Symptoms of Alzheimer’s disease can emerge years before diagnosis, but detailed temporal mapping of morbidity and medication use in the prodromal period is lacking. We conducted a nationwide retrospective, incidence density-matched nested case–control study including individuals diagnosed with late-onset Alzheimer’s disease in Danish memory clinics from 2016 to 2022 and cognitively healthy matched controls. Exposures were primary and secondary discharge diagnoses from hospital contacts, and redeemed prescriptions. A total of 19,102 patients and 57,306 matched controls were included. At 10 years before diagnosis, individuals who later developed late-onset Alzheimer’s disease had more mental health and behavioral diagnoses and increased use of psychopharmaceuticals, as well as more injuries and hospital contacts for non-specific symptoms. During the five years and one-year preceding diagnosis, morbidity increased across multiple diagnostic categories, while most medication categories decreased. Our findings suggest that prodromal late-onset Alzheimer’s disease is characterized by gradual accumulation of morbidity, with injuries and neuropsychiatric symptoms as the most persistent. This knowledge can guide future hypothesis-driven studies towards better characterization of the prodromal phase that may improve early detection, reduce the burden of unexplained symptoms experienced by patients and their caregivers, and support clinicians facing diagnostic uncertainty.

Dementia with Lewy bodies is characterized by a high burden of autonomic dysfunction and Lewy pathology in peripheral organs and components of the sympathetic and parasympathetic nervous system. Parasympathetic terminals may be quantified with 18F-fluoroetoxybenzovesamicol, a PET tracer that binds to the vesicular acetylcholine transporter in cholinergic presynaptic terminals. Parasympathetic imaging may be useful for diagnostics, improving our understanding of autonomic dysfunction and for clarifying the spatiotemporal relationship of neuronal degeneration in prodromal disease. Therefore, we aimed to investigate the cholinergic parasympathetic integrity in peripheral organs and central autonomic regions of subjects with dementia with Lewy bodies and its association with subjective and objective measures of autonomic dysfunction. We hypothesized that organs with known parasympathetic innervation, especially the pancreas and colon, would have impaired cholinergic integrity. To achieve these aims, we conducted a cross-sectional comparison study including 23 newly diagnosed non-diabetic subjects with dementia with Lewy bodies (74 ± 6 years, 83% male) and 21 elderly control subjects (74 ± 6 years, 67% male). We obtained whole-body images to quantify PET uptake in peripheral organs and brain images to quantify PET uptake in regions of the brainstem and hypothalamus. Autonomic dysfunction was assessed with questionnaires and measurements of orthostatic blood pressure. Subjects with dementia with Lewy bodies displayed reduced cholinergic tracer uptake in the pancreas (32% reduction, P = 0.0003) and colon (19% reduction, P = 0.0048), but not in organs with little or no parasympathetic innervation. Tracer uptake in a region of the medulla oblongata overlapping the dorsal motor nucleus of the vagus correlated with autonomic symptoms (rs = -0.54, P = 0.0077) and changes in orthostatic blood pressure (rs = 0.76, P < 0.0001). Tracer uptake in the pedunculopontine region correlated with autonomic symptoms (rs = -0.52, P = 0.0104) and a measure of non-motor symptoms (rs = -0.47, P = 0.0230). In conclusion, our findings provide the first imaging-based evidence of impaired cholinergic integrity of the pancreas and colon in dementia with Lewy bodies. The observed changes may reflect parasympathetic denervation, implying that this process is initiated well before the point of diagnosis. The findings also support that cholinergic denervation in the brainstem contributes to dysautonomia.

Identifying biomarkers for Alzheimer’s disease (AD) is crucial, due to its complex pathology, which involves dysfunction in lipid transport, contributing to neuroinflammation, synaptic loss, and impaired amyloid-β clearance. Nuclear magnetic resonance (NMR) is able to quantify and stratify lipoproteins. The study investigated lipoproteins in blood from AD patients, aiming to evaluate their diagnostic potential. Serum and plasma were collected from AD patients (n = 25) and healthy individuals (n = 25). We conducted a comprehensive lipoprotein profiling on serum samples using NMR spectroscopy, analysing 112 lipoprotein subfractions. In plasma, we measured unspecific markers of neuronal damage and AD hallmark proteins using single molecule array technology. Additionally, clinical data and cerebrospinal fluid biomarker levels were also collected to enrich our data. Our findings, after adjusting for age and sex differences, highlight significant alterations in two specific lipoproteins; high-density lipoprotein (HDL)-1 Apo-A2 (H1A2) and HDL-2 Apo-A2 (H2A2), both with area under the curve (AUC) values of 0.67, 95% confidence interval (CI) = 0.52–0.82). These results indicate that these lipoprotein subfractions may have potential as indicators of AD-related metabolic changes.

