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

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Kaori Miwa ◽  
Shuhei Okazaki ◽  
Yoshiki Yagita ◽  
Manabu Sakaguchi ◽  
Hideki Mochizuki ◽  
...  

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.

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Yuan Wang ◽  
Haiqing Song ◽  
Kai Dong ◽  
Ran Meng ◽  
Shuying Wang ◽  
...  

Objective: To evaluate the preliminary efficacy of remote ischemic conditioning (RIC) on patients with cerebral small vessel disease (SVD). Methods: Thirty patients diagnosed with symptomatic SVD within 30 days of onset were enrolled in this prospectively randomized controlled study for 1 year. All patients received routine medical treatment including treating vascular risk factors according to the guideline. Patients in the experimental group (n=14) were administered 5 cycles consisting of ischemia followed by reperfusion for 5 minutes on bilateral upper limbs twice daily for 1 year. Those in the control group (n=16) underwent sham ischemia-reperfusion cycles. Primary outcome was the change of cognitive function measured by mini-mental state examination (MMSE) and montreal cognitive assessment scale (MoCA), and secondary outcomes were changes of plasma biomarkers, cerebral hemodynamic parameters measured by vascular ultrasound and brain lesions measured by MRI FLAIR both at baseline and at the end of 1 year visit. Results: Compared with patients in the control group, patients in the RIC group had higher flow velocity (FV), and lower pulsatility index (PI), but without statistical difference. Patients in the RIC group had improvement in visuospatial and executive abilities (3.86±1.03 vs. 4.43±0.85, p=0.026), reduced plasma triglyceride (1.60±0.74 vs. 1.25±0.38, p=0.019), low density lipoprotein (2.89±0.81 vs. 2.26±0.67, p=0.003) and homocysteine (15.66±10.11 vs. 13.66±9.80 p=0.017). Similarly in the RIC group, the diastolic flow velocity (DFV) of middle cerebral artery (MCA) (right: 33.93±7.67 vs. 36.93±6.12, p=0.032; left: 33.93±7.67 vs. 36.93± 6.12, p=0.032) and the mean flow velocity (MFV) of left MCA (35.00±5.04 vs. 39.50±5.59, p=0.003) increased, and the PI of MCA (right: 1.11±0.19 vs. 1.02±0.14 p=0.030; left: 1.10±0.22 vs. 0.99±0.14, p=0.037) decreased. Conclusion: RIC appears to be potentially effective for improving cognition, enhancing cerebral perfusion, and modifying vascular risk factors in SVD patients. Further studies focusing on long-term neurological outcomes and potential mechanisms underlying RIC on SVD patients are needed.


2020 ◽  
Vol 9 (16) ◽  
Author(s):  
Anna Laveskog ◽  
Rui Wang ◽  
Davide L. Vetrano ◽  
Lena Bronge ◽  
Lars‐Olof Wahlund ◽  
...  

Background Evidence suggests that enlarged perivascular spaces (PVSs) may represent a marker for cerebral small‐vessel disease. We investigated whether vascular risk factors are correlated with visible PVS in older adults. Methods and Results This population‐based study included 530 participants (age ≥60 years) who were free from dementia and functional dependence, derived from the Swedish National study on Aging and Care in Kungsholmen (2001–2003). We collected data on demographics, vascular risk factors, and health conditions through interviews, clinical examinations, laboratory tests, and patient registers. Cerebral PVSs and white matter hyperintensities on magnetic resonance images were visually assessed with semiquantitative visual rating scales. Data were analyzed using the general linear regression models. After controlling for demographics and cardiovascular disease, very high blood pressure (≥160/100 mm Hg) was significantly associated with global PVS score (β‐coefficient, 1.30; 95% CI, 0.06–2.53) and orthostatic hypotension was associated with PVS score in the basal ganglia (β‐coefficient 0.37; 0.03–0.70), but the associations became non‐significant when adjusting for white matter hyperintensity load. Orthostatic hypotension was significantly associated with global and lobar PVS scores in carriers but not in noncarriers of the APOE ε4 allele. Global or regional PVS score was not significantly associated with other traditional vascular risk factors such as smoking, diabetes mellitus, physical inactivity, and overweight or obesity. Conclusions This study provides limited evidence supporting a correlation of magnetic resonance imaging–visible PVS with traditional vascular risk factors in older adults. The association of orthostatic hypotension with lobar PVS among APOE ε4 carriers suggests that lobar PVS may be a marker for amyloid‐associated small‐vessel disease.


Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Matthew S Markert ◽  
Chuanhui Dong ◽  
David Della-Morte ◽  
Eugene Roberts ◽  
Susanne Bartels ◽  
...  

