Cyprien A. Rivier

Yale University | YU · Department of Neurology

BACKGROUND Epilepsy is highly heritable, with numerous known genetic risk loci. However, the genetic predisposition’s role in poststroke epilepsy (PSE) remains understudied. This study assesses whether a higher genetic predisposition to epilepsy raises poststroke survivor’s risk of PSE. METHODS We conducted a case-control genetic association study...

Background and objectives: The 21-point Brain Care Score (BCS) is an index that ranks behaviors and clinical measurements with the aim of encouraging lifestyle adjustments to lower the incidence of age-related brain disease, including stroke, late-life depression (LLD), and dementia. A higher BCS at baseline is associated with a lower risk of thes...

Objective The limited existing evidence on sex differences in the clinical characteristics of patients with spontaneous, non‐traumatic intracerebral hemorrhage (ICH) comes from small, single‐center studies. Here, we performed an individual patient data meta‐analysis of 3 randomized clinical trials and 1 multi‐ethnic observational study of ICH to in...

Background and objectives: Sexual and gender minority (SGM) groups have been historically underrepresented in neurologic research, and their brain health disparities are unknown. We aim to evaluate whether SGM persons are at higher risk of adverse brain health outcomes compared with cisgender straight (non-SGM) individuals. Methods: We conducted...

Objectives: To investigate associations between health-related behaviors as measured using the Brain Care Score (BCS) and neuroimaging markers of white matter injury. Methods: This prospective cohort study in the UK Biobank assessed the BCS, a novel tool designed to empower patients to address 12 dementia and stroke risk factors. The BCS ranges...

Introduction The 21-point Brain Care Score (BCS) is a novel tool designed to motivate individuals and care providers to take action to reduce the risk of stroke and dementia by encouraging lifestyle changes. Given that late-life depression is increasingly recognized to share risk factors with stroke and dementia, and is an important clinical endpoi...

Background: At least 60% of stroke, 40% of dementia, and 35% of late-life depression (LLD) are attributable to modifiable risk factors, with great overlap due to a shared underlying pathophysiology. This study aims to systematically identify overlapping risk factors for these diseases and calculate their relative impact on a composite outcome. Meth...

Background: Clinical trials in older adults are increasingly focused on functional outcomes, and the composite outcome of dementia, disability, and death is gaining pivotal importance. Genetic variation, particularly the APOE epsilon(ε) variants, may modify responses to new treatments. Although APOE ε4 is known to influence these outcomes separate...

Background Predicting functional impairment after intracerebral hemorrhage (ICH) provides valuable information for planning of patient care and rehabilitation strategies. Current prognostic tools are limited in making long term predictions and require multiple expert-defined inputs and interpretation that make their clinical implementation challeng...

Importance: The risk of multiple sclerosis (MS) is significantly influenced by polygenic inheritance. Polygenic risk scores (PRS) for MS can help identify high-risk individuals and stratify populations for clinical trials. However, most genome-wide association studies (GWAS) have been conducted in populations of European ancestry, raising questions...

Here we present Genal, a python module for population genetic analyses. It includes functionalities for cleaning and formatting Single Nucleotide Polymorphism (SNP)-level data, clumping, lifting, SNP association testing, polygenic risk scoring, and mendelian randomization analyses, all within a single module. It was designed with user-friendliness...

Chronological age offers an imperfect estimate of the molecular changes that occur with aging. Epigenetic age, which is derived from DNA methylation data, provides a more nuanced representation of aging-related biological processes. This study examines the bidirectional relationship between epigenetic age and the occurrence of brain health events (...

Background The implementation of preventive therapies among patients with stroke remains inadequately explored, especially when compared with patients with myocardial infarction (MI), despite sharing similar vascular risk profiles. We tested the hypothesis that participants with a history of stroke have a worse cardiovascular prevention profile in...

Increased blood pressure variability (BPV) is linked to cardiovascular disease and mortality, yet few modifiable BPV risk factors are known. We aimed to assess the relationship between sleep quality and activity level on longitudinal BPV in a cohort of community-dwelling adults (age ≥18) from 17 countries. Using Withings home measurement devices, w...

Importance Intracerebral hemorrhage (ICH) is a serious complication of brain arteriovenous malformation (AVM). Apolipoprotein E ( APOE ) ε4 is a well-known genetic risk factor for ICH among persons without AVM, and cerebral amyloid angiopathy is a vasculopathy frequently observed in APOE ε4 carriers that may increase the risk of ICH. Objective To...

