The impact of vascular risk factors on brain volume and lesion load in patients with early multiple sclerosis

Background: Vascular risk factors (VRF) in multiple sclerosis (MS) patients have been associated with lower brain volumes. It is currently unknown if this association already exists in early MS and how it develops over time. Methods: We identified 82 patients with clinically isolated syndrome (CIS) ( n = 61) or with early relapsing-remitting MS ( n = 21) and assessed their VRF including arterial hypertension, hyperlipidaemia, diabetes mellitus and smoking. We analysed T2-lesion load, normalized brain volume (NBV), cortical grey (cGMV) and white matter volumes (WMV), thalamic and basal ganglia volumes at baseline and follow-up magnetic resonance imaging (MRI) and assessed the percentage of brain volume change (PBVC) using SIENA. Results: Patient mean age was 32.4 (±8.7) years and 54 (65%) were women. Median follow-up period was 42 (29–54) months. In total, 26 patients (31.7%) had one or more VRF (VRF+). At baseline, VRF+ patients had a lower NBV (1530.9 cm3 vs 1591.2 cm3, p = 0.001), a lower cGMV (628.5 cm3 vs 668.6 cm3, p = 0.002) and WMV (752.2 cm3 vs 783.9 cm3, p = 0.009) than VRF-negative patients. Similar results were obtained at follow-up. PBVC was comparable between patients with and without VRF. Conclusion: VRF are associated with lower brain volume already in early MS but do not lead to increased brain volume loss during 3.5 years of follow-up.

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Childhood multiple sclerosis is associated with reduced brain volumes at first clinical presentation and brain growth failure

Multiple Sclerosis Journal ◽

10.1177/1352458519829698 ◽

2019 ◽

Vol 25 (7) ◽

pp. 927-936 ◽

Cited By ~ 8

Author(s):

Frederik Bartels ◽

Katharina Nobis ◽

Graham Cooper ◽

Eva Wendel ◽

Robert Cleaveland ◽

...

Keyword(s):

Multiple Sclerosis ◽

White Matter ◽

Clinical Presentation ◽

Brain Volume ◽

Volume Loss ◽

Brain Growth ◽

Whole Brain ◽

Brain Volumes ◽

Brain Volume Loss

Background: Paediatric multiple sclerosis (pedMS) patients at a single site were shown to have reduced brain volumes and failure of age-expected brain growth compared to healthy controls. However, the precise time of onset of brain volume loss remains unclear. Objective: To longitudinally study brain volumes in a multi-centre European cohort at first presentation and after 2 years. Methods: Brain volumes of high-resolution magnetic resonance imaging (MRI) data from 37 pedMS patients at first presentation prior to steroid therapy and at 2-year follow-up ( n = 21) were compared to matched longitudinal MRI data from the NIH Paediatric MRI Data Repository. Results: Patients showed significantly reduced whole brain, grey and white matter and increased ventricular volumes at initial presentation and at follow-up compared to controls. Over 2 years, patients exhibited significant reduction of whole brain and white matter volumes, accompanied by increased ventricular volume. Brain volume loss at follow-up correlated with a higher number of infratentorial lesions, relapses and an increased Expanded Disability Status Scale (EDSS) score. Conclusions: In pedMS patients, brain volume loss is present already at first clinical presentation and accelerated over 2 years. Increased disease activity is associated with more severe brain volume loss. MRI brain volume change might serve as an outcome parameter in future prospective pedMS studies.

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The impact of vascular risk factors on the thickness and volume of the choroid in AMD patients

Scientific Reports ◽

10.1038/s41598-021-94676-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Elżbieta Krytkowska ◽

Aleksandra Grabowicz ◽

Katarzyna Mozolewska-Piotrowska ◽

Zofia Ulańczyk ◽

Krzysztof Safranow ◽

...

