Five-year stroke prognosis. Influence of post-stroke delirium and post-stroke dementia on mortality and disability (Research Study - Part of the PROPOLIS Study).

INTRODUCTION: With increasing life expectancy and the rising incidence of stroke in young adults, it is important to know the long-term prognosis of this condition. Post-stroke delirium and post-stroke dementia are common complications of stroke that negatively affect prognosis. The purpose of this study was to evaluate five-year mortality from stroke and to assess the influence of post-stroke delirium and post-stroke dementia on mortality and disability over the five-year period. METHODS: Consecutive patients admitted to the stroke unit for acute stroke or transient ischemic attacks were screened for in-hospital delirium. At the three- and twelve-month follow-up, the same patients underwent neurocognitive testing. Diagnoses of in-hospital delirium and dementia after three and twelve months based on DSM-5 criteria. Five years after stroke surviving patients were reevaluated. Outcome assessment included place of stay, current functional status assessed by the modified Rankin Scale (mRS), or death. RESULTS: At the five-years of follow-up, data were collected from 575 of 750 patients originally included in the study (76.67%). The mortality rate was 51.65%. In-hospital post-stroke delirium and post-stroke dementia diagnosed three and twelve months after stroke were independent risk factors for death and an increase in mRS score of ≥ 1 or ≥ 2 points. There was no significant association with institutionalization rate. CONCLUSIONS: More than half of post-stroke patients die within five years of follow-up. Post-stroke delirium and post-stroke dementia are associated with an increased risk of death and disability.

Network analysis of neuropsychiatric, cognitive, and functional complications of stroke: implications for novel treatment targets.

AIM: Recovery from stroke is adversely affected by neuropsychiatric complications, cognitive impairment, and functional disability. Better knowledge of their mutual relationships is required to inform effective interventions. Network theory enables the conceptualization of symptoms and impairments as dynamic and mutually interacting systems. We aimed to identify interactions of poststroke complications using network analysis in diverse stroke samples. METHODS: Data from 2185 patients were sourced from member studies of STROKOG (Stroke and Cognition Consortium), an international collaboration of stroke studies. Networks were generated for each cohort, whereby nodes represented neuropsychiatric symptoms, cognitive deficits, and disabilities on activities of daily living. Edges characterized associations between them. Centrality measures were used to identify hub items. RESULTS: Across cohorts, a single network of interrelated poststroke complications emerged. Networks exhibited dissociable depression, apathy, fatigue, cognitive impairment, and functional disability modules. Worry was the most central symptom across cohorts, irrespective of the depression scale used. Items relating to activities of daily living were also highly central nodes. Follow-up analysis in two studies revealed that individuals who worried had more densely connected networks than those free of worry (CASPER [Cognition and Affect after Stroke: Prospective Evaluation of Risks] study: S = 9.72, P = 0.038; SSS [Sydney Stroke Study]: S = 13.56, P = 0.069). CONCLUSION: Neuropsychiatric symptoms are highly interconnected with cognitive deficits and functional disabilities resulting from stroke. Given their central position and high level of connectedness, worry and activities of daily living have the potential to drive multimorbidity and mutual reinforcement between domains of poststroke complications. Targeting these factors early after stroke may have benefits that extend to other complications, leading to better stroke outcomes.

Drugs with a negative impact on cognitive functions (Part 2): drug classes to consider while prescribing in CKD patients.

There is growing evidence that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment, especially due to vascular damage, blood-brain barrier disruption and uremic toxins. Given the presence of multiple comorbidities, the medication regimen of CKD patients often becomes very complex. Several medications such as psychotropic agents, drugs with anticholinergic properties, GABAergic drugs, opioids, corticosteroids, antibiotics and others have been linked to negative effects on cognition. These drugs are frequently included in the treatment regimen of CKD patients. The first review of this series described how CKD could represent a risk factor for adverse drug reactions affecting the central nervous system. This second review will describe some of the most common medications associated with cognitive impairment (in the general population and in CKD) and describe their effects.

