Background
Dual‐venc 4D flow MRI, recently introduced for the assessment of intracranial hemodynamics, may provide a promising complementary approach to well‐established tools such as transcranial ...Doppler ultrasound (TCD) and overcome some of their disadvantages. However, data comparing intracranial flow measures from dual‐venc 4D flow MRI and TCD are lacking.
Purpose
To compare cerebral blood flow velocity measures derived from dual‐venc 4D flow MRI and TCD.
Study Type
Prospective cohort.
Subjects
A total of 25 healthy participants (56 ± 4 years old, 44% female).
Field Strength/Sequence
A 3 T/dual‐venc 4D flow MRI using a time‐resolved three‐dimensional phase‐contrast sequence with three‐dimensional velocity encoding.
Assessment
Peak velocity measurements in bilateral middle cerebral arteries (MCA) were quantified from dual‐venc 4D flow MRI and TCD. The MRI data were quantified by two independent observers (S.M and Y.M.) and TCD was performed by a trained technician (A.L.M.). We assessed the agreement between 4D flow MRI and TCD measures, and the interobserver agreement of 4D flow MRI measurements.
Statistical Tests
Peak velocity from MRI and TCD was compared using Bland–Altman analysis and coefficient of variance. Intraclass correlation coefficient (ICC) was used to assess MRI interobserver agreement. A P value < 0.05 was considered statistically significant.
Results
There was excellent interobserver agreement in dual‐venc 4D flow MRI‐based measurements of peak velocity in bilateral MCA (ICC = 0.97 and 0.96 for the left and right MCA, respectively). Dual‐venc 4D flow MRI significantly underestimated peak velocity in the left and right MCA compared to TCD (bias = 0.13 0.59, −0.33 m/sec and 0.15 0.47, −0.17 m/sec, respectively). The coefficient of variance between dual‐venc 4D flow MRI and TCD measurements was 26% for the left MCA and 22% for the right MCA.
Data Conclusion
There was excellent interobserver agreement for the assessment of MCA peak velocity using dual‐venc 4D flow MRI, and ≤20% under‐estimation compared with TCD.
Evidence Level
3
Technical Efficacy
Stage 2
The vascular contributions to neurodegeneration and neuroinflammation may be assessed by magnetic resonance imaging (MRI) and ultrasonography (US). This review summarises the methodology for these ...widely available, safe and relatively low cost tools and analyses recent work highlighting their potential utility as biomarkers for differentiating subtypes of cognitive impairment and dementia, tracking disease progression and evaluating response to treatment in various neurocognitive disorders.
At the 9th International Congress on Vascular Dementia (Ljubljana, Slovenia, October 2015) a writing group of experts was formed to review the evidence on the utility of US and arterial spin labelling (ASL) as neurophysiological markers of normal ageing, vascular cognitive impairment (VCI) and Alzheimer's disease (AD). Original articles, systematic literature reviews, guidelines and expert opinions published until September 2016 were critically analysed to summarise existing evidence, indicate gaps in current knowledge and, when appropriate, suggest standards of use for the most widely used US and ASL applications.
Cerebral hypoperfusion has been linked to cognitive decline either as a risk or an aggravating factor. Hypoperfusion as a consequence of microangiopathy, macroangiopathy or cardiac dysfunction can promote or accelerate neurodegeneration, blood-brain barrier disruption and neuroinflammation. US can evaluate the cerebrovascular tree for pathological structure and functional changes contributing to cerebral hypoperfusion. Microvascular pathology and hypoperfusion at the level of capillaries and small arterioles can also be assessed by ASL, an MRI signal. Despite increasing evidence supporting the utility of these methods in detection of microvascular pathology, cerebral hypoperfusion, neurovascular unit dysfunction and, most importantly, disease progression, incomplete standardisation and missing validated cut-off values limit their use in daily routine.
US and ASL are promising tools with excellent temporal resolution, which will have a significant impact on our understanding of the vascular contributions to VCI and AD and may also be relevant for assessing future prevention and therapeutic strategies for these conditions. Our work provides recommendations regarding the use of non-invasive imaging techniques to investigate the functional consequences of vascular burden in dementia.
