Jaap Kappelle

The Basilar Artery International Cooperation Study (BASICS): study protocol for a randomised controlled trial

BackgroundDespite recent advances in acute stroke treatment, basilar artery occlusion (BAO) is associated with a death or disability rate of close to 70%. Randomised trials have shown the safety and efficacy of intravenous thrombolysis (IVT) given within 4.5 h and have shown promising results of intra-arterial thrombolysis given within 6 h of symptom onset of acute ischaemic stroke, but these results do not directly apply to patients with an acute BAO because only few, if any, of these patients were included in randomised acute stroke trials.Recently the results of the Basilar Artery International Cooperation Study (BASICS), a prospective registry of patients with acute symptomatic BAO challenged the often-held assumption that intra-arterial treatment (IAT) is superior to IVT. Our observations in the BASICS registry underscore that we continue to lack a proven treatment modality for patients with an acute BAO and that current clinical practice varies widely.DesignBASICS is a randomised controlled, multicentre, open label, phase III intervention trial with blinded outcome assessment, investigating the efficacy and safety of additional IAT after IVT in patients with BAO. The trial targets to include 750 patients, aged 18 to 85 years, with CT angiography or MR angiography confirmed BAO treated with IVT. Patients will be randomised between additional IAT followed by optimal medical care versus optimal medical care alone. IVT has to be initiated within 4.5 h from estimated time of BAO and IAT within 6 h. The primary outcome parameter will be favourable outcome at day 90 defined as a modified Rankin Scale score of 0–3.DiscussionThe BASICS registry was observational and has all the limitations of a non-randomised study. As the IAT approach becomes increasingly available and frequently utilised an adequately powered randomised controlled phase III trial investigating the added value of this therapy in patients with an acute symptomatic BAO is needed (clinicaltrials.gov: NCT01717755).

Remarkable Decline in Ischemic Stroke Mortality is Not Matched by Changes in Incidence

Background and Purpose— In Western Europe, mortality from ischemic stroke (IS) has declined over several decades. Age–sex-specific IS mortality, IS incidence, 30-day case fatality, and 1-year mortality after hospital admission are essential for explaining recent trends in IS mortality in the new millennium. Methods— Data for all IS deaths (1980–2010) in the Netherlands were grouped by year, sex, and age. A joinpoint regression was fitted to detect points in time at which significant changes in the trends occur. By linking nationwide registers, a cohort of patients first admitted for IS between 1997 and 2005 was constructed and age–sex-specific 30-day case fatality and 1-year mortality were computed. IS incidence (admitted IS patients and out-of-hospital IS deaths) was computed by age and sex. Mann–Kendall tests were used for trend evaluation. Results— IS mortality declined continuously between1980 and 2000 with an attenuation of decline in the 1990s in some of the age–sex groups. A remarkable decline in IS mortality after 2000 was observed in all age–sex groups, except for young men. An improved decline in 30-day case fatality and in 1-year mortality was also observed in almost all age–sex groups. In contrast, IS incidence remained stable between 1997 and 2005 or even increased slightly. Conclusions— The recent remarkable decline in IS mortality was not matched by a decline in the number of incident nonfatal IS events. This is worrying, because IS is already a leading cause of adult disability, claiming a heavy human and economic burden. Prevention of IS is therefore now of the greatest importance.

