Cerebrovascular Changes Research Articles

ACE Inhibitor, Lisinopril, Affects Age‐Associated Changes in Cardiovascular and Cognitive Function in Female Dahl Salt‐Sensitive Rats

Background Aged Dahl Salt-Sensitive (DSS) rats develop central arterial stiffness (CAS) and hypertension on a normal salt (NS) diet. These changes have effects on cognition via brain structural changes associated with CAS. Previous results showed that ACE inhibitor lisinopril (Lis) improved cardiovascular and cognitive function in male DSS rats. Here we determined whether these effects of Lis on physiology and behavior could be achieved in age-matched female DSS rats. Methods Female DSS rats (n=23) were kept on a NS diet (0.5% NaCl) for the duration of the study. Baseline (BL) measurements were taken at 3- and 6-mo of age. After 6-mo measurements, rats were given either Lis in drinking water (15mg/kg/day, n=12) or control treatment (n=11). Final measurements were taken after 7-mo of Lis treatment, before tissues were collected for histochemistry using Verhoeff's stain for collagen and elastin. Systolic blood pressure (SBP) was measured using tail-cuff plethysmography. Pulse wave velocity (PWV), a measure of CAS, was measured by echocardiography. Open field test (OFT) was performed to assess anxiety-like behavior, and Morris water maze (MWM) was performed to assess spatial memory function. Rats were tested in an operant chambers attention challenge to assess attention and impulsivity. Statistical analyses were performed using Pearson correlation and 2-way ANOVA mixed effects model. Data are presented as mean ± SEM. Results At 3 and 6-mo of age, the treatment groups did not display differences in SBP or PWV. Following treatment, the Lis treated rats had lower SBP vs. controls (116 ± 3.7 vs. 187 ± 9.5 mmHg; p<0.01). Similarly, PWV was lower at 13-mo in treated vs. control rats (4.4 ± 0.3 vs. 5.7 ± 1.0 m/s; p<0.05) (Fig. 1A-B). Histochemical analysis revealed that the aortic media collagen abundance, a measure of fibrosis, was lower (18.5 ± 0.9% vs. 21.5 ± 0.8%, p<0.05) and the elastin/collagen ratio in the aortic media of treated rats was higher (2.5 ± 0.1 vs. 2.0 ± 0.1, p<0.05) than that of controls (Fig. 1C-D). Performance on the OFT at 13-mo compared to 6-mo BL indicated that the treated group had an increase in activity in the center of the field with age (+25% vs. BL) i.e., lower anxiety levels, while in control rats there was an opposite effect (-32% vs. BL) (Fig. 2A). PWV was negatively correlated with distance traveled in the center of the OFT at 13-mo (R=-0.672, P<0.05). MWM results showed that treated rats traveled a shorter distance to a hidden platform compared to control rats (6.5 ± 0.7 vs. 8.8 ± 0.9 m; p=0.039), indicating better spatial memory in the treated group (Fig. 2B). In the attention test at 13-mo of age, treated rats had more correct and fewer premature responses vs. control rats (Fig. 2C-D). Conclusion Female DSS rats show beneficial effects of Lis on cardiovascular and cognitive function. Lower SBP, reduced aortic fibrosis, and stabilized PWV in Lis treated female DSS rats were associated with improved behavioral test performance. The mechanistic basis of the effects of Lis on cognition via cerebrovascular and brain changes is being further investigated.

A Novel MRA-Based Framework for Segmenting the Cerebrovascular System and Correlating Cerebral Vascular Changes to Mean Arterial Pressure

