Small Vessel Cerebral Disease Research Articles

Reader Response: White Matter Hyperintensities Mediate the Association of Nocturnal Blood Pressure With Cognition.

Chesebro et al.1 bring us full circle on the consensus that hypertension is a multisystem illness with small vessel cerebral disease with related parenchymal changes as part of its spectrum. As for animal models of hypertension—and, certainly, now in human chronic hypertension—the position of hypertensive cerebrovascular disease is variable along the dynamic interactions and outcomes that arise once these processes begin. Such realizations are consistent with the recent review that illustrates how peripheral and cerebral autoregulation and reactivity are invariably intertwined in hypertension.2 In reviewing the Classification of Cerebrovascular Diseases published in 1958, Raymond Adams posited, “It must be remembered that in the final analysis the distinguishing attributes of all these diseases are the vascular changes themselves and not merely the parenchymal lesion which they induce.”3 From a clinical and pathology viewpoint, a more complete perspective of hypertension becomes apparent and fundamentally corroborates the 1978 WHO classification of cerebrovascular disease.4 As reiterated by Harsha5 recently, there is danger in assigning imprecise eponyms for cerebrovascular diseases. Rather than being exclusory, it becomes both scientific and practical that hypertension and cerebrovascular disease are spoken of in the same breath.

Accelerated atherosclerosis in ANCA-associated vasculitis.

Cardiovascular disease, including myocardial infarction and stroke, is a major cause of mortality in ANCA-associated vasculitis (AAV). Although AAV affects small vessels, an accelerated atherosclerosis not explained by traditional cardiovascular risk factors (CVRF) has been demonstrated. We aimed to investigate the association of atherosclerosis measured by carotid intima-media thickness (CIMT) and cerebral small vessel disease in AAV-patients. Twenty-three AAV-patients in complete remission were recruited. Carotid ultrasonography (US), transcranial Doppler (TCD), brain magnetic resonance imaging (MRI), and SPECT after intravenous administration of tracer 99mTc-HMPAO (dose: 720MBq) were performed. AAV-patients presented higher CIMT compared to normative population. Multivariate linear regression analysis demonstrated an association of higher CIMT with increased pulsatility index in middle cerebral artery (PI-MCA) (P=.011), higher lesion load on ARWMC scale (P=.011) and abnormal SPECT (P=.008). No association between higher CIMT and CVRF (diabetes or hypertension) was demonstrated. Increasing internal carotid artery pulsatility index (PI-ICA) was associated with decreasing mean flow velocity (MFV)-MCA (P=.038), increasing PI-MCA (P=.008) and increasing white matter lesions on MRI (P=.011). Our study adds weight to the presence of increased atherosclerosis in AAV-patients. The association observed between CIMT and PI-ICA with small vessel cerebral disease, points the possible association of easy to use carotid US in predicting microvascular brain injury.

Abstract P217: Parathyroid Hormone is Not Independently Associated With Cognitive Decline: 20 Year Follow-up From the Atherosclerosis Risk in Communities (ARIC) Study

Background: Little is known about the role of parathyroid hormone (PTH) in cognitive decline. Elevated PTH may contribute to cognitive impairment and dementia by mechanisms of endothelial dysfunction, increased vascular stiffness, hypertension, and atherosclerosis, as well as via small vessel cerebral disease. We hypothesized that elevated PTH levels will be independently associated with 20-year cognitive decline in a large population-based cohort study. Methods: We studied 12,964 middle-aged white and black ARIC participants without history of prior stroke who had serum PTH levels and cognitive function testing measured in 1990-92 (baseline) and repeat cognitive testing at up to 2 follow-up visits in 1996-98 and 2011-13. The cognitive tests included the Delayed Word Recall, Digit Symbol Substitution, and Word Fluency tests, which were summed as a global z score. Using mixed-effects models, we compared the relative decline in global cognitive score between each of the top three quartiles of PTH levels to the reference bottom quartile. Time since baseline was modeled by using a linear spline with a knot at 6 years. We adjusted for demographic variables, education, vascular risk factors, and calcium, phosphorous, and vitamin D levels. We imputed missing covariates and follow-up cognitive data using multiple imputation by chained equations (MICE) methods to account for attrition during study follow-up. Results: The mean (SD) age of our cohort was 57(6) years, 57% were women, and 24% black race. There was no cross-sectional association of elevated PTH with cognitive global Z score at baseline (all p>0.05). Over a median of 20.7 years, participants in each PTH quartile showed decline in cognitive function ( Table Part A ). However, cognitive decline was not steeper in participants with PTH levels in the higher quartiles than participants with the lowest PTH levels (all p>0.05). [ Table Part B ]. Conclusions: Our work does not support an independent influence of PTH on cognitive decline in this biracial population-based cohort study.

Intermittent hypoxia training protects cerebrovascular function in Alzheimer's disease.