Introduction: It is increasingly recognized that chronological age provides an incomplete assessment of true biological age. Epigenetic clocks use DNA methylation data to estimate biological age more accurately. We hypothesize that brain health events (BHe) lead to epigenetic age acceleration and that, conversely, accelerated epigenetic age leads t...

Introduction: The association between neighborhood deprivation and risk of disease is well-documented. However, the role of neighborhood deprivation in long-term outcomes following acute brain injury remains understudied. We tested the hypothesis that neighborhood deprivation leads to unfavorable long-term functional outcomes following acute ischem...

Background: Blood pressure (BP) reduction is associated with better neuroimaging and clinical outcomes in patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH). Because this evidence comes from studies that overwhelmingly enrolled deep hemorrhages, the impact of BP reduction in patients with lobar ICH remains understudied. Methods...

Background: Poor oral health is a highly prevalent and modifiable risk factor that is associated with higher risk of cardiovascular disease, including ischemic stroke. However, the relationship between oral health and spontaneous intracerebral hemorrhage (ICH) has not been studied. We tested the hypothesis that genetically-determined poor oral heal...

Background: The Brain Care Score (BCS) was developed through a modified Delphi process with practitioners and patients for implementation into primary care to stimulate behavioral changes and lifestyle choices to sustainably reduce the incidence of dementia and stroke ( Fig 1) . Methods: To assess its validity as associated with incidence of dement...

The 21-point Brain Care Score (BCS) is a novel tool designed to motivate individuals and care providers to take action to reduce the risk of stroke and dementia by motivating lifestyle changes (Fig 1). In this study we aimed to assess if the BCS is also associated with brain changes on MRI in people who have not yet developed dementia or stroke. Me...

Background: Growing evidence shows that SDOH and care setting affect ischemic stroke recovery. Impact on non-traumatic SAH is unclear. We studied SDOH and academic hospital influence on SAH outcomes. Methods: We conducted a retrospective study using data from the GWTG Stroke. All analyses were conducted using the Precision Medicine Platform. Hospit...

Introduction: The association between neighborhood deprivation and risk of disease is well-documented. However, the role of neighborhood deprivation in long-term outcomes following acute brain injury remains understudied. We tested the hypothesis that neighborhood deprivation leads to unfavorable long-term functional outcomes following acute ischem...

Introduction: Chronic kidney disease (CKD) is a well-established risk factor for spontaneous intracerebral hemorrhage (ICH). However, the biological pathway underlying this association remains unclear. We therefore conducted a phenome-wide association study (PheWAS) to assess for mediators of the association between CKD and ICH risk. Methods: We co...

Background: Mounting evidence points to a connection between cardiovascular risk during middle age and brain health later in life. The American Heart Association’s Life’s Essential 8 (LE8) constitute a research and public health construct capturing key determinants of cardiovascular health. We tested the hypothesis that worse LE8 profiles are assoc...

Background: There is mounting evidence that sexual and gender minority (SGM) groups experience health disparities, but research on brain health status of this underrepresented group is limited. We evaluated whether SGM persons are at higher risk of adverse brain health outcomes compared to cisgender heterosexual (non-SGM) individuals. Methods: We c...

Background: There is mounting evidence that sexual and gender minority (SGM) groups experience health disparities, but research on brain health status of this underrepresented group is limited. We evaluated whether SGM persons are at higher risk of adverse brain health outcomes compared to cisgender heterosexual (non-SGM) individuals. Methods: We c...

Introduction: The 21-point Brain Care Score (BCS), developed via a modified Delphi process with practitioners and patients, is a novel instrument designed to motivate behavioral and lifestyle changes, ultimately aiming to decrease incidence of dementia and stroke (Fig 1). Whether or not BCS components are associated with longitudinal changes in moo...

Background: Adherence to the American Heart Association's Life’s Essential 8 (LE8) reduces the risk of cardiovascular disease. While the epsilon (ε) 4 variants within the APOE gene have been extensively investigated as a risk factor for dementia and stroke, APOE ε4 carriers have not been thoroughly studied as an at-risk population. We hypothesized...

Background: Common genetic variation explains up to 40% of blood pressure variation. Despite this compelling physiological impact, the role of common genetic variation in blood pressure treatment and their sequelae remains understudied. We hypothesize that a higher polygenic predisposition to hypertension leads to a poorer response to blood pressur...

Background Patients with ischemic stroke and concomitant COVID‐19 infection have worse outcomes than those without this infection, but the impact of COVID‐19 on hemorrhagic stroke remains unclear. We aimed to assess if COVID‐19 worsens outcomes in intracerebral hemorrhage (ICH). Methods and Results We conducted an observational study of ICH outcom...