Cognitive disorders in patients with chronic kidney disease: Approaches to prevention and treatment.

BACKGROUND: Cognitive impairment is common in patients with chronic kidney disease (CKD), and early intervention may prevent the progression of this condition. METHODS: Here, we review interventions for the complications of CKD (anemia, secondary hyperparathyroidism, metabolic acidosis, harmful effects of dialysis, the accumulation of uremic toxins) and for prevention of vascular events, interventions that may potentially be protective against cognitive impairment. Furthermore, we discuss nonpharmacological and pharmacological methods to prevent cognitive impairment and/or minimize the latter's impact on CKD patients' daily lives. RESULTS: A particular attention on kidney function assessment is suggested during work-up for cognitive impairment. Different approaches are promising to reduce cognitive burden in patients with CKD but the availabe dedicated data are scarce. CONCLUSIONS: There is a need for studies assessing the effect of interventions on the cognitive function of patients with CKD.

Transient cognitive impairment in the acute phase of stroke - prevalence, risk factors and influence on long-term prognosis in population of patients with stroke (research study - part of the PROPOLIS study).

BACKGROUND: Cognitive impairment is a common complication of the acute phase of stroke, which can be transient and resolve while still in the hospital. This study evaluated the prevalence and risk factors for transient cognitive impairment and their impact on long-term prognosis in a population of acute-phase stroke patients. METHODS: Consecutive patients admitted to a stroke unit with acute stroke or transient ischemic attack were screened twice for cognitive impairment using the parallel version of Montreal Cognitive Assessment: the first time between the first and third day and the second time between the fourth and seventh day of hospitalization. If the second test score increased by two or more points, transient cognitive impairment was diagnosed. Patients were scheduled for follow-up visits three and 12 months after stroke. Outcome assessment included place of discharge, current functional status, dementia, or death. RESULTS: Four hundred forty-seven patients were included in the study, 234 (52.35%) were diagnosed with transient cognitive impairment. Delirium was the only independent risk factor for transient cognitive impairment (OR 2.417, 95%CI 1.096-5.333, p = 0.029). In the analysis of effects on three- and twelve-month prognosis, patients with transient cognitive impairment had a lower risk of hospital or institution stay 3 months after stroke compared with patients with permanent cognitive impairment (OR 0.396, 95%CI 0.217-0.723, p = 0.003). There was no significant effect on mortality, disability or risk of dementia. CONCLUSIONS: Transient cognitive impairment, which often occurs in the acute phase of stroke, does not increase the risk of long-term complications.

Application of a custom NGS gene panel revealed a high diagnostic utility for molecular testing of hereditary ataxias.

Hereditary ataxias (HA) are a rare group of heterogeneous disorders. Here, we present the results of molecular testing of a group of ataxia patients using a custom-designed next-generation sequencing (NGS) panel. Due to the genetic and clinical overlapping of hereditary ataxias and spastic paraplegias (HSP), the panel encompasses together HA and HSP genes. The NGS libraries, comprising coding sequences for 152 genes, were performed using KAPA HyperPlus and HyperCap Target Enrichment Kit, sequenced on the MiSeq instrument. The results were analyzed using the BaseSpace Variant Interpreter and Integrative Genomics Viewer. All pathogenic and likely pathogenic variants were confirmed using Sanger sequencing. A total of 29 patients with hereditary ataxias were enrolled in the NGS testing, and 16 patients had a confirmed molecular diagnosis with diagnostic accuracy rate of 55.2%. Pathogenic or likely pathogenic mutations were identified in 10 different genes: POLG (PEOA1, n = 3; SCAE, n = 2), CACNA1A (EA2, n = 2), SACS (ARSACS, n = 2), SLC33A1 (SPG42, n = 2), STUB1 (SCA48, n = 1), SPTBN2 (SCA5, n = 1), TGM6 (SCA35, n = 1), SETX (AOA2, n = 1), ANO10 (SCAR10, n = 1), and SPAST (SPG4, n = 1). We demonstrated that an approach based on the targeted use of the NGS panel can be highly effective and a useful tool in the molecular diagnosis of ataxia patients. Furthermore, we highlight the fact that a sequencing panel targeting both ataxias and HSP genes increases the diagnostic success level.