Blood pressure (BP) changes with age are widespread, and systemic high blood pressure (HBP) is a serious factor in developing strokes and cognitive impairment. A non-invasive methodology to detect changes in human brain’s vasculature using Magnetic Resonance Angiography (MRA) data and correlation of cerebrovascular changes to mean arterial pressure (MAP) is presented. MRA data and systemic blood pressure measurements were gathered from patients (n = 15, M = 8, F = 7, Age = 49.2 ± 7.3 years) over 700 days (an initial visit and then a follow-up period of 2 years with a final visit.). A novel segmentation algorithm was developed to delineate brain blood vessels from surrounding tissue. Vascular probability distribution function (PDF) was calculated from segmentation data to correlate the temporal changes in cerebral vasculature to MAP calculated from systemic BP measurements. A 3D reconstruction of the cerebral vasculature was performed using a growing tree model. Segmentation results recorded 99.9% specificity and 99.7% sensitivity in identifying and delineating the brain’s vascular tree. The PDFs had a statistically significant correlation to MAP changes below the circle of Willis (p-value = 0.0007). This non-invasive methodology could be used to detect alterations in the cerebrovascular system by analyzing MRA images, which would assist clinicians in optimizing medical treatment plans of HBP.

Apolipoprotein E genotype predicts subarachnoid extension in spontaneous intracerebral haemorrhage

Spontaneous intracerebral haemorrhage (ICH) with subarachnoid extension (SAHE) predicts poor outcomes and haematoma expansion in spontaneous ICH and is also a potential predictor of the severity of vascular amyloid deposition. The biological underpinnings of SAHE remain elusive. A study was conducted to identify risk factors associated with SAHE. A retrospective analysis was performed of an ongoing prospective cohort of primary spontaneous supratentorial ICH patients admitted to Tongji Hospital. SAHE was rated on baseline noncontrast computed tomography images by investigators blinded to the clinical data. A total of 189 patients were enrolled. Apolipoprotein E (APOE) ε2 copies (p=0.020), but not APOE ε4 copies (p>0.2), were more common in patients with SAHE in univariate analysis. After controlling for confounding factors in multiple logistic regression, lobar haematoma (odds ratio [OR] 14.21, 95% confidence interval [CI] 5.89-34.33; p<0.001), large haematoma volume (OR 1.04, 95% CI 1.02-1.06; p<0.001) and APOE ε2 copies (OR 3.07, 95% CI 1.05-8.97; p=0.041) were three independent predictors of SAHE. For subgroup analysis stratified by location, APOE ε2 showed a possible association with SAHE in lobar ICH (p=0.026) but not in deep ICH (p>0.2). No significant association was found between APOE ε4 copies and either lobar (p>0.2) or deep ICH (p>0.2). The APOE ε2 allele predicts SAHE in spontaneous supratentorial ICH. The association may predominantly apply to lobar ICH. Given the established relationship between the APOE ε2 allele and pathological cerebrovascular changes, our findings suggest that SAHE involves genetically driven vessel pathology.

Hippocampal Sclerosis in Frontotemporal Dementia: When Vascular Pathology Meets Neurodegeneration.

Hippocampal sclerosis (HS) is a common neuropathological finding and has been associated with advanced age, TDP-43 proteinopathy, and cerebrovascular pathology. We analyzed neuropathological data of an autopsy cohort of early-onset frontotemporal dementia patients. The study aimed to determine whether in this cohort HS was related to TDP-43 proteinopathy and whether additional factors could be identified. We examined the relationship between HS, proteinopathies in frontotemporal cortices and hippocampus, Alzheimer disease, cerebrovascular changes, and age. We confirmed a strong association between HS and hippocampal TDP-43, whereas there was a weaker association between HS and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Nearly all of the FTLD-TDP cases had TDP-43 pathology in the hippocampus. HS was present in all FTLD-TDP type D cases, in 50% of the FTLD-TDP A cohort and in 6% of the FTLD-TDP B cohort. Our data also showed a significant association between HS and vascular changes. We reviewed the literature on HS and discuss possible pathophysiological mechanisms between TDP-43 pathology, cerebrovascular disease, and HS. Additionally, we introduced a quantitative neuronal cell count in CA1 to objectify the semiquantitative visual appreciation of HS.

