Strategic white matter tracts for processing speed deficits in age-related small vessel disease

Some degree of ischemic injury to white matter tracts occurs naturally with age and is visible on magnetic resonance imaging as focal or confluent white matter hyperintensities (WMHs). Its relationship to cognition, however, remains unclear. To explore this, community-dwelling adults between the ages 55-80 years old completed structural imaging, neuropsychological testing, and questionnaires to provide objective measures and subjective experience of executive functioning. Volumetric lesion burden derived from structural MRI identified those with significant WMH burden (~10 cubic cm). Half of those recruited met this criterion and were designated as the cerebral small vessel disease (CSVD) group. Subjective complaints but not objective test scores differentiated adults with and without CSVD. Hierarchical clustering revealed two CSVD subgroups that differentiated those with impaired versus preserved executive function relative to controls. Overall these results provide some explanation for behavioural heterogeneity often observed in studies of age-related white matter changes. They also support the use of questionnaires to assess subjective complaints that may be able to detect subtle effects of pathology not evident on standardized cognitive scores.

Download Full-text

Superficial white matter microstructure affects processing speed in cerebral small vessel disease

10.1101/2021.12.30.474604 ◽

2022 ◽

Author(s):

Shuyue Wang ◽

Fan Zhang ◽

Peiyu Huang ◽

Hui Hong ◽

Yeerfan Jiaerken ◽

...

Keyword(s):

White Matter ◽

Processing Speed ◽

Diffusion Mri ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Large Contribution ◽

Vessel Disease ◽

White Matter Microstructure ◽

Patient Subgroups

White matter hyperintensities (WMH) are a typical feature of cerebral small vessel disease (CSVD). This condition contributes to about 50% of dementias worldwide, a massive health burden in aging. Microstructural alterations in the deep white matter (DWM) have been widely examined in CSVD. However, little is known about abnormalities in the superficial white matter (SWM) and their relevance for processing speed, the main cognitive deficit in CSVD. In this paper, 141 patients with CSVD were studied. Processing speed was assessed by the completion time of the Trail Making Test Part A. White matter abnormalities were assessed by WMH burden (lesion volume on T2-FLAIR) and diffusion MRI, including DTI and free-water (FW) imaging microstructure measures. The results of our study indicate that the superficial white matter may play a particularly important role in cognitive decline in CSVD. SWM imaging measures resulted in a large contribution to processing speed, despite a relatively small WMH burden in the SWM. SWM FW had the strongest association with processing speed among all imaging markers and, unlike the other diffusion MRI measures, significantly increased between two patient subgroups with the lowest WMH burdens (possibly representing early stages of disease). When comparing two patient subgroups with the highest WMH burdens, the involvement of WMH in the SWM was accompanied by significant differences in processing speed and white matter microstructure. Given significant effects of WMH volume and regional FW on processing speed, we performed a mediation analysis. SWM FW was found to fully mediate the association between WMH volume and processing speed, while no mediation effect of DWM FW was observed. Overall, our findings identify SWM abnormalities in CSVD and suggest that the SWM has an important contribution to processing speed. Results indicate that FW in the SWM is a sensitive marker of microstructural changes associated with cognition in CSVD. This study extends the current understanding of CSVD-related dysfunction and suggests that the SWM, as an understudied region, can be a potential target for monitoring pathophysiological processes in future research.

Download Full-text

Brain White Matter: A Substrate for Resilience and a Substance for Subcortical Small Vessel Disease

Brain Sciences ◽

10.3390/brainsci9080193 ◽

2019 ◽

Vol 9 (8) ◽

pp. 193 ◽

Cited By ~ 1

Author(s):

Farzaneh A. Sorond ◽

Philip B. Gorelick

Keyword(s):