Background: Hematoma expansion (HE) following an intracerebral hemorrhage (ICH) is a modifiable risk factor and a treatment target. We examined the association of HE with neurological deterioration (ND), functional outcome, and mortality based on the time gap from onset to baseline CT. Methods: We included 567 consecutive patients with supratentori...

Background Vascular brain injury (VBI) may be an under-recognised contributor to mobility impairment. We examined associations between MRI VBI biomarkers and impaired mobility. Methods We separately analysed Atherosclerosis Risk in Communities (ARIC) and UK Biobank (UKB) study cohorts. Inclusion criteria were no prevalent clinical stroke, and avai...

Background The American Heart Association's Life's Simple 7, a public health construct capturing key determinants of cardiovascular health, became the Life's Essential 8 after the addition of sleep duration. The authors tested the hypothesis that suboptimal sleep duration is associated with poorer neuroimaging brain health profiles in asymptomatic...

Importance Cerebral amyloid angiopathy (CAA) is a common cause of spontaneous intracerebral hemorrhage in older patients. Although other types of intracranial hemorrhage can occur in conjunction with CAA-related intracerebral hemorrhage, the association between CAA and other subtypes of intracranial hemorrhage, particularly in the absence of intrac...

Background and Objectives Poor oral health is a modifiable risk factor that is associated with clinically observed cardiovascular disease. However, the relationship between oral and brain health is not well understood. We tested the hypothesis that poor oral health is associated with worse neuroimaging brain health profiles in middle-aged persons w...

Introduction The 21-point Brain Care Score (BCS) was developed through a modified Delphi process in partnership with practitioners and patients to promote behavior changes and lifestyle choices in order to sustainably reduce the risk of dementia and stroke. We aimed to assess the associations of the BCS with risk of incident dementia and stroke. M...

Importance: Type 2 diabetes mellitus is a highly heritable disease with numerous identified genetic risk variants. However, the concrete role of these variants in the clinical care of stroke patients remains poorly understood. Objective: To evaluate whether higher polygenic susceptibility to type 2 diabetes mellitus (PSD) is associated with worse g...

Background and Aims: Epilepsy is highly heritable, with numerous known genetic risk loci. However, the genetic predisposition's role in post-acute brain injury epilepsy remains understudied. This study assesses whether a higher genetic predisposition to epilepsy raises post-stroke or Transient Ischemic Attack (TIA) survivor's risk of Post-Stroke Ep...

Background and Objectives Mounting evidence indicates that hypertension leads to a higher risk of dementia. Hypertension is a highly heritable trait, and a higher polygenic susceptibility to hypertension (PSH) is known to associate with higher risk of dementia. We tested the hypothesis that a higher PSH leads to worse cognitive performance in middl...

Background: Frailty is a prevalent state associated with several aging-related traits and conditions. The relationship between frailty and stroke remains understudied. Here we aim to investigate whether the hospital frailty risk score (HFRS) is associated with the risk of stroke and determine whether a significant association between genetically d...

Background Patients with ischemic stroke and concomitant coronavirus 2019 (COVID-19) infection have worse outcomes than those without this infection. However, research on the impact of COVID-19 infection on outcomes following hemorrhagic stroke remains limited. We aim to study whether concomitant COVID-19 infection leads to worse outcomes in sponta...

Background: Cardiovascular health optimization during middle age benefits brain health. The American Heart Association′s Life′s Simple 7 recently added sleep duration as a key determinant of cardiovascular health becoming the Life′s Essential 8. We tested the hypothesis that suboptimal sleep duration is associated with poorer neuroimaging brain hea...

Importance: Poor oral health is a modifiable risk factor that is associated with a variety of health outcomes. However, the relationship between oral and brain health is not well understood. Objective: To test the hypothesis that poor oral health is associated with worse neuroimaging brain health profiles in persons without stroke or dementia. Desi...

Background and objectives: We aimed to investigate the white matter (WM) microstructural/cytostructural disintegrity patterns related to higher systolic blood pressure (SBP), and whether they mediate SBP effects on cognitive performance in middle-aged adults. Methods: Using the UK Biobank study of community-dwelling volunteers aged 40-69 years,...

Following a stroke in regions of the brain responsible for motor activity, patients can lose their ability to control parts of their body. Over time, some patients recover almost completely, while others barely recover at all. It is known that lesion volume, initial motor impairment and cortico-spinal tract asymmetry significantly impact motor chan...

Background and objective: Small, single-center studies point to biological and clinical differences in women and men who sustain a spontaneous, non-traumatic intracerebral hemorrhage (ICH). Leveraging data from four landmark studies of ICH, we investigated the impact of sex on risk factors, location, severity and outcome of ICH. Design: Individual...