Background: Changes in the extracranial vasculature may be associated with small vessel disease in the brain. We sought to examine the association of carotid stiffness and carotid diastolic diameter with white matter hyperintensity volume (WMHV), a magnetic resonance imaging (MRI) measure for cerebral small vessel disease, in a multi-ethnic community-based cohort. Methods: We evaluated 1140 stroke-free participants in the Northern Manhattan study who underwent brain MRIs and high-resolution carotid ultrasounds. We used linear regression to examine carotid stiffness and diastolic diameter with WMHV after adjusting for sociodemographics, lifestyle behaviors, and traditional vascular risk factors. Results: Among 1140 participants (mean age: 70.6±9.0 years; 61% women; 15% White, 16% Black, 59% Hispanics), the mean carotid stiffness was 8.19 ± 5.39, mean carotid diastolic diameter was 6.16 ± 0.93 mm, and mean WMHV 0.68 ± 0.84. In a fully adjusted model, diastolic diameter was associated with log-WMHV (β=0.10, p=0.001). In a stratified multivariable linear model, greater carotid arterial stiffness and diastolic diameter were associated with log-WMHV among Hispanics (β=0.15, p=0.005 and β=0.13, p<0.001, respectively), but not among blacks or whites. Conclusion: Greater carotid stiffness and diastolic diameter were associated with greater WMHV independent of demographics and traditional vascular risk factors, especially among Hispanics. Further studies are needed to understand how these large artery characteristics relate to WMH formation and lesion load. Carotid ultrasound may be a useful tool to assess the risk of increased brain white matter disease in a pre-clinical stage.


2020 ◽  
Vol 12 (3) ◽  
pp. 416-421
Author(s):  
Hilde van den Brink ◽  
Nick A. Weaver ◽  
Geert Jan Biessels

Sporadic cerebral small vessel disease (cSVD) is primarily attributed to heritability and vascular risk factors. Still, our understanding of the causative factors in cSVD lesion burden in the brain is far from complete. This is exemplified by this case of identical twins with remarkably similar vascular risk profiles, where one twin had developed severe cSVD on neuroimaging with cognitive deficits, while the other twin had no cSVD. This case highlights the need to search for further causes of cSVD, also beyond genetic and conventional vascular risk factors. Identification of other potential risk factors or disease mechanisms should be a priority for cSVD research to improve our understanding, prevention and treatment of this common cause of vascular brain injury with major clinical consequences.


Neurology ◽  
2014 ◽  
Vol 83 (14) ◽  
pp. 1228-1234 ◽  
Author(s):  
J. Staals ◽  
S. D. J. Makin ◽  
F. N. Doubal ◽  
M. S. Dennis ◽  
J. M. Wardlaw

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Kaori Miwa ◽  
Shuhei Okazaki ◽  
Manabu Sakaguchi ◽  
Hideki Mochizuki ◽  
Kazuo Kitagawa

Objective: Long-chain omega-3 polyunsaturated fatty acids (PUFAs) have been identified as a potential protective factor for vascular events and cognitive impairment. However, few prospective studies have so far explored the impact of PUFAs on dementia while simultaneously controlling for MRI-findings, such as cerebral small-vessel disease (SVD) and brain atrophy. Methods: Within a cohort of Japanese participants with vascular risk factors and free of dementia, we evaluated the association between PUFAs levels, MRI-findings at baseline, and incident all-cause dementia. Circulating plasma levels of omega-3 (ie, eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]) and omega-6 (ie, dihomo-γ-linolenic acid [DGLA], arachidonic acid [AA]) PUFAs were measured at baseline. Baseline brain MRI was used to determine SVD (lacunas, white matter hyperintensities and cerebral microbleeds) and atrophy (medial-temporal lobe atrophy and bicaudate ratio). Logistic regression analyses were used to estimate the cross-sectional association between tertile of each PUFAs and MRI-findings. Cox proportional hazards analyses were performed to estimate the longitudinal association between PUFAs and dementia, adjusting for age, sex, APOEε4, educational level, vascular risk factors, cerebrovascular events, estimated glomerular filtration rate, and MRI-findings. Results: In the 613 subjects (age: 67.3 ± 8.4 years, male: 59%), multivariable analyses adjusted for potential confounders showed that any PUFAs was not significantly associated with each of SVD. During the mean 7.5-year follow-up (range: 3-13), 48 subjects were diagnosed with dementia (Alzheimer’s disease:24; vascular dementia:18; mixed-type:4; other: 2). In multivariable Cox models adjusted for confounders, the relative risk of all-cause dementia was 0.42 (95%CI, 0.17-0.96, p=0.040) in the highest versus lowest tertile of DHA levels. However, no significant associations with dementia were observed for circulating EPA, EPA/AA ratio, or omega-6 PUFAs. Conclusions: Our results provide additional evidence of DHA may be associated with lower risk of dementia.


Sign in / Sign up

Export Citation Format

Share Document