Altered offspring neurodevelopment in an arginine vasopressin preeclampsia model

Preeclampsia is a severe gestational hypertensive condition linked to child neuropsychiatric disorders, although underlying mechanisms are unclear. We used a recently developed, clinically relevant animal model of preeclampsia to assess offspring. C57BL/6J mouse dams were chronically infused with arginine vasopressin (AVP) or saline (24 ng/h) throughout pregnancy. Adult offspring were behaviorally tested (Y-maze, open field, rotarod, social approach, and elevated plus maze). Offspring brain was assessed histologically and by RNA sequencing. Preeclampsia-exposed adult males exhibited increased anxiety-like behavior and social approach while adult females exhibited impaired procedural learning. Adult AVP-exposed males had reduced total neocortical volume. Adult AVP-exposed females had increased caudate–putamen volume, increased caudate–putamen cell number, and decreased excitatory synapse density in hippocampal dentate gyrus (DG), CA1, and CA3. At postnatal day 7 (P7), AVP-exposed male and female offspring both had smaller neocortex. At P7, AVP-exposed males also had smaller caudate–putamen volume, while females had increased caudate–putamen volume relative to neocortical size. Similar to P7, E18 AVP-exposed offspring had smaller dorsal forebrain, mainly in reduced intermediate, subventricular, and ventricular zone volume, particularly in males. Decreased volume was not accounted for by cell size or cerebrovascular vessel diameter changes. E18 cortical RNAseq revealed 49 differentially-expressed genes in male AVP-exposed offspring, over-representing cytoplasmic translation processes. In females, 31 genes were differentially-expressed, over-representing collagen-related and epithelial regulation pathways. Gene expression changes in E18 AVP-exposed placenta indicated potential underlying mechanisms. Deficits in behavior and forebrain development in this AVP-based preeclampsia model were distinctly different in males and females, implicating different neurobiological bases.

Association between neurofibromatosis type 1 and cerebrovascular diseases in children: A systematic review.

BackgroundNeurofibromatosis type 1 (NF-1) is an autosomal dominant disease that affects one in every 3000 individuals. This disease can present a wide range of clinical manifestations, ranging from skin abnormalities to severe vascular damage. Although not commonly recognized in the context of NF-1, cerebrovascular disease (CVD), can be often present since childhood and diagnosed just later in life. When present, NF-1-associated CVD clinical manifestations may include headache, cognitive deficits and ultimately aneurysm rupture, causing death. Thus, CVD plays an important role in the clinical manifestations, disease severity and prognosis of patients with NF-1. This systematic review aims to summarize the body of evidence linking NF-1 and CVD in children.MethodsTwo independent investigators performed a systematic review on the PubMed and EMBASE search platforms, using the following key terms: “neurofibromatosis type 1”, “Von Recklinghausen’s disease”, "children", "adolescents", "stroke", "Moyamoya disease", "vascular diseases", "cerebrovascular disorders", "aneurysm" and "congenital abnormalities". Studies focused on assessing the development of CVD in children with NF-1 were included.ResultsSeven studies met the inclusion criteria. Twelve different clinical manifestations have been associated with cerebrovascular changes in children with NF-1; 44,5% of diagnosed patients were asymptomatic.ConclusionThe available evidence suggests that CVDs are related with the progression of NF-1, even in the absence of a clear clinical manifestation. In addition, improved prognosis was observed when imaging tests were performed to screen for cerebrovascular alterations early during the clinical investigation. Early diagnosis of CVD in NF-1 patients foster implementation of timely interventions, directly impacting clinical outcomes.

Multimodal therapeutic strategies in the treatment of cerebrovascular disease

The review presents the scientific substantiation of the relationship between age-related cerebrovascular changes and dysregulation of cerebral perfusion, blood-brain barrier (BBB) function and neurovascular units. The ischemic cascade in cerebrovascular disease (CVD) is considered, the main links of which are glutamate excitoxicosis, oxidative stress and neuroinflammation. Endothelial dysfunction and increased BBB permeability play an important role in the development of neuroinflammation. The use of multifunctional drugs aimed at various pathological targets of acute and chronic cerebral ischemia for the purpose of neuroprotection has been substantiated. These drugs include the peptide Cortexin (cattle cerebral cortex polypeptides). Experimental data on the study of its molecular partners in the brain are presented. The clinical efficacy of Cortexin as a neuroprotective drug in CVD has been established in many studies.

