Background Personal continuity is an important dimension of continuity of care in general practice and is associated with many benefits including a higher quality of GP care and lower mortality rate. Over time, changes in society and health care have challenged the provision of personal continuity. Older patients in particular experience more negative consequences from receiving discontinuous care. Aim To explore the perspectives of GPs, older patients, practice nurses, and assistants on improving personal continuity in general practice, and to identify barriers and facilitators that affect this improvement process. Design and setting A qualitative study using focus groups was conducted from May to August 2019. Method We organised four focus groups: two with GPs ( n = 17), one with patients ( n = 7), and one with practice assistants ( n = 4) and practice nurses ( n = 2). Focus groups were analysed using reflexive thematic analysis. Results Personal continuity was viewed as being provided by the entire general practice team and not just by the patient’s own GP. It was suggested that investing in team communication and stability (for example, by efficient use of the electronic health records) and retaining the availability and accessibility of the patient’s own GP for patient care, especially for frail older persons, (for example, by delegating tasks) could improve personal continuity. Barriers and facilitators were perceived at the individual (for example, GPs’ involvement in tasks), organisation (for example, staff shortages), and societal level (for example, payment system). Conclusion As general practice moves towards a more team-based approach to ensure personal continuity, efforts to improve personal continuity should focus on supporting team-based provision of continuous care.
Abstract This paper is a proposal for an update on the characterization of cognitive impairments associated with sporadic cerebral small vessel disease (SVD). We pose a series of questions about the nature of SVD‐related cognitive impairments and provide answers based on a comprehensive review and meta‐analysis of published data from 69 studies. Although SVD is thought primarily to affect executive function and processing speed, we hypothesize that SVD affects all major domains of cognitive ability. We also identify low levels of education as a potentially modifiable risk factor for SVD‐related cognitive impairment. Therefore, we propose the use of comprehensive cognitive assessments and the measurement of educational level both in clinics and research settings, and suggest several recommendations for future research.
Abstract There is evidence that blood pressure variability (BPV) is associated with cerebral small vessel disease (SVD) and may therefore increase the risk of stroke and dementia. It remains unclear if BPV is associated with SVD progression over years. We examined whether visit-to-visit BPV is associated with White Matter Hyperintensity (WMH) progression over 14 years and MRI markers after 14 years. We included participants with SVD from the Radboud University Nijmegen Diffusion tensor Magnetic resonance imaging Cohort (RUNDMC) who underwent baseline assessment in 2006 and follow-up in 2011, 2015 and 2020. BPV was calculated as coefficient of variation of BP at all visits. Association between WMH progression rates over 14 years and BPV was examined using linear-mixed effects model. Regression models were used to examine association between BPV and MRI markers at final visit in participants. A total of 199 participants (60.5 SD 6.6 years) who underwent four MRI scans and blood pressure measurements were included, with mean follow-up of 13.7 (SD 0.5) years. Systolic BPV was associated with higher progression of WMH (β = 0.013, 95% CI 0.005 – 0.022) and higher risk of incident lacunes (OR: 1.10, 95% CI 1.01-1.21). There was no association between systolic BPV and grey and white matter volumes, Peak Skeleton of Mean Diffusivity (PSMD) or microbleed count after 13.7 years. Visit-to-visit systolic BPV is associated with increased progression of WMH volumes and higher risk of incident lacunes over 14 years in participants with SVD. Future studies are needed to examine causality of this association.
Blood-brain barrier (BBB) is known to be impaired in cerebral small vessel disease (SVD), and is measurable by dynamic-contrast enhancement (DCE)-MRI. In a cohort of 69 patients (42 sporadic, 27 monogenic SVD), who underwent 3T MRI, including DCE and cerebrovascular reactivity (CVR) sequences, we assessed the relationship of BBB-leakage hotspots to SVD lesions (lacunes, white matter hyperintensities (WMH), and microbleeds). We defined as hotspots the regions with permeability surface area product highest decile on DCE-derived maps within the white matter. We assessed factors associated with the presence and number of hotspots corresponding to SVD lesions in multivariable regression models adjusted for age, WMH volume, number of lacunes, and SVD type. We identified hotspots at lacune edges in 29/46 (63%) patients with lacunes, within WMH in 26/60 (43%) and at the WMH edges in 34/60 (57%) patients with WMH, and microbleed edges in 4/11 (36%) patients with microbleeds. In adjusted analysis, lower WMH-CVR was associated with presence and number of hotspots at lacune edges, and higher WMH volume with hotspots within WMH and at WMH edges, independently of the SVD type. In conclusion, SVD lesions frequently collocate with high BBB-leakage in patients with sporadic and monogenic forms of SVD.
