Cerebrovascular Research Articles

Baseline and Longitudinal MRI Markers Associated With 16-Year Mortality in Patients With Cerebral Small Vessel Disease.

Information on whether small vessel disease (SVD) reduces life expectancy is limited. Moreover, the excess mortality risk attributed specifically to SVD compared with controls from the general population has not been evaluated. This study aimed to investigate the baseline and progression of MRI markers of SVD associated with mortality in a 16-year follow-up cohort study and to determine the excess long-term mortality risk of patients with SVD. Participants with SVD from the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC) study (with MRI assessments in 2006, 2011, 2015, and 2020) were followed until their death or December 1, 2021. Adjusted Cox regression analyses and linear mixed-effect regression models were used to investigate the association between MRI markers of SVD and mortality. The excess mortality risk of SVD was calculated by comparing mortality data of the RUN DMC study with the general population matched by sex, age, and calendar year. 200 of 503 (39.9%) participants died during a follow-up period of 15.9 years. Cause of death was available for 182 (91%) participants. Baseline white matter hyperintensity volume (HR 1.3 per 1-SD increase [95% CI 1.1-1.5], p = 0.010), presence of lacunes (1.5 [95% CI 1.1-2.0], p = 0.008), mean diffusivity (HR 1.1 per 1-SD increase [95% CI 1.1-1.2], p = 0.001), and total brain volume (HR 1.5 per 1-SD decrease [95% CI 1.3-1.9], p < 0.001) were associated with all-cause mortality after adjusting for age, sex, and vascular risk factors. Total brain volume decrease over time was associated with all-cause mortality after adjusting for age, sex, and vascular risk factors (HR 1.3 per 1-SD decrease [95% CI 1.1-1.7], p = 0.035), and gray matter volume decrease remained significant after additionally adjusting for its baseline volume (1.3 per 1-SD decrease [1.1-1.6], p = 0.019). Participants with a Fazekas score of 3, presence of lacunes, or lower microstructural integrity had an excess long-term mortality risk (21.8, 15.7, 10.1 per 1,000 person-years, respectively) compared with the general population. Excess long-term mortality risk only exists in patients with severe SVD (Fazekas score of 3, presence of lacunes, or lower microstructural integrity). This could help in assisting clinicians to predict the clinical outcomes of patients with SVD by severity.

Evolution of antiplatelet therapy in Japan for the management of cerebrovascular and cardiovascular disease: a survey using data from an insurance claims data information service

ABSTRACT Background Non-cardioembolic ischemic stroke (NCIS) and ischemic heart disease (IHD) require secondary prevention with antiplatelet therapy (APT). We investigated APT prescription status for patients with NCIS and IHD. Research design and methods This retrospective study utilized claims data from patients with NCIS and those who underwent percutaneous coronary intervention for IHD and received antiplatelet drugs. The study included Phases A (2015–2016), B (2017–2018), and C (2019–2020). We evaluated patient characteristics, APT prescription rates (dual [DAPT] and single [SAPT]), and prescriptions by NCIS subtype. Results In the NCIS cohort, the initial DAPT prescription rate increased over time (Phase A: 14.9%, B: 19.2%, C: 28.0%), but decreased to 6% after 3 months. Subsequently, 25% of patients did not receive APT. For IHD, DAPT duration decreased over time, with 12-month prescription rates of 48.0%, 43.1%, and 32.6% for Phases A, B, and C, respectively. SAPT prescriptions, predominantly aspirin, increased, and use of P2Y12 inhibitors also rose. Few patients (10%) did not receive APT. Conclusions Shorter DAPT duration/earlier switching to SAPT for NCIS and IHD have gained acceptance in regional medical care. A higher proportion of NCIS vs IHD patients did not receive APT in the chronic phase. Trial registration UMIN000052198.

Obstructive Sleep Apnea and Cerebral Small Vessel disease in Community-based Older People: An ASPREE Imaging Substudy

Obstructive Sleep Apnea and Cerebral Small Vessel disease in Community-based Older People: An ASPREE Imaging Substudy

Additional predictors of stroke and transient ischaemic attack in BEFAST positive patients in out-of-hours emergency primary care