Dementia risk score predicts cognitive impairment after a period of 15 years in a nondemented population

Background/Aim: Cardiovascular risk factors play an important role in the development of cognitive impairment and dementia. We examined whether a previously designed dementia risk score based on midlife vascular risk profiles also predicts cognitive impairment 15 years later. Methods: 322 individuals without dementia from the population-based Hoorn study (aged 50–64 years) underwent a medical examination at baseline and a detailed cognitive assessment 15 years later. The relation between the risk score and late-life cognitive impairment in each of 6 domains was analyzed with logistic regression analysis. Results: The risk score was significantly related to impairment on the domains information-processing speed (p = 0.04), visuoconstruction (p = 0.04) and abstract reasoning (p = 0.02). Participants with a risk score of 9 points or more had a markedly increased risk of late-life impairment in the domains information-processing speed (OR 3.07, 95% CI 1.37–6.90; p = 0.007) and abstract reasoning (OR 3.97, 95% CI 1.07–14.71; p = 0.04). Conclusion: A previously designed risk score for dementia also predicts late-life cognitive impairment. Because such impairment can lead to complaints and functional consequences, also in individuals who do not progress to dementia, identification of individuals at risk is important and can help to target preventive strategies.

Trends in vascular risk factors and medication use in patients with various manifestations of vascular diseases or type 2 diabetes mellitus from 1996 to 2007: the Second Manifestations of ARTerial disease study.

Aims To investigate time trends in vascular risk factors and medication use for patients referred to a vascular specialist with manifest vascular disease or type 2 diabetes mellitus (DM2). Methods and results Change in risk factor profile and medication use at referral over a 12-year period was evaluated and compared between patients with coronary heart disease, cerebrovascular disease, peripheral arterial disease, abdominal aortic aneurysm, and DM2, who participated in the Second Manifestations of ARTerial disease study in the period of 1996–2007. A total of 4731 patients were included (mean age 59 ± 11 years, 75% male) in the period 1996–2007. Obesity (body mass index ≥ 30 kg/m2) prevalence increased from 14 to 24%, and no change in smoking behavior was observed. The prevalence of hyperlipidemia (total cholesterol ≥ 4.5 mmol/l or low-density lipoprotein cholesterol ≥ 2.5 mmol/l) at referral declined from 92% in 1996–1997 to 45% in 2006–2007. The proportion of patients with blood pressure above 140/90 mmHg decreased from 66 to 51%. The use of lipid-lowering, blood pressure-lowering, and antithrombotic medication at referral increased over the observation period. Conclusion An improvement in risk factor profile was seen in patients referred with manifest vascular disease or DM2 over a 12-year period. Nevertheless, the prevalence of modifiable risk factors is still high leaving patients at elevated vascular risk.

Effects of Bobath-based therapy on depression, shoulder pain and health-related quality of life in patients after stroke.

OBJECTIVE To measure the effects of Bobath-based (BB) therapy on depression, shoulder pain and health-related quality of life (HRQoL) of patients during one year after stroke. DESIGN In a prospective, non-randomized design, the use of BB therapy was compared with a more task-oriented therapy and no BB therapy. SUBJECTS A total of 324 patients in 12 hospitals. METHODS Patients in the intervention group received BB therapy, whereas patients in the control group received no BB therapy and a more task-oriented therapy. HRQoL was measured using the SF-36; depression was measured with the Center of Epidemiological Studies Depression Scale and shoulder pain was measured with the Visual Analogue Scale at discharge, 6 and 12 months. Linear and logistic regression analyses were performed. RESULTS No effects of BB therapy on HRQoL or shoulder pain were found. After one year fewer patients were depressed in the BB group (30%) than in the non-BB group (43%); the adjusted odds ratio was 0.6 (95% confidence interval 0.3-1.0). CONCLUSION BB therapy did not have any effect on HRQoL or shoulder pain in stroke patients. Healthcare professionals should reconsider the use of BB therapy in the care of stroke patients.