Background Patients with young onset Alzheimer's disease (YOAD) face long diagnostic delays. Prescription medication use may provide insights into early signs and symptoms, which may help facilitate timely diagnosis. Methods In a register-based nested case-control study, we examined medication use for everyone diagnosed with YOAD in a Danish memory clinic during 2016-2020 compared to cognitively healthy controls. Prescription medication use were grouped into 13 overall categories (alimentary tract and metabolism, blood and blood forming organs, cardiovascular system, dermatologicals, genitourinary system and sex hormones, systemic hormonal preparations, antiinfectives for systemic use, antineoplastic and immunomodulating agents, musculo-skeletal system, nervous system, antiparasitic products, respiratory system, and sensory organs). Further stratifications were done for predetermined subcategories with a use-prevalence of at least 5% in the study population. Conditional logistic regression produced odds ratios, which given the use of incidence-density matching is interpretable as incidence rate ratios (IRRs). The association between prescription medication use and subsequent YOAD diagnosis was examined in the entire 10-year study period and in three time-intervals. Results The study included 1745 YOAD cases and 5235 controls. In the main analysis, several overall categories showed significant associations with YOAD in one or more time-intervals, namely blood and blood forming organs and nervous system. Prescription medication use in the nervous system category was increased for YOAD cases compared to controls already 10->5 years prior to diagnosis (IRR 1.17, 95% CI 1.05-1.31), increasing to 1.57 (95% CI 1.39-1.78) in the year preceding diagnosis. This was largely driven by antidepressant and antipsychotic use, and especially prominent for first-time users. Conclusions In this study, medication use in several categories was associated with YOAD. Onset of treatment-requiring psychiatric symptoms such as depression or psychosis in mid-life may serve as potential early indicators of YOAD.

Introduction Alzheimer’s Disease (AD) is complex and novel approaches are urgently needed to aid in diagnosis. Blood is frequently used as a source for biomarkers; however, its complexity prevents proper detection. The analytical power of metabolomics, coupled with statistical tools, can assist in reducing this complexity. Objectives Thus, we sought to validate a previously proposed panel of metabolic blood-based biomarkers for AD and expand our understanding of the pathological mechanisms involved in AD that are reflected in the blood. Methods In the validation cohort serum and plasma were collected from 25 AD patients and 25 healthy controls. Serum was analysed for metabolites using nuclear magnetic resonance (NMR) spectroscopy, while plasma was tested for markers of neuronal damage and AD hallmark proteins using single molecule array (SIMOA). Results The diagnostic performance of the metabolite biomarker panel was confirmed using sparse-partial least squares discriminant analysis (sPLS-DA) with an area under the curve (AUC) of 0.73 (95% confidence interval: 0.59–0.87). Pyruvic acid and valine were consistently reduced in the discovery and validation cohorts. Pathway analysis of significantly altered metabolites in the validation set revealed that they are involved in branched-chain amino acids (BCAAs) and energy metabolism (glycolysis and gluconeogenesis). Additionally, strong positive correlations were observed for valine and isoleucine between cerebrospinal fluid p-tau and t-tau. Conclusions Our proposed panel of metabolites was successfully validated using a combined approach of NMR and sPLS-DA. It was discovered that cognitive-impairment-related metabolites belong to BCAAs and are involved in energy metabolism.

INTRODUCTION: Early symptoms in young onset Alzheimer's disease (YOAD) may be misinterpreted, causing delayed diagnosis. This population-based study aimed to map morbidity prior to YOAD diagnosis. METHODS: In a register-based incidence density matched nested case-control study, we examined hospital-diagnosed morbidity for people diagnosed with YOAD in Danish memory clinics during 2016-2020 compared to controls in a 10-year period. Conditional logistic regression produced incidence rate ratios (IRRs). RESULTS: The study included 1745 cases and 5235 controls. YOAD patients had a higher morbidity burden in the year immediately before dementia diagnosis, for certain disorders up to 10 years before. This was especially evident for psychiatric morbidity with the highest increased IRRs throughout the entire period and IRR 1.43 (95% confidence interval 1.14-1.79) in the 5-10-years before dementia diagnosis. DISCUSSION: YOAD patients display a different pattern of morbidity up to 10 years prior to diagnosis. Awareness of specific alterations in morbidity may improve efforts toward a timely diagnosis.