Keyword(s):

Risk Factors ◽

Vascular Risk Factors ◽

Age Related Macular Degeneration ◽

Control Group ◽

Vascular Risk ◽

Average Volume ◽

Central Ring ◽

Age Related ◽

The Impact ◽

Wet Amd

AbstractDisturbances in choroidal microcirculation may lead to the onset and progression of age-related macular degeneration (AMD). We aimed to assess changes in the choroidal volume and thickness in the macular region in AMD eyes and to investigate whether coexisting vascular risk factors alter choroidal status. We enrolled 354 AMD patients (175 dry, 179 wet AMD) and 121 healthy controls. All participants underwent a complete ophthalmologic examination and assessment of choroidal thickness and volume. A multivariate analysis adjusted for age, sex, and smoking status revealed that wet AMD was an independent factor associated with higher average thickness of the central ring area (ATC) and average volume of the central ring area (AVC) and lower choroidal vascularity index (CVI) compared to controls (β = + 0.18, p = 0.0007, β = + 0.18, p = 0.0008, respectively) and to dry AMD (β = + 0.17, p = 0.00003 for both ATC and AVC and β = − 0.30 p < 0.0001 for CVI). ATC, AVC and average volume (AV) were lower in AMD patients with hypertension and ischaemic heart disease (IHD). The duration of hypertension was inversely correlated with ATC, AVC and AV (Rs = − 0.13, p < 0.05; Rs = − 0.12; p < 0.05, Rs = − 0.12; p < 0.05, respectively) while IHD duration negatively correlated with AV (Rs = − 0.15, p < 0.05). No such associations were observed in the control group. Our findings show that the choroidal vascular system in eyes with AMD is much more susceptible to damage in the presence than in the absence of systemic vascular disease.

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Abstract WP244: Applicability of the Compass Trial Criteria Among Stable Outpatients With Established Atherothrombotic Disease or Major Risk Factors

Stroke ◽

10.1161/str.51.suppl_1.wp244 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Carlos Cantu-Brito ◽

Erwin Chiquete ◽

Jose L Ruiz-Sandoval ◽

Fernando Flores-Silva

Keyword(s):

Risk Factors ◽

Cerebrovascular Disease ◽

Selection Criteria ◽

Vascular Risk Factors ◽

Cox Proportional Hazards Model ◽

Vascular Risk ◽

Similar Frequency ◽

History Of ◽

Atherothrombotic Disease

Background and Purpose: The objective of this study were to describe the proportion of patients eligible for the COMPASS trial among stable outpatients with either established atherothrombotic disease or major vascular risk factors, and to analyze 6-month incident stroke risk according vascular risk factors at baseline. Methods: We prospectively recruited 5,101 stable outpatients in 172 sites, within the Mexican INDAGA cohort study. Inclusion criteria were age >18 years and established atherothrombotic disease [history of either acute coronary syndromes (ACS), acute ischemic stroke (AIS)/transient ischemic attack (TIA) or peripheral artery disease (PAD)] or major vascular risk factors (age <55 years plus ≥2 major vascular risk factors, or age ≥55 years plus ≥1 vascular risk factors). Among these patients, we applied the selection criteria of the COMPASS trial for analysis, dividing the population in no COMPASS criteria met and COMPASS criteria met, and this last group subdivided among patients with previous AIS/TIA and without this antecedent, in order to stratify the risk for stroke during 6-month follow-up (incident AIS/TIA). Results: Among 5,101 stable outpatients with either established atherothrombotic disease (n=2,827) or major vascular risk factors (n=2,274), a total of 1,927 (37.8%) met COMPASS trial criteria: 1,054 (54.7%) with established cerebrovascular disease (past history of AIS/TIA) and 873 (45.3%) without. During 6-month follow-up, there were 89 incident AIS/TIA (39 AIS and 54 TIA): 1.7% among the whole population and 2.2% among the COMPASS subgroup. AIS/TIA occurred in a similar frequency among the COMPASS subgroup with established cerebrovascular disease (1.6%) and COMPASS without cerebrovascular disease (0.9%) (P=0.18). After a Cox-proportional hazards model, independent predictors of incident AIS/TIA were age ≥65 years (HR: 1.99, 95% CI: 1.29-3.07) and established cerebrovascular disease at baseline (HR: 1.61, 95% CI: 1.02-2.53). Conclusions: The majority of stable outpatients at vascular risk met COMPASS selection criteria and could be good candidates for low-dose rivaroxaban in addition to aspirin. Short-term predictors of AIS/TIA were old age and history of cerebrovascular disease

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Vascular risk at younger ages most strongly associates with current and future brain volume

Neurology ◽

10.1212/wnl.0000000000006360 ◽

2018 ◽

Vol 91 (16) ◽

pp. e1479-e1486 ◽

Cited By ~ 14

Author(s):