Background and Objectives: Vascular brain injury (VBI) may contribute to imbalance and slow walk speed, but this is uncertain. We hypothesize that MRI biomarkers of VBI associate with impaired balance and slow walk speed. Methods: We performed separate, cross-sectional analyses in the Atherosclerosis Risk in Communities (ARIC) and UK Biobank (UKB)...

Background: The interaction between social determinants of health and genetic risk factors in causing acute ischemic stroke (AIS) is poorly understood. We hypothesize that community deprivation, a geographic metric that captures several social determinants of health, modifies the effect of genetic variation on risk of AIS. Methods: We analyzed data...

Introduction: Though uncontrolled diabetes leads to recurrent cardiovascular events in stroke survivors, many don’t achieve appropriate glycemic control. We hypothesize an adverse polygenic risk profile leads to worse glycemic control and higher risk of recurrent cardiovascular events in stroke survivors. Methods: We conducted a population genetic...

Background: Oral health is a modifiable risk factor for stroke. However, the role of oral health in the brain health of clinically asymptomatic persons remains understudied. We hypothesize that genetically-determined poor oral health leads to worse neuroimaging brain health profiles in persons without stroke. Methods: We conducted a two-sample Mend...

Background: Following an acute ischemic stroke, some patients recover almost completely, while others barely recover. It is known that lesion volume, initial motor impairment, and cortico-spinal tract asymmetry (benchmark features) significantly impact motor changes over time. However, accurate prediction models of patients’ recovery are still miss...

Introduction: Neighborhood disadvantage is associated with various health factors. Given the mounting evidence linking social determinants to risk of, and outcomes after, spontaneous intracerebral hemorrhage (ICH), we tested the hypothesis that higher neighborhood disadvantage leads to poorer outcomes following ICH. Methods: We conducted a nested s...

Background: Area deprivation is one of the leading social determinants of health and is associated with lower access to clinical care. We hypothesize that undiagnosed hypertension is more prevalent in highly deprived areas as well as in people from black race and that undiagnosed hypertension is associated with a higher risk of incident stroke. Met...

Background: The interaction between social determinants of health and genetic risk factors in causing acute ischemic stroke (AIS) is poorly understood. We hypothesize that community deprivation, a geographic metric that captures several social determinants of health, modifies the effect of genetic variation on risk of AIS. Methods: We analyzed data...

Background: Social determinants of health are emerging as a key group of risk factors for cerebrovascular disease. Carotid artery stenosis (CAS) is an important risk factor for ischemic stroke. We hypothesize that community deprivation, an exposure that captures several social determinants for health, leads to significant disparities in healthcare...

Background: Evidence indicates that optimization of cardiovascular health during middle age leads to brain health benefits later in life. The AHA Life’s Simple 7, a research and public health construct capturing determinants of cardiovascular health, recently added sleep as a risk factor, becoming the Life’s Essential 8 (LE8). We hypothesize that s...

Background: Patients with brain arteriovenous malformation (AVM) are at risk of intracranial hemorrhage (ICH). The epsilon 2 and 4 alleles within the APOE gene are well-described genetic risk factors for spontaneous, non-traumatic intraparenchymal hemorrhages. We tested the hypothesis that the APOE epsilon variants lead to higher risk of ICH in pat...

Background: Cerebral amyloid angiopathy (CAA) is a condition characterized by amyloid deposition in the brain’s blood vessels. CAA is a common cause of spontaneous intracerebral hemorrhage (ICH) in older patients. Although other types of intracranial hemorrhages can occur in conjunction with CAA-related ICH, it is unknown whether CAA is a risk fact...

Introduction: Ischemic Stroke survivors are at high risk of stroke recurrence. Understanding the genetic risk factors for stroke recurrence will help guide future prevention strategies. Hypothesis: Genetically-elevated LDL-cholesterol (LDL-c) negatively impact clinical trajectories after stroke, leading to higher risk of post-stroke acute vascular...

Background: Social determinants of health are emerging as a key group of risk factors for cerebrovascular disease. Carotid artery stenosis (CAS) is an important risk factor for ischemic stroke. We hypothesize that community deprivation, an exposure that captures several social determinants for health, leads to significant disparities in healthcare...

Introduction: Existing observational evidence indicates that blood pressure (BP) differs by race/ethnicity in the first 24 hours after spontaneous intracerebral hemorrhage (ICH). However, differences in BP across race/ethnic groups beyond this acute period remain understudied. Hypothesis: Race/ethnic differences in BP levels and variability persist...