Role of small acute hyperintense lesions in long-term progression of cerebral small vessel disease and clinical outcome: a 14-year follow-up study

Verburgt, Esmée; Janssen, Esther; Jacob, Mina A.; Cai, Mengfei; Telgte, Annemieke ter; Wiegertjes, Kim; Kessels, Roy P. C.; Norris, David G.; Marques, José P.; Duering, Marco; Tuladhar, Anil M.; Leeuw, Frank‐Erik de

doi:10.1136/jnnp-2022-330091

Cited by 6 publications

(2 citation statements)

References 33 publications

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“… 21 Their clinical significance, and whether they relate to disease progression, remains to be fully determined although a recent report associated them with greater radiological progression of SVD and cognitive decline compared with patients without DWI + lesions. 22 It has also been suggested that WMH lesion volume may regress in some patients, and not only progress. 23 …”

Section: Insights From Brain Imagingmentioning

confidence: 99%

Cerebral small vessel disease: Recent advances and future directions

Markus

Leeuw

2022

International Journal of Stroke

147

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Cerebral small vessel disease (SVD) causes lacunar stroke and intracerebral hemorrhage, and is the most common pathology underlying vascular cognitive impairment. Increasingly, the importance of other clinical features of SVD is being recognized including motor impairment, (vascular) parkinsonism, impaired balance, falls, and behavioral symptoms, such as depression, apathy, and personality change. Epidemiological data show a high prevalence of the characteristic magnetic resonance imaging (MRI) features of white matter hyperintensities and lacunar infarcts in community studies, and recent data suggest that it is also a major health burden in low- and middle-income countries. In this review, we cover advances in diagnosis, imaging, clinical presentations, pathogenesis, and treatment. The two most common pathologies underlying SVD are arteriolosclerosis caused by aging, hypertension, and other conventional vascular risk factors, and cerebral amyloid angiopathy (CAA) caused by vascular deposition of β-amyloid. We discuss the revised Boston criteria of CAA based on MRI features, which have been recently validated. Imaging is providing important insights into pathogenesis, including improved detection of tissue damage using diffusion tensor imaging (DTI) leading to its use to monitor progression and surrogate endpoints in clinical trials. Advanced MRI techniques can demonstrate functional or dynamic abnormalities of the blood vessels, while the high spatial resolution provided by ultrahigh field MRI at 7 T allows imaging of individual perforating arteries for the first time, and the measurement of flow velocity and pulsatility within these arteries. DTI and structural network analysis have highlighted the importance of network disruption in mediating the effect of different SVD pathologies in causing a number of symptoms, including cognitive impairment, apathy, and gait disturbance. Despite the public health importance of SVD, there are few proven treatments. We review the evidence for primary prevention, and recent data showing how intensive blood pressure lowering reduces white matter hyperintensities (WMH) progression and delays the onset of cognitive impairment. There are few treatments for secondary prevention, but a number of trials are currently evaluating novel treatment approaches. Recent advances have implicated molecular processes related to endothelial dysfunction, nitric oxide synthesis, blood–brain barrier integrity, maintenance and repair of the extracellular matrix, and inflammation. Novel treatment approaches are being developed to a number of these targets. Finally, we highlight the importance of large International collaborative initiatives in SVD to address important research questions and cover a number which have recently been established.

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Section: Insights From Brain Imagingmentioning

confidence: 99%

Cerebral small vessel disease: Recent advances and future directions

Markus

Leeuw

2022

International Journal of Stroke

147

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“…Small diffusion-weighted imaging-positive asymptomatic lesions on serial diffusion-weighted imaging are more common that previously observed and strongly associated with cognitive decline. 20 Ongoing international collaborative consortia are established to evaluate the impact of CSVD imaging markers on the risk of stroke and dementia across multiple populations. These have performed lesion-symptom mapping to identify strategic white matter hyperintensity locations for cognitive impairment 21 and established diffusion tensor imaging as a method to accurately predict dementia in CSVD.…”

Section: Csvd Is On the Risementioning

confidence: 99%

Advances in Stroke: Brain Health in 2023

Rundek,

Chen

2023

Stroke

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Cortical folding correlates to aging and Alzheimer’s Disease’s cognitive and CSF biomarkers

de Moraes,

Sudo,

Carneiro Monteiro

et al. 2024

Sci Rep

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This manuscript presents the quantification and correlation of three aspects of Alzheimer’s Disease evolution, including structural, biochemical, and cognitive assessments. We aimed to test a novel structural biomarker for neurodegeneration based on a cortical folding model for mammals. Our central hypothesis is that the cortical folding variable, representative of axonal tension in white matter, is an optimal discriminator of pathological aging and correlates with altered loadings in Cerebrospinal Fluid samples and a decline in cognition and memory. We extracted morphological features from T1w 3T MRI acquisitions using FreeSurfer from 77 Healthy Controls (age = 66 ± 8.4, 69% females), 31 Mild Cognitive Impairment (age = 72 ± 4.8, 61% females), and 13 Alzheimer’s Disease patients (age = 77 ± 6.1, 62% females) of recruited volunteers in Brazil to test its discriminative power using optimal cut-point analysis. Cortical folding distinguishes the groups with reasonable accuracy (Healthy Control-Alzheimer’s Disease, accuracy = 0.82; Healthy Control-Mild Cognitive Impairment, accuracy = 0.56). Moreover, Cerebrospinal Fluid biomarkers (total Tau, A$$\beta $$ β 1-40, A$$\beta $$ β 1-42, and Lipoxin) and cognitive scores (Cognitive Index, Rey’s Auditory Verbal Learning Test, Trail Making Test, Digit Span Backward) were correlated with the global neurodegeneration in MRI aiming to describe health, disease, and the transition between the two states using morphology.

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Role of small acute hyperintense lesions in long-term progression of cerebral small vessel disease and clinical outcome: a 14-year follow-up study

Cited by 6 publications

References 33 publications

Cerebral small vessel disease: Recent advances and future directions

Cerebral small vessel disease: Recent advances and future directions

Advances in Stroke: Brain Health in 2023

Cortical folding correlates to aging and Alzheimer’s Disease’s cognitive and CSF biomarkers

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