Cerebrovascular Reservoir and Arterial Transit Time Changes Assessed by Acetazolamide-Challenged Multi-Phase Arterial Spin Labeling Perfusion MRI in Chronic Cerebrovascular Steno-Occlusive Disease.

PurposeTo explore cerebrovascular reservoir (CVR) and arterial transit time (ATT) changes using acetazolamide-challenged multi-phase arterial spin labeling (MP-ASL) perfusion-weighted MRI in chronic cerebrovascular steno-occlusive disease.Materials and MethodsThis retrospective study enrolled patients with chronic steno-occlusion who underwent acetazolamide-challenged MP-ASL between June 2019 and October 2020. Cerebral blood flow, CVR, basal ATT, and ATT changes associated with severe stenosis, total occlusion, and chronic infarction lesions were compared.ResultsThere were 32 patients (5 with bilateral steno-occlusion) in our study sample. The CVR was significantly reduced during total occlusion compared with severe stenosis (26.2% ± 28.8% vs. 41.4% ± 34.1%, respectively, p = 0.004). The ATT changes were not significantly different (p = 0.717). The CVR was marginally lower in patients with chronic infarction (29.6% ± 39.1% vs. 38.9% ± 28.7%, respectively, p = 0.076). However, the ATT was less shortened in patients with chronic infarction (−54 ± 135 vs. −117 ± 128 ms, respectively, p = 0.013).ConclusionAcetazolamide-challenged MP-ASL provides an MRI-based CVR evaluation tool for chronic steno-occlusive disease.

Hair glucocorticoids and resting-state frontal lobe oxygenation: Findings from The Irish Longitudinal Study on Ageing

Cerebral blood flow and oxygenation are crucial for maintaining healthy brain structure and function, with hypoperfusion and hypometabolism associated with neurodegenerative and neuropsychiatric conditions. Chronic stress and elevated cortisol have also been associated with cognitive decline, poor mental health and peripheral vascular and cerebrovascular changes. It is plausible that glucocorticoids could alter brain structure and function through increased vulnerability to hypoperfusion and reduced oxygenation. The aim of the current study was to investigate the association between hair glucocorticoids (GCs) and frontal lobe oxygenation using near-infra red spectroscopy (NIRS) in a population sample of 1078 older adults. Data from Wave 3 of The Irish Longitudinal Study of Ageing was analysed. Hair samples were taken for the analysis of glucocorticoids and NIRS was used to measure frontal lobe oxygenation. After both minimal and full adjustment for covariates, hair cortisol and the cortisol-to-cortisone ratio were associated with lower Tissue Saturation Index (TSI; cortisol: B = −0.37, CI −0.60 to −0.14, p = .002; ratio: B = −0.43, CI −0.70 to −0.16, p = .002). Cortisone was not significantly associated with TSI (B = −0.17, CI −0.55 to.21, p = .388). The finding of an inverse relationship between frontal lobe oxygenation and GCs as assessed over a period of months may indicate that reduced oxygenation is one pathway through which chronically elevated GCs affect brain health and function. However, no causality can be inferred from the current data and prospective studies are required to interrogate this.

STAT3-Mediated Astrocyte Reactivity Associated with Brain Metastasis Contributes to Neurovascular Dysfunction

