scholarly journals Serum Neurofilament Light Chain Is Associated with Incident Lacunes in Progressive Cerebral Small Vessel Disease

2020 ◽  
Vol 22 (3) ◽  
pp. 369-376
Author(s):  
Nils Peters ◽  
Esther van Leijsen ◽  
Anil M. Tuladhar ◽  
Christian Barro ◽  
Marek J. Konieczny ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Analysis Of Covariance ◽  
Small Vessel ◽  
Cognitive Measures ◽  
Neurofilament Light ◽  
Baseline Serum ◽  
Vessel Disease

Background and Purpose Serum neurofilament light (NfL)-chain is a circulating marker for neuroaxonal injury and is also associated with severity of cerebral small vessel disease (SVD) cross-sectionally. Here we explored the association of serum-NfL with imaging and cognitive measures in SVD longitudinally.Methods From 503 subjects with SVD, baseline and follow-up magnetic resonance imaging (MRI) was available for 264 participants (follow-up 8.7±0.2 years). Baseline serum-NfL was measured by an ultrasensitive single-molecule-assay. SVD-MRI-markers including white matter hyperintensity (WMH)-volume, mean diffusivity (MD), lacunes, and microbleeds were assessed at both timepoints. Cognitive testing was performed in 336 participants, including SVD-related domains as well as global cognition and memory. Associations with NfL were assessed using linear regression analyses and analysis of covariance (ANCOVA).Results Serum-NfL was associated with baseline WMH-volume, MD-values and presence of lacunes and microbleeds. SVD-related MRI- and cognitive measures showed progression during follow-up. NfL-levels were associated with future MRI-markers of SVD, including WMH, MD and lacunes. For the latter, this association was independent of baseline lacunes. Furthermore, NfL was associated with incident lacunes during follow-up (P=0.040). NfL-levels were associated with future SVD-related cognitive impairment (processing speed: β=–0.159; 95% confidence interval [CI], –0.242 to –0.068; P=0.001; executive function β=–0.095; 95% CI, –0.170 to –0.007; P=0.033), adjusted for age, sex, education, and depression. Dementia-risk increased with higher NfL-levels (hazard ratio, 5.0; 95% CI, 2.6 to 9.4; P<0.001), however not after adjusting for age.Conclusions Longitudinally, serum-NfL is associated with markers of SVD, especially with incident lacunes, and future cognitive impairment affecting various domains. NfL may potentially serve as an additional marker for disease monitoring and outcome in SVD, potentially capturing both vascular and neurodegenerative processes in the elderly.

scholarly journals Serum neurofilament light is sensitive to active cerebral small vessel disease

Neurology ◽  
2017 ◽  
Vol 89 (20) ◽  
pp. 2108-2114 ◽  
Author(s):  
Thomas Gattringer ◽  
Daniela Pinter ◽  
Christian Enzinger ◽  
Thomas Seifert-Held ◽  
Markus Kneihsl ◽  
...  
Keyword(s):  
Single Molecule ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Cerebral Small Vessel Disease ◽  
Community Dwelling ◽  
Small Vessel ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Vessel Disease

Objective:To explore whether serum neurofilament light chain protein (NfL) levels are increased in patients with MRI-confirmed recent small subcortical infarcts (RSSI) compared to healthy controls and to determine the subsequent course and determinants of NfL levels in a longitudinal manner.Methods:In a prospectively collected group of symptomatic patients with an RSSI (n = 79, mean age 61 ± 11 years, 67% male), we analyzed brain MRI and serum NfL using a Single Molecule Array (Simoa) assay at baseline and at 3 and 15 months after stroke. Community-dwelling healthy age- and sex-matched individuals with comparable severity of MRI white matter hyperintensities (WMH) (n = 53) served as controls.Results:Patients with an RSSI had higher NfL baseline levels compared to controls (73.45 vs 34.59 pg/mL, p < 0.0001), and they were increasingly higher with the time from stroke symptom onset to blood sampling (median 4 days, range 1–11 days, rs = 0.51, p < 0.0001). NfL levels remained increased at the 3-month follow-up but returned to normal at 15 months after stroke. NfL levels were associated with RSSI size and baseline WMH severity and were especially high in patients with new, clinically silent cerebral small vessel disease (CSVD)–related lesions at follow-up.Conclusions:Serum NfL is increased in patients with an RSSI and the occurrence of new CSVD-related MRI lesions, even when clinically silent. This suggests NfL as a blood biomarker for active CSVD.

