| 1. |
- Aam, Stina, et al.
(author)
-
The Impact of Vascular Risk Factors on Post-stroke Cognitive Impairment : The Nor-COAST Study
- 2021
-
In: Frontiers in Neurology. - : Frontiers Media S.A.. - 1664-2295. ; 12
-
Journal article (peer-reviewed)abstract
- Introduction: Post-stroke cognitive impairment (PSCI) is common, but evidence on the impact of vascular risk factors is lacking. We explored the association between pre-stroke vascular risk factors and PSCI and studied the course of PSCI.Materials and Methods: Vascular risk factors were collected at baseline in stroke survivors (n = 635). Cognitive assessments of attention, executive function, memory, language, and the Montreal Cognitive Assessment (MoCA) were performed at 3 and/or 18 months post-stroke. Stroke severity was assessed with the National Institutes of Health Stroke Scale (NIHSS). PSCI was measured with global z; MoCA z-score; and z-score of the four assessed cognitive domains. Mixed-effect linear regression was applied with global z, MoCA z-score, and z-scores of the cognitive domains as dependent variables. Independent variables were the vascular risk factors (hypertension, hypercholesterolemia, smoking, diabetes mellitus, atrial fibrillation, coronary heart disease, previous stroke), time, and the interaction between these. The analyses were adjusted for age, education, and sex. There were between 5 and 25% missing data for the variables for PSCI.Results: Mean age was 71.6 years (SD 11.7); 42% were females; and the mean NIHSS score at admittance was 3.8 (SD 4.8). Regardless of vascular risk factors, global z, MoCA, and all the assessed cognitive domains were impaired at 3 and 18 months, with MoCA being the most severely impaired. Atrial fibrillation (AF) was associated with poorer language at 18 months and coronary heart disease (CHD) with poorer MoCA at 18 months (LR =12.80, p = 0.002, and LR = 8.32, p = 0.004, respectively). Previous stroke was associated with poorer global z and attention at 3 and 18 months (LR = 15.46, p < 0.001, and LR = 16.20, p < 0.001). In patients without AF, attention improved from 3 to 18 months, and in patients without CHD, executive function improved from 3 to 18 months (LR = 10.42, p < 0.001, and LR = 9.33, p = 0.009, respectively).Discussion: Our findings indicate that a focal stroke lesion might be related to pathophysiological processes leading to global cognitive impairment. The poorer prognosis of PSCI in patients with vascular risk factors emphasizes the need for further research on complex vascular risk factor interventions to prevent PSCI.
|
|
| 2. |
- Aksnes, Mari, et al.
(author)
-
Differences in metalloproteinases and their tissue inhibitors in the cerebrospinal fluid are associated with delirium
- 2024
-
In: COMMUNICATIONS MEDICINE. - 2730-664X. ; 4:1
-
Journal article (peer-reviewed)abstract
- BackgroundThe aetiology of delirium is not known, but pre-existing cognitive impairment is a predisposing factor. Here we explore the associations between delirium and cerebrospinal fluid (CSF) levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), proteins with important roles in both acute injury and chronic neurodegeneration.MethodsUsing a 13-plex Discovery Assay (R), we quantified CSF levels of 9 MMPs and 4 TIMPs in 280 hip fracture patients (140 with delirium), 107 cognitively unimpaired individuals, and 111 patients with Alzheimer's disease dementia. The two delirium-free control groups without acute trauma were included to unravel the effects of acute trauma (hip fracture), dementia, and delirium.ResultsHere we show that delirium is associated with higher levels of MMP-2, MMP-3, MMP-10, TIMP-1, and TIMP-2; a trend suggests lower levels of TIMP-4 are also associated with delirium. Most delirium patients had pre-existing dementia and low TIMP-4 is the only marker associated with delirium in adjusted analyses. MMP-2, MMP-12, and TIMP-1 levels are clearly higher in the hip fracture patients than in both control groups and several other MMP/TIMPs are impacted by acute trauma or dementia status.ConclusionsSeveral CSF MMP/TIMPs are significantly associated with delirium in hip fracture patients, but alterations in most of these MMP/TIMPs could likely be explained by acute trauma and/or pre-fracture dementia. Low levels of TIMP-4 appear to be directly associated with delirium, and the role of this marker in delirium pathophysiology should be further explored. Delirium is a syndrome in which there are substantial changes in a person's ability to focus, understand, or pay attention to events. Delirium often occurs in response to sudden trauma and is more common in persons with pre-existing cognitive impairment. What happens in the brain during delirium is not well understood. To learn more, we have studied whether markers in the cerebrospinal fluid were altered in people with delirium compared to people without delirium. To understand differences specifically caused by delirium, we included two control groups without acute trauma, one with cognitively healthy participants and one with dementia patients. We found several markers altered in people with delirium, with most of the markers similarly altered in people with cognitive impairment due to dementia. One marker was directly linked to delirium and could potentially shed light on the brain processes that cause the syndrome. Aksnes et al. evaluate the association between matrix metalloproteinases and their tissue inhibitors with delirium. Multivariate regression analyses find that while most associations are explained by acute trauma or pre-existing cognitive impairment, low TIMP-4 could be directly linked to delirium.
|
|
| 3. |
- Hageman, Steven H. J., et al.
