Increased Total Homocysteine Levels Predict the Risk of Incident Dementia Independent of Cerebral Small-Vessel Diseases and Vascular Risk Factors

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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Association between carotid stenosis or lacunar infarction and incident dementia in patients with vascular risk factors

European Journal of Neurology ◽

10.1111/ene.12553 ◽

2014 ◽

Vol 22 (1) ◽

pp. 187-192 ◽

Cited By ~ 10

Author(s):

K. Kitagawa ◽

K. Miwa ◽

Y. Yagita ◽

S. Okazaki ◽

M. Sakaguchi ◽

...

Keyword(s):

Risk Factors ◽

Carotid Stenosis ◽

Vascular Risk Factors ◽

Lacunar Infarction ◽

Vascular Risk ◽

Incident Dementia

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Abstract W MP58: The Relationship Between Carotid Stiffness, Diastolic Diameter, and White Matter Hyperintensity Volume: The Northern Manhattan Study

Stroke ◽

10.1161/str.45.suppl_1.wmp58 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Matthew S Markert ◽

Chuanhui Dong ◽

David Della-Morte ◽

Eugene Roberts ◽

Susanne Bartels ◽

...

Keyword(s):

Risk Factors ◽

White Matter ◽

Small Vessel Disease ◽

Vascular Risk Factors ◽

Small Vessel ◽

White Matter Hyperintensity ◽

Large Artery ◽

Vascular Risk ◽

Vessel Disease ◽

Carotid Stiffness

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.

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Vascular risk factors as independent predictors of neurocognitive impairments in patients with late-onset epilepsy who have small-vessel disease

Epilepsy & Behavior ◽

10.1016/j.yebeh.2019.106443 ◽

2020 ◽

Vol 104 ◽

pp. 106443 ◽

Cited By ~ 1

Author(s):

Marc Turon ◽

Laura Abraira ◽

Sonia Cazorla ◽

Elena Fonseca ◽

Manuel Quintana ◽

...

Keyword(s):

Risk Factors ◽

Small Vessel Disease ◽

Late Onset ◽

Vascular Risk Factors ◽

Small Vessel ◽

Vascular Risk ◽

Vessel Disease ◽

Neurocognitive Impairments

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Serum high‐molecular‐weight adiponectin level and incident dementia in patients with vascular risk factors

European Journal of Neurology ◽

10.1111/ene.12915 ◽

2015 ◽

Vol 23 (3) ◽

pp. 641-647 ◽

Cited By ~ 15

Author(s):

K. Kitagawa ◽

K. Miwa ◽

S. Okazaki ◽

M. Sakaguchi ◽

H. Mochizuki

Keyword(s):

Risk Factors ◽

Molecular Weight ◽

High Molecular Weight ◽

Adiponectin Level ◽

Vascular Risk Factors ◽

Vascular Risk ◽

High Molecular Weight Adiponectin ◽

Incident Dementia

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Characterization of Lenticulostriate Arteries and Its Associations With Vascular Risk Factors in Community-Dwelling Elderly

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2021.685571 ◽

2021 ◽

Vol 13 ◽

Author(s):

Xiaopei Xu ◽

Xiao Wu ◽

Chengcheng Zhu ◽

Ruiting Zhang ◽

Yeerfan Jiaerken ◽

...

Keyword(s):

Risk Factors ◽

Cerebral Artery ◽

Vascular Risk Factors ◽

Community Dwelling ◽

Small Vessel ◽

Imaging Biomarkers ◽

Elderly Subjects ◽

Vascular Risk ◽

Lenticulostriate Arteries ◽

Vessel Tortuosity

Lenticulostriate arteries (LSAs) supply blood to important subcortical areas and are, therefore, essential for maintaining the optimal functioning of the brain’s most metabolically active nuclei. Past studies have demonstrated the potential for quantifying the morphology of LSAs as biomarkers of vascular fragility or underlying arteriopathies. Thus, the current study aims to evaluate the morphological features of LSAs, their potential value in cerebrovascular risk stratification, and their concordance with other vascular risk factors in community-dwelling elderly people. A total of 125 community-dwelling elderly subjects who underwent a brain MRI scan were selected from our prospectively collected imaging database. The morphological measures of LSAs were calculated on the vascular skeletons obtained by manual tracing, and the number of LSAs was counted. Additionally, imaging biomarkers of small vessel disease were evaluated, and the diameters of major cerebral arteries were measured. The effects of vascular risk factors on LSA morphometry, as well as the relationship between LSA measures and other imaging biomarkers, were investigated. We found that smokers had shorter (p = 0.04) and straighter LSAs (p < 0.01) compared to nonsmokers, and the presence of hypertension is associated with less tortuous LSAs (p = 0.03) in community-dwelling elderly. Moreover, the middle cerebral artery diameter was positively correlated with LSA count (r = 0.278, p = 0.025) and vessel tortuosity (r = 0.257, p = 0.04). The posterior cerebral artery diameter was positively correlated with vessel tortuosity and vessel length. Considering the scarcity of noninvasive methods for measuring small artery abnormalities in the brain, the LSA morphological measures may provide valuable information to better understand cerebral small vessel degeneration during aging.

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Abstract 98: Midlife Vascular Risk Factors and Incident Dementia in the ARIC Cohort

Stroke ◽

10.1161/str.48.suppl_1.98 ◽

2017 ◽

Vol 48 (suppl_1) ◽

Author(s):

Rebecca F Gottesman ◽

Marilyn Albert ◽

Laura Coker ◽

Josef Coresh ◽

Sonia M Davis ◽

...

Keyword(s):

Risk Factors ◽

Cognitive Status ◽

Vascular Risk Factors ◽

Vascular Risk ◽

Atherosclerosis Risk In Communities ◽

Black And White ◽

Apoe Ε4 ◽

Phone Calls ◽

Incident Dementia ◽

Increased Risk

Background: Vascular risk factors have been associated with risk of cognitive decline, with increasing evidence that midlife exposure to these risk factors may be most important in conferring late-life risk of cognitive impairment. We explored associations between vascular risk factors measured in midlife and the development of dementia over 25 years in the biracial Atherosclerosis Risk in Communities (ARIC) cohort. Methods: Participants in the ARIC study were recruited from four U.S. communities in 1987-1989, at ages 45-64, with four additional in-person visits, surveillance for hospitalizations, annual phone calls, and repeated cognitive evaluations over a 25-year period. In 2011-2013, ARIC participants were seen for the ARIC Neurocognitive Study (ARIC-NCS), and underwent a detailed neurocognitive battery and informant interviews. Through adjudicated review, dementia cases were defined. Additional dementia cases were identified through the telephone interview for cognitive status (TICS) or informant interview for those participants not attending ARIC-NCS; or by a prior dementia ICD-9 code during a hospitalization. Results: Of 15,744 participants in the cohort, 1516 cases of dementia were identified, of whom over one third were among black participants. Risk of dementia was highest in individuals of black race, with less than a high school education, older age, APOE ε4 carriage, and who, at ARIC baseline, had hypertension, diabetes, or were current smokers (table). APOE ε4 and smoking were each stronger risk factors for dementia in whites than in blacks. Discussion: Vascular risk factors measured in midlife are associated with increased risk of dementia in this biracial cohort, in black and white participants. The risk associated with diabetes nears the increased risk associated with having an APOE ε4 allele. Further studies are needed to evaluate the mechanism of and opportunities for prevention of the cognitive sequelae of these risk factors in midlife.

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