Astrocytes are thought to play a pivotal role in coupling neural activity and cerebral blood flow. However, it has been shown that astrocytes undergo morphologic changes in response to brain metastasis, switching to a reactive phenotype, which has the potential to significantly compromise cerebrovascular function and contribute to the neurological sequelae associated with brain metastasis. Given that STAT3 is a key regulator of astrocyte reactivity, we aimed here to determine the impact of STAT3-mediated astrocyte reactivity on neurovascular function in brain metastasis. Rat models of brain metastasis and ciliary neurotrophic factor were used to induce astrocyte reactivity. Multimodal imaging, electrophysiology, and IHC were performed to determine the relationship between reactive astrocytes and changes in the cerebrovascular response to electrical and physiological stimuli. Subsequently, the STAT3 pathway in astrocytes was inhibited with WP1066 to determine the role of STAT3-mediated astrocyte reactivity, specifically, in brain metastasis. Astrocyte reactivity associated with brain metastases impaired cerebrovascular responses to stimuli at both the cellular and functional level and disrupted astrocyte-endothelial interactions in both animal models and human brain metastasis samples. Inhibition of STAT3-mediated astrocyte reactivity in rats with brain metastases restored cerebrovascular function, as shown by in vivo imaging, and limited cerebrovascular changes associated with tumor growth. Together these findings suggest that inhibiting STAT3-mediated astrocyte reactivity may confer significant improvements in neurological outcome for patients with brain metastases and could potentially be tested in other brain tumors. SIGNIFICANCE: These findings demonstrate that selectively targeting STAT3-mediated astrocyte reactivity ameliorates the cerebrovascular dysfunction associated with brain metastasis, providing a potential therapeutic avenue for improved patient outcome.

Plasma Aβ in cerebral microbleeds‐positive subjects with cognitive impairment

AbstractBackgroundCerebral amyloid angiopathy (CAA) is strongly related to Alzheimer’s disease (AD). Accumulation of amyloid affects pathophysiology of parenchyma and vessels in amyloidosis. Continuum of amyloid pathology may result in complicated clinical symptoms due to overlap of vascular and neurodegenerative factors during amyloidosis. MRI can detect hemosiderin deposits as cerebral microbleeds (CMBs) and cortical superficial siderosis. CMBs may be involved in amyloid pathology in AD and mixed dementia. Here, we analyzed relationship of these cerebrovascular changes to plasma Aβ42 and Aβ40 levels.MethodAge‐matched subjects with cognitive impairment were classified into CMBs‐positive, ‐suspective and ‐negative groups by MRI. Plasma Aβ42, Aβ40, BACE1 levels were determined by ELISA (ADx, Euroimun).ResultThere is no significant changes of MMSE score and hippocampal atrophy among the CMBs groups. CMBs‐positive subjects showed lower Aβ42 levels and higher Aβ40/42 ratio in plasma. Plasma BACE1 levels showed no significant change in CMBs‐positive subjects.ConclusionCMBs, plasma Aβ42 and Aβ40/42 ratio may be potential biomarkers for amyloid pathology in cognitive impairment.

Differential Changes in Arteriolar Cerebral Blood Volume between Parkinson's Disease Patients with Normal and Impaired Cognition and Mild Cognitive Impairment (MCI) Patients without Movement Disorder - An Exploratory Study.

Cognitive impairment amongst Parkinson’s disease (PD) patients is highly prevalent and associated with an increased risk of dementia. There is growing evidence that altered cerebrovascular functions contribute to cognitive impairment. Few studies have compared cerebrovascular changes in PD patients with normal and impaired cognition and those with mild-cognitive-impairment (MCI) without movement disorder. Here, we investigated arteriolar-cerebral-blood-volume (CBVa), an index reflecting the homeostasis of the most actively regulated segment in the microvasculature, using advanced MRI in various brain regions in PD and MCI patients and matched controls. Our goal is to find brain regions with altered CBVa that are specific to PD with normal and impaired cognition, and MCI-without-movement-disorder, respectively. In PD patients with normal cognition (n=10), CBVa was significantly decreased in the substantia nigra, caudate and putamen when compared to controls. In PD patients with impaired cognition (n=6), CBVa showed a decreasing trend in the substantia nigra, caudate and putamen, but was significantly increased in the presupplementary motor area and intracalcarine gyrus compared to controls. In MCI-patients-without-movement-disorder (n=18), CBVa was significantly increased in the caudate, putamen, hippocampus and lingual gyrus compared to controls. These findings provide important information for efforts towards developing biomarkers for the evaluation of potential risk of PD dementia (PDD) in PD patients. The current study is limited in sample size and therefore is exploratory in nature. The data from this pilot study will serve as the basis for power analysis for subsequent studies to further investigate and validate the current findings.