Introduction In patients suspected of stroke or transient ischemic attack (TIA), rapid triaging is imperative to improve clinical outcomes. For this purpose, balance-eye-face-arm-speech-time (BEFAST) items are used in out-of-hours primary care (OHS-PC). We explored the risk of stroke and TIA among BEFAST positive patients calling to the OHS-PC, and assessed whether additional predictors could improve risk stratification. Methods This is a cross-sectional study of retrospectively gathered routine care data from telephone triage tape-recordings of patients calling the OHS-PC with neurological deficit symptoms, classified as BEFAST positive. Four models–with the predictors age, sex, a history of cardiovascular or cerebrovascular disease, and cardiovascular risk factors–were fitted using logistic regression to predict the outcome stroke or TIA. Likelihood ratio testing was used to select the best model, which was subsequently internally validated. Results The risk of stroke or TIA diagnosis was 52% among 1,289 BEFAST positive patients, median age 72 years, 56% female sex. Of patients with the outcome stroke/TIA, 24% received a low urgency allocation, while 92% had signs or symptoms when calling. Only the addition of age and sex improved predicting stroke or TIA (internally validated c-statistic 0.72, 95%CI 0.69–0.75). The predicted risk of stroke or TIA remained below 20% in those aged below 40. Females aged 70 or over and males aged 55 or over, had a predicted risk above 50%. Discussion Urgency allocation appears to be suboptimal in BEFAST positive patients calling the OHS-PC. Risk stratification could be improved in this setting by adding age and sex.

Advances in retinal imaging biomarkers for the diagnosis of cerebrovascular disease

The increasing incidence and mortality rates of cerebrovascular disease impose a heavy burden on both patients and society. Retinal imaging techniques, such as fundus photography, optical coherence tomography, and optical coherence tomography angiography, can be used for rapid, non-invasive evaluation of cerebral microcirculation and brain function since the retina and the central nervous system share similar embryonic origin characteristics and physiological features. This article aimed to review retinal imaging biomarkers related to cerebrovascular diseases and their applications in cerebrovascular diseases (stroke, cerebral small vessel disease [CSVD], and vascular cognitive impairment [VCI]), thus providing reference for early diagnosis and prevention of cerebrovascular diseases.

IL-33 in Ischemic Stroke: Brainvs.Periphery.

Cerebrovascular disease is the second-leading cause of death and disability worldwide, with stroke being the most common cause. In ischemic stroke, several processes combine to produce immunosuppression, leaving the post-stroke body susceptible to infection, which in turn affects neuroinflammation. Interleukin-33 (IL-33), a member of the interleukin-1 family (IL-1), functions as a modulator of immune responses and inflammation, playing a crucial role in the establishment of immunologic responses. IL-33 has been shown to have a protective effect on brain injury and represents a potential target by modulating inflammatory cytokines and stimulating immune regulatory cells. With an emphasis on preclinical and clinical studies, this review covers the impact of IL-33 on immune system mechanisms following ischemic stroke.

Lactylation: A Novel Post-Translational Modification with Clinical Implications in CNS Diseases

Lactate, an important metabolic product, provides energy to neural cells during energy depletion or high demand and acts as a signaling molecule in the central nervous system. Recent studies revealed that lactate-mediated protein lactylation regulates gene transcription and influences cell fate, metabolic processes, inflammation, and immune responses. This review comprehensively examines the regulatory roles and mechanisms of lactylation in neurodevelopment, neuropsychiatric disorders, brain tumors, and cerebrovascular diseases. This analysis indicates that lactylation has multifaceted effects on central nervous system function and pathology, particularly in hypoxia-induced brain damage. Highlighting its potential as a novel therapeutic target, lactylation may play a significant role in treating neurological diseases. By summarizing current findings, this review aims to provide insights and guide future research and clinical strategies for central nervous system disorders.

Cerebral small vessel disease markers and long-term prognosis in spontaneous intracerebral hemorrhage: the HAGAKURE-ICH study

Cerebral small vessel disease markers and long-term prognosis in spontaneous intracerebral hemorrhage: the HAGAKURE-ICH study

Idiopathic intracranial hypertension following childbirth: a case report and management strategies