Background Neuron-derived extracellular vesicles (NDEVs) in blood may be used to derive biomarkers for the effects of exercise in Alzheimer’s disease (AD). For this purpose, we studied changes in neuroprotective proteins proBDNF, BDNF, and humanin in plasma NDEVs from patients with mild to moderate AD participating in the randomized controlled trial (RCT) of exercise ADEX. Methods proBDNF, BDNF, and humanin were quantified in NDEVs immunocaptured from the plasma of 95 ADEX participants, randomized into exercise and control groups, and collected at baseline and 16 weeks. Exploratorily, we also quantified NDEV levels of putative exerkines known to respond to exercise in peripheral tissues. Results NDEV levels of proBDNF, BDNF, and humanin increased in the exercise group, especially in APOE ε4 carriers, but remained unchanged in the control group. Inter-correlations between NDEV biomarkers observed at baseline were maintained after exercise. NDEV levels of putative exerkines remained unchanged. Conclusions Findings suggest that the cognitive benefits of exercise could be mediated by the upregulation of neuroprotective factors in NDEVs. Additionally, our results indicate that AD subjects carrying APOE ε4 are more responsive to the neuroprotective effects of physical activity. Unchanged NDEV levels of putative exerkines after physical activity imply that exercise engages different pathways in neurons and peripheral tissues. Future studies should aim to expand upon the effects of exercise duration, intensity, and type in NDEVs from patients with early AD and additional neurodegenerative disorders. Trial registration The Effect of Physical Exercise in Alzheimer Patients (ADEX) was registered in ClinicalTrials.gov on April 30, 2012 with the identifier NCT01681602. Graphical abstract

Introduction Aerobic exercise has been shown to modify Alzheimer pathology in animal models, and in patients with multiple sclerosis to reduce neurofilament light (NfL), a biomarker of neurodegeneration. Objective To investigate whether a 16-week aerobic exercise program was able to reduce serum NfL in patients with mild Alzheimer’s disease (AD). Methods This is a secondary analysis of data from the multi-center Preserving Cognition, Quality of Life, Physical Health, and Functional Ability in Alzheimer’s disease: The Effect of Physical Exercise (ADEX) study. Participants were randomized to 16 weeks of moderate intensity aerobic exercise or usual care. Clinical assessment and measurement of serum NfL was done at baseline and after the intervention. Results A total of 136 participants were included in the analysis. Groups were comparable at baseline except for APOEε4 carriership which was higher in the usual care group (75.3 versus 60.2%; p = 0.04). There was no effect of the intervention on serum NfL [intervention: baseline NfL (pg/mL) 25.76, change from baseline 0.87; usual care: baseline 27.09, change from baseline −1.16, p = 0.09]. Conclusion The findings do not support an effect of the exercise intervention on a single measure of neurodegeneration in AD. Further studies are needed using other types and durations of exercise and other measures of neurodegeneration. Clinical trial registration clinicaltrials.gov, identifier NCT01681602.

Background and purpose: The aims of this study were to examine the psychometric properties of the Brief Assessment of Impaired Cognition (BASIC) case--finding instrument in clinical settings focusing on (i) test--retest reliability, (ii) the discriminative validity of BASIC and its components for identification of Alzheimer disease (AD) dementia and non--AD dementia, and (iii) the association of expert clinical rating of cognitive status with BASIC performance. Methods: The test--retest reliability analysis was based on a sample of general practice patients (n = 59) retested with a mean interval of 19 days. Discriminative validity analyses and analysis of the association of cognitive status with BASIC performance were based on data from the primary validation study of BASIC in memory clinics. Results: The test--retest reliability of BASIC was high (r = 0.861). No significant difference in discriminative validity was found for identification of AD dementia (sensitivity = 0.99, specificity = 0.98) and non--AD dementia (sensitivity = 0.90, specificity = 0.98). All components of BASIC contributed to the high discriminative validity of both AD and non--AD dementia. BASIC performance was significantly correlated with expert clinical rating of the cognitive status of patients. A crude staging model for cognitive status using BASIC score intervals had superior classification accuracy (70%) compared to a Mini--Mental State Examination (MMSE) score range--based model (58% accuracy). Conclusions: BASIC is a reliable and valid case--finding instrument for AD dementia and non--AD dementia in clinical settings. BASIC performance is significantly associated with the degree of cognitive impairment, and BASIC seems to be superior to MMSE for staging of impairment.