Presence of coronary collaterals is associated with a decreased incidence of cognitive decline after coronary artery bypass surgery

OBJECTIVE Coronary artery bypass grafting (CABG) is associated with significant cerebral morbidity, usually manifested as cognitive decline or stroke. The underlying mechanism leading to cognitive decline is still unclear. Presence of coronary collateral arteries, which may reflect an overall better cardiovascular condition, recently appeared to relate to a better cardiac outcome after CABG. In this study, we investigated the hypothesis that presence of coronary collaterals is associated with less cognitive decline after coronary artery bypass grafting. METHODS Data from 281 patients undergoing first-time coronary artery bypass grafting were used. Presence of coronary collaterals was determined on the preoperative angiogram. Cognitive function was evaluated before the operation, at 3 and 12 months and 5 years thereafter by standardised neuropsychological assessment. Cognitive decline in individuals was determined by calculating the reliable change score, a cognitive change score corrected for natural testing variability and practice effects. RESULTS Cognitive decline was found in 19 (8%) patients at 3 months, in 31 (12%) patients at 12 months and in 82 (34%) at 5 years follow-up. Presence of coronary collaterals was independently associated with a better cognitive outcome at both 3 months (odds ratio (OR) 0.30; 95% confidence interval (CI) 0.09-0.95; p=0.04) and 12 months (OR 0.42; 95% CI 0.18-0.97; p=0.04) after coronary artery bypass grafting. At 5 years, the OR was 0.57 (95% CI 0.31-1.05; p=0.07). CONCLUSIONS In patients undergoing first-time coronary artery bypass grafting, presence of coronary collaterals is associated with a decreased risk of cognitive decline at both 3 and 12 months of follow-up. This trend persists at 5-year follow-up. Preoperative differences in the cardiac vascular condition may therefore predict cognitive outcome in patients undergoing coronary artery bypass grafting.

Cerebrale micro-infarcten

Dementie is een steeds vaker voorkomende ziekte. Van oudsher wordt er een indeling gemaakt in verschillende vormen van dementie, waarbij de ziekte van Alzheimer de meest voorkomende is, gevolgd door vasculaire dementie. De laatste tijd is het echter duidelijk geworden dat deze strikte scheiding in verschillende vormen van dementie niet te handhaven is. Een spectrum met aan de ene kant puur degeneratieve hersenschade (alzheimer-type-afwijkingen) en aan de andere kant puur vasculaire schade, waarbij de meeste patiënten een combinatie hebben van beide typen schade, lijkt meer realistisch.AbstractBackground:Vascular brain damage is in important cause of cognitive impairment and dementia. Autopsy studies have identified microinfarcts as an important neuropathological correlate of dementia that escapes detection by conventional magnetic resonance imaging (MRI).Methods:As a frame of reference for future high-resolution MRI studies, we systematically reviewed the literature on neuropathological studies on cerebral microinfarcts in the context of vascular disease, vascular risk factors and cognitive decline and dementia.Results:We identified 32 original patient studies involving 10,515 people. The overall picture is that microinfarcts are common, particularly in patients with vascular dementia (weighted average 62%), Alzheimer’s disease (43%) and demented patients with both Alzheimertype and cerebrovascular pathology (33%) compared to non-demented individuals (24%). In many patients multiple microinfarcts were detected. Microinfarcts are described as minute foci with neuronal loss, gliosis, pallor or more cystic lesions. They are found in all brain regions, possibly more so in the cerebral cortex, particularly in watershed areas. Reported sizes vary from 50 m to a few mm.Conclusions:Reported sizes of cerebral microinfarcts are within the detection limit of current high resolution MRI. Detection of these lesions in vivo would have a high potential for future pathophysiological studies in vascular brain damage en cognitive impairment.