Evaluation of cerebrovascular hemodynamics in patients with idiopathic intracranial hypertension using transcranial Doppler

BackgroundIdiopathic intracranial hypertension (IIH) is a disorder of increased intracranial pressure without a clear cause and can have serious visual effects. Previous research work suggests that transcranial Doppler measurements of pulsatility index correlate accurately with elevated intracranial pressure.ObjectiveTo assess the cerebrovascular hemodynamic changes in patients with IIH using transcranial Doppler before and after lumbar puncture and CSF withdrawal.MethodsAn interventional study conducted on 40 patients (31 females and 9 males) fulfilling the modified Dandy criteria for diagnosis of idiopathic intracranial hypertension, MRI brain, and MRV was done to the patients. Lumbar puncture was done for all included patients to measure intracranial pressure and CSF withdrawal. Transcranial Doppler was performed for all included before and after lumbar puncture and CSF withdrawal and the following parameters were measured: peak systolic velocity (PSV), end diastolic velocity (EDV), resistivity index (RI), and pulsatility index (PI).ResultsSignificant relation was found between grades of papilledema and PSV, RI, and PI (p value 0.012, 0.025, 0.016) but no significant relation was found between grades of papilledema and EDV (0.102). Significant changes occurred in parameters of TCD pre- and post-CSF withdrawal including PSV, EDV, and PI (p value 0.001, 0.015, 0.019) denoting a significant change in cerebral hemodynamics after CSF withdrawal which denotes a decrease in intracranial pressure.ConclusionIncreased intracranial pressure significantly affects cerebral blood flow. A normalization of transcranial Doppler parameters occurs following lowering of intracranial pressure through lumbar puncture and CSF withdrawal.

Repetitive Head Impact Exposure and Cerebrovascular Function in Adolescent Athletes.

The purpose of this study was to determine how subconcussive head impact exposure in high school collision sport student-athletes influenced cerebrovascular function. Transcranial Doppler was used to assess pre- to post-season changes in: (1) resting middle (MCA) and posterior cerebral arteries (PCA), (2) cerebrovascular reactivity (CVR) via breath-holding index (BHI), vasomotor reactivity response (VMRr) and overall MCA response curve, and (3) neurovascular coupling (NVC) via NVC response magnitude and overall PCA response curve. Fifty-three high school-aged athletes (age = 15.8 ± 1.2years, height = 175.8 ± 8.1cm, mass = 69.4 ± 13.5kg) were recruited into two groups (collision vs. non-collision sport). All participants completed a pre-season cerebrovascular function assessment. Following a 4- to 5-month window (118.6 ± 12.2 days), 48 athletes from the original sample (age = 16.0 ± 1.2 years, height = 175.5 ± 8.1 cm, mass = 68.6 ± 4.0 kg) repeated the cerebrovascular assessment. There were no group differences in any cerebrovascular measures at pre-season testing (p > 0.05). At post-season testing, collision sport athletes demonstrated greater positive change in BHI (t44 = -2.21, p = 0.03) while non-collision sport athletes demonstrated greater negative change in the NVC response magnitude to the reading task (t44 = 1.98, p = 0.048), and lower overall PCA response curve to the reading task (F1,2710 = 101.54, p < 0.001). All other pre- to post-season change values were non-significant (p > 0.05). Our data indicate that single-season changes in cerebrovascular outcomes may differ between collision and non-collision sport athletes. Although the clinical interpretation is still unclear, our study demonstrates that CVR and NVC assessments may be sensitive to the dynamic cerebrovascular changes occurring in adolescent athletes. Future research should continue to assess these outcomes following both subconcussive head impact exposure and throughout the recovery trajectory following concussion.

Lipodystrophies-Disorders of the Fatty Tissue.

