years. Baseline VEGF family protein levels (VEGFA, VEGFC, VEGFD, PGF, and FLT1) were measured in fasting plasma using high-sensitivity immunoassays. Using linear mixed effects models, we examined the interactive effects of baseline plasma VEGF proteins and amyloid PET …

This chapter reviews several recent advances in the use of artificial intelligence and machine learning (supervised and unsupervised) in the domain of neurologic disease, with a focus on its use in dementia, Parkinson's disease, epilepsy, multiple sclerosis, and stroke. Several relevant papers in each area are described, including their impact in the area.

(AD) is the most frequent neurodegenerative disorder to cause cognitive impairment, other types of dementia exist. The high prevalence of cardiovascular risk factors in the elderly makes vascular cognitive impairment (VCI) an important entity that physicians need to be aware of, especially because its prognosis and clinical symptoms are different from other neurodegenerative causes. Given the recent advancements in the management of cardiovascular risk factors and stroke, more effort needs to be done educating health care workers and the population about this important cause of cognitive impairment.

JAMA

First, it is unclear why this study focused on women with hysterectomy without oophorectomy. Perhaps the authors excluded women with oophorectomy because this procedure immediately triggers menopause. However, hysterectomy without oophorectomy can also induce ovarian failure, 2 possibly due to interruption of ovarian blood supply. Without knowledge of hormone levels or reproductive status after hysterectomy, it remains unknown whether rates of early ovarian failure differed between estrogen-only hormone therapy users and nonusers. This is important because early loss of endogenous estradiol increases dementia risk, 3 and estrogen-only hormone therapy use may be more likely to be prescribed after early ovarian failure. Other differences that could contribute to greater dementia risk in women prescribed estrogen-only hormone therapy include vasomotor symptoms, cognitive difficulties, and sleep …

The American Journal of Geriatric Psychiatry

ObjectivesRecent evidence suggests attention-deficit/hyperactivity disorder (ADHD) is a risk factor for cognitive impairment in later life. Here, we investigated cerebrovascular burden, quantified using white matter hyperintensity (WMH) volumes, as a potential mediator of this relationship.DesignThis was a cross-sectional observational study.SettingParticipants were recruited from a cognitive neurology clinic where they had been referred for cognitive assessment, or from the community.ParticipantsThirty-nine older adults with clinical ADHD and 50 age- and gender-matched older adults without ADHD.MeasurementsA semiautomated structural MRI pipeline was used to quantify periventricular (pWMH) and deep WMH (dWMH) volumes. Cognition was measured using standardized tests of memory, processing speed, visuo-construction, language, and executive functioning. Mediation models, adjusted for sex, were …

Journal of Cognitive Neuroscience

Humans have the capacity to form new memories of events that are, at times, highly similar to events experienced in the past, as well as the capacity to integrate and associate new information within existing knowledge structures. The former process relies on mnemonic discrimination and is believed to depend on hippocampal pattern separation, whereas the latter is believed to depend on generalization signals and conceptual categorization supported by the neocortex. Here, we examine whether and how the ventromedial prefrontal cortex (vMPFC) supports discrimination and generalization on a widely used task that was primarily designed to tax hippocampal processes. Ten individuals with lesions to the vMPFC and 46 neurotypical control participants were administered an adapted version of the mnemonic similarity task [Stark, S. M., Yassa, M. A., Lacy, J. W., & Stark, C. E. L. A task to assess behavioral …

Alzheimer's & Dementia

INTRODUCTION Effective longitudinal biomarkers that track disease progression are needed to characterize the presymptomatic phase of genetic frontotemporal dementia (FTD). We investigate the utility of cerebral perfusion as one such biomarker in presymptomatic FTD mutation carriers. METHODS We investigated longitudinal profiles of cerebral perfusion using arterial spin labeling magnetic resonance imaging in 42 C9orf72, 70 GRN, and 31 MAPT presymptomatic carriers and 158 non‐carrier controls. Linear mixed effects models assessed perfusion up to 5 years after baseline assessment. RESULTS Perfusion decline was evident in all three presymptomatic groups in global gray matter. Each group also featured its own regional pattern of hypoperfusion over time, with the left thalamus common to all groups. Frontal lobe regions featured lower perfusion in those who symptomatically converted versus …

