Pharmacological Treatment and Prevention of Cerebral Small Vessel Disease: A Review of Potential Interventions

Bath, Philip M.W.; Wardlaw, Joanna M.

doi:10.1111/ijs.12466

Cited by 153 publications

(200 citation statements)

References 69 publications

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“…43 Of these, observational studies have shown a reduced risk of dementia associated with long-term use of nonsteroidal anti-inflammatory drugs, statins, H2-receptor antagonists, and calcium channel blockers, which may, in part, be attributable to anti-inflammatory or antiangiogenic effects. Although none have proven effective in treatment of AD, [44][45][46] the effect of longterm use on prevention of dementia has not been assessed in trials.…”

Section: Discussionmentioning

confidence: 99%

Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia

Wolters

Bruijn

Hofman

et al. 2016

ATVB

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A bout 44 million people worldwide are living with dementia, and because of a rapidly aging population this number is predicted to nearly double every 20 years until 2050. 1,2 Consequently, the social and economic burden of dementia will increase enormously, unless preventive or curative measures can be established. Cardiovascular health is increasingly acknowledged as a key determinant in prevention of dementia, including Alzheimer disease (AD).3,4 Yet, the mechanism by which vascular damage leads to cognitive decline remains largely unknown.Although many studies have related cognitive function to static markers of cerebrovascular pathology, such as small vessel disease on magnetic resonance imaging and the retinal vasculature, few provide a functional measure of cerebral vascular disease. Cerebral vasoreactivity (CVR) reflects the ability of the cerebral arterioles and capillaries to dilate in response to increased neuronal metabolic demand, 5 and can be quantified in vivo using transcranial Doppler (TCD) or magnetic resonance imaging. Vasoreactivity is essential for maintenance of continuous cerebral perfusion, and impaired vasoreactivity is associated with (cardiovascular) mortality in the general population 6 and risk of stroke in the presence of flow-limiting carotid artery stenosis. 7 In addition, lower vasoreactivity correlates with higher volumes of cerebral white matter lesions, 8 which are strongly associated with cognitive decline and dementia.9 Several small cross-sectional studies have found CVR to be reduced in patients with dementia or mild cognitive impairment compared with healthy controls, 10-12 but its impact on cognitive decline and the risk of dementia is uncertain.We hypothesized that impaired CVR precedes dementia, and aimed to determine the association of CVR with cognitive decline and the risk of dementia in a population-based study.© 2015 American Heart Association, Inc. Materials and MethodsThis study is embedded within the Rotterdam study, an ongoing population-based cohort study in The Netherlands. TCD investigation with induction of hypercapnia was added to the core protocol for the second follow-up examination, from July 1997 to December 1999. Materials and Methods are available in the online-only Data Supplement. ResultsAmong 2569 eligible participants undergoing TCD with induced hypercapnia, no temporal bone window was present on either side in 632 (24.6%) individuals. Measurements could not be completed in 214 (8.3%) cases because of participants feeling anxious or unwell (n=54), lack of time (n=3), or other undocumented causes (n=157). In addition, in 94 participants we failed to obtain a reliable measurement of CVR despite adequate CO 2 induction, thus leaving a total of 1629 cases for analysis. Baseline characteristics of participants in comparison with nonparticipants are shown in Table 1. CVR was strongly impaired in current smokers and to a lesser extent in participants with a history of hypertension or diabetes mellitus. Conversely, higher systolic and diastoli...

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Section: Discussionmentioning

confidence: 99%

Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia

Wolters

Bruijn

Hofman

et al. 2016

ATVB

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“…Introduction Small vessel diseases of the brain are an important cause of stroke and dementia (Pantoni, 2010;Bath and Wardlaw, 2015). Our ability to accurately identify these diseases using neuroimaging markers has improved considerably in recent years (Wardlaw et al, 2013c), with increasing interest in the role of small vessel pathology in traditionally "non-vascular" dementias, such as Alzheimer's disease (AD).…”

Section: Svci Subcortical Vascular Cognitive Impairment (Svmci and Svad)mentioning

confidence: 99%

MRI-visible perivascular space location is associated with Alzheimer's disease independently of amyloid burden

