Can transcranial Doppler ultrasound be used for screening cerebral small vessel diseases in the community?

https://doi.org/10.1016/j.jns.2019.116439Get rights and content

Highlights

  • We used the pulsatility index (PI) of the middle cerebral artery (MCA) to identify severe white matter hyperintensity (WMH).

  • The MCA PI was unable to identify severe WMH in asymptomatic elders.

  • Well-controlled vascular risk factors had no significant associations with severe WMH.

  • Physiological measures of vascular resistance may not reflect structural white matter lesions.

Abstract

Objectives

Elderly persons harbouring severe white matter hyperintensity (WMH), a radiological manifestation of cerebral small vessel disease (SVD), have an increased risk of dementia, stroke and poor functional outcomes. A simple screening tool will enhance their recruitment into preventive trials for SVD. We explored the clinical utility of the pulsatility index (PI) of the middle cerebral artery (MCA), obtained from transcranial Doppler ultrasound (TCD), in identifying severe WMH among community elderly persons with vascular risk factors.

Methods

Three hundred and thirty-one dementia- and stroke-free community elderly subjects with hypertension and/or diabetes mellitus underwent TCD to obtain the MCA PI. The WMH volume on 3.0 Tesla MRI was quantified and normalized to each subject's brain volume. The normalized WMH volumes were classified as low (<14.5 ml, 1 standard deviation [SD] above the mean, 84th percentile) or high (≥14.5 ml). The severity of WMH was also rated visually with the Fazekas score. Logistic regression and receiver-operator characteristics (ROC) analysis were performed to evaluate the association between the MCA PI and the severity of WMH.

Results

The MCA PI was not an independent predictor of severe WMH. An MCA PI ≥1.095 detected high normalized WMH volumes with an area under the curve (AUC) of 0.553 (95% CI 0.473–0.633), sensitivity of 0.556, and specificity of 0.523. ROC analysis of the MCA PI in predicting high Fazekas scores yielded similar findings.

Conclusion

In stroke- and dementia-free elderly persons with vascular risk factors, the MCA PI was unable to identify severe WMH. (Word count: 260).

Introduction

Cerebral small vessel disease (SVD) is arguably the commonest brain disease among elderly persons and predicted to incur an enormous burden as the society ages. SVD is a result of multiple pathophysiological processes, ranging from ischemia, inflammation and endothelial dysfunction to blood-brain barrier leakage and venous insufficiency [1]. The most widely used neuroimaging marker of SVD is the age-related white matter hyperintensity (WMH), which appears as areas with high signal intensities ≥5 mm on fluid attenuated inversion recovery (FLAIR) images of T2-weighted Magnetic Resonance Imaging (MRI). Severe WMH predicts an increased risk of stroke, dementia and death [2]. Longitudinal studies demonstrate that the progression of WMH is an independent contributor to cortical atrophy and cognitive decline [2,3].

Over 90% of the elderly population harbor WMH. Confluent WMH, a result of small punctate WMH merging into extensive patches, are observed in a third of the elderly population and associated with a host of poor functional outcomes, such as urinary incontinence, gait disturbances, falls and depression [[4], [5], [6], [7]]. As WMH takes years to evolve before symptoms appear, there exists a golden window for early therapeutic intervention. Whereas age and hypertension are consistently identified as the top risk factors of WMH [8], associations with diabetes mellitus, cholesterol, smoking, and homocysteinemia are also reported [9]. The progression of WMH may be retarded by modifying these vascular risk factors. Previous cohort studies have shown that optimal blood pressure control [9], statins [10], homocysteine-lowering therapy by B vitamins [11], multi-domain vascular care [12], and remote ischemic conditioning may slow the progression of WMH [13]. Their efficacies await clarification by randomized controlled trials in subjects with severe WMH.

The European Task Force on age-related WMH recommended that clinical trials on SVD should target patients with severe WMH in 2004 [14]. While recognising the clinical significance of WMH, the American Heart Association/American Stroke Association (AHA/ASA) did not recommend population screening for severe WMH as no clinical trials had demonstrated a reduction of adverse health outcomes from early screening. Nevertheless, a recent AHA/ASA guideline began to call for such trials [15].

The recruitment of subjects into the preventive trials for SVD is precluded by a lack of simple screening tool for asymptomatic elderly persons with severe WMH. MRI is impractical for community screening in view of its high monetary and time cost. The pulsatility index (PI), as defined by Gosling and King [16], can be obtained easily from transcranial Doppler ultrasound (TCD) and appears to be an attractive screening tool. A higher PI reflects an increased downstream resistance in the cerebral circulation, which is often due to SVD-related narrowing of the distal cerebral vessels.

Distal branches of the middle cerebral artery (MCA) supply the bulk of the cortical and subcortical regions responsible for sensory perception, psychomotor activity, language processing, and memory. Our pilot study of 159 elderly subjects suggested the MCA PI was able to guide selective MRI scanning for elderly persons with asymptomatic severe WMH and facilitate their recruitment into clinical trials for SVD [17]. In this study, we aimed to evaluate the clinical utility of the MCA PI in identifying severe WMH among a larger sample of community elderly persons with vascular risk factors.

Section snippets

Subjects

Subjects were recruited from the CU-RISK (The Chinese University of Hong Kong- Risk Index for Subclinical brain Lesions in Hong Kong) study [7], which is a population-based, cross-sectional study approved by the Joint Chinese University of Hong Kong-New Territories East Cluster Ethics Committee. Subjects were recruited on a voluntary basis by convenient sampling between November 2011 and April 2015 from community centres in Shatin. The inclusion criteria were 1) age 60–90; 2) Chinese ethnicity;

Results

Among the 500 initially recruited subjects, seven (1.4%) withdrew due to old age or cardiac stenting. Another 149 (29.8%) and 13 (2.6%) subjects were excluded due to the absence of a viable temporal window and suboptimal quality of MRI scans, respectively. Three hundred and thirty-one stroke- and dementia-free elderly subjects with vascular risk factors remained in the study. Subject characteristics were summarized in Table 1.

The visually rated Fazekas score demonstrated a strong correlation

Discussion

This is the largest community-based study investigating the ability of the MCA PI in identifying severe WMH in community elderly persons with vascular risk factors. The MCA PI had no independent association with severe WMH and demonstrated suboptimal AUC, sensitivity and specificity for predicting severe WMH.

Previous small cohort studies of Caucasian subjects with recent stroke established an association between the MCA PI and a visually rated severity of WMH [26]. A study of 100 Chinese

Conclusions

In stroke- and dementia-free elderly persons with vascular risk factors, the MCA PI was unable to identify severe WMH. Longitudinal studies will help to elucidate the time course of the disturbances in the MCA PI relative to the progression of WMH and the onset of SVD symptoms. At this stage, we recommended against the use of MCA PI alone in the community screening of asymptomatic SVD.

Source of funding

This study was supported by the National Key Research and Development Program of China (2016YFC1300600), the Hong Kong General Research Fund (HHSRF 09100131), the Lui Che Woo Institute of Innovative Medicine, and Therese Pei Fong Chow Research Centre for Prevention of Dementia (in memory of Donald H. K. Chow).

Disclosure

The authors reported no conflicts of interest

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