Movement disorders clinical practice

Changes in Caregiver Burden Following Unilateral Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor Changes in Caregiver Burden Following Unilateral Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Essential Tremor Mov Disord Clin Pract. 2024 Apr 4. doi: 10.1002/mdc3.14034. Online ahead of print. Authors Georgia Gopinath 1 , Nadia Scantlebury 2 , Isabella J Sewell 1 , Camryn R Rohringer 1 , Shayan Sivadas 1 , Melissa McSweeney 1 , Silina Z Boshmaf 1 , Benjamin Lam 1 3 , Clement Hamani 1 2 4 , Agessandro Abrahao 1 2 3 , Michael L Schwartz 1 4 , Nir Lipsman 1 2 4 5 , Jennifer S Rabin 1 2 3 6 Affiliations 1 Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada. 2 Harquail Centre for Neuromodulation, Sunnybrook Research Institute, Toronto, ON, Canada. 3 Division of Neurology, Department of Medicine, Sunnybrook …

Neurology

Background and ObjectivesHeterozygous variants in RAR-related orphan receptor B (RORB) have recently been associated with susceptibility to idiopathic generalized epilepsy. However, few reports have been published so far describing pathogenic variants of this gene in patients with epilepsy and intellectual disability (ID). In this study, we aimed to delineate the epilepsy phenotype associated with RORB pathogenic variants and to provide arguments in favor of the pathogenicity of variants.MethodsThrough an international collaboration, we analyzed seizure characteristics, EEG data, and genotypes of a cohort of patients with heterozygous variants in RORB. To gain insight into disease mechanisms, we performed ex vivo cortical electroporation in mouse embryos of 5 selected variants, 2 truncating and 3 missense, and evaluated on expression and quantified changes in axonal morphology.ResultsWe identified …

Neurology

Background and ObjectivesStudies suggest that clonal hematopoiesis of indeterminate potential (CHIP) may increase risk of hematologic malignancy and cardiovascular disease, including stroke. However, few studies have investigated plausible environmental risk factors for CHIP such as radon, despite the climate-related increases in and documented infrequency of testing for this common indoor air pollutant.The purpose of this study was to estimate the risk of CHIP related to radon, an established environmental mutagen.MethodsWe linked geocoded addresses of 10,799 Women's Health Initiative Trans-Omics for Precision Medicine (WHI TOPMed) participants to US Environmental Protection Agency–predicted, county-level, indoor average screening radon concentrations, categorized as follows: Zone 1 (>4 pCi/L), Zone 2 (2–4 pCi/L), and Zone 3 (<2 pCi/L). We defined CHIP as the presence of one or more …

Neurology

Background and ObjectivesRed blood cell (RBC) concentrations are known to associate with ischemic stroke. It is unclear whether RBC concentrations associate specifically with small vessel disease lacunar infarcts. We investigated the hypothesis that RBC concentrations associate with both chronic covert and acute symptomatic brain MRI lacunar infarcts.MethodsA cross-sectional observational analysis was performed across 2 cohorts with available hematocrit (as the assessment of RBC concentration exposure) and MRI outcome data. The primary setting was a population-based cohort of stroke-free, older adult (>50 years) participants from the Northern Manhattan Study (NOMAS) enrolled between 2003 and 2009. A second replication sample consisted of patients admitted with acute stroke and enrolled into the Columbia Stroke Registry (CSR) between 2005 and 2020. Associations of hematocrit with (1) chronic …

Neurology

Background and ObjectivesThe impact of immunomodulatory therapies on the risk of cervical pre-cancer and invasive cancer development is important for the health and safety of women with multiple sclerosis (wwMS). We investigate the risk of cervical abnormalities in wwMS treated with disease-modifying therapies (DMTs).MethodsThis is a multicenter cohort study with data collected from 1998 to 2019 in Victoria, Australia. Data linkage was performed using matching records from the MSBase Registry, the National Human Papillomavirus (HPV) Vaccination Program Register, and the Victorian Cervical Cytology Register. The primary outcome was the detection of any type of cervical abnormality as determined by cytology or histology. Survival methods were used to assess the time to cervical abnormality detection on cervical screening tests (CSTs). Crude and adjusted Cox proportional hazards models were used …

