Cerebrovascular function in presymptomatic and symptomatic individuals with hereditary cerebral amyloid angiopathy: a case-control study

Opstal, Anna M. van; Rooden, Sanneke van; Harten, Thijs van; Ghariq, Eidrees; Labadie, Gerda; Fotiadis, Panagiotis; Gurol, M. Edip; Terwindt, Gisela M.; Wermer, Marieke J.H.; Buchem, Mark A. van; Greenberg, Steven M.; Grond, Jeroen van der

doi:10.1016/s1474-4422(16)30346-5

Cited by 77 publications

(121 citation statements)

References 21 publications

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“…(37) Van Opstal et al (n=60) demonstrated BOLD reactivity in the occipital cortex is reduced in individuals with symptomatic hereditary cerebral amyloid angiopathy who had severe WMH and microbleeds compared to controls and presymptomatic carriers. (38)…”

Section: Discussionmentioning

confidence: 99%

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Intracranial functional haemodynamic relationships in patients with cerebral small vessel disease

Blair

Thrippleton

Shi

et al. 2019

Preprint

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BackgroundCerebral small vessel disease (SVD) is a major cause of stroke and dementia. The underlying cerebrovascular dysfunction is poorly understood. We investigated cerebrovascular reactivity, blood flow, vascular and cerebrospinal fluid (CSF) pulsatility, and their independent relationship to SVD features, in patients with minor ischaemic stroke and MRI evidence of SVD.MethodsWe recruited patients with minor ischaemic stroke and assessed CVR using Blood Oxygen Level Dependent (BOLD) MRI during a hypercapnic challenge, cerebral blood flow, vascular and CSF pulsatility using phase contrast MRI, and structural MR brain imaging to quantify white matter hyperintensities (WMH) and perivascular spaces (PVS). We quantified CVR in seven white matter and six subcortical grey matter regions, measured blood flow in carotid and vertebral arteries, intracranial venous sinuses, internal jugular veins and CSF flow at the aqueduct and foramen magnum. We used multiple regression to identify SVD features, blood flow and pulsatility parameters associated with CVR, controlling for patient characteristics.ResultsIn 53 of 60 patients with complete data (age 68.0±8.8, 74% male, 75% hypertensive), CVR in grey and white matter decreased with increasing blood pressure (BP, respectively −0.001%/mmHg, p=0.01 and −0.006%/mmHg, p=0.01, per mmHg increase in BP). After controlling for age, gender and systolic BP, white matter CVR decreased with increasing WMF volume (−0.01%/mmHg per log10 increase in WMH volume, p=0.02) and basal ganglia PVS (−0.01%/mmHg per point increase in PVS score, p=0.02). White matter CVR decreased with increasing venous pulsatility (superior sagittal sinus −0.03%/mmHg, p=0.02, per unit increase in pulsatility index) but not with cerebral blood flow (p=0.58). Lower foramen magnum CSF stroke volume was associated with worse white matter CVR (0.04%/mmHg per ml increase in stroke volume, p=0.04) and increased basal ganglia PVS.ConclusionsContemporaneous assessment of CVR, intracranial vascular and CSF pulsatility demonstrates important interrelationships of these vascular functions in humans. Decreased CVR, increased venous pulsatility and reduced foramen magnum CSF stroke volume suggests that dynamic vascular dysfunctions underpin PVS dysfunction and WMH development. Improved understanding of microvascular dysfunction and CSF dynamics offers new intervention targets to reduce SVD lesion development and their impact on cognitive dysfunction and stroke.

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Section: Discussionmentioning

confidence: 99%

“…(4, 23) Studies of SVD mechanisms and potential interventions should consider using measures of dynamic vascular function such as CVR or pulsatility rather than resting CBF. (5, 38)…”

Section: Discussionmentioning

confidence: 99%

Intracranial functional haemodynamic relationships in patients with cerebral small vessel disease

Blair

Thrippleton

Shi

et al. 2019

Preprint

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“…In the cortical gray matter, which may be less susceptible to ischemia because of a richer network of collateral vessels than the white matter, intermittent reduction in blood flow could nonetheless lead to microinfarction. Alterations in vascular reactivity appear early in CAA and are progressive (Switzer et al 2016;van Opstal et al 2017). A study of presymptomatic Dutch CAA mutation carriers found that they exhibited abnormal functional magnetic resonance imaging responses at an early stage of disease, prior to the onset of symptomatic hemorrhages, cognitive impairment, or neuroimaging evidence of brain atrophy (van Opstal et al 2017).…”

Section: Non-ad Pathomechanisms Of Neurodegeneration In Caamentioning

confidence: 99%

“…Alterations in vascular reactivity appear early in CAA and are progressive (Switzer et al 2016;van Opstal et al 2017). A study of presymptomatic Dutch CAA mutation carriers found that they exhibited abnormal functional magnetic resonance imaging responses at an early stage of disease, prior to the onset of symptomatic hemorrhages, cognitive impairment, or neuroimaging evidence of brain atrophy (van Opstal et al 2017). Thus, impaired vasodilation precedes evidence of neurodegeneration and may cause it.…”

Section: Non-ad Pathomechanisms Of Neurodegeneration In Caamentioning

confidence: 99%

Cerebral amyloid angiopathy as a cause of neurodegeneration

Smith

2017

Journal of Neurochemistry

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Sporadic, age-related cerebral amyloid angiopathy (CAA) is most commonly recognized clinically as a cause of hemorrhagic stroke and transient focal neurological episodes in older persons. But a growing body of research in the last 5 years shows that the pathophysiology of CAA is much more complex than previously believed, leading to many different types of brain injury. CAA has now been linked with brain atrophy in regions remote from those directly affected by intracerebral hematomas, and with risk for progressive cognitive decline in the absence of new hemorrhagic strokes. Therefore, CAA is associated with features -brain atrophy and progressive cognitive decline -that are typically considered hallmarks of neurodegenerative disease. Although CAA is usually accompanied by some degree of Alzheimer's disease pathology, the profiles of cortical thinning and cognitive impairment do not fully overlap with those seen in Alzheimer's disease, suggesting that there are CAA-specific pathways of neurodegeneration. CAA-related brain ischemia may be an important mechanism that leads to brain injury, cortical disconnection, and cognitive impairment.

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“…The amplitude of the functional MRI response to visual stimulation is reduced not only in symptomatic carriers who had already suffered CAA-related bleeding, but even in presymptomatic mutation carriers without prior hemorrhage. 33 These results point squarely to vascular reactivity as an early step in CAA pathogenesis and thus a candidate target for early intervention strategies.…”

Section: Links Between Cerebral Small Vessel Disease and Dementia: Lementioning

confidence: 98%

William M. Feinberg Award for Excellence in Clinical Stroke

Greenberg

2017

Stroke

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Cerebrovascular function in presymptomatic and symptomatic individuals with hereditary cerebral amyloid angiopathy: a case-control study

Cited by 77 publications

References 21 publications

Intracranial functional haemodynamic relationships in patients with cerebral small vessel disease

Intracranial functional haemodynamic relationships in patients with cerebral small vessel disease

Cerebral amyloid angiopathy as a cause of neurodegeneration

William M. Feinberg Award for Excellence in Clinical Stroke

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