Carotid Intima-Media Thickness Is Associated With White Matter Hyperintensities

Della-Morte, David; Dong, Chuanhui; Markert, Matthew; Elkind, Mitchell S.V.; Sacco, Ralph L.; Wright, Clinton B.; Rundek, Tatjana

doi:10.1161/strokeaha.117.018943

Cited by 36 publications

(34 citation statements)

References 57 publications

(61 reference statements)

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“…In line with this, we found significant associations between higher midlife IMT and all‐cause dementia and VaD. We also found higher midlife IMT to be significantly associated with late‐life small vessel disease, as previously suggested in other cohorts . In a review on vascular risk factors and AD, the authors concluded that prospective studies with autopsy (highest evidence level) did not support an association between vascular risk factors and AD pathology …”

Section: Discussionsupporting

confidence: 88%

“…We also found higher midlife IMT to be significantly associated with late-life small vessel disease, as previously suggested in other cohorts. 35,36 In a review on vascular risk factors and AD, the authors concluded that prospective studies with autopsy (highest evidence level) did not support an association between vascular risk factors and AD pathology. 37 Epidemiological studies that do report associations between vascular risk factors and clinical AD generally show that the relative risks of mixed dementia or VaD are higher.…”

Section: Discussionmentioning

confidence: 99%

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Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia

Gustavsson

Westen

Stomrud

et al. 2019

Annals of Neurology

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Objective To investigate whether midlife atherosclerosis is associated with different dementia subtypes and related underlying pathologies. Methods Participants comprised the cardiovascular cohort of the Swedish prospective population‐based Malmö Diet and Cancer Study (N = 6,103). Carotid plaques and intima media thickness (IMT) were measured at baseline (1991–1994). Dementia incidence until 2014 was obtained from national registers. Diagnoses were reviewed and validated in medical records. In a cognitively unimpaired subcohort (n = 330), β‐amyloid42 and tau were quantified in cerebrospinal fluid (CSF), and white matter hyperintensity volume, lacunar infarcts, and cerebral microbleeds were estimated on magnetic resonance imaging (2009–2015). Results During 20 years of follow‐up, 462 individuals developed dementia (mean age at baseline = 57.5 ± 5.9 years, 58% women). Higher IMT in midlife was associated with an increased hazard ratio (HR) of all‐cause dementia (adjusted HR = 1.14 [95% confidence interval (CI) = 1.03–1.26]) and vascular dementia (adjusted HR = 1.32 [95% CI = 1.10–1.57]) but not Alzheimer disease (AD) dementia (adjusted HR = 0.95 [95% CI = 0.77–1.17]). Carotid plaques were associated with vascular dementia when assessed as a 3‐graded score (adjusted HR = 1.90 [95% CI = 1.07–3.38]). In the cognitively unimpaired subcohort (53.8 ± 4.6 years at baseline, 60% women), higher IMT in midlife was associated with development of small vessel disease (adjusted odds ratio [OR] = 1.47 [95% CI = 1.05–2.06]) but not significantly with abnormal CSF AD biomarkers (adjusted OR = 1.28 [95% CI = 0.87–1.90] for Aβ42 and 1.35 [95% CI = 0.86–2.13] for Aβ42/p‐tau). Carotid plaques revealed no significant association with any of the underlying brain pathologies. Interpretation Our findings support an association between midlife atherosclerosis and development of vascular dementia and cerebral small vessel disease but not between atherosclerosis and subsequent AD dementia or AD pathology. ANN NEUROL 2020;87:52–62

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia

Gustavsson

Westen

Stomrud

et al. 2019

Annals of Neurology

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“… [ 35 ] Della-Morte et al, 2018 1299 subjects WMH volume was directly correlated with carotid intima-media thickness. [ 36 ] Moroni et al, 2016 5306 free living subjects Meta-analysis of observational studies. The presence of carotid artery plaque is associated to an OR of WMH of 1.42 [ 41 ] Ataf et al, 2006 57 stroke patients undergoing carotid endarterectomy Plaque features of vulnerability on histology were associated with higher WMH burden in the subtended hemisphere [ 42 ] Baradaran et al, 2017 Systematic review The Authors conclude that there is insufficient and contradicting evidence linking carotid plaque to ipsilateral hemispherical WMH burden.…”