Lifestyle factors have been shown to increase the risk of developing Alzheimer's disease (AD) later in life. Specifically, an unfavorable cholesterol profile, and insulin resistance are associated with increased risk of developing AD. One way to non-pharmacologically affect the levels of plasma lipids is by exercise, which has been shown to be beneficial in cognitively healthy individuals. In this randomized controlled trial y, we therefore aimed to clarify the effect of physical exercise on the lipid profile, insulin and glucose in patients with AD. In addition, we investigated the effect of apolipoproteinE genotype on total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TG) in plasma from patients with AD. Plasma samples from 172 patients who underwent 16 weeks of moderate-to-high intensity exercise (n= 90) or treatment as usual (n= 82) were analyzed change from baseline for the levels of total cholesterol, LDL-C, HDL-C, TG, glucose, and insulin. In addition, we analyzed those from the exercise group who adhered to the protocol with an attendance of 2/3 or more of the exercise session and who followed the protocol of an intensity of 70% of the maximum heart rate. We found a significant increase in plasma HDL-C levels between the "high exercise sub-group" compared to control group. After intervention HDL-C was increased by 4.3% in the high-exercise group, and decreased by 0.7% in the control group, after adjustment for statin use. In conclusion, short term physical activity may be beneficial on the cholesterol profile in patients with AD.

Background Although general recommendations for diagnostic disclosure of dementia are available, little is known about how these recommendations are implemented. The aim of the current study was to investigate the process and content of dementia diagnostic disclosure meetings, and to compare key aspects of disclosing a diagnosis of dementia and mild cognitive impairment. Method A total of 54 specialist physicians in Danish dementia diagnostic departments completed an online survey on their practices regarding diagnostic disclosure of dementia and mild cognitive impairment. The influence of respondent characteristics was assessed, and differences on key aspects of disclosing a diagnosis of dementia and mild cognitive impairment were analyzed. Results The results suggest that among Danish specialist physicians, there is a general consensus regarding the organization of diagnostic disclosure meetings. However, differences in employed terminology and information provided when disclosing a dementia diagnosis were evident. Significant differences were present on key aspects of the diagnostic disclosure of dementia and mild cognitive impairment. For instance, 91% would use the term dementia during diagnostic disclosures compared to just 72% for mild cognitive impairment. Conclusion The range of practices reflected in the present study confirms the complexity of diagnostic disclosure and highlights the importance of preparation and follow-up strategies to tailor the disclosure process to the needs of individual patients with dementia and their caregivers. Due to earlier diagnosis of neurodegenerative disorders, more research is urgently needed on this aspect of the diagnostic process, especially to develop evidence-based models for the disclosure of mild cognitive impairment.

Objectives The aim of this study was to develop and validate a new brief and accurate case-finding instrument for dementia and cognitive impairment. Previous research indicates that combining cognitive tests with informant and/or patient report may improve accuracy in dementia case-finding. The Brief Assessment of Impaired Cognition (BASIC) integrates these three sources of information. Methods BASIC was prospectively validated in five memory clinics. Patients consecutively referred from general practice were tested at their initial visit prior to diagnosis. Control participants were primarily recruited among participating patients' relatives. Expert clinical diagnosis was subsequently used as gold standard for estimation of the classification accuracy of BASIC. Results A very high discriminative validity (specificity 0.98, sensitivity 0.95) for dementia (n = 122) versus socio-demographically matched control participants (n = 109) was found. In comparison, the MMSE had 0.90 specificity and 0.82 sensitivity. Extending the discriminative validity analysis to cognitive impairment (both dementia and MCI, n = 162) only slightly reduced the discriminative validity of BASIC whereas the discriminative validity of the MMSE was substantially attenuated. Administration time for BASIC was approximately 5 minutes compared with 10 to 15 minutes for the MMSE. Conclusions BASIC was found to be an efficient and valid case-finding instrument for dementia and cognitive impairment in a memory clinic setting.