Lipodystrophies are a heterogeneous group of physiological changes characterized by a selective loss of fatty tissue. Here, no fat cells are present, either through lack of differentiation, loss of function or premature apoptosis. As a consequence, lipids can only be stored ectopically in non-adipocytes with the major health consequences as fatty liver and insulin resistance. This is a crucial difference to being slim where the fat cells are present and store lipids if needed. A simple clinical classification of lipodystrophies is based on congenital vs. acquired and generalized vs. partial disturbance of fat distribution. Complications in patients with lipodystrophy depend on the clinical manifestations. For example, in diabetes mellitus microangiopathic complications such as nephropathy, retinopathy and neuropathy may develop. In addition, due to ectopic lipid accumulation in the liver, fatty liver hepatitis may also develop, possibly with cirrhosis. The consequences of extreme hypertriglyceridemia are typically acute pancreatitis or eruptive xanthomas. The combination of severe hyperglycemia with dyslipidemia and signs of insulin resistance can lead to premature atherosclerosis with its associated complications of coronary heart disease, peripheral vascular disease and cerebrovascular changes. Overall, lipodystrophy is rare with an estimated incidence for congenital (<1/1.000.000) and acquired (1–9/100.000) forms. Due to the rarity of the syndrome and the phenotypic range of metabolic complications, only studies with limited patient numbers can be considered. Experimental animal models are therefore useful to understand the molecular mechanisms in lipodystrophy and to identify possible therapeutic approaches.

Long-term effects of adjuvant treatment for breast cancer on carotid plaques and brain perfusion

PurposeBreast cancer treatment has been associated with vascular pathology. It is unclear if such treatment is also associated with long-term cerebrovascular changes. We studied the association between radiotherapy and chemotherapy with carotid pathology and brain perfusion in breast cancer survivors.MethodsWe included 173 breast cancer survivors exposed to radiotherapy and chemotherapy, assessed ± 21.2 years after cancer diagnosis, and 346 age-matched cancer-free women (1:2) selected from the population-based Rotterdam Study. Outcome measures were carotid plaque score, intima-media thickness (IMT), total cerebral blood flow (tCBF), and brain perfusion. Additionally, we investigated the association between inclusion of the carotid artery in the radiation field (no/small/large part), tumor location, and these outcome measures within cancer survivors.ResultsCancer survivors had lower tCBF (− 19.6 ml/min, 95%CI − 37.3;− 1.9) and brain perfusion (− 2.5 ml/min per 100 ml, 95%CI − 4.3;− 0.7) than cancer-free women. No statistically significant group differences were observed regarding plaque score or IMT. Among cancer survivors, a large versus a small part of the carotid artery in the radiation field was associated with a higher IMT (0.05, 95%CI0.01;0.09). Also, survivors with a right-sided tumor had lower left carotid plaque score (− 0.31, 95%CI − 0.60;− 0.02) and higher brain perfusion (3.5 ml/min per 100 ml, 95%CI 0.7;6.2) than those with a left-sided tumor.ConclusionsOn average two decades post-diagnosis, breast cancer survivors had lower tCBF and brain perfusion than cancer-free women. Also, survivors with a larger area of the carotid artery within the radiation field had a larger IMT. Future studies should confirm if these cerebrovascular changes underlie the frequently observed cognitive problems in cancer survivors.

Comorbidity of Cerebrovascular andAlzheimer's Disease in Aging.

Cerebrovascular disease often coexists with Alzheimer's disease (AD). While both diseases share common risk factors, their interrelationship remains unclear. Increasing the understanding of how cerebrovascular changes interact with AD is essential to develop therapeutic strategies and refine biomarkers for early diagnosis. We investigate the prevalence and risk factors for the comorbidity of amyloid-β (Aβ) and cerebrovascular disease in the Australian Imaging, Biomarkers and Lifestyle Study of Ageing, and further examine their cross-sectional association. A total of 598 participants (422 cognitively normal, 89 with mild cognitive impairment, 87 with AD) underwent positron emission tomography and structural magnetic resonance imaging for assessment of Aβ deposition and cerebrovascular disease. Individuals were categorized based on the comorbidity status of Aβ and cerebrovascular disease (V) as Aβ-V-, Aβ-V+, Aβ+V-, or Aβ+V+. Advancing age was associated with greater likelihood of cerebrovascular disease, high Aβ load and their comorbidity. Apolipoprotein E ɛ4 carriage was only associated with Aβ positivity. Greater total and regional WMH burden were observed in participants with AD. However, no association were observed between Aβ and WMH measures after stratification by clinical classification, suggesting that the observed association between AD and cerebrovascular disease was driven by the common risk factor of age. Our observations demonstrate common comorbid condition of Aβ and cerebrovascular disease in later life. While our study did not demonstrate a convincing cross-sectional association between Aβ and WMH burden, future longitudinal studies are required to further confirm this.