Risk Factors for Apathy in Polish Patients with Parkinson's Disease.

Apathy, a feeling of indifference or a general lack of interest and motivation to engage in activity, is one of the most common neuropsychiatric symptoms in Parkinson's disease (PD). The large variation in prevalence and the underlying pathophysiological processes remain unclear due to heterogeneous PD populations. The purpose of this study was to identify risk factors for apathy, the modification or treatment of which may be clinically relevant and improve quality of life and caregiver burden for patients with Parkinson's disease. Caucasian subjects with Parkinson's disease were included in the study. Baseline demographics, neurological deficit, medications taken, cognitive and neuropsychiatric status, and the polymorphisms in the brain-derived neurotrophic factor gene were assessed. Apathy was diagnosed in 53 (50.5%) patients. They were less educated (OR 0.76 CI 0.64-0.89; p = 0.001), more frequently depressed (OR 1.08 CI 1.01-1.15; p = 0.018), and less frequently treated with inhibitors of monoamine oxidase-B (MAOB-I) (OR 0.07 CI 0.01-0.69; p = 0.023). Although apathetic patients were more likely to carry the Met/Met genotype, differences in the brain-derived neurotrophic factor BDNF rs6265 polymorphism between apathetic and non-apathetic PD patients were not statistically significant in multivariate analysis. Some risk factors for apathy may be clinically modifiable. Further studies are needed to assess whether modeling modifiable apathy risk factors will affect the prevalence of this neuropsychiatric symptom in patients with Parkinson's disease.

Current Knowledge on the Background, Pathophysiology and Treatment of Levodopa-Induced Dyskinesia-Literature Review.

Levodopa remains the primary drug for controlling motor symptoms in Parkinson's disease through the whole course, but over time, complications develop in the form of dyskinesias, which gradually become more frequent and severe. These abnormal, involuntary, hyperkinetic movements are mainly characteristic of the ON phase and are triggered by excess exogenous levodopa. They may also occur during the OFF phase, or in both phases. Over the past 10 years, the issue of levodopa-induced dyskinesia has been the subject of research into both the substrate of this pathology and potential remedial strategies. The purpose of the present study was to review the results of recent research on the background and treatment of dyskinesia. To this end, databases were reviewed using a search strategy that included both relevant keywords related to the topic and appropriate filters to limit results to English language literature published since 2010. Based on the selected papers, the current state of knowledge on the morphological, functional, genetic and clinical features of levodopa-induced dyskinesia, as well as pharmacological, genetic treatment and other therapies such as deep brain stimulation, are described.

Cognitive disorders in patients with chronic kidney disease: specificities of clinical assessment.

Neurocognitive disorders are frequent among chronic kidney disease (CKD) patients. Identifying and characterizing cognitive impairment (CI) can help to assess the ability of adherence to CKD risk reduction strategy, identify potentially reversible causes of cognitive decline, modify pharmacotherapy, educate the patient and caregiver and provide appropriate patient and caregiver support. Numerous factors are associated with the development and progression of CI in CKD patients and various conditions can influence the results of cognitive assessment in these patients. Here we review clinical warning signs that should lead to cognitive screening; conditions frequent in CKD at risk to interfere with cognitive testing or performance, including specificities of cognitive assessment in dialysis patients or after kidney transplantation; and available tests for screening and observed cognitive patterns in CKD patients.

The Utility of Next-Generation Sequencing for Identifying the Genetic Basis of Dementia.