Abstract P626: Periodontal Disease is Independently Associated With Cerebral Small Vessel Disease

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Forrest Lowe ◽  
Souvik Sen ◽  
Hamdi S Adam ◽  
Ryan Demmer ◽  
Bruce A Wasserman ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Periodontal Disease ◽  
Small Vessel Disease ◽  
Multinomial Logistic Regression ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
White Matter Hyperintensity ◽  
Periodontal Health ◽  
Vessel Disease ◽  
The Relationship

Background: Prior studies have shown the association between periodontal disease, lacunar strokes and cognitive impairment. Using the Atherosclerosis Risk in Communities (ARIC) cohort study we investigated the relationship between periodontal disease (PD) and the development of MRI verified small vessel disease. Methods: Using the ARIC database data we extracted data for 1143 (mean age 77 years, 76% white, 24% African-American and 45% male) participants assessed for PD (N=800) versus periodontal health (N=343). These participants were assessed for small vessel disease on 3T MRI as measured by the log of white matter hyperintensity volume (WMHV). WMHV were derived from a semiautomated segmentation of FLAIR images. Student t-test was then used to evaluate the relationship between small vessel disease as the log of WMHV in subjects with PD or periodontal health. Based on WMHV the patients were grouped into quartiles and the association of PD with WMHV were tested using the group in periodontal health and lowest quartile of WMHV as the reference groups. Multinomial logistic regression was used to compute crude and adjusted odds ratio (OR) for the higher quartiles of WMHV compared to the reference quartile. Results: There was a significant increase in the presence of small vessel disease measured as log WMHV in the PD cohort as compared to periodontal health cohort with p= 0.023 on Independent Sample t-est. Based on WMHV the subjects were grouped into quartiles 0-6.41, >6.41-11.56, >11.56-21.36 and >21.36 cu mm3). PD was associated with only the highest quartile of WMHV on univariate (crude OR 1.77, 95% CI 1.23-2.56) and multivariable (adjusted OR 1.61, 95% CI 1.06-2.44) analyses. The later was adjusted for age, race, gender, hypertension, diabetes and smoking. Conclusion: Based on this prospective cohort there is data to suggest that PD may be associated with cerebral small vessel disease. Maintaining proper dental health may decrease future risk for the associated lacunar strokes and vascular cognitive impairment.

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

2009 ◽  
Vol 15 (6) ◽  
pp. 898-905 ◽  
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.)

Abstract TMP119: High Homocysteine Level is not Associated With White Matter Changes, Dementia nor Mortality After Ischemic Stroke

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Susanna Melkas ◽  
Sami Curtze ◽  
Gerli Sibolt ◽  
Niku K Oksala ◽  
Jukka Putaala ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Homocysteine Level ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Cross Sectional ◽  
White Matter Changes ◽  
Vessel Disease

Background: Association between high homocysteine level and cerebral small-vessel disease has been implicated in cross-sectional studies, but results from longitudinal studies have been less clear. The aim of this study was to investigate whether homocysteine level at 3-months poststroke relates to the occurrence of white matter changes (WMC), the surrogate of cerebral small-vessel disease. We also investigated whether it relates to the prognosis after ischemic stroke regarding the risk of dementia at 3-months and mortality in long-term follow-up. Methods: A total of 321 consecutive acute ischemic stroke patients aged 55 to 85 were included in the study and followed up to 12 years. Plasma homocysteine level and occurrence of WMC in MRI were measured 3 months poststroke and dementia according to DSM-III was evaluated at the same time. Findings: The median homocysteine level was 13.50 μmol/l (interquartile range [IQR] 10.60-18.50 μmol/l). Total of 81 patients (25.2%) had homocysteine level above 18.50 μmol/l. In logistic regression analysis, homocysteine level above 18.50 μmol/l was not associated with severe WMC nor with dementia at 3 months poststroke. In Kaplan-Meier analysis, homocysteine level above 18.50 μmol/l was not associated with survival in 12-year follow-up. For further analysis, the group was divided in quartiles according to homocysteine level. The quartiles did not differ in occurrence of severe WMC at baseline, in the risk of dementia at 3 months, nor in the risk of mortality in 12-year follow-up. Interpretation: In our poststroke cohort homocysteine level is not associated with WMC. Further, it does not relate to impaired prognosis manifested as dementia at 3 months or mortality in 12-year follow-up.

Brain amyloid β, cerebral small vessel disease, and cognition

Neurology ◽  
2020 ◽  
Vol 95 (21) ◽  
pp. e2845-e2853 ◽  
Author(s):  
Francis N. Saridin ◽  
Saima Hilal ◽  
Steven G. Villaraza ◽  
Anthonin Reilhac ◽  
Bibek Gyanwali ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Small Vessel Disease ◽  
Neuropsychological Testing ◽  
Amyloid Β ◽  
Standardized Uptake Value ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Memory Clinic ◽  
Alzheimer Dementia ◽  
Vessel Disease

ObjectiveTo evaluate the association between brain amyloid β (Aβ) and cerebral small vessel disease (CSVD) markers, as well as their joint effect on cognition, in a memory clinic study.MethodsA total of 186 individuals visiting a memory clinic, diagnosed with no cognitive impairment, cognitive impairment no dementia (CIND), Alzheimer dementia (AD), or vascular dementia were included. Brain Aβ was measured by [11C] Pittsburgh compound B–PET global standardized uptake value ratio (SUVR). CSVD markers including white matter hyperintensities (WMH), lacunes, and cerebral microbleeds (CMBs) were graded on MRI. Cognition was assessed by neuropsychological testing.ResultsAn increase in global SUVR is associated with a decrease in Mini-Mental State Examination (MMSE) in CIND and AD, as well as a decrease in global cognition Z score in AD, independent of age, education, hippocampal volume, and markers of CSVD. A significant interaction between global SUVR and WMH was found in relation to MMSE in CIND (P for interaction: 0.009), with an increase of the effect size of Aβ (β = −6.57 [−9.62 to −3.54], p < 0.001) compared to the model without the interaction term (β = −2.91 [−4.54 to −1.29], p = 0.001).ConclusionHigher global SUVR was associated with worse cognition in CIND and AD, but was augmented by an interaction between global SUVR and WMH only in CIND. This suggests that Aβ and CSVD are independent processes with a possible synergistic effect between Aβ and WMH in individuals with CIND. There was no interaction effect between Aβ and lacunes or CMBs. Therefore, in preclinical phases of AD, WMH should be targeted as a potentially modifiable factor to prevent worsening of cognitive dysfunction.