Cardiorespiratory Fitness Associates with Cerebral Vessel Pulsatility in a Cohort Enriched with Risk for Alzheimer's Disease.

Background:There is increasing evidence that vascular disease risk factors contribute to evolution of the dementia syndrome of Alzheimer’s disease (AD). One important measure of cerebrovascular health is pulsatility index (PI) which is thought to represent distal vascular resistance, and has previously been reported to be elevated in AD clinical syndrome. Physical inactivity has emerged as an independent risk factor for cardiovascular disease.Objective:This study aims to examine the relationship between a measure of habitual physical activity, cardiorespiratory fitness (CRF), and PI in the large cerebral vessels.Methods:Ninety-two cognitively-healthy adults (age = 65.34±5.95, 72% female) enrolled in the Wisconsin Registry for Alzheimer’s Prevention participated in this study. Participants underwent 4D flow brain MRI to measure PI in the internal carotid artery (ICA), basilar artery, middle cerebral artery (MCA), and superior sagittal sinus. Participants also completed a self-report physical activity questionnaire. CRF was calculated using a previously-validated equation that incorporates sex, age, body-mass index, resting heart rate, and self-reported physical activity. A series of linear regression models adjusted for age, sex, APOE4 status, and 10-year atherosclerotic cardiovascular disease risk were used to analyze the relationship between CRF and PI.Results:Inverse associations were found between CRF and mean PI in the inferior ICA (p = .001), superior ICA (p = .035), and basilar artery (p = .040). No other cerebral vessels revealed significant associations between CRF and PI (p≥.228).Conclusions:Higher CRF was associated with lower PI in several large cerebral vessels. Since increased pulsatility has been associated with poor brain health and reported in persons with AD, this suggests that aerobic fitness might provide protection against cerebrovascular changes related to the progression of AD clinical syndrome.

Earlier detection of cerebrovascular disorders in Parkinson's disease

The purpose of research: To determine early cerebrovascular changes in the clinical picture of Parkinson's disease and identify possible mechanisms of their formation.

Interictal hemodynamic abnormality during motor activation in sporadic hemiplegic migraine: An explorative study

IntroductionThe motor weakness in sporadic hemiplegic migraine (SHM) is a poorly understood aura manifestation. Cortical spreading depression affecting motor excitability and alterations of neurovascular coupling may be integral to the development of migraine aura. MethodsWe studied 10 right-handed SHM patients and 17 healthy controls with functional near-infrared spectroscopy (fNIRS) in the interictal period. Subjects performed a finger opposition task and had real time determination of oxyhemoglobin (OxyHb) and deoxyhemoglobin (deOxyHb) changes. Recordings were completed with 10 left and 10 right sided cortical channels. ResultsMean baseline to peak changes were significantly reduced in SHM patients as compared to controls bilaterally only for OxyHb measurements in the anteromedial channels. Mean time to peak changes were significant delayed in SHM patients compared to controls bilaterally largely for OxyHb measurements in the posterolateral channels, with the exception of 2 recording channels. ConclusionsOur findings suggest presence of abnormal interictal hemodynamic responses to increased metabolic demands during motor activation in SHM. These bilateral cerebrovascular changes involve OxyHb to a much larger degree than deOxyHb. Baseline to peak changes were evident more in the anteromedial channels, whereas time to peak changes were more evident in the posterolateral channels. These findings suggest that oxygen inflow into specific brain regions may be defective in SHM as opposed to oxygen utilization. Our findings suggest that in SHM, enduring hemodynamic deficits in response to an impending motor task are evident, which can be further explored in future studies, and possibly therapeutic trials.