The clinical manifestations of dementia are often rapidly matched to a specific clinical syndrome, but the underlying neuropathology is not always obvious. A genetic factor often plays an important role in early onset dementia, but there are cases in which the phenotype has a different genetic basis than is assumed. Two patients, at different times, presented to the Memory Clinic because of memory problems and difficulty in performing daily activities and work. Neither caregiver complained of marked behavioural or personality changes, except for apathy. Patients underwent standard dementia evaluation procedures including clinical symptoms, family history, neuroimaging, neuropsychological evaluation, and genetic analysis of selected genes. Based on specific clinical phenotypes and genetic analysis of selected genes, both patients were diagnosed with frontal variant of Alzheimer's disease. The presence of a rare polymorphism in PSEN2 in both patients allowed the discovery that they belong to the same family. This fact reinforced the belief that there is a strong genetic factor responsible for causing dementia in the family. Next-generation sequencing based on a panel of 118 genes was performed to identify other potential genetic factors that may determine the background of the disease. A mutation in the GRN gene was identified, and the previous diagnosis was changed to frontotemporal dementia. The described cases show how important it is to combine all diagnostic tests available in the diagnostic centre, including new generation genetic tests, in order to establish/confirm the pathological background of clinical symptoms of dementia. If there is any doubt about the final diagnosis, persistent efforts should be made to verify the cause.

Headache Associated with Sexual Activity-A Narrative Review of Literature.

Headache associated with sexual activity (HAWSA) has accompanied humanity since ancient times. However, it is only since the 1970s that it has become the subject of more extensive and detailed scientific interest. The purpose of this review is to provide an overview of the development of the concept of HAWSA, its clinical presentation, etiopathogenesis, diagnosis and treatment especially from the research perspective of the last 20 years. Primary HAWSA is a benign condition, whose etiology is unknown; however, at the first occurrence of headache associated with sexual activity, it is necessary to exclude conditions that are usually immediately life-threatening. Migraine, hypnic headache or hemicrania continua have been reported to co-occur with HAWSA, but their common pathophysiologic basis is still unknown. Recent advances in the treatment of HAWSA include the introduction of topiramate, progesterone, and treatments such as greater occipital nerve injection, arterial embolization, and manual therapy. Whether these new therapeutic options will stand the test of time remains to be seen.

Elevated plasma levels of galectin-3 binding protein are associated with post-stroke delirium - A pilot study.

To explore the role of systemic inflammation in post-stroke delirium, we investigated the level of two inflammatory mediators: high mobility group box 1 (HMGB1) and galectin-3 binding protein (Gal-3BP). Of 571 stroke patients, we compared plasma levels of HMGB1 and Gal-3BP in 79 delirious patients with 81 non-delirious patients matched for age and stroke severity. Delirious patients had higher Gal-3BP level (median: 1440 vs 1053 ng/mL, P < 0.01). An elevated level of Gal-3BP was associated with an increased risk of delirium. HMGB1 levels did not differ between groups. Our results suggest that pro-inflammatory monocytes and macrophages might be involved in delirium pathophysiology.

Current view on post-stroke dementia.

Dementia is one of the leading complications after stroke affecting about one third of survivors. Prevalence of post-stroke dementia (PSD) differs between studies due to variability in methodology, characteristics of included patients, type of stroke, diagnostic tools used to identify patients with dementia, or time when the assessment was performed. Patients diagnosed with PSD are at higher risk of mortality, disability, and institutionalization. Aetiology of PSD may include mixed overlapping processes such as vascular brain pathology or Alzheimer's disease. Several risk factors have been found to increase PSD incidence, involving demographics, vascular factors, stroke characteristics, abnormalities on neuroimaging, and stroke complications. However, the influence of some other factors still remains unclear. PSD may coexist with other neuropsychiatric disorders and its association with post-stroke depression seems to be the most significant. There is a strong need for further research on possible genetic, biological, and inflammatory biomarkers. Also, there are no unambiguously efficacious methods of management. Continuing to address these issues will help to find more effective interventions directly targeting prevention and treatment of PSD in the future.