Hoe weet je of cognitieve stoornissen waarschijnlijk zijn

SamenvattingInleiding Het kan voor huisartsen lastig zijn om bij patiënten met cognitieve klachten vast te stellen of er sprake is van milde cognitieve stoornissen of dementie. Wij stelden een diagnostisch algoritme op dat hierbij behulpzaam kan zijn, met als belangrijkste uitgangspunt dat de voorafkans op een cognitieve stoornis – ingeschat op basis van de (hetero) anamnese – bepaalt welke aanvullende test het meeste nut heeft.Methode De voorafkans is als volgt ingedeeld: niet waarschijnlijk, mogelijk en waarschijnlijk. Voor elk van deze situaties hebben we op basis van literatuuronderzoek en vooraf opgestelde criteria over de gewenste testkarakteristieken de meest geschikte test gekozen.Resultaten Is een cognitieve stoornis niet waarschijnlijk, dan kan een foutloze kloktekentest helpen om de patiënt gerust te stellen. Is er mogelijk sprake van een cognitieve stoornis, dan lijkt de Montreal Cognitive Assessment het meest geschikt om deze uit te sluiten of juist waarschijnlijker te maken. Is het waarschijnlijk dat de patiënt een cognitieve stoornis heeft, dan kan de Mini-Mental State Examination een stoornis nog waarschijnlijker maken.Conclusie Wij hopen dat huisartsen met dit algoritme zo optimaal mogelijk gebruik kunnen maken van cognitieve tests.

PHYSICAL PERFORMANCE IN RELATION TO COGNITIVE FUNCTIONING IN PATIENTS WITH DISORDERS ALONG THE HEART-BRAIN AXIS

At baseline, conscientiousness and neuroticism were correlated with CSF tau and ptau suggesting that personality tracks disease progression. Importantly, panel analyses indicate that changes in biomarkers occur first which lead to changes in self-assessed personality. Thus, accumulation of AD biomarkers induces changes in personality as opposed to personality traits predisposing an individual to developing pathology in DIAN.

OCCURRENCE AND PROFILE OF COGNITIVE IMPAIRMENT IN PATIENTS WITH HEART FAILURE, CAROTID OCCLUSIVE DISEASE AND VASCULAR COGNITIVE IMPAIRMENT: THE HEART-BRAIN CONNECTION STUDY

Background:As focus increases on the early treatment of patients with preclinicalAD, there is a need tounderstandhowearlymeasuresof disease progression may predict long-term patient outcomes. One measure proposed for the early detection of decline is the ADCS-PACC. We sought to evaluate the correlation between early measurements of ADCS-PACC and long-term cognition in subjects with normal cognition, but evidence of elevated amyloid. Methods:We simulated the progression of 5000 patients (mean age 1⁄4 75; 49% male) with normal cognition (mean MMSE 1⁄4 29.1; CDR 1⁄4 0) but evidence of amyloid pathology (CSF ab42< 192 pg/ml) over their remaining lifetimes using the AD Archimedes Condition-Event (ACE) simulator. The ADACE incorporates a system of disease progression equations which predict temporal evolution using data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and literature. The ADCSPACC was computed following Donohue et al. (JAMA Neurol, 2014) for ADNI data. Mortality was dependent on patient age, sex, and disease stage, based on published risk equations. The prognostic value of ADCS-PACC was assessed using the linear correlation between early ADCS-PACC scores and later MMSE scores. Results: The majority of patients (75%) in the simulations survived for 5 years, with a small fraction (16%) surviving 15 years. ADCS-PACC at year 1 had limited prognostic value for long-term cognition, with an r-squared ranging from 0.08 (for MMSE at 5 years) to 0.05 (for MMSE at 15 years). As patients progressed, ADCS-PACC becamemore predictive. At 2 years (mean MMSE 1⁄4 27.9, 90% survival), the r-squared values rose to 0.40 and 0.29 for MMSE at 5 years and 15 years respectively. The prognostic value ofADCS-PACC continued to improve reaching 0.56 when predicting 15 year MMSE, for ADCS-PACC at 5 years, respectively. Though MMSE is a component of ADCS-PACC, it was not the primary driver of the prognostic value of ADCS-PACC, as MMSEhas lowsensitivity in cognitivelynormal subjects. For example, MMSE at 2 years had modest correlation with MMSE at 15 years (rsquared 1⁄4 0.13). Conclusions:ADCS-PACC showed good prognostic value for long-term changes in cognition when measured during earliest stages in amyloid positive patients.