White matter hyperintensities (WMH) in elderly individuals with vascular diseases are presumed to be due to ischemic small vessel diseases; however, their etiology is unknown. We examined the ...cross-sectional relationship between cerebrovascular hemodynamics and white matter structural integrity in elderly individuals with vascular risk factors. White matter hyperintensity volumes, fractional anisotropy (FA), and mean diffusivity (MD) were obtained from MRI in 48 subjects (75±7years). Pulsatility index (PI) and dynamic cerebral autoregulation (dCA) was assessed using transcranial Doppler ultrasound of the middle cerebral artery. Dynamic cerebral autoregulation was calculated from transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations in the low (LF, 0.03 to 0.15 Hz) and high (HF, 0.16 to 0.5 Hz) frequency ranges. Higher PI was associated with greater WMH (P<0.005). Higher phase across all frequency ranges was associated with greater FA and lower MD (P<0.005). Lower gain was associated with higher FA in the LF range (P=0.001). These relationships between phase and FA were significant in the territories limited to the middle cerebral artery as well as across the entire brain. Our results show a strong relationship between impaired cerebrovascular hemodynamics (PI and dCA) and loss of cerebral white matter structural integrity (WMH and DTI metrics) in elderly individuals.
Effective cerebral autoregulation (CA) may protect the vulnerable ischemic penumbra from blood pressure fluctuations and minimize neurological injury. We aimed to measure dynamic CA within 6 h of ...ischemic stroke (IS) symptoms onset and to evaluate the relationship between CA, stroke volume, and neurological outcome.
We enrolled 30 patients with acute middle cerebral artery IS. Within 6 h of IS, we measured for 10 min arterial blood pressure (Finometer), cerebral blood flow velocity (transcranial Doppler), and end-tidal-CO
. Transfer function analysis (coherence, phase, and gain) assessed dynamic CA, and receiver-operating curves calculated relevant cut-off values. National Institute of Health Stroke Scale was measured at baseline. Computed tomography at 24 h evaluated infarct volume. Modified Rankin Scale (MRS) at 3 months evaluated the outcome.
The odds of being independent at 3 months (MRS 0-2) was 14-fold higher when 6 h CA was intact (Phase > 37°) (adjusted OR = 14.0 (IC 95% 1.7-74.0),
= 0.013). Similarly, infarct volume was significantly smaller with intact CA median (range) 1.1 (0.2-7.0) vs 13.1 (1.3-110.5) ml,
= 0.002.
In this pilot study, early effective CA was associated with better neurological outcome in patients with IS. Dynamic CA may carry significant prognostic implications.
Impaired Cardiac Function and Cognitive Brain Aging van der Velpen, Isabelle F.; Yancy, Clyde W.; Sorond, Farzaneh A. ...
Canadian journal of cardiology,
December 2017, 2017-12-00, 20171201, Letnik:
33, Številka:
12
Journal Article
Recenzirano
It is well established that patients with heart failure are at a greater risk for dementia. Recent evidence suggests that the heart-brain link goes beyond advanced heart failure, and even suboptimal ...cardiac function is associated with brain structural and functional changes leading to cognitive impairment. In this review, we address several pathophysiological mechanisms underlying this association, including hemodynamic stress and cerebral hypoperfusion, neuroinflammation, cardiac arrhythmias, and hypercoagulation. The close link between cardiac function and brain health has numerous clinical and public health implications. Cardiac dysfunction and cognitive impairment are both common in older adults. However, in our current clinical practice, these medical conditions are generally evaluated and treated in isolation. Emerging evidence on the significance of the heart-brain link calls for comprehensive cardiovascular risk assessment in patients with cognitive impairment and a neurocognitive workup in patients with impaired cardiac function. A multidisciplinary approach by cardiologists, neurologists, and geriatricians would benefit the diagnostic process and disease management and ultimately improve the quality of life for patients with cardiac and cognitive dysfunction.