Introduction: A postpartum headache, also known as pseudotumor cerebri, is defined as a headache and shoulder or neck pain that occur in the first six weeks following childbirth. Common causes of headaches during puerperium include pre-eclampsia, subarachnoid hemorrhage, cerebral venous thrombosis, meningitis, brain tumors, cerebrovascular diseases, and posterior reversible encephalopathy syndrome. Pseudotumor cerebri is an extremely rare cause of postpartum severe headache with visual disturbance with or without papilledema. Case Presentation: Here we present a 32-year-old postpartum female patient who presented with a severe headache and visual disturbance for 10 days. Neurological examination did not show any focal or lateralizing deficit. However, a fundus examination showed severe bilateral papilledema. A contrast-enhanced brain MRI did not reveal a space-occupying mass lesion. MRV excluded venous occlusion. A lumbar puncture demonstrated high opening pressure of 75 cmH2O with a normal cell count and protein and glucose levels. The patient was diagnosed with idiopathic intracranial hypertension. After 8 weeks of treatment with diazomid and topiramate, the patient improved clinically and her papilledema regressed. Clinical Discussion: The occurrence of IIH is very rare among postpartum females. To our knowledge, very few cases of postpartum IIH have been reported in the medical literature. Although rare, patients with postpartum headache with visual disturbances should have a fundoscopic examination. The patient was diagnosed and managed in time, which led to significant clinical improvement and salvage of her vision. Conclusion: As described in this case, idiopathic intracranial hypertension can cause severe headaches with and without visual disturbance during the postpartum period (despite being rare in this period), it should be considered in the differential diagnosis.

Association of education attainment, smoking status, and alcohol use disorder with dementia risk in older adults: a longitudinal observational study

BackgroundPrevious research on the risk of dementia associated with education attainment, smoking status, and alcohol use disorder (AUD) has yielded inconsistent results, indicating potential heterogeneous treatment effects (HTEs) of these factors on dementia risk. Thus, this study aimed to identify the important variables that may contribute to HTEs of these factors in older adults.MethodsUsing 2005–2021 data from the National Alzheimer’s Coordinating Center (NACC), we included older adults (≥ 65 years) with normal cognition at the first visit. The exposure of interest included college education or above, current smoking, and AUD and the outcome was all-cause dementia. We applied doubly robust learning to estimate risk differences (RD) and 95% confidence intervals (CI) between exposed and unexposed groups in the overall cohort and subgroups identified through a decision tree model.ResultsOf 10,062 participants included, 929 developed all-cause dementia over a median 4.4-year follow-up. College education or above was associated with a lower risk of all-cause dementia in the overall population (RD, -1.5%; 95%CI, -2.8 to -0.3), especially among the subpopulations without hypertension, regardless of the APOE4 status. Current smoking was not related to increased dementia risk overall (2.8%; -1.5 to 7.2) but was significantly associated with increased dementia risk among men with (21.1%, 3.1 to 39.1) and without (8.4%, 0.9 to 15.8) cerebrovascular disease. AUD was not related to increased dementia risk overall (2.0%; -7.7 to 11.7) but was significantly associated with increased dementia risk among men with neuropsychiatric disorders (31.5%; 7.4 to 55.7).ConclusionsOur studies identified important factors contributing to HTEs of education, smoking, and AUD on risk of all-cause dementia, suggesting an individualized approach is needed to address dementia disparities.

Comorbidity and Disease Activity in Multiple Sclerosis

Multiple studies suggest that comorbidity worsens clinically relevant outcomes in multiple sclerosis (MS), including the severity of disability at diagnosis and rate of disability worsening after diagnosis. However, less is known regarding the association of comorbidity with measures of disease activity, such as relapse rate and magnetic resonance imaging lesion accrual, which are relevant to clinicians and clinical trialists. To evaluate the association of comorbidities with disease activity in clinical trials of disease-modifying therapies (DMTs) in populations with MS. A 2-stage meta-analytic approach was used in this cohort study of individual participant data from phase 3 clinical trials of MS DMTs that had 2 years of follow-up and were conducted from November 2001 to March 2018. Data were analyzed from February 2023 to June 2024. Comorbidity burden and individual comorbidities present at trial enrollment, including hypertension; hyperlipidemia; functional cardiovascular disease, ischemic heart, cerebrovascular, and peripheral vascular disease; diabetes; autoimmune thyroid and miscellaneous autoimmune conditions; migraine; lung and skin conditions; depression; anxiety; and other psychiatric disorders. The main outcome was evidence of disease activity (EDA) over 2 years of follow-up, defined as confirmed relapse activity, disability worsening, or any new lesions on magnetic resonance imaging. A total of 16 794 participants with MS were included from 17 clinical trials (67.2% female). Over the 2-year follow-up, 61.0% (95% CI, 56.2%-66.3%; I2 = 97.9%) of the pooled trials had EDA. After adjusting for multiple factors, the presence of 3 or more comorbidities was associated with an increased hazard of EDA (adjusted hazard ratio [AHR], 1.14; 95% CI, 1.02-1.28) compared with no comorbidity. Presence of 2 or more cardiometabolic conditions was also associated with an increased hazard of EDA (AHR, 1.21; 95% CI, 1.08-1.37) compared with no cardiometabolic comorbidity. Presence of 1 psychiatric disorder was associated with an increased hazard of EDA (AHR, 1.07; 95% CI, 1.02-1.14). In this study, a higher burden of comorbidity was associated with worse clinical outcomes in people with MS, although comorbidity could potentially be a partial mediator of other negative prognostic factors. Our findings suggest a substantial adverse association of the comorbidities investigated with MS disease activity and that prevention and management of comorbidities should be a pressing concern in clinical practice.