White Matter ◽

Small Vessel Disease ◽

Small Vessel ◽

White Matter Disease ◽

Perivascular Spaces ◽

Vessel Disease ◽

Brain White Matter ◽

Age Related ◽

Vascular Origin ◽

White Matter Development

Age-related brain white matter disease is a form of small vessel disease (SVD) that may be associated with lacunar and other small subcortical infarcts, cerebral microbleeds, and perivascular spaces. This common form of cerebrovascular disease may manifest clinically as cognitive impairment of varying degrees and difficulty with mobility. Whereas some persons show cognitive decline and mobility failure when there are brain white matter hyperintensities (WMH) and acute stroke, others recover, and not everyone with brain white matter disease is disabled. Thus, repair or compensation of brain white matter may be possible, and furthermore, certain vascular risks, such as raised blood pressure, are targets for prevention of white matter disease or are administered to reduce the burden of such disease. Vascular risk modification may be useful, but alone may not be sufficient to prevent white matter disease progression. In this chapter, we specifically focus on WMH of vascular origin and explore white matter development, plasticity, and enduring processes of myelination across the health span in the context of experimental and human data, and compare and contrast resilient brain white matter propensity to a diseased white matter state. We conclude with thoughts on novel ways one might study white matter resilience, and predict future healthy cognitive and functional outcomes.

Download Full-text

Gliovascular Disruption and Cognitive Deficits in a Mouse Model with Features of Small Vessel Disease

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2015.12 ◽

2015 ◽

Vol 35 (6) ◽

pp. 1005-1014 ◽

Cited By ~ 54

Author(s):

Philip R Holland ◽

James L Searcy ◽

Natalia Salvadores ◽

Gillian Scullion ◽

Guiquan Chen ◽

...

Keyword(s):

White Matter ◽

Mouse Model ◽

Cognitive Deficits ◽

Diffusion Tensor ◽

Small Vessel Disease ◽

Water Channel ◽

Cerebral Hypoperfusion ◽

Small Vessel ◽

Vessel Disease ◽

Age Related

Cerebral small vessel disease (SVD) is a major cause of age-related cognitive impairment and dementia. The pathophysiology of SVD is not well understood and is hampered by a limited range of relevant animal models. Here, we describe gliovascular alterations and cognitive deficits in a mouse model of sustained cerebral hypoperfusion with features of SVD (microinfarcts, hemorrhage, white matter disruption) induced by bilateral common carotid stenosis. Multiple features of SVD were determined on T2-weighted and diffusion-tensor magnetic resonance imaging scans and confirmed by pathologic assessment. These features, which were absent in sham controls, included multiple T2-hyperintense infarcts and T2-hypointense hemosiderin-like regions in subcortical nuclei plus increased cerebral atrophy compared with controls. Fractional anisotropy was also significantly reduced in several white matter structures including the corpus callosum. Investigation of gliovascular changes revealed a marked increase in microvessel diameter, vascular wall disruption, fibrinoid necrosis, hemorrhage, and blood–brain barrier alterations. Widespread reactive gliosis, including displacement of the astrocytic water channel, aquaporin 4, was observed. Hypoperfused mice also demonstrated deficits in spatial working and reference memory tasks. Overall, gliovascular disruption is a prominent feature of this mouse, which could provide a useful model for early-phase testing of potential SVD treatment strategies.

Download Full-text

A Novel Imaging Marker for Small Vessel Disease Based on Skeletonization of White Matter Tracts and Diffusion Histograms

Annals of Neurology ◽

10.1002/ana.24758 ◽

2016 ◽

Vol 80 (4) ◽

pp. 581-592 ◽

Cited By ~ 86

Author(s):

Ebru Baykara ◽

Benno Gesierich ◽

Ruth Adam ◽

Anil Man Tuladhar ◽

J. Matthijs Biesbroek ◽

...

Keyword(s):

White Matter ◽

Small Vessel Disease ◽

Small Vessel ◽

White Matter Tracts ◽

Vessel Disease ◽

And Diffusion

Download Full-text

Higher Cerebral Small Vessel Disease Burden in Patients with White Matter Recent Small Subcortical Infarcts

Journal of Stroke and Cerebrovascular Diseases ◽

10.1016/j.jstrokecerebrovasdis.2021.105824 ◽

2021 ◽

Vol 30 (7) ◽

pp. 105824

Author(s):

Salvatore Rudilosso ◽

Luis Mena ◽

Diana Esteller ◽

Marta Olivera ◽

Juan José Mengual ◽

...