Il est bien établi que les patients atteints d’insuffisance cardiaque sont exposés à un risque plus élevé de démence. Des données scientifiques récentes montrent que le lien entre le cœur et le cerveau ne se limite pas à l’insuffisance cardiaque avancée, mais que même la fonction sous-optimale du cœur est associée à des changements structurels et fonctionnels dans le cerveau qui mènent aux troubles cognitifs. Dans la présente revue, nous nous penchons sur plusieurs mécanismes physiopathologiques qui sous-tendent cette association, à savoir le stress hémodynamique et l’hypoperfusion cérébrale, la neuro-inflammation, les arythmies cardiaques et l’hypercoagulation. Le lien étroit entre la fonction cardiaque et la santé du cerveau a de nombreuses répercussions cliniques et en santé publique. La dysfonction cardiaque et les troubles cognitifs sont fréquents chez les personnes âgées. Toutefois, dans notre pratique clinique actuelle, ces états de santé sont généralement évalués et traités séparément. Des données scientifiques émergentes sur l’importance du lien entre le cœur et le cerveau demandent une évaluation exhaustive du risque cardiovasculaire chez les patients ayant des troubles cognitifs et un bilan neurocognitif chez les patients ayant une dégradation de la fonction cardiaque. Une approche multidisciplinaire d’une équipe composée de cardiologues, de neurologues et de gériatres serait utile au processus de diagnostic et à la prise en charge de la maladie, puis ultimement améliorerait la qualité de vie des patients ayant une dysfonction cardiaque et cognitive.
High blood pressure (BP) negatively affects brain structure and function. Hypertension is associated with white matter hyperintensities, cognitive and mobility impairment in late-life. However, the ...impact of BP exposure from young adulthood on brain structure and function in mid-life is unclear. Identifying early brain structural changes associated with BP exposure, before clinical onset of cognitive dysfunction and mobility impairment, is essential for understanding mechanisms and developing interventions. We examined the effect of cumulative BP exposure from young adulthood on brain structure in a substudy of 144 (61 female) individuals from the CARDIA (Coronary Artery Risk Development in Young Adults) study. At year 30 (Y
, ninth visit), participants (56±4 years old) completed brain magnetic resonance imaging and gait measures (pace, rhythm, and postural control). Cumulative systolic and diastolic BP (cumulative systolic blood pressure, cDBP) over 9 visits were calculated, multiplying mean values between 2 consecutive visits by years between visits. Surface-based analysis of basal ganglia and thalamus was achieved using FreeSurfer-initiated Large Deformation Diffeomorphic Metric Mapping. Morphometric changes were regressed onto cumulative BP to localize regions of shape variation. Y
white matter hyperintensity volumes were small and positively correlated with cumulative BP but not gait. Negative morphometric associations with cumulative systolic blood pressure were seen in the caudate, putamen, nucleus accumbens, pallidum, and thalamus. A concave right medial putamen shape mediated the relationship between cumulative systolic blood pressure and stride width. Basal ganglia and thalamic morphometric changes, rather than volumes, may be earlier manifestation of gray matter structural signatures of BP exposure that impact midlife gait.
We tested the hypothesis that admission serum magnesium levels are associated with hematoma volume, hematoma growth, and functional outcomes in patients with intracerebral hemorrhage (ICH).
Patients ...presenting with spontaneous ICH were enrolled in an observational cohort study that prospectively collected demographic, clinical, laboratory, radiographic, and outcome data. We performed univariate and adjusted multivariate analyses to assess for associations between serum magnesium levels and initial hematoma volume, final hematoma volume, and in-hospital hematoma growth as radiographic measures of hemostasis, and functional outcome measured by the modified Rankin Scale (mRS) at 3 months.
We included 290 patients for analysis. Admission serum magnesium was 2.0 ± 0.3 mg/dL. Lower admission magnesium levels were associated with larger initial hematoma volumes on univariate (
= 0.02), parsimoniously adjusted (
= 0.002), and fully adjusted models (
= 0.006), as well as greater hematoma growth (
= 0.004,
= 0.005, and
= 0.008, respectively) and larger final hematoma volumes (
= 0.02,
= 0.001, and
= 0.002, respectively). Lower admission magnesium level was associated with worse functional outcomes at 3 months (i.e., higher mRS; odds ratio 0.14, 95% confidence interval 0.03-0.64,
= 0.011) after adjustment for age, admission Glasgow Coma Scale score, initial hematoma volume, time from symptom onset to initial CT, and hematoma growth, with evidence that the effect of magnesium is mediated through hematoma growth.