Alzheimer's disease (AD) is a leading cause of death and disability among older adults. Modifiable vascular risk factors for AD (VRF) include obesity, hypertension, type 2 diabetes mellitus, sleep apnea, and metabolic syndrome. Here, interactions between cerebrovascular function and development of AD are reviewed, as are interventions to improve cerebral blood flow and reduce VRF. Atherosclerosis and small vessel cerebral disease impair metabolic regulation of cerebral blood flow and, along with microvascular rarefaction and altered trans-capillary exchange, create conditions favoring AD development. Although currently there are no definitive therapies for treatment or prevention of AD, reduction of VRFs lowers the risk for cognitive decline. There is increasing evidence that brief repeated exposures to moderate hypoxia, i.e. intermittent hypoxic training (IHT), improve cerebral vascular function and reduce VRFs including systemic hypertension, cardiac arrhythmias, and mental stress. In experimental AD, IHT nearly prevented endothelial dysfunction of both cerebral and extra-cerebral blood vessels, rarefaction of the brain vascular network, and the loss of neurons in the brain cortex. Associated with these vasoprotective effects, IHT improved memory and lessened AD pathology. IHT increases endothelial production of nitric oxide (NO), thereby increasing regional cerebral blood flow and augmenting the vaso- and neuroprotective effects of endothelial NO. On the other hand, in AD excessive production of NO in microglia, astrocytes, and cortical neurons generates neurotoxic peroxynitrite. IHT enhances storage of excessive NO in the form of S-nitrosothiols and dinitrosyl iron complexes. Oxidative stress plays a pivotal role in the pathogenesis of AD, and IHT reduces oxidative stress in a number of experimental pathologies. Beneficial effects of IHT in experimental neuropathologies other than AD, including dyscirculatory encephalopathy, ischemic stroke injury, audiogenic epilepsy, spinal cord injury, and alcohol withdrawal stress have also been reported. Further research on the potential benefits of IHT in AD and other brain pathologies is warranted.

Influence of Acute Jugular Vein Compression on the Cerebral Blood Flow Velocity, Pial Artery Pulsation and Width of Subarachnoid Space in Humans

PurposeThe aim of this study was to assess the effect of acute bilateral jugular vein compression on: (1) pial artery pulsation (cc-TQ); (2) cerebral blood flow velocity (CBFV); (3) peripheral blood pressure; and (4) possible relations between mentioned parameters.MethodsExperiments were performed on a group of 32 healthy 19–30 years old male subjects. cc-TQ and the subarachnoid width (sas-TQ) were measured using near-infrared transillumination/backscattering sounding (NIR-T/BSS), CBFV in the left anterior cerebral artery using transcranial Doppler, blood pressure was measured using Finapres, while end-tidal CO2 was measured using medical gas analyser. Bilateral jugular vein compression was achieved with the use of a sphygmomanometer held on the neck of the participant and pumped at the pressure of 40 mmHg, and was performed in the bend-over (BOPT) and swayed to the back (initial) position.ResultsIn the first group (n = 10) during BOPT, sas-TQ and pulse pressure (PP) decreased (−17.6% and −17.9%, respectively) and CBFV increased (+35.0%), while cc-TQ did not change (+1.91%). In the second group, in the initial position (n = 22) cc-TQ and CBFV increased (106.6% and 20.1%, respectively), while sas-TQ and PP decreases were not statistically significant (−15.5% and −9.0%, respectively). End-tidal CO2 remained stable during BOPT and venous compression in both groups. Significant interdependence between changes in cc-TQ and PP after bilateral jugular vein compression in the initial position was found (r = −0.74).ConclusionsAcute bilateral jugular venous insufficiency leads to hyperkinetic cerebral circulation characterised by augmented pial artery pulsation and CBFV and direct transmission of PP into the brain microcirculation. The Windkessel effect with impaired jugular outflow and more likely increased intracranial pressure is described. This study clarifies the potential mechanism linking jugular outflow insufficiency with arterial small vessel cerebral disease.

Associations of Retinal Microvascular Signs and Intracranial Large Artery Disease

Intracranial large artery disease (ICLAD) is a major cause of ischemic stroke. Retinal microvascular changes are associated with stroke, including small vessel cerebral disease and extracranial carotid disease. We examined the relationship between ICLAD and retinal microvascular changes. This is a prospective cohort of 802 acute ischemic stroke patients. Retinal changes were assessed from photographs by graders masked to clinical data. ICLAD was evaluated using prespecified criteria. ICLAD was not associated with ipsilateral retinal arteriolar/venular caliber, focal arteriolar narrowing, or arteriovenous nicking. Severe enhanced arteriolar light reflex was independently associated with any ICLAD (P=0.006) and severe ICLAD (P<0.001). Enhanced arteriolar light reflex, but not retinal vessel caliber, was related to ICLAD. These data suggest that retinal microvascular signs have specific associations with large cerebral vessel disease.

CADASIL: (small vessel cerebral disease): From bed to bench and contrary

CADASIL: (small vessel cerebral disease): From bed to bench and contrary