Changes in Vascular Risk Factors from Midlife to Late Life and White Matter Lesions: A 20-Year Follow-Up Study

Vuorinen, Miika; Solomon, Alina; Rovio, Suvi; Nieminen, Lasse J.; Kåreholt, Ingemar; Tuomilehto, Jaakko; Soininen, Hilkka; Kivipelto, Miia

doi:10.1159/000323810

Cited by 60 publications

(49 citation statements)

References 80 publications

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“…Results were similar after adding one study using a 3-class variable for WMH with ordinal logistic regression (n 5 106, p z score 5 0.44). 13 Four small studies (n 5 420 in high-risk populations) could not be included in this meta-analysis e21,e22,e25,e28 : one found a significant association between APOE e41 and WMH. e22 APOE e41 and WMH progression.…”

Section: Resultsmentioning

confidence: 99%

“…e32,e33 APOE e44 and WMH. When meta-analyzing 12 studies (n 5 7,494, 6,254 in the general population, 1,240 in high-risk populations, tables e-2 and e-3) 3,11,13,21,28,30,31,[37][38][39] (Sydney-MAS, FHS, unpublished data) in a sample size-weighted meta-analysis, APOE e44 was significantly associated with increasing WMH burden: p z score 5 0.0030.…”

Section: Resultsmentioning

confidence: 99%

“…Adding one study using a 3-class WMH variable with ordinal logistic regression (n 5 74) did not modify this association (p z score 5 0.039). 13 One study (n 5 56 in high-risk populations) could not be included in this meta-analysis and reported a significant association between APOE e44 and increasing WMH. e22 APOE e44 and WMH progression.…”

Section: Resultsmentioning

confidence: 99%

“…7 MRI markers of CVD-white matter hyperintensities (WMH), brain infarcts (BI), and cerebral microbleeds (CMB)-are powerful predictors of stroke and dementia. [10][11][12][13] They are highly prevalent in older community-dwelling persons, [14][15][16] and can be assessed noninvasively and quantitatively in large population-based samples. Dissecting the relationship between APOE and MRI markers of CVD could provide important clues to the mechanisms underlying the association between APOE and risk of dementia.…”

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confidence: 99%

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APOE genotype and MRI markers of cerebrovascular disease

et al. 2013

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Objective: We aimed to examine the association of APOE e genotype with MRI markers of cerebrovascular disease (CVD): white matter hyperintensities, brain infarcts, and cerebral microbleeds.Methods: We performed a systematic review and meta-analysis of 42 cross-sectional or longitudinal studies identified in PubMed from 1966 to June 2012 (n 5 29,965). This included unpublished data from 3 population-based studies: 3C-Dijon, Framingham Heart Study, and Sydney Memory and Ageing Study. When necessary, authors were contacted to provide effect estimates for the meta-analysis. Conclusions: APOE e4 and APOE e2 were associated with increasing burden in MRI markers for both hemorrhagic and ischemic CVD. While the association of APOE e4 with an increased burden of CVD could be partly contributing to the relationship between APOE e4 and AD, APOE e2 was associated with MRI markers of CVD in the opposite direction compared to AD. The e4 allele of the APOE gene is a major risk factor for dementia and Alzheimer disease (AD). Results 1-6The association of APOE with cerebrovascular disease (CVD) is more controversial.7 APOE e4 is a risk factor for cerebral amyloid angiopathy (CAA), a major determinant of intracerebral hemorrhage (ICH) in older individuals.1 Recent data from the International Stroke Genetics Consortium suggest an association of APOE e4 with an increased risk of ICH, mostly lobar, 8 and an association of the APOE e2 allele with an increased risk and size of lobar ICH. 8,9 Whether the epsilon polymorphism is also associated with an increased risk of ischemic stroke and MRI markers of CVD is unclear.7 MRI markers of CVD-white matter hyperintensities (WMH), brain infarcts (BI), and cerebral microbleeds (CMB)-are powerful predictors of stroke and dementia.10-13 They are highly prevalent in older community-dwelling persons, [14][15][16] and can be assessed noninvasively and quantitatively in large population-based samples. Dissecting the relationship between APOE and MRI

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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APOE genotype and MRI markers of cerebrovascular disease

et al. 2013

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“…[4][5][6][7][8][9][10][11][12][13] More recently, studies have used longitudinal designs and found similar results.…”

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High Blood Pressure and Cerebral White Matter Lesion Progression in the General Population

Verhaaren

Vernooij²,

Boer³

et al. 2013

Hypertension

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C erebral white matter lesions (WMLs) are highly prevalent in the elderly population and increase the risk of dementia and stroke.1 Although believed to be vascular in origin, the exact etiology of WMLs is still unknown. On the basis of pathological and epidemiological studies, blood pressure is considered to be one of the most important factors by damaging the cerebral small vessels.2,3 Because blood pressure is modifiable, blood pressure control seems an important candidate for the prevention of WML progression.The earliest studies demonstrating an association between high blood pressure and WMLs were cross-sectional by design, which limits causal inferences. [4][5][6][7][8][9][10][11][12][13] More recently, studies have used longitudinal designs and found similar results.14-23 Yet, because WML progression is strongly influenced by the WML load at baseline, 15 it is unknown to what extent associations of blood pressure with WML progression are affected by the baseline WML load. Moreover, to provide stronger evidence for a temporal relationship, blood pressure should preferably be measured before the window in which WML progression is determined, instead of during this window. In addition, the use of different MRI scanners or scanning protocols when measuring WML progression can possibly lead to systematic biases. Previous studies have addressed 1 or 2 of these issues, but none of them addressed all.It is also unknown whether the associations between blood pressure and WML progression are present for systolic, diastolic, and pulse pressure. Moreover, the influence of medication use and control of hypertension on WML progression remains unclear. We hypothesized that blood pressure would relate to WML progression even when taking baseline WML load into account and that medication use and adequate control of hypertension would reduce this progression.We tested this hypothesis in a population-based longitudinal MRI study in which we measured systolic, diastolic, and pulse pressure before MRI scanning; evaluated the influence of the WML load at baseline; and used exactly the same scanners and scanning protocol at baseline and follow-up.Abstract-High blood pressure is considered an important risk factor for cerebral white matter lesions (WMLs) in the aging population. In a longitudinal population-based study of 665 nondemented persons, we investigated the longitudinal relationship of systolic blood pressure, diastolic blood pressure, and pulse pressure with annual progression of WMLs.Means of blood pressure were calculated over a 5-year period before longitudinal MRI scanning. WML progression was subsequently measured on 2 scans 3.5 years apart. We performed analyses with linear regression models and evaluated adjustments for age, sex, cardiovascular risk factors, and baseline WML volume. In addition, we evaluated whether treatment of hypertension is related to less WML progression. Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz.

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