Abstract Background Cognitive impairment is a key clinical feature of cerebral small vessel disease (SVD), but the full range of SVD-related cognitive impairments is unclear, and little is known about how they might vary across clinical and non-clinical manifestations of SVD. Methods In systematic searches of OVID MEDLINE, Embase, and PsychINFO from 1 st January 1985 to 6 th October 2019, we identified studies reporting cognitive test results for study participants with SVD and control participants without SVD. Using standardised group-level cognitive test data, we performed random effects meta-analyses in seven cognitive domains to test whether cognitive test scores differed between SVD and control groups. We conducted meta-regression analyses to test whether differences in age, education, or vascular risk factors between SVD and control groups, or whether different clinical manifestations of SVD (e.g. stroke, cognitive impairment, or non-clinical presentations) accounted for cognitive effect sizes. Findings Of 8562 studies identified, we included 69 studies from six continents, published in four languages. These studies included 3229 participants with SVD and 3679 controls. Meta-analyses demonstrated that on average, control groups outperformed SVD cohorts on cognitive tests in all cognitive domains examined: executive function (estimate: -0.928; 95%CI: -1.08, -0.78); processing speed (-0.885; -1.17, -0.60); delayed memory (-0.898; -1.10, -0.69); language (-0.808; -1.01, -0.60); visuospatial ability (-0.720; -0.96, -0.48); reasoning (-0.634; -0.93, -0.34); and attention (-0.622; -0.94, -0.31; all p≤0.001). Meta-regression analyses suggested that differences in years of education between SVD and control groups may account for a proportion of the differences in performance on tests of executive function, visuospatial ability and language, and that cohorts with cognitive impairments performed more poorly on tests of executive function, delayed memory and visuospatial ability than cohorts with stroke or non-clinical presentations of SVD. Interpretation Participants with SVD demonstrated poorer cognitive performance relative to control groups in all cognitive domains we examined. This effect was present for all presentations of SVD, reinforcing the need to test a range of cognitive domains in both clinical and research settings. Lower levels of education in SVD versus control participants may contribute to these effects, highlighting the need to account for educational level in the assessment of SVD-related cognitive impairment. Funding None.
Neuroimaging markers of cerebral small vessel disease (SVD) are common in older individuals, but the pathophysiological mechanisms causing these lesions remain poorly understood. Although hypertension is a major risk factor for SVD, the direct causal effects of increased blood pressure are unknown. The Hyperintense study is designed to examine cerebrovascular and structural abnormalities, possibly preceding SVD, in young adults with hypertension. These patients undergo a diagnostic work-up that requires patients to temporarily discontinue their antihypertensive agents, often leading to an increase in blood pressure followed by a decrease once effective medication is restarted. This allows examination of the effects of blood pressure increase and decrease on the cerebral small vessels.Hyperintense is a prospective observational cohort study in 50 hypertensive adults (18-55 years) who will temporarily discontinue antihypertensive medication for diagnostic purposes. MRI and clinical data is collected at four timepoints: before medication withdrawal (baseline), once antihypertensives are largely or completely withdrawn (T = 1), when patients have restarted medication (T = 2) and reached target blood pressure and 1 year later (T = 3). The 3T MRI protocol includes conventional structural sequences and advanced techniques to assess various aspects of microvascular integrity, including blood-brain barrier function using Dynamic Contrast Enhanced MRI, white matter integrity, and microperfusion. Clinical assessments include motor and cognitive examinations and blood sampling.The Hyperintense study will improve the understanding of the pathophysiological mechanisms following hypertension that may cause SVD. This knowledge can ultimately help to identify new targets for treatment of SVD, aimed at prevention or limiting disease progression.