Banerjee

Kim

Fox

et al. 2017

Brain

202

216

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MRI-visible perivascular spaces are a neuroimaging marker of cerebral small vessel disease.Their location may relate to the type of underlying small vessel pathology: those in the white matter centrum semi-ovale have been associated with cerebral amyloid angiopathy, whilst those in the basal ganglia have been associated with deep perforating artery arteriolosclerosis.Since cerebral amyloid angiopathy is an almost invariable pathological finding in Alzheimer's disease, we hypothesized that MRI-visible perivascular spaces in the centrum semi-ovale would be associated with a clinical diagnosis of Alzheimer's disease, whereas those in the basal ganglia would be associated with subcortical vascular cognitive impairment. We also hypothesised that MRI-visible perivascular spaces in the centrum semiovale would be associated with brain amyloid burden, as detected by amyloid-PET using subcortical vascular cognitive impairment n=116) with standardised MRI and PiB-PET imaging were included. MRI-visible perivascular spaces were rated using a validated 4-point visual rating scale, and then categorised by severity ("none/mild", "moderate" or "frequent/severe").

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“…Whether the treatment of CVRFs can prevent WMH progression and LI occurrence in community-dwelling older people is not well known. 4,6 Some study results suggest that antihypertensive treatment might reduce WMH progression.7-9 Cholesterol-lowering drugs might also hinder WMH increase, although results are inconclusive. 4,6,[10][11][12] Clinical guidelines recommend secondary prevention after symptomatic LI, involving BP lowering, smoking cessation, antiplatelet…”

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Effect of Long-Term Vascular Care on Progression of Cerebrovascular Lesions

Dalen

Charante

Caan

et al. 2017

Stroke

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C erebrovascular lesions, including white matter hyperintensities (WMH) and lacunar infarcts (LI), are common findings on brain magnetic resonance imaging (MRI) in older persons.1 Their occurrence and progression are associated with cognitive decline, dementia, stroke, and mortality.2,3 The most important risk factors for WMH progression are age and hypertension. 4 Associations with other cardiovascular risk factors (CVRFs), including diabetes mellitus, body mass index (BMI), cholesterol levels, physical activity, and smoking, have been reported less consistently. Whether the treatment of CVRFs can prevent WMH progression and LI occurrence in community-dwelling older people is not well known. 4,6 Some study results suggest that antihypertensive treatment might reduce WMH progression.7-9 Cholesterol-lowering drugs might also hinder WMH increase, although results are inconclusive. 4,6,[10][11][12] Clinical guidelines recommend secondary prevention after symptomatic LI, involving BP lowering, smoking cessation, antiplateletBackground and Purpose-This study aimed to evaluate the effect of a nurse-led multidomain cardiovascular intervention on white matter hyperintensity (WMH) progression and incident lacunar infarcts in community-dwelling elderly with hypertension. Methods-The preDIVA trial (Prevention of Dementia by Intensive Vascular Care) was an open-label, cluster-randomized controlled trial in community-dwelling individuals aged 70 to 78 years. General practices were assigned by computergenerated randomization to 6-year nurse-led, multidomain intensive vascular care or standard care. Of 3526 preDIVA participants, 195 nondemented participants with a systolic blood pressure ≥140 mm Hg were consecutively recruited to undergo magnetic resonance imaging at 2 to 3 and 5 to 6 years after baseline. WMH volumes were measured automatically, lacunar infarcts assessed visually, blinded to treatment allocation. Results-One hundred and twenty-six participants were available for longitudinal analysis (64 intervention and 62 control).Annual WMH volume increase in milliliter was similar for intervention (mean=0.73, SD=0.84) and control (mean=0.70, SD=0.59) participants (adjusted mean difference, −0.08 mL; 95% confidence interval, −0.30 to 0.15; P=0.50). Analyses suggested greater intervention effects with increasing baseline WMH volumes (P for interaction=0.03). New lacunar infarcts developed in 6 (9%) intervention and 2 (3%) control participants (odds ratio, 2.2; 95% confidence interval, 0.4-12.1; P=0.36). Conclusions-Nurse-led vascular care in hypertensive community-dwelling older persons did not diminish WMH accumulation over 3 years. However, our results do suggest this type of intervention could be effective in persons with high WMH volumes. There was no effect on lacunar infarcts incidence but numbers were low. Clinical Trial Information-URL: http://www.isrctn.com/ISRCTN29711771. Unique identifier: ISRCTN29711771.

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Pharmacological Treatment and Prevention of Cerebral Small Vessel Disease: A Review of Potential Interventions

Cited by 153 publications

References 69 publications

Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia

Cerebral Vasoreactivity, Apolipoprotein E, and the Risk of Dementia

MRI-visible perivascular space location is associated with Alzheimer's disease independently of amyloid burden

Effect of Long-Term Vascular Care on Progression of Cerebrovascular Lesions

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