These data support the hypothesis that magnesium exerts a clinically meaningful influence on hemostasis in patients with ICH.
Conflicting data on the relationship between antihypertensive medications and falls in elderly people may lead to inappropriate undertreatment of hypertension in an effort to prevent falls. We aimed ...to clarify the relationships between the chronic use of different classes of antihypertensive medications and different types of falls, to determine the effect of medication dose, and to assess whether the risk of falls is associated with differences in cerebral blood flow. We assessed demographics, clinical characteristics, and chronic antihypertensive medication use in 598 community-dwelling people with hypertension, aged 70 to 97 years, then followed them prospectively for self-reported falls using monthly calendar postcards and telephone interviews. Antihypertensive medication use was not associated with an increased risk of falls. Participants reporting use of angiotensin-converting enzyme inhibitors had a significantly decreased 1-year risk of injurious falls (odds ratio, 0.62; 95% confidence interval, 0.39-0.96), whereas those using calcium channel blockers had a decreased risk of all falls (odds ratio, 0.62; 95% confidence interval, 0.42-0.91) and indoor falls (odds ratio, 0.57; 95% confidence interval, 0.36-0.91), compared with participants not taking these drugs. Larger doses of these classes were associated with a lower fall risk. Participants taking calcium channel blockers had higher cerebral blood flow than those not taking these medications. In relatively healthy community-dwelling elderly people, high doses of antihypertensive agents are not associated with an increased risk of falls.
Mobility is crucial for successful aging and is impaired in many older adults. We know very little about the subtle, subclinical age-related changes in the central nervous system (CNS) that mediate ...mobility impairment.
A conference series focused on aging, the CNS, and mobility was launched. The second conference addressed major age-associated mechanisms of CNS-mediated mobility impairment. Speakers and conference attendees recommended key areas for future research, identified barriers to progress, and proposed strategies to overcome them.
Priorities identified for future research include (a) studying interactions among different mechanisms; (b) examining effects of interventions targeting these mechanisms; (c) evaluating the effect of genetic polymorphisms on risks and course of age-related mobility impairment; and (d) examining the effect of age on CNS repair processes, neuroplasticity, and neuronal compensatory mechanisms. Key strategies to promote research include (a) establish standard measures of mobility across species; (b) evaluate the effect of aging in the absence of disease on CNS and mobility; and (c) use advanced computational methods to better evaluate the interactions between CNS and other systems involved in mobility.
CNS is a major player in the process, leading to mobility decline with aging. Future research in this area has the potential to prolong independence in older persons. Better interactions among disciplines and shared research paradigms are needed to make progress. Research priorities include the development of innovative approaches to integrate research on aging, cognition, and movement with attention to neurovascular function, neuroplasticity, and neurophysiological reserve.
Vascular aging affects multiple organ systems, including the brain, where it can lead to vascular dementia. However, a concrete understanding of how aging specifically affects the brain vasculature, ...along with molecular readouts, remains vastly incomplete. Here, we demonstrate that aging is associated with a marked decline in Notch3 signaling in both murine and human brain vessels. To clarify the consequences of Notch3 loss in the brain vasculature, we used single-cell transcriptomics and found that Notch3 inactivation alters regulation of calcium and contractile function and promotes a notable increase in extracellular matrix. These alterations adversely impact vascular reactivity, manifesting as dilation, tortuosity, microaneurysms, and decreased cerebral blood flow, as observed by MRI. Combined, these vascular impairments hinder glymphatic flow and result in buildup of glycosaminoglycans within the brain parenchyma. Remarkably, this phenomenon mirrors a key pathological feature found in brains of patients with CADASIL, a hereditary vascular dementia associated with NOTCH3 missense mutations. Additionally, single-cell RNA sequencing of the neuronal compartment in aging Notch3-null mice unveiled patterns reminiscent of those observed in neurodegenerative diseases. These findings offer direct evidence that age-related NOTCH3 deficiencies trigger a progressive decline in vascular function, subsequently affecting glymphatic flow and culminating in neurodegeneration.
PDF