Objective Cerebral small vessel diseases (SVDs) are associated with cerebrovascular dysfunction, such as increased blood–brain barrier leakage (permeability surface area product), vascular pulsatility, and decreased cerebrovascular reactivity (CVR). No studies assessed all 3 functions concurrently. We assessed 3 key vascular functions in sporadic and genetic SVD to determine associations with SVD severity, subtype, and interrelations. Methods In this prospective, cross‐sectional, multicenter INVESTIGATE‐SVDs study, we acquired brain magnetic resonance imaging in patients with sporadic SVD/cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), including structural, quantitative microstructural, permeability surface area product, blood plasma volume fraction, vascular pulsatility, and CVR (in response to CO 2 ) scans. We determined vascular function and white matter hyperintensity (WMH) associations, using covariate‐adjusted linear regression; normal‐appearing white matter and WMH differences, interrelationships between vascular functions, using linear mixed models; and major sources of variance using principal component analyses. Results We recruited 77 patients (45 sporadic/32 CADASIL) at 3 sites. In adjusted analyses, patients with worse WMH had lower CVR ( B = −1.78, 95% CI −3.30, −0.27) and blood plasma volume fraction ( B = −0.594, 95% CI −0.987, −0.202). CVR was worse in WMH than normal‐appearing white matter (eg, CVR: B = −0.048, 95% CI −0.079, −0.017). Adjusting for WMH severity, SVD subtype had minimal influence on vascular function (eg, CVR in CADASIL vs sporadic: B = 0.0169, 95% CI −0.0247, 0.0584). Different vascular function mechanisms were not generally interrelated (eg, permeability surface area product~CVR: B = −0.85, 95% CI −4.72, 3.02). Principal component analyses identified WMH volume/quantitative microstructural metrics explained most variance in CADASIL and arterial pulsatility in sporadic SVD, but similar main variance sources. Interpretation Vascular function was worse with higher WMH, and in WMH than normal‐appearing white matter. Sporadic SVD‐CADASIL differences largely reflect disease severity. Limited vascular function interrelations may suggest disease stage‐specific differences. ANN NEUROL 2024
Cerebral small vessel disease-a major cause of stroke and dementia-is associated with cerebrovascular dysfunction. We investigated whether short-term isosorbide mononitrate (ISMN) and cilostazol, alone or in combination, improved magnetic resonance imaging-measured cerebrovascular function in patients with lacunar ischemic stroke.Participants were randomized to ISMN alone, cilostazol alone, both ISMN and cilostazol, or no medication. Participants underwent structural, cerebrovascular reactivity (to 6% carbon dioxide) and phase-contrast pulsatility magnetic resonance imaging at baseline and after 8 weeks of medication.Of 27 participants (mean age, 68±7.7; 44% female), 22 completed cerebrovascular reactivity and pulsatility imaging with complete datasets. White matter cerebrovascular reactivity increased in the ISMN (β=0.021%/mm Hg [95% CI, 0.003-0.040]) and cilostazol (β=0.035%/mm Hg [95% CI, 0.014-0.056]) monotherapy groups and in those taking any versus no medication (β=0.021%/mm Hg [95% CI, 0.005-0.037]).While limited by small sample size, we demonstrate that measuring cerebrovascular function with magnetic resonance imaging is feasible in clinical trials and that ISMN and cilostazol may improve cerebrovascular function. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02481323. URL: www.isrctn.com; Unique identifier: ISRCTN12580546. URL: www.clinicaltrialsregister.eu; Unique identifier: EudraCT 2015-001953-33.
Background Small hyperintense lesions are found on diffusion-weighted imaging (DWI) in patients with sporadic small vessel disease (SVD). Their exact role in SVD progression remains unclear due to their asymptomatic and transient nature. The main objective is to investigate the role of DWI+lesions in the radiological progression of SVD and their relationship with clinical outcomes. Methods Participants with SVD were included from the Radboud University Nijmegen Diffusion tensor MRI Cohort. DWI+lesions were assessed on four time points over 14 years. Outcome measures included neuroimaging markers of SVD, cognitive performance and clinical outcomes, including stroke, all-cause dementia and all-cause mortality. Linear mixed-effect models and Cox regression models were used to examine the outcome measures in participants with a DWI+lesion (DWI+) and those without a DWI+lesion (DWI−). Results DWI+lesions were present in 45 out of 503 (8.9%) participants (mean age: 66.7 years (SD=8.3)). Participants with DWI+lesions and at least one follow-up (n=33) had higher white matter hyperintensity progression rates (β=0.36, 95% CI=0.05 to 0.68, p = 0.023), more incident lacunes (incidence rate ratio=2.88, 95% CI=1.80 to 4.67, p<0.001) and greater cognitive decline (β=−0.03, 95% CI=−0.05 to −0.01, p=0.006) during a median follow-up of 13.2 (IQR: 8.8–13.8) years compared with DWI− participants. No differences were found in risk of all-cause mortality, stroke or dementia. Conclusion Presence of a DWI+lesion in patients with SVD is associated with greater radiological progression of SVD and cognitive decline compared with patients without DWI+lesions.
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