Keyword(s):

White Matter ◽

Disease Burden ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Vessel Disease

Download Full-text

Cerebral small-vessel disease and decline in information processing speed, executive function and memory

Brain ◽

10.1093/brain/awh553 ◽

2005 ◽

Vol 128 (9) ◽

pp. 2034-2041 ◽

Cited By ~ 420

Author(s):

Niels D. Prins ◽

Ewoud J. van Dijk ◽

Tom den Heijer ◽

Sarah E. Vermeer ◽

Jellemer Jolles ◽

...

Keyword(s):

Information Processing ◽

Executive Function ◽

Processing Speed ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Information Processing Speed ◽

Vessel Disease

Download Full-text

Abstract P499: The Effect of Small Vessel Disease Burden on Core/Penumbra Mismatch and Outcomes in Extended Window Thrombectomy

Stroke ◽

10.1161/str.52.suppl_1.p499 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Destiny Hooper ◽

Tariq Nisar ◽

Meryim Poursheykhi ◽

Andy Lin ◽

C. David McCane ◽

...

Keyword(s):

White Matter ◽

Perfusion Imaging ◽

Functional Outcomes ◽

Time Window ◽

Small Vessel Disease ◽

Small Vessel ◽

Collateral Flow ◽

Anterior Circulation ◽

Vessel Occlusion ◽

Vessel Disease

Objective: Recent studies have shown the benefit of revascularization in select patients with extended window large vessel occlusion (EWLVO). We sought to assess the effect of cerebral small vessel disease (CSVD) burden on eligibility for intervention with mechanical thrombectomy (MT) and functional outcomes in patients with EWLVO. Methods: We conducted a retrospective single-center study of 135 patients with anterior circulation LVO who presented in the extended time window, 6 to 24 hours from LKW, between August 2018 and March 2020. All patients underwent perfusion imaging at initial presentation and those with target ischemic core to penumbra mismatch profiles, as defined by DAWN/DEFUSE3 criteria, were treated with MT. Included patients were evaluated for CSVD burden using T2-FLAIR MRI. The Fazekas scale (0-3) was used to quantify the amount of white matter T2 hyperintense lesions in both the periventricular (PVWM) and deep white matter (DWM). Patients’ functional outcomes were assessed at 90 days using the mRS. Multivariate ordinal logistic regression models were used and adjusted for age, gender, thrombus location and LKW to perfusion imaging time. Patient information was collected from the Houston Methodist Hospital Outcomes Based Prospective Endpoints in Stroke (HOPES) registry. Results: Of the 135 patients, 111 met imaging inclusion criteria for revascularization with MT for EWLVO. MT was deferred in 44 of these patients due to other clinical exclusions or patient refusal. Patients ineligible for MT were approximately 13 times more likely to have a higher PVWM Fazekas grade (OR =13.53, 95% CI. [2.94 - 62.39], p=0.001) and 17 times more likely to have a higher DWM Fazekas grade (OR =17.54, 95% CI. [4.20 - 73.17], p<0.001), when compared to patients who were eligible for MT. Patients who did not meet criteria for MT were nearly 7 times more likely to have poor functional outcomes at 90 days (OR =6.85, 95% CI. [2.09 - 22.44], p=0.001). Conclusion: Based on our analytical cohort of EWLVO patients, those with severe CSVD burden were more likely to be excluded from MT and had worse functional outcomes. Poor cerebrovascular reserve and diminished collateral flow leading to rapid infarct progression in patients with greater CSVD burden may be a potential explanation.

