Managing blood pressure in older adults

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Long-term morphological changes of symptomatic lacunar infarcts and surrounding white matter on structural MRI

The contributing studies were funded by the Chief Scientist Office of the Scottish Executive (grant 217 NTU R37933), the Wellcome Trust (grants 075611 and WT088134/Z/09/A), and Row Fogo Charitable Trust. The imaging was performed at the Brain Research Imaging Centre Edinburgh, which is supported by the SINAPSE (Scottish Imaging Network, A Platform for Scientific Excellence) collaboration and the Chief Scientist Office of the Scottish Government (http://www.bric.ed.ac.uk/). This work was supported by European Union Horizon 2020 (EU H2020), PHC- 03 to 15, project No. 666881, SVDs@Target, and the Fondation Leducq Transatlantic Network of Excellence for Study of Perivascular Spaces in Small Vessel Disease, ref No. 16 CVD 05. Dr Loos was supported by the Dutch Alzheimer Foundation.Peer reviewedPublisher PD

The effect of different combinations of vascular, dependency and cognitive endpoints on the sample size required to detect a treatment effect in trials of treatments to improve outcome after lacunar and non-lacunar ischaemic stroke

Background Endpoints that are commonly used in trials of moderate/severe stroke may be less frequent in patients with minor, non-disabling stroke thus inflating sample sizes. We tested whether trial efficiency might be improved with composite endpoints. Methods We prospectively recruited patients with lacunar and minor non-lacunar ischaemic stroke (NIHSS ≤ 7) and assessed recurrent vascular events (stroke, transient ischaemic attack (TIA), ischemic heart disease (IHD)), modified Rankin Score (mRS) and cognitive testing with the Addenbrooke’s Cognitive Examination (ACE-R) one year post-stroke. For a potential secondary prevention randomised controlled trial (RCT), we estimated sample sizes using individual or combined outcomes, at power 80% (and 90%), alpha 5%, required to detect a relative 10% risk reduction. Results Amongst 264 patients (118 lacunar, 146 non-lacunar), at one year, 30/264 (11%) patients had a recurrent vascular event, 5 (2%) had died, 3 (1%) had clinically-diagnosed dementia, 53/264 (20%) had mRS ≥ 3 and 29/158 (19%) had ACE-R ≤ 82 (57 could not attend for cognitive testing). For a potential trial, at 80% power, using mRS ≥ 3 alone would require n > 5000 participants, recurrent vascular events alone n = 9908 participants, and a composite of any recurrent vascular event, ACE-R ≤ 82, dementia or mRS ≥ 2 (present in 56% of patients) n = 2224 patients. However, including cognition increased missing data. Results were similar for lacunar and non-lacunar minor ischaemic stroke. Conclusions Composite outcomes including vascular events, dependency, and cognition reduce sample size and increase efficiency, feasibility, and relevance to patients of RCTs in minor ischaemic stroke. Efficiency might be improved further with more practical cognitive test strategies

Potential recruitment into a clinical trial of vascular secondary prevention medications in cerebral small vessel disease, based on concomitant medication use

This research has been conducted using the UK Biobank resource. The authors are grateful to UK Biobank participants. UK Biobank was established by the Wellcome Trust medical charity, Medical Research Council, Department of Health, Scottish Government, and the Northwest Regional Development Agency. It has also had funding from the Welsh Assembly Government and the British Heart Foundation.Peer reviewedPublisher PD

Accuracy of the short-form Montreal Cognitive Assessment: systematic review and validation

Introduction: Short‐form versions of the Montreal Cognitive Assessment (SF‐MoCA) are increasingly used to screen for dementia in research and practice. We sought to collate evidence on the accuracy of SF‐MoCAs and to externally validate these assessment tools. Methods: We performed systematic literature searching across multidisciplinary electronic literature databases, collating information on the content and accuracy of all published SF‐MoCAs. We then validated all the SF‐MoCAs against clinical diagnosis using independent stroke (n = 787) and memory clinic (n = 410) data sets. Results: We identified 13 different SF‐MoCAs (21 studies, n = 6477 participants) with differing test content and properties. There was a pattern of high sensitivity across the range of SF‐MoCA tests. In the published literature, for detection of post stroke cognitive impairment, median sensitivity across included studies: 0.88 (range: 0.70‐1.00); specificity: 0.70 (0.39‐0.92). In our independent validation using stroke data, median sensitivity: 0.99 (0.80‐1.00); specificity: 0.40 (0.14‐0.87). To detect dementia in older adults, median sensitivity: 0.88 (0.62‐0.98); median specificity: 0.87 (0.07‐0.98) in the literature and median sensitivity: 0.96 (range: 0.72‐1.00); median specificity: 0.36 (0.14‐0.86) in our validation. Horton's SF‐MoCA (delayed recall, serial subtraction, and orientation) had the most favorable properties in stroke (sensitivity: 0.90, specificity: 0.87, positive predictive value [PPV]: 0.55, and negative predictive value [NPV]: 0.93), whereas Cecato's “MoCA reduced” (clock draw, animal naming, delayed recall, and orientation) performed better in the memory clinic (sensitivity: 0.72, specificity: 0.86, PPV: 0.55, and NPV: 0.93). Conclusions: There are many published SF‐MoCAs. Clinicians and researchers using a SF‐MoCA should be explicit about the content. For all SF‐MoCA, sensitivity is high and similar to the full scale suggesting potential utility as an initial cognitive screening tool. However, choice of SF‐MoCA should be informed by the clinical population to be studied

Tracer kinetic assessment of blood–brain barrier leakage and blood volume in cerebral small vessel disease: Associations with disease burden and vascular risk factors