Neurology

Background and ObjectivesMore than 2,900 US children aged younger than 4 years die from unknown causes each year, accounting for more than 219,000 life years lost annually. They are mostly sleep-related and unwitnessed with unremarkable autopsies, limiting our understanding of death mechanisms. We sought to understand potential mechanisms of death by evaluating videos of sudden deaths in toddlers.MethodsIn our registry of 301 sudden unexplained child deaths, a series of 7 consecutively enrolled cases with home video recordings of the child's last sleep period were independently assessed by 8 physicians for video quality, movement, and sound.ResultsFour boys and 3 girls (13–27 months at death) with terminal videos shared similar demographic features to the 293 other registry cases without video recordings. Five video recordings were continuous and 2 were triggered by sound or motion. Two …

Neurology

Background and ObjectivesSleep disturbances are implicated as risk factors of both stroke and dementia. However, whether these associations are causal and whether treatment of sleep disorders could reduce stroke and dementia risk remain uncertain. We aimed to evaluate associations and ascertain causal relationships between sleep characteristics and stroke/dementia risk and MRI markers of small vessel disease (SVD).MethodsWe used data sets from a multicenter population-based study and summary statistics from genome-wide association studies (GWASs) of sleep characteristics and outcomes. We analyzed 502,383 UK Biobank participants with self-reported sleep measurements, including sleep duration, insomnia, chronotype, napping, daytime dozing, and snoring. In observational analyses, the primary outcomes were incident stroke, dementia, and their subtypes, alongside SVD markers. Hazard …

Neurology

Background and ObjectivesMounting evidence supports sex differences in Alzheimer disease (AD) risk. Vascular and hormonal factors may together contribute to AD risk in female adults. We investigated whether age at menopause, vascular risk, and history of hormone therapy (HT) containing estrogens together influence cognition over a 3-year follow-up period. We hypothesized that earlier menopause and elevated vascular risk would have a synergistic association with lower cognitive scores at follow-up and that HT containing estrogens would attenuate this synergistic association to preserve cognition.MethodsWe used data from postmenopausal female participants and age-matched male participants in the Canadian Longitudinal Study on Aging. Vascular risk was calculated using a summary score of elevated blood pressure, antihypertensive medications, elevated low-density lipoprotein cholesterol, diabetes …

Neurology

Background and ObjectivesThe objective was to characterize the acute effects of concussion (a subset of mild traumatic brain injury) on serum interleukin (IL)-6 and IL-1 receptor antagonist (RA) and 5 additional inflammatory markers in athletes and military service academy members from the Concussion Assessment, Research, and Education Consortium and to determine whether these markers aid in discrimination of concussed participants from controls.MethodsAthletes and cadets with concussion and matched controls provided blood at baseline and postinjury visits between January 2015 and March 2020. Linear models investigated changes in inflammatory markers measured using Meso Scale Discovery assays across time points (baseline and 0–12, 12–36, 36–60 hours). Subanalyses were conducted in participants split by sex and injury population. Logistic regression analyses tested whether acute levels …

Neurology

Background and ObjectivesCurrently approved therapies for spinal muscular atrophy (SMA) reverse the degenerative course, leading to better functional outcome, but they do not address the impairment arising from preexisting neurodegeneration. Apitegromab, an investigational, fully human monoclonal antibody, inhibits activation of myostatin (a negative regulator of skeletal muscle growth), thereby preserving muscle mass. The phase 2 TOPAZ trial assessed the safety and efficacy of apitegromab in individuals with later-onset type 2 and type 3 SMA.MethodsIn this study, designed to investigate potential meaningful combinations of eligibility and treatment regimen for future studies, participants aged 2–21 years received IV apitegromab infusions every 4 weeks for 12 months in 1 of 3 cohorts. Cohort 1 stratified ambulatory participants aged 5–21 years into 2 arms (apitegromab 20 mg/kg alone or in combination with …

Neurology

Background and ObjectiveFollowing the outbreak of viral infections from the severe acute respiratory syndrome coronavirus 2 virus in 2019 (coronavirus disease 2019 [COVID-19]), reports emerged of long-term neurologic sequelae in survivors. To better understand the burden of neurologic health care and incident neurologic diagnoses in the year after COVID-19 vs influenza, we performed an analysis of patient-level data from a large collection of electronic health records (EMR).MethodsWe acquired deidentified data from TriNetX, a global health research network providing access to EMR data. We included individuals aged 18 years or older during index event, defined as hospital-based care for COVID-19 (from April 1, 2020, until November 15, 2021) or influenza (from 2016 to 2019). The study outcomes were subsequent health care encounters over the following year for 6 neurologic diagnoses including …