(author)
-
Estimation of recurrent atherosclerotic cardiovascular event risk in patients with established cardiovascular disease : the updated SMART2 algorithm
- 2022
-
In: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 43:18, s. 1715-1727
-
Journal article (peer-reviewed)abstract
- Aims The 10-year risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events in patients with established ASCVD can be estimated with the Secondary Manifestations of ARTerial disease (SMART) risk score, and may help refine clinical management. To broaden generalizability across regions, we updated the existing tool (SMART2 risk score) and recalibrated it with regional incidence rates and assessed its performance in external populations.Methods and results Individuals with coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysms were included from the Utrecht Cardiovascular Cohort-SMART cohort [n = 8355; 1706 ASCVD events during a median follow-up of 8.2 years (interquartile range 4.2-12.5)] to derive a 10-year risk prediction model for recurrent ASCVD events (non-fatal myocardial infarction, non-fatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. The model was recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation used data from seven cohorts [Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and Bialystok PLUS/Polaspire] and included 369 044 individuals with established ASCVD of whom 62 807 experienced an ASCVD event. C-statistics ranged from 0.605 [95% confidence interval (CI) 0.547-0.664] in BACS/BAMI to 0.772 (95% CI 0.659-0.886) in REACH Europe high-risk region. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options.Conclusion The SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based upon quantitative rather than qualitative estimates of residual risk.
|
|
| 4. |
- Jansen, Iris E, et al.
(author)
-
Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
- 2022
-
In: Acta neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 144:5, s. 821-842
-
Journal article (peer-reviewed)abstract
- Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n=8074; replication n=5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.
|
|
| 5. |
- Rongve, Arvid, et al.
(author)
-
GBA and APOE ε4 associate with sporadic dementia with Lewy bodies in European genome wide association study
- 2019
-
In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
-
Journal article (peer-reviewed)abstract
- Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder with poor prognosis and mainly unknown pathophysiology. Heritability estimates exceed 30% but few genetic risk variants have been identified. Here we investigated common genetic variants associated with DLB in a large European multisite sample. We performed a genome wide association study in Norwegian and European cohorts of 720 DLB cases and 6490 controls and included 19 top-associated single-nucleotide polymorphisms in an additional cohort of 108 DLB cases and 75545 controls from Iceland. Overall the study included 828 DLB cases and 82035 controls. Variants in the ASH1L/GBA (Chr1q22) and APOE ε4 (Chr19) loci were associated with DLB surpassing the genome-wide significance threshold (p < 5 × 10 −8 ). One additional genetic locus previously linked to psychosis in Alzheimer’s disease, ZFPM1 (Chr16q24.2), showed suggestive association with DLB at p-value < 1 × 10 −6 . We report two susceptibility loci for DLB at genome-wide significance, providing insight into etiological factors. These findings highlight the complex relationship between the genetic architecture of DLB and other neurodegenerative disorders.
|
|
| 6. |
- Wæhler, Idunn Snorresdatter, et al.
(author)
-
Association between in-hospital frailty and health-related quality of life after stroke : the Nor-COAST study
- 2021
-
In: BMC Neurology. - : BioMed Central. - 1471-2377. ; 21:1
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Stroke survivors are known to have poorer health-related quality of life (HRQoL) than the general population, but less is known about characteristics associated with HRQoL decreasing through time following a stroke. This study aims to examine how in-hospital frailty is related to HRQoL from 3 to 18 months post stroke.METHOD: Six hundred twenty-five participants hospitalised with stroke were included and followed up at 3 and/or 18 months post stroke. Stroke severity was assessed the day after admission with the National Institutes of Health Stroke Scale (NIHSS). A modified Fried phenotype was used to assess in-hospital frailty; measures of exhaustion, physical activity, and weight loss were based on pre-stroke status, while gait speed and grip strength were measured during hospital stay. HRQoL at 3- and 18-months follow-up were assessed using the five-level version of the EuroQol five-dimensional descriptive system (EQ-5D-5L) and the EuroQol visual analogue scale (EQ-5D VAS). We conducted linear mixed effect regression analyses unadjusted and adjusted for sex, age, and stroke severity to investigate the association between in-hospital frailty and post-stroke HRQoL.RESULTS: Mean (SD) age was 71.7 years (11.6); mean NIHSS score was 2.8 (4.0), and 263 (42.1%) were female. Frailty prevalence was 10.4%, while 58.6% were pre-frail. The robust group had EQ-5D-5L index and EQ-5D VAS scores at 3 and 18 months comparable to the general population. Also at 3 and 18 months, the pre-frail and frail groups had significantly lower EQ-5D-5L indices than the robust group (p < 0.001), and the frail group showed a larger decrease from 3 to 18 months in the EQ-5D-5L index score compared to the robust group (- 0.056; 95% CI - 0.104 to - 0.009; p = 0.021). There were no significant differences in change in EQ-5D VAS scores between the groups.CONCLUSION: This study on participants mainly diagnosed with mild strokes suggests that robust stroke patients have fairly good and stable post-stroke HRQoL, while post-stroke HRQoL is impaired and continues to deteriorate among patients with in-hospital frailty. This emphasises the importance of a greater focus on frailty in stroke units.TRIAL REGISTRATION: ClinicalTrials.gov ( NCT02650531 ).
|
|