V3 segment of the right vertebral artery taking an anomalous posterosuperior course and penetrating occipital bone (wall of the jugular foramen) diagnosed by magnetic resonance angiography.

To describe a case of an anomalous posterosuperior course of the V3 segment of the right vertebral artery (VA) that penetrated the occipital bone (wall of the jugular foramen). A 33-year-old healthy woman underwent cranial magnetic resonance (MR) imaging and MR angiography from the upper cervical to the intracranial region using a 3-Tesla scanner to screen for asymptomatic brain lesions, including cerebrovascular diseases. MR angiography showed no pathological arterial lesions such as aneurysms; however, there was an anomalous posterosuperior course of the V3 segment of the right VA. On MR angiographic source images and coronal reformatted images, the right VA was observed to penetrate the occipital bone lateral to the right hypoglossal canal and is located on the inferoposteromedial wall of the right jugular foramen and enter the posterior fossa at a higher level than the foramen magnum. We present a case in which the right VA showed an anomalous posterosuperior course at the craniovertebral junction. It is extremely rare for a VA to take a higher course. To our knowledge, this is the first report of such a VA variation in the relevant English-language literature. We speculated that the right VA of our patient was formed by the persistence of one more cephalad primitive artery than the first intersegmental artery, not by the persistence of the primitive hypoglossal artery. Careful observation of MR angiographic source is useful and important for identifying the VA penetrating the occipital bone.

First manifestation of cardiovascular disease according to age and sex in a Mediterranean country

BackgroundCardiovascular (CV) diseases are the most common cause of death worldwide. This study aimed to investigate the incidence and type of first CV event in a broad cohort of Spaniards, focusing on age and sex differences.MethodsThis was a retrospective study using the SIDIAP database. Subjects aged 30–89 years in 2010 were included. Individuals with prevalent CV disease or atrial fibrillation were excluded. Subjects were followed until the occurrence of a CV event, death, or the study end (December 2016). CV outcomes (coronary heart disease [CHD], cerebrovascular or peripheral artery disease and heart failure [HF]) during follow-up were analyzed. Clinical, anthropometrical, and laboratory data were retrieved from clinical records.ResultsOverall, 3,769,563 at-risk individuals (51.2 ± 15.2 years) were followed for a median of 7 years. The cumulative incidence of a first CV event was 6.66% (men vs. women, 7.48% vs. 5.90%), with the highest incidence (25.97%) among individuals &amp;gt;75 years. HF (29%) and CHD (28.8%) were the most common first events overall; in men it was CHD (33.6%), while in women it was HF and cerebrovascular disease (37.4% and 27.4%). In younger age groups, CHD was more prevalent, with HF in older age groups. Baseline CV risks factors conferred more risk in younger ages and differed between men and women.ConclusionsThe incidence and type of the first CV event in this Mediterranean region were significantly influenced by age and sex. This information is relevant for tailoring primary prevention strategies including the treatment of risk factors.

Novel Metal-Free Nanozyme for Targeted Imaging and Inhibition of Atherosclerosis via Macrophage Autophagy Activation to Prevent Vulnerable Plaque Formation and Rupture.

Atherosclerosis is a primary cause of cardiovascular and cerebrovascular diseases, with the unpredictable rupture of vulnerable atherosclerotic plaques enriched with lipid-laden macrophages being able to lead to heart attacks and strokes. Activating macrophage autophagy presents itself as a promising strategy for preventing vulnerable plaque formation and reducing the risk of rupture. In this study, we have developed a novel metal-free nanozyme (HCN@DS) that integrates the functions of multimodal imaging-guided therapy for atherosclerosis. HCN@DS has demonstrated high macrophage-targeting abilities due to its affinity toward scavenger receptor A (SR-A), along with excellent photoacoustic and photothermal imaging capabilities for guiding the precise treatment. It combines mild photothermal effects with moderate reactive oxygen species (ROS) generation to treat atherosclerosis. This controlled approach activates autophagy in atherosclerotic macrophages, inhibiting foam cell formation by reducing the uptake of oxidized low-density lipoproteins (oxLDL) and promoting efferocytosis and cholesterol efflux in macrophages. Additionally, it prevents plaque rupture by inhibiting apoptosis and inflammation within the plaque. Therefore, this metal-free nanozyme holds great potential for reducing the risk of atherosclerosis due to its high biosafety, excellent targeting ability, dual-modality imaging capability, and appropriate modulation of autophagy.