Introduction: Knowledge about the feasibility and effects of exercise programs to persons with Alzheimer's disease is lacking. This study investigated the effect of aerobic exercise on physical performance in community-dwelling persons with mild Alzheimer's disease.Methods: The single blinded multi-center RCT (ADEX) included 200 patients, median age 71 yrs (50-89). The intervention group received supervised moderate-to-high intensity aerobic exercise 1 hour X 3/week for 16 weeks. Assessments included cardiorespiratory fitness, single-task physical performance, dual-task performance and exercise self-efficacy.Results: Significant between-group differences in change from baseline (mean [95%CI]) favored the intervention group for cardiorespiratory fitness (4.0 [2.3-5.8] ml/kg/min, P <0.0001) and exercise self-efficacy (1.7 [0.5-2.8] points, P =0.004). Furthermore, an exercise attendance of >= 66.6% resulted in significant positive effects on single-task physical performance and dual-task performance.Discussion: Aerobic exercise has the potential to improve cardiorespiratory fitness, single-task physical performance, dual-task performance and exercise self-efficacy in community-dwelling patients with mild Alzheimer's disease. (C) 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

BACKGROUND:Studies of physical exercise in patients with Alzheimer's disease (AD) are few and results have been inconsistent.OBJECTIVE:To assess the effects of a moderate-to-high intensity aerobic exercise program in patients with mild AD.METHODS:In a randomized controlled trial, we recruited 200 patients with mild AD to a supervised exercise group (60-min sessions three times a week for 16 weeks) or to a control group. Primary outcome was changed from baseline in cognitive performance estimated by Symbol Digit Modalities Test (SDMT) in the intention-to-treat (ITT) group. Secondary outcomes included changes in quality of life, ability to perform activities of daily living, and in neuropsychiatric and depressive symptoms.RESULTS:The ITT analysis showed no significant differences between intervention and control groups in change from baseline of SDMT, other cognitive tests, quality of life, or activities of daily living. The change from baseline in Neuropsychiatric Inventory differed significantly in favor of the intervention group (mean: -3.5, 95% confidence interval (CI) -5.8 to -1.3, p = 0.002). In subjects who adhered to the protocol, we found a significant effect on change from baseline in SDMT as compared with the control group (mean: 4.2, 95% CI 0.5 to 7.9, p = 0.028), suggesting a dose-response relationship between exercise and cognition.CONCLUSIONS:This is the first randomized controlled trial with supervised moderate-to-high intensity exercise in patients with mild AD. Exercise reduced neuropsychiatric symptoms in patients with mild AD, with possible additional benefits of preserved cognition in a subgroup of patients exercising with high attendance and intensity.

Introduction: Several studies have demonstrated the beneficial effects of intravenous tissue-type plasminogen activator (IV-tPA) on neurological outcome in acute ischemic stroke. It is uncertain whether the improved neurological outcome also translates into less morbidity and lower need for hospital admissions during follow-up. Methods: We conducted a register-based nationwide propensity score-matched follow-up study among ischemic stroke patients in Denmark (2004-2011). IV-tPA-treated patients were propensity-score matched with IV-tPA eligible but non-treated ischemic stroke patients from stroke centers not offering tPA. The adjusted Hazard ratio (HR) for first readmission was estimated by multivariable Cox regression among patients who survived the initial stroke admission. Total all-cause bed day use in the first year after stroke admission was determined for patients with a potential follow-up time of at least one year and was compared between groups by a paired t-test after logarithmic transformation. Results: We identified 1896 IV-tPA-treated and 1896 corresponding propensity-score matched non-treated patients surviving the initial stroke admission. A total of 43.2% of the patients were readmitted to hospital during a median of 0.8 years. The adjusted HR for first readmission was 0.93 (95% CI: 0.79-1.09) when comparing IV-tPA-treated with non-treated patients. In 1462 matched pairs followed the first year after stroke the median all-cause bed day use was 10 (IQR: 4-37) in the group of tPA-treated and 16 (IQR: 6-43) in the group of non-treated patients. The relative bed day use was 0.81 (95% CI: 0.74-0.88) when comparing IV-tPA-treated with non-treated patients. Conclusion: Use of IV-tPA in ischemic stroke patients was associated with lower long-term all-cause hospital bed day use.