Section: Cardiovascular Risk Factors and Wmhmentioning

confidence: 99%

“…Subclinical carotid atherosclerosis evaluated as carotid intima-media thickness (cIMT), a marker of increased cardiovascular risk was also shown to be associated with an increased WMH burden. In a cohort of 1229 participants in the Northern Manhattan Study, cIMT was directly correlated with WMH volume [ 36 ]. Significant stenosis of the carotid artery due to atherosclerosis is very common in the general population [ 37 ], while the presence of carotid artery atherosclerotic plaques in the absence of a hemodynamically significant stenosis appears to be even more widespread, reaching up to 40% of otherwise healthy individuals [ 38 ].…”

Section: Carotid Atherosclerosis and Wmhmentioning

confidence: 99%

Cardiovascular disease and brain health: Focus on white matter hyperintensities

Moroni¹,

Ammirati

Rocca

et al. 2018

IJC Heart & Vasculature

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Diseases affecting the brain contribute to a substantial proportion of morbidity and mortality in the general population. Conditions such as stroke, dementia and cognitive impairment have a prominent impact on global public health. Despite the heterogeneous clinical manifestations of these conditions and their diverse prognostic implications, current evidence supports a role for cardiovascular disease as a common pathophysiological ground. Brain white matter hyperintensities (WMH) are patchy white matter signal hyperintensity on T2-weighted magnetic resonance imaging sequences commonly found in elderly individuals. WMH appear to have a vascular pathogenesis and have been shown to confer an increased risk of stroke and cognitive decline. Indeed, they were proposed as a marker for central nervous system frailty. Cardiovascular diseases seem to play a key role in the etiology of WMH. Carotid atherosclerosis and atrial fibrillation were shown to be associated with higher WMH burden, while adequate blood pressure control has been reported reducing WMH progression. Aim of the present work is to review the available evidence linking WMH to cardiovascular disease, highlighting the complex interplay between cerebral and cardiovascular health.

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“…Cerebral white matter lesions in craniocerebral computed tomography (CT) or magnetic resonance imaging (MRI) are characterized by a patchy or diffusive shadow in the paraventricular and (or) semioval center, showing low density in CT and high T2 and Flair signals in MRI [9]. WML causes cognitive dysfunction, declined capability in memory, computing and execution, dysarthria and gait instability in the elderly population, which not only seriously affects the life quality of the patients, but also brings a heavy burden to the family and society [5,11]. Thus, it is necessary to study the risk factors and pathogenesis of WML.…”

Section: Introductionmentioning

confidence: 99%

Correlations between plasma homocysteine and MTHFR gene polymorphism and white matter lesions

Li¹,

Fu²,

Dong³

2018

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This study aims to investigate the correlation between the plasma homocysteine (Hcy) level and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism, and white matter lesions (WML). The plasma Hcy level and MTHFR C677T gene polymorphism in 104 patients with white matter lesions and 74 controls were measured. The severity of cerebral white matter was scored on the magnetic resonance imaging (MRI) images by the modified Scheltens scale (score of 0-30). The plasma Hcy level in the WML group was remarkably higher than that in the control group (p < 0.05), and the proportion of the patients with a high Hcy level in the WML group was notably higher than that in the control group (p < 0.05). Moreover, the patients with TT genotype in MTHFR gene had a significantly higher plasma Hcy level than those with CT or CC genotype. In addition, the plasma Hcy level in the patients with CT genotype was also significantly different from that in the patients with CC genotype (p < 0.05). The severity of cerebral white matter lesions among the patients with different genotypes in MTHFR gene was not significantly different (p > 0.05). The plasma Hcy level is positively correlated with WML and significantly correlated with C677T gene polymorphism in MTHFR gene. The severity of white matter lesions is not correlated with MTHFR C677T gene polymorphism.

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Carotid Intima-Media Thickness Is Associated With White Matter Hyperintensities

Abstract: Larger cIMT was associated with greater burden of cerebral WM lesions independently of demographics and traditional vascular risk factors, particularly among elderly and Hispanic participants, who are at high risk for stroke and cognitive decline.

Cited by 36 publications

References 57 publications

Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia

Midlife Atherosclerosis and Development of Alzheimer or Vascular Dementia

Cardiovascular disease and brain health: Focus on white matter hyperintensities

Correlations between plasma homocysteine and MTHFR gene polymorphism and white matter lesions

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