Endolysosomal dysfunction in radial glia progenitor cells leads to defective cerebral angiogenesis and compromised blood-brain barrier integrity

The neurovascular unit (NVU) is a complex multicellular structure that helps maintain cerebral homeostasis and blood-brain barrier (BBB) integrity. While extensive evidence links NVU alterations to cerebrovascular diseases and neurodegeneration, the underlying molecular mechanisms remain unclear. Here, we use zebrafish embryos carrying a mutation in Scavenger Receptor B2, a highly conserved endolysosomal protein expressed predominantly in Radial Glia Cells (RGCs), to investigate the interplay among different NVU components. Through live imaging and genetic manipulations, we demonstrate that compromised acidification of the endolysosomal compartment in mutant RGCs leads to impaired Notch3 signaling, thereby inducing excessive neurogenesis and reduced glial differentiation. We further demonstrate that alterations to the neuron/glia balance result in impaired VEGF and Wnt signaling, leading to severe vascular defects, hemorrhages, and a leaky BBB. Altogether, our findings provide insights into NVU formation and function and offer avenues for investigating diseases involving white matter defects and vascular abnormalities.

Orthostatic hypotension and cerebral small vessel disease: A systematic review.

Orthostatic hypotension(OH) is highly prevalent in ageing populations and may contribute to cognitive decline through cerebral small vessel disease(CSVD). Research on the association between OH and CSVD is fragmented and inconsistent. We systematically reviewed the literature for studies assessing the association between OH and CSVD, published until December 1st 2023 in MEDLINE, PubMed or Web of Science. We included studies with populations aged ≥60, that assessed OH in relation to CSVD including white matter hyperintensities(WMH), lacunes and cerebral microbleeds. Modified JBI checklist was used to assess risk of bias. A narrative synthesis of the results was presented. Of 3180 identified studies, eighteen were included. Fifteen studies reported on WMH, four on lacunes, seven on microbleeds. Six of fifteen studies on WMH found that OH was related to an increased burden of WMH, neither longitudinal studies found associations with WMH progression. Findings were inconsistent across studies concerning lacunes and microbleeds. Across outcomes, adequate adjustment for systolic blood pressure tended to coincide with smaller effect estimates. Current evidence on the OH-CSVD association originates mostly from cross-sectional studies, providing inconsistent and inconclusive results. Longitudinal studies using standardized and fine-grained assessment of OH and CSVD and adequate adjustment for supine blood pressure are warranted.

Motor function is associated with cerebral small vessel disease and can predict mortality and poor functional outcome.

Primary outcome of this study is to elucidate the predictive role of subtle motor impairment evaluated using the Unified Parkinson's Disease Rating Scale (UPDRS) Part III on mortality and functional outcome. Secondary outcome is to evaluate the association of motor impairment with small vessel disease (SVD) severity. We derived data from a Japanese cohort of patients with evidence of SVD who were enrolled from 2015 to 2019, and followed until 2023. The present study included 586 participants who agreed for UPDRS Part III evaluation. The severity of white matter hyperintensities (WMH) and the presence of lacunes were evaluated. Cox proportional hazard models and multiple logistic regression analysis were used to examine the association between UPDRS Part III score, and all-cause death and functional outcome defined by the modified Rankin Scale (mRS) score at last visit, respectively. The median age was 71 years, and the median UPDRS Part III score was 2. The UPDRS Part III score was associated with the severity of WMH (r=0.225, P&lt;0.001) and the number (0, 1, &gt;2) of lacunes (P&lt;0.001). During a mean follow-up period of 4.8 years, 29 patients died. The Cox proportional hazard analysis revealed that high UPDRS Part III scores (&gt;5) were associated with higher risk of all-cause death compared to low (score 0) and middle (score 1-4) scores (adjusted hazard ratio 3.04; 95% confidence interval, 1.50-7.34, P=0.005). In multivariate logistic analysis, high UPDRS Part III scores were associated with poor functional outcome (mRS of 3 or more) compared with low and middle scores after adjusting for confounding factors (adjusted odds ratio 1.86; 95% confidence interval 1.02-3.41, P=0.043). Subtle motor impairment was associated with the severity of WMH and numbers of lacunes, and could predict mortality and poor functional outcome independently of vascular risk factors and severity of WMH and lacunes.