Download Full-text

Different cognitive profiles between mild cognitive impairment due to cerebral small vessel disease and mild cognitive impairment of Alzheimer’s disease origin

Journal of the International Neuropsychological Society ◽

10.1017/s1355617709990816 ◽

2009 ◽

Vol 15 (6) ◽

pp. 898-905 ◽

Cited By ~ 25

Author(s):

AIHONG ZHOU ◽

JIANPING JIA

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Processing Speed ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Cognitive Domains ◽

Vessel Disease

AbstractControversy surrounds the differences of the cognitive profile between mild cognitive impairment resulting from cerebral small vessel disease (MCI-SVD) and mild cognitive impairment associated with prodromal Alzheimer’s disease (MCI-AD). The aim of this study was to explore and compare the cognitive features of MCI-SVD and MCI-AD. MCI-SVD patients (n = 56), MCI-AD patients (n = 30), and normal control subjects (n = 80) were comprehensively evaluated with neuropsychological tests covering five cognitive domains. The performance was compared between groups. Tests that discriminated between MCI-SVD and MCI-AD were identified. Multiple cognitive domains were impaired in MCI-SVD group, while memory and executive function were mainly impaired in MCI-AD group. Compared with MCI-SVD, MCI-AD patients performed relatively worse on memory tasks, but better on processing speed measures. The AVLT Long Delay Free Recall, Digit Symbol Test, and Stroop Test Part A (performance time) in combination categorized 91.1% of MCI-SVD patients and 86.7% of MCI-AD patients correctly. Current study suggested a nonspecific neuropsychological profile for MCI-SVD and a more specific cognitive pattern in MCI-AD. MCI-AD patients demonstrated greater memory impairment with relatively preserved mental processing speed compared with MCI-SVD patients. Tests tapping these two domains might be potentially useful for differentiating MCI-SVD and MCI-AD patients. (JINS, 2009, 15, 898–905.)

Download Full-text

Associations between blood and cerebrospinal fluid flow impairments assessed with phase-contrast MRI and brain damage in patients with age-related cerebral small vessel disease

Bulletin of Russian State Medical University ◽

10.24075/brsmu.2019.054 ◽

2019 ◽

pp. 16-23

Author(s):

E.I. Kremneva ◽

B.M. Akhmetzyanov ◽

L.A. Dobrynina ◽

M.V. Krotenkova

Keyword(s):

Cerebrospinal Fluid ◽

Brain Damage ◽

Phase Contrast ◽

Small Vessel Disease ◽

Cerebral Small Vessel Disease ◽

Small Vessel ◽

Csf Flow ◽

Phase Contrast Mri ◽

Vessel Disease ◽

Age Related

Hemodynamic parameters of blood and cerebrospinal fluid (CSF) flow can be measured in vivo using phase-contrast MRI (PC-MRI). This opens new horizons for studying the mechanisms implicated in the development and progression of age-related cerebral small vessel disease (SVD). In this paper, we analyze associations between cerebral arterial, venous and CSF flow impairments and SVD features visible on MRI. The study was carried out in 96 patients with SVD (aged 60.91 ± 6.57 years) and 23 healthy volunteers (59.13 ± 6.56 years). The protocol of the MRI examination included routine MRI sequences (T2, FLAIR, T1, SWI, and DWI) applied to assess the severity of brain damage according to STRIVE advisory standards and PC-MRI used to quantify blood flow in the major arteries and veins of the neck, the straight and upper sagittal sinuses, and CSF flow at the aqueduct level. We analyzed the associations between linear and volumetric parameters of blood/CSF flow and the degree of brain matter damage using the Fazekas scale. We observed a reduction in tABF, stVBF, sssVBF, aqLF, Saq, and ICC values and a rise in Pi associated with WMH progression, as well as a gradual decline in tABF and an increase in Pi, Saq and ICC associated with a growing number of lacunes (р < 0.05). Patients with early (< 5) MB had lower sssVBF and stVBF rates in comparison with patients without MB; aqLF, Saq, and ICC values were elevated in patients with 5 to 10 MB, as compared to patients without MB or early (< 5) MB. The established associations between MRI findings in patients with SVD and blood/CSF flow impairments suggest the important role of mechanisms implicated in the disruption of Monro–Kellie intracranial homeostasis in promoting SVD.

Download Full-text