scholarly journals Microstructural Predictors of Cognitive Impairment in Cerebral Small Vessel Disease and the Conditions of Their Formation

Diagnostics ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 720
Author(s):  
Larisa A. Dobrynina ◽  
Zukhra Sh. Gadzhieva ◽  
Kamila V. Shamtieva ◽  
Elena I. Kremneva ◽  
Bulat M. Akhmetzyanov ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cognitive Impairment ◽  
White Matter ◽  
Diffusion Tensor ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Venous Blood Flow ◽  
Csf Flow ◽  
Vessel Disease

Introduction: Cerebral small vessel disease (CSVD) is the leading cause of vascular and mixed degenerative cognitive impairment (CI). The variability in the rate of progression of CSVD justifies the search for sensitive predictors of CI. Materials: A total of 74 patients (48 women, average age 60.6 ± 6.9 years) with CSVD and CI of varying severity were examined using 3T MRI. The results of diffusion tensor imaging with a region of interest (ROI) analysis were used to construct a predictive model of CI using binary logistic regression, while phase-contrast magnetic resonance imaging and voxel-based morphometry were used to clarify the conditions for the formation of CI predictors. Results: According to the constructed model, the predictors of CI are axial diffusivity (AD) of the posterior frontal periventricular normal-appearing white matter (pvNAWM), right middle cingulum bundle (CB), and mid-posterior corpus callosum (CC). These predictors showed a significant correlation with the volume of white matter hyperintensity; arterial and venous blood flow, pulsatility index, and aqueduct cerebrospinal fluid (CSF) flow; and surface area of the aqueduct, volume of the lateral ventricles and CSF, and gray matter volume. Conclusion: Disturbances in the AD of pvNAWM, CB, and CC, associated with axonal damage, are a predominant factor in the development of CI in CSVD. The relationship between AD predictors and both blood flow and CSF flow indicates a disturbance in their relationship, while their location near the floor of the lateral ventricle and their link with indicators of internal atrophy, CSF volume, and aqueduct CSF flow suggest the importance of transependymal CSF transudation when these regions are damaged.

scholarly journals Protocol: The Lacunar Intervention Trial 2 (LACI-2). A trial of two repurposed licenced drugs to prevent progression of cerebral small vessel disease

2020 ◽  
Vol 5 (3) ◽  
pp. 297-308
Author(s):  
Joanna Wardlaw ◽  
Philip M W Bath ◽  
Fergus Doubal ◽  
Anna Heye ◽  
Nikola Sprigg ◽  
...  
Keyword(s):  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Large Trial ◽  
Intervention Trial ◽  
Vascular Events ◽  
Phase 3 ◽  
Full Dose ◽  
Vessel Disease

Background Small vessel disease causes a quarter of ischaemic strokes (lacunar subtype), up to 45% of dementia either as vascular or mixed types, cognitive impairment and physical frailty. However, there is no specific treatment to prevent progression of small vessel disease. Aim We designed the LACunar Intervention Trial-2 (LACI-2) to test feasibility of a large trial testing cilostazol and/or isosorbide mononitrate (ISMN) by demonstrating adequate participant recruitment and retention in follow-up, drug tolerability, safety and confirm outcome event rates required to power a phase 3 trial. Methods and design LACI-2 is an investigator-initiated, prospective randomised open label blinded endpoint (PROBE) trial aiming to recruit 400 patients with prior lacunar syndrome due to a small subcortical infarct. We randomise participants to cilostazol v no cilostazol and ISMN or no ISMN, minimising on key prognostic factors. All patients receive guideline-based best medical therapy. Patients commence trial drug at low dose, increment to full dose over 2–4 weeks, continuing on full dose for a year. We follow-up participants to one year for symptoms, tablet compliance, safety, recurrent vascular events, cognition and functional outcomes, Trails B and brain MRI. LACI-2 is registered ISRCTN 14911850, EudraCT 2016–002277-35. Trial outcome: Primary outcome is feasibility of recruitment and compliance; secondary outcomes include safety (cerebral or systemic bleeding, falls, death), efficacy (recurrent cerebral and cardiac vascular events, cognition on TICS, Trails B) and tolerability. Summary LACI-2 will determine feasibility, tolerability and provide outcome rates to power a large phase 3 trial to prevent progression of cerebral small vessel disease.

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