Matthew P. Pase ◽

Kendra Davis-Plourde ◽

Jayandra J. Himali ◽

Claudia L. Satizabal ◽

Hugo Aparicio ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Stroke Risk ◽

Brain Volume ◽

Vascular Risk Factor ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Cross Sectional ◽

Strength Of Association ◽

Risk Factor Burden

ObjectiveGiven the potential therapeutic effect of vascular disease control timing to reduce dementia risk, we investigated the age-related influences of vascular risk factor burden on brain structure throughout the lifespan.MethodsWe studied participants from the community-based prospective Framingham Heart Study. Overall vascular risk factor burden was calculated according to the Framingham Stroke Risk Profile, a validated algorithm that predicts stroke risk. Brain volume was estimated by MRI. We used cross-sectional data to examine how the strength of association between vascular risk factor burden and brain volume changed across each age decade from age 45–54 years through to 85–94 years (N = 2,887). Second, we leveraged up to 40 years of longitudinal data to determine how the strength of association between vascular risk factor burden and brain volume changed when vascular risk factors were examined at progressively earlier ages (N = 7,868).ResultsIn both cross-sectional and longitudinal analyses, higher vascular risk factor burden was associated with lower brain volume across each age decade. In the cross-sectional analysis, the strength of this association decreased with each decade of advancing age (p for trend < 0.0001). In longitudinal analysis, the strength of association between vascular risk factor burden and brain volume was stronger when vascular risk factors were measured at younger ages. For example, vascular risk factor burden was most strongly associated with lower brain volume in later life when vascular risk factors were measured at age 45 years.ConclusionVascular risk factors at younger ages appear to have detrimental effects on current and future brain volume.

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Abstract 224: Increased Total Homocysteine Levels Are Associated With the Risk of Dementia Independently of Cerebral Small-vessel Disease

Stroke ◽

10.1161/str.46.suppl_1.224 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Kaori Miwa ◽

Shuhei Okazaki ◽

Yoshiki Yagita ◽

Manabu Sakaguchi ◽

Hideki Mochizuki ◽

...

Keyword(s):

Risk Factors ◽

Small Vessel Disease ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Mri Findings ◽

Vessel Disease ◽

Cerebrovascular Events ◽

Multivariable Analyses ◽

Total Homocysteine

Objectives: Increased serum total homocysteine (tHcy) levels have been associated with not only vascular injury but also dementia. However, given an association between Hcy and vascular injury, such as cerebral small-vessel disease (SVD) or renal impairment, to what extent Hcy would impact future dementia beyond these confouders is unknown. We assessed the predictive value of tHcy levels with the risk of dementia in patients with vascular risk factors, when controlling for the MRI-findings and renal imapirment. Methods: Within a Japanese cohort of partients with vascular risk factors in an observational study from 2001, we evaluated the association between tHcy levels at baseline, defined as a continuous variable (per 1 μmol/L) and as a categorical variable (the tertile of tHcy), the prevalence of MRI-findings, and incident all-cause dementia during follow-up. Baseline brain MRI was used to determine SVD (lacuna, white matter hyperintensities and cerebral microbleeds [CMBs]) and atrophy (medial-temporal lobe atrophy). Cox proportional hazards analyses were performed for predictors of dementia adjusting for age, sex, APOEε4 allele, educational level, cerebrovascular events, estimated glomerular filtration rate (eGFR), vascular risk factors, and MRI-findings. Results: Of the 643 subjects (mean:67.2±8.4years, male:59%, 12.9±2.6years of schooling), in multivariable analyses adjusted for age, sex, hypertension, cerebrovascular events, eGFR, and intima-media thickness, the highest tHcy tertile (vs lowest) were associated with lacuna, CMBs and strictly deep CMBs, respectively. During the mean 7.3-year follow-up (range:3-13), 47 incident dementia patients (Alzheimer’s disease:24; vascular dementia:18; mixed-type:3; other:2) were diagnosed. In multivariable analyses adjusted for age, sex, cerebrovascular events, eGFR, and MRI-findings, tHcy level or the highest tertile of tHcy for all-cause dementia remained significant, respectively (relative risk [RR]1.09: p=0.02, RR;2.59: p=0.021). Conclusions: Our results provide additional evidence of Hcy that leads to increased susceptibility to the risk of dementia, suggesting that this association may be mediated by independent mechanisms.

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