Neurology

Background and ObjectivesFine particulate matter (PM2.5) exposure has been found to be associated with Alzheimer disease (AD) and is hypothesized to cause inflammation and oxidative stress in the brain, contributing to neuropathology. The APOE gene, a major genetic risk factor of AD, has been hypothesized to modify the association between PM2.5 and AD. However, little prior research exists to support these hypotheses. This study investigates the association between traffic-related PM2.5 and AD hallmark pathology, including effect modification by APOE genotype, in an autopsy cohort.MethodsA cross-sectional study was conducted using brain tissue donors enrolled in the Emory Goizueta AD Research Center who died before 2020 (n = 224). Donors were assessed for AD pathology including the Braak stage, Consortium to Establish a Registry for AD (CERAD) score, and combined AD neuropathologic …

Neurology

Background and ObjectivesPatients with isolated/idiopathic REM sleep behavior disorder (iRBD) are at high risk for developing mild cognitive impairment (MCI) and dementia with Lewy bodies (DLB). However, there is a lack of scientific knowledge regarding the accuracy of cognitive screening tools to identify these conditions in iRBD. This study aimed to determine in iRBD the psychometrics of 2 screening tests to discriminate patients with MCI and those at risk of DLB.MethodsWe retrospectively selected and followed 64 patients with polysomnography-confirmed iRBD seen in sleep clinic between 2006 and 2021, 32 with MCI (mean age 68.44 years, 72% men), 32 without MCI (67.78 years, 66% men), and 32 controls (69.84 years, 47% men). Participants underwent a neurologic evaluation and neuropsychological assessment for MCI diagnosis. They also completed the Montreal Cognitive Assessment (MoCA) and …

Neurology

The National Association of Epilepsy Centers first published the guidelines for epilepsy centers in 1990, which were last updated in 2010. Since that update, epilepsy care and the science of guideline development have advanced significantly, including the importance of incorporating a diversity of stakeholder perspectives such as those of patients and their caregivers. Currently, despite extensive published data examining the efficacy of treatments and diagnostic testing for epilepsy, there remain significant gaps in data identifying the essential services needed for a comprehensive epilepsy center and the optimal manner for their delivery. The trustworthy consensus-based statements (TCBS) process produces unbiased, scientifically valid guidelines through a transparent process that incorporates available evidence and expert opinion. A systematic literature search returned 5937 relevant studies from which 197 …

Neurology

Background and ObjectivesIt is unclear to what extent cognitive outcome measures are sensitive to capture decline in Alzheimer disease (AD) prevention trials. We aimed to analyze the sensitivity to changes over time of a range of neuropsychological tests in several cognitively unimpaired, biomarker-defined patient groups.MethodsCognitively unimpaired individuals from the Amsterdam Dementia Cohort and the SCIENCe project with available AD biomarkers, obtained from CSF, PET scans, and plasma at baseline, were followed over time (4.5 ± 3.1 years, range 0.6–18.9 years). Based on common inclusion criteria for clinical trials, we defined groups (amyloid, phosphorylated tau [p-tau], APOE ε4). Linear mixed models, adjusted for age, sex, and education, were used to estimate change over time in neuropsychological tests, a functional outcome, and 2 cognitive composite measures. Standardized regression …

Neurology

Background and ObjectivesNarcolepsy type 1 (NT1) is still largely underdiagnosed or diagnosed too late in children. Difficulties in obtaining rapid and reliable diagnostic evaluations of the condition in clinical practice partially explain this problem. Predictors of NT1 include cataplexy and sleep-onset REM periods (SOREMPs), documented during nocturnal polysomnography (N-PSG) or through the multiple sleep latency test (MSLT), although low CSF hypocretin-1 (CSF hcrt-1) is the definitive biological disease marker. Obtaining reliable MSLT results is not always feasible in children; therefore, this study aimed to validate daytime continuous polysomnography (D-PSG) as an alternative diagnostic tool.MethodsTwo hundred consecutive patients aged younger than 18 years (112 with NT1; 25 with other hypersomnias, including narcolepsy type 2 and idiopathic hypersomnia; and 63 with subjective excessive daytime …