Funding Information: The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: Wellcome Trust [grant number WT088134/Z/09/A ; SDJM, FC]; Row Fogo Charitable Trust (MCVH, FC, AKH, PAA); Scottish Funding Council Scottish Imaging Network A Platform for Scientific Excellence collaboration (JMW); NHS Lothian R + D Department (MJT); the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK MRC, Alzheimer’s Research UK and the Alzheimer’s Society (MS, FC, ES, JMW); the Fondation Leducq Transatlantic Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease [reference number 16 CVD 05] (MS); and European Union Horizon 2020 [project number 666881, SVDs@Target] (MS, FC). We acknowledge the participants, their relatives, and carers for their participation in this study, and the staff of NHS Lothian Stroke Services and Brain Research Imaging Centre Edinburgh for their assistance in recruiting and assessing the patients.Peer reviewedPublisher PD

Identification of the presence of ischaemic stroke lesions by means of texture analysis on brain magnetic resonance images

Study funding This work was funded by the Row Fogo Charitable Trust (MVH, VGC) grant no. BRO-D.FID3668413, and the Wellcome Trust (patient recruitment, scanning, primary study Ref No. 088134/Z/09). The study was conducted independently of the funders who do not hold the data and did not participate in the study design or analyses. The Lothian Birth Cohort 1936 is funded by Age UK (Disconnected Mind grant) and the Medical Research Council (MRC; MR/M01311/1, G1001245, 82800), and the latter supported BSA. IJD was supported by the Centre for Cognitive Ageing and Cognitive Epidemiology, which is funded by the MRC and the Biotechnology and Biological Sciences Research Council (MR/K026992/1). David Moratal acknowledges financial support from the Spanish Ministerio de Economía y Competitividad (MINECO) and FEDER funds under Grant BFU2015-64380-C2-2-R, and from the Conselleria d'Educació, Investigació, Cultura i Esport, Generalitat Valenciana (grants AEST/2017/013 and AEST/2018/021). Rafael Ortiz-Ramón was supported by grant ACIF/2015/078 and grant BEFPI/2017/004 from the Conselleria d’Educació, Investigació, Cultura i Esport of the Valencian Community (Spain).Peer reviewedPublisher PD

Integrity of normal-appearing white matter: influence of age, visible lesion burden and hypertension in patients with small vessel disease

White matter hyperintensities accumulate with age and occur in patients with stroke, but their pathogenesis is poorly understood. We measured multiple magnetic resonance imaging biomarkers of tissue integrity in normal-appearing white matter and white matter hyperintensities in patients with mild stroke, to improve understanding of white matter hyperintensities origins. We classified white matter into white matter hyperintensities and normal-appearing white matter and measured fractional anisotropy, mean diffusivity, water content (T1-relaxation time) and blood–brain barrier leakage (signal enhancement slope from dynamic contrast-enhanced magnetic resonance imaging). We studied the effects of age, white matter hyperintensities burden (Fazekas score) and vascular risk factors on each biomarker, in normal-appearing white matter and white matter hyperintensities, and performed receiver-operator characteristic curve analysis. Amongst 204 patients (34.3–90.9 years), all biomarkers differed between normal-appearing white matter and white matter hyperintensities (P < 0.001). In normal-appearing white matter and white matter hyperintensities, mean diffusivity and T1 increased with age (P < 0.001), all biomarkers varied with white matter hyperintensities burden (P < 0.001; P = 0.02 signal enhancement slope), but only signal enhancement slope increased with hypertension (P = 0.028). Fractional anisotropy showed complex age-white matter hyperintensities-tissue interactions; enhancement slope showed white matter hyperintensities-tissue interactions. Mean diffusivity distinguished white matter hyperintensities from normal-appearing white matter best at all ages. Blood–brain barrier leakage increases with hypertension and white matter hyperintensities burden at all ages in normal-appearing white matter and white matter hyperintensities, whereas water mobility and content increase as tissue damage accrues, suggesting that blood–brain barrier leakage mediates small vessel disease-related brain damage

White matter hyperintensity reduction and outcomes after minor stroke

Objective: To assess factors associated with white matter hyperintensity (WMH) change in a large cohort after observing obvious WMH shrinkage 1 year after minor stroke in several participants in a longitudinal study. Methods: We recruited participants with minor ischemic stroke and performed clinical assessments and brain MRI. At 1 year, we assessed recurrent cerebrovascular events and dependency and repeated the MRI. We assessed change in WMH volume from baseline to 1 year (normalized to percent intracranial volume [ICV]) and associations with baseline variables, clinical outcomes, and imaging parameters using multivariable analysis of covariance, model of changes, and multinomial logistic regression. Results: Among 190 participants (mean age 65.3 years, range 34.3–96.9 years, 112 [59%] male), WMH decreased in 71 participants by 1 year. At baseline, participants whose WMH decreased had similar WMH volumes but higher blood pressure (p = 0.0064) compared with participants whose WMH increased. At 1 year, participants with WMH decrease (expressed as percent ICV) had larger reductions in blood pressure (β = 0.0053, 95% confidence interval [CI] 0.00099–0.0097 fewer WMH per 1–mm Hg decrease, p = 0.017) and in mean diffusivity in normal-appearing white matter (β = 0.075, 95% CI 0.0025–0.15 fewer WMH per 1-unit mean diffusivity decrease, p = 0.043) than participants with WMH increase; those with WMH increase experienced more recurrent cerebrovascular events (32%, vs 16% with WMH decrease, β = 0.27, 95% CI 0.047–0.50 more WMH per event, p = 0.018). Conclusions: Some WMH may regress after minor stroke, with potentially better clinical and brain tissue outcomes. The role of risk factor control requires verification. Interstitial fluid alterations may account for some WMH reversibility, offering potential intervention targets