Background Thrombolysis with intravenous recombinant tissue-type plasminogen activator improves functional outcome in acute ischemic stroke. Few studies have investigated the effects of thrombolysis in a real-world setting. We evaluated the impact of thrombolysis on long-term hospital bed day use and the risk of readmission due to stroke-related complications. Methods We conducted a register-based nationwide propensity score-matched follow-up study among ischemic stroke patients in Denmark (2004-2011). Thrombolysed patients were propensity-score matched with non-thrombolysed acute ischemic stroke patients admitted to stroke centers not yet offering thrombolysis in 2004-2006. The outcomes were length of the stroke admission, total all-cause hospital bed day use during the first year after the stroke, and the long-term risk of readmissions. Thrombolysed and non-thrombolysed patients were compared using multivariable log-linear regression and Cox regression. Results We identified 1095 thrombolysed and 1095 propensity score matched eligible but non-thrombolysed acute ischemic stroke patients. The median length of the stroke admission was 9 days in the thrombolysed group and 13 days in the non-thrombolysed group (adjusted geometric mean ratio, 0.88; 95% CI: 0.78-1.00). The median all-cause hospital bed day use within the first year was 12 days in the thrombolysed group and 19 days in the non-thrombolysed group (adjusted geometric mean ratio, 0.82; 95% CI: 0.73-0.92). There was no significant difference in the overall risk of readmission (adjusted hazard ratio, 0.91; 95% CI: 0.79-1.04); however, thrombolysis was associated with reduced risk of pneumonia (adjusted hazard ratio, 0.59; 95% CI: 0.35-0.97). Conclusions Thrombolysis in ischemic stroke was associated with lower long-term hospital bed day use and decreased risk of readmission due to pneumonia.

Background and Purpose— Data on long-term outcome after intravenous tissue-type plasminogen activator (tPA) in ischemic stroke are limited. We examined the risk of long-term mortality, recurrent ischemic stroke, and major bleeding, including intracranial and gastrointestinal bleeding, in intravenous tPA-treated patients when compared with intravenous tPA eligible but nontreated patients with ischemic stroke. Methods— We conducted a register-based nationwide propensity score–matched follow-up study among patients with ischemic stroke in Denmark (2004–2011). Cox regression analysis was used to compute adjusted hazard ratios for all outcomes. Results— Among 4292 ischemic strokes (2146 intravenous tPA-treated and 2146 propensity score–matched nonintravenous tPA-treated patients), with a follow-up for a median of 1.4 years, treatment with intravenous tPA was associated with a lower risk of long-term mortality (adjusted hazard ratio, 0.66; 95% confidence interval, 0.49–0.88). The long-term risk of recurrent ischemic stroke (adjusted hazard ratio, 1.05; 95% confidence interval, 0.68–1.64) and major bleeding (adjusted hazard ratio, 0.59; 95% confidence interval, 0.24–1.47) did not differ significantly between the intravenous tPA-treated and nontreated patients. Conclusions— Treatment with intravenous tPA in patients with ischemic stroke was associated with improved long-term survival.

Background:The validity of the registration of patients in stroke-specific registries has seldom been investigated, nor compared with administrative hospital discharge registries.The objective of this study was to examine the validity of the registration of patients in a stroke-specific registry (The Danish Stroke Registry [DSR]) and a hospital discharge registry (The Danish National Patient Registry [DNRP]).Methods: Assuming that all patients with stroke were registered in either the DSR, DNRP or both, we first identified a sample of 75 patients registered with stroke in 2009; 25 patients in the DSR, 25 patients in the DNRP, and 25 patients registered in both data sources.Using the medical record as a gold standard, we then estimated the sensitivity and positive predictive value of a stroke diagnosis in the DSR and the DNRP.Secondly, we reviewed 160 medical records for all potential stroke patients discharged from four major neurologic wards within a 7-day period in 2010, and estimated the sensitivity, specificity, positive predictive value, and negative predictive value of the DSR and the DNRP.Results: Using the first approach, we found a sensitivity of 97% (worst/best case scenario 92%-99%) in the DSR and 79% (worst/best case scenario 73%-84%) in the DNRP.The positive predictive value was 90% (worst/best case scenario 72%-98%) in the DSR and 79% (worst/best case scenario 62%-88%) in the DNRP.Using the second approach, we found a sensitivity of 91% (95% confidence interval [CI] 81%-96%) and 58% (95% CI 46%-69%) in the DSR and DNRP, respectively.The negative predictive value was 91% (95% CI 83%-96%) in the DSR and 72% (95% CI 62%-80%) in the DNRP.The specificity and positive predictive value did not differ among the registries.Conclusion: Our data suggest a higher sensitivity in the DSR than the DNRP for acute stroke diagnoses, whereas the positive predictive value was comparable in the two data sources.

Thrombolysis is the only effective medical therapy for acute ischaemic stroke. The treatment has been approved in Europe since 2002. This article briefly summarises the pharmacological background of thrombolysis in cerebral ischaemic stroke. International experience with thrombolysis within the last decade as well as the successful implementation of thrombolysis in Denmark within the last 3 years is reviewed. Attention is drawn to new neuroradiological diagnostic techniques and future therapeutic possibilities.