Neurology

Background and ObjectivesThe optic nerve is not one of the areas of the CNS that can be used to demonstrate dissemination in space (DIS) within the 2017 McDonald criteria for the diagnosis of multiple sclerosis (MS). Objectives were (1) to assess whether optic nerve-MRI (ON-MRI), optical coherence tomography (OCT), and visual evoked potentials (VEP) detect optic nerve involvement in clinically isolated syndrome (CIS) and (2) to evaluate the contribution of the optic nerve topography to the current diagnostic criteria in a prospective, multicenter cohort.MethodsMAGNIMS centers were invited to provide prospective data on patients with CIS who underwent a visual assessment with at least 2 of 3 investigations (ON-MRI, OCT, or VEP) within 6 months of onset. Modified DIS criteria were constructed by adding the optic nerve topography, defined by each investigation separately and any combination of them, as the …

Neurology

Background and ObjectivesSleep disturbances are implicated as risk factors of both stroke and dementia. However, whether these associations are causal and whether treatment of sleep disorders could reduce stroke and dementia risk remain uncertain. We aimed to evaluate associations and ascertain causal relationships between sleep characteristics and stroke/dementia risk and MRI markers of small vessel disease (SVD).MethodsWe used data sets from a multicenter population-based study and summary statistics from genome-wide association studies (GWASs) of sleep characteristics and outcomes. We analyzed 502,383 UK Biobank participants with self-reported sleep measurements, including sleep duration, insomnia, chronotype, napping, daytime dozing, and snoring. In observational analyses, the primary outcomes were incident stroke, dementia, and their subtypes, alongside SVD markers. Hazard …

Neurology

Background and ObjectivesPrevious studies have linked the MRI measures of perivascular spaces (PVSs), diffusivity along the perivascular spaces (DTI-ALPS), and free water (FW) to cerebral small vessel disease (SVD) and SVD-related cognitive impairments. However, studies on the longitudinal associations between the three MRI measures, SVD progression, and cognitive decline are lacking. This study aimed to explore how PVS, DTI-ALPS, and FW contribute to SVD progression and cognitive decline.MethodsThis is a cohort study that included participants with SVD who underwent neuroimaging and cognitive assessment, specifically measuring Mini-Mental State Examination (MMSE), cognitive index, and processing speed, at 2 time points. Three MRI measures were quantified: PVS in basal ganglia (BG-PVS) volumes, FW fraction, and DTI-ALPS. We performed a latent change score model to test inter …

Neurology

Background and ObjectivesCorticobasal syndrome (CBS) with underlying 4-repeat tauopathy is a progressive neurodegenerative disease characterized by declining cognitive and motor functions. Biomarkers for assessing pathologic brain changes in CBS including tau-PET, 18 kDa translocator protein (TSPO)-PET, structural MRI, neurofilament light chain (NfL), or glial fibrillary acidic protein (GFAP) have recently been evaluated for differential diagnosis and disease staging, yet their association with disease trajectories remains unclear. Therefore, we performed a head-to-head comparison of neuroimaging (tau-PET, TSPO-PET, structural MRI) and plasma biomarkers (NfL, GFAP) as prognostic tools for longitudinal clinical trajectories in β-amyloid (Aβ)–negative CBS.MethodsWe included patients with clinically diagnosed Aβ-negative CBS with clinical follow-up data who underwent baseline structural MRI and …

Neurology

Background and ObjectivesPatients with isolated/idiopathic REM sleep behavior disorder (iRBD) are at high risk for developing mild cognitive impairment (MCI) and dementia with Lewy bodies (DLB). However, there is a lack of scientific knowledge regarding the accuracy of cognitive screening tools to identify these conditions in iRBD. This study aimed to determine in iRBD the psychometrics of 2 screening tests to discriminate patients with MCI and those at risk of DLB.MethodsWe retrospectively selected and followed 64 patients with polysomnography-confirmed iRBD seen in sleep clinic between 2006 and 2021, 32 with MCI (mean age 68.44 years, 72% men), 32 without MCI (67.78 years, 66% men), and 32 controls (69.84 years, 47% men). Participants underwent a neurologic evaluation and neuropsychological assessment for MCI diagnosis. They also completed the Montreal Cognitive Assessment (MoCA) and …