Vascular cognitive impairment and dementia: Mechanisms, treatment, and future directions.

Worldwide, around 50 million people live with dementia, and this number is projected to triple by 2050. It has been estimated that 20% of all dementia cases have a predominant cerebrovascular pathology, while perhaps another 20% of vascular diseases contribute to a mixed dementia picture. Therefore, the vascular contribution to dementia affects 20 million people currently and will increase markedly in the next few decades, particularly in lower- and middle-income countries.In this review, we discuss the mechanisms of vascular cognitive impairment (VCI) and review management. VCI refers to the spectrum of cerebrovascular pathologies that contribute to any degree of cognitive impairment, ranging from subjective cognitive decline, to mild cognitive impairment, to dementia. While acute cognitive decline occurring soon after a stroke is the most recognized form of VCI, chronic cerebrovascular disease, in particular cerebral small-vessel disease, can cause insidious cognitive decline in the absence of stroke. Moreover, cerebrovascular disease not only commonly co-occurs with Alzheimer's disease (AD) and increases the probability that AD pathology will result in clinical dementia, but may also contribute etiologically to the development of AD pathologies.Despite its enormous health and economic impact, VCI has been a neglected research area, with few adequately powered trials of therapies, resulting in few proven treatments. Current management of VCI emphasizes prevention and treatment of stroke and vascular risk factors, with most evidence for intensive hypertension control. Reperfusion therapies in acute stroke may attenuate the risk of VCI. Associated behavioral symptoms such as apathy and poststroke emotionalism are common. We also highlight novel treatment strategies that will hopefully lead to new disease course-modifying therapies. Finally, we highlight the importance of including cognitive endpoints in large cardiovascular prevention trials and the need for an increased research focus and funding for this important area.

Acute Vision Impairment Caused by Internal Carotid Artery Plaque Hemorrhage Combined With Thrombosis.

Atherosclerosis (As) is an important pathologic basis for ischemic cerebrovascular disease and easily causes stenosis of the origin of the internal carotid artery (ICA). As the main source of intracranial blood supply, the ICA accounts for 70% to 80% of blood flow. This stenosis can cause various ocular symptoms in patients. In the existing literature, it is rare to report cases with only acute vision loss caused by ICA plaque hemorrhage combined with thrombosis. The authors report a case of acute vision impairment caused by ICA plaque hemorrhage. The clinical manifestations, imaging characteristics, differential diagnosis, and treatment methods were discussed based on relevant literature, and the diagnosis and differentiation of the disease were considered to deepen the understanding of the disease.

The vasoprotective role of IGF-1 signaling in the cerebral microcirculation: prevention of cerebral microhemorrhages in aging.

Aging is closely associated with various cerebrovascular pathologies that significantly impact brain function, with cerebral small vessel disease (CSVD) being a major contributor to cognitive decline in the elderly. Consequences of CSVD include cerebral microhemorrhages (CMH), which are small intracerebral bleeds resulting from the rupture of microvessels. CMHs are prevalent in aging populations, affecting approximately 50% of individuals over 80, and are linked to increased risks of vascular cognitive impairment and dementia (VCID). Hypertension is a primary risk factor for CMHs. Vascular smooth muscle cells (VSMCs) adapt to hypertension by undergoing hypertrophy and producing extracellular matrix (ECM) components, which reinforce vessel walls. Myogenic autoregulation, which involves pressure-induced constriction, helps prevent excessive pressure from damaging the vulnerable microvasculature. However, aging impairs these adaptive mechanisms, weakening vessel walls and increasing susceptibility to damage. Insulin-like Growth Factor 1 (IGF-1) is crucial for vascular health, promoting VSMC hypertrophy, ECM production, and maintaining normal myogenic protection. IGF-1 also prevents microvascular senescence, reduces reactive oxygen species (ROS) production, and regulates matrix metalloproteinase (MMP) activity, which is vital for ECM remodeling and stabilization. IGF-1 deficiency, common in aging, compromises these protective mechanisms, increasing the risk of CMHs. This review explores the vasoprotective role of IGF-1 signaling in the cerebral microcirculation and its implications for preventing hypertension-induced CMHs in aging. Understanding and addressing the decline in IGF-1 signaling with age are crucial for maintaining cerebrovascular health and preventing hypertension-related vascular injuries in the aging population.