Early Depression Independently of Other Neuropsychiatric Conditions, Influences Disability and Mortality after Stroke (Research Study-Part of PROPOLIS Study).

Post-stroke depression (PSD) is the most frequent neuropsychiatric consequence of stroke. The nature of the relationship between PSD and mortality still remains unknown. One hypothesis is that PSD could be more frequent in those patients who are more vulnerable to physical disability, a mediator variable for higher level of physical damage related to higher risk of mortality. Therefore, the authors' objective was to explore the assumption that PSD increases disability after stroke, and secondly, that mortality is higher among patients with PSD regardless of stroke severity and other neuropsychiatric conditions. We included 524 consecutive patients with acute stroke or transient ischemic attack, who were screened for depression between 7-10 days after stroke onset. Physical impairment and death were the outcomes measures at evaluation check points three and 12 months post-stroke. PSD independently increased the level of disability three (OR = 1.94, 95% CI 1.31-2.87, p = 0.001), and 12 months post-stroke (OR = 1.61, 95% CI 1.14-2.48, p = 0.009). PSD was also an independent risk factor for death three (OR = 5.68, 95% CI 1.58-20.37, p = 0.008) and 12 months after stroke (OR = 4.53, 95% CI 2.06-9.94, p = 0.001). Our study shows the negative impact of early PSD on the level of disability and survival rates during first year after stroke and supports the assumption that depression may act as an independent mediator for disability leading to death in patients who are more vulnerable for brain injury.

Delirium Post-Stroke-Influence on Post-Stroke Dementia (Research Study-Part of the PROPOLIS Study).

BACKGROUND: Previous research confirmed association between delirium and subsequent dementia in different clinical settings, but the impact of post-stroke delirium on cognitive functioning is still under-investigated. Therefore, we aimed to assess the risk of dementia among patients with stroke and in-hospital delirium. METHODS: A total of 750 consecutive patients admitted to the stroke unit with acute stroke or transient ischemic attacks were screened for delirium, during the first seven days after admission. At the three- and twelve-month follow-up, patients underwent cognitive evaluation. The DSM-5 definition for dementia was used. Cases with pre-stroke dementia were excluded from the analysis. RESULTS: Out of 691 included cases, 423 (61.22%) and 451 (65.27%) underwent cognitive evaluation, three and twelve months after stroke; 121 (28.61%) and 151 (33.48%) patients were diagnosed with dementia, respectively. Six (4.96%) patients with dementia, three months post-stroke did not meet the diagnostic criteria for dementia nine months later. After twelve months, 37 (24.50%) patients were diagnosed with dementia, first time after stroke. Delirium in hospital was an independent risk factor for dementia after three months (OR = 7.267, 95%CI 2.182-24.207, p = 0.001) but not twelve months after the stroke. CONCLUSIONS: Patients with stroke complicated by in-hospital delirium are at a higher risk for dementia at three but not twelve months post-stroke.

Delirium Post-Stroke: Short- and Long-Term Effect on Depression, Anxiety, Apathy and Aggression (Research Study-Part of PROPOLIS Study).

BACKGROUND: Stroke patients are particularly vulnerable to delirium episodes, but very little is known about its subsequent adverse mental health outcomes. The author's objective was to explore the association between in-hospital delirium and depression, anxiety, anger and apathy after stroke. METHODS: A total of 750 consecutive patients with acute stroke or transient ischemic attack, were screened for delirium during hospitalization. Patients underwent mental health evaluation in hospital, 3 and 12 months post-stroke; depression, apathy, anxiety and anger were the outcomes measured at all evaluation check points. RESULTS: Delirium was an independent risk factor for depression (OR = 2.28, 95%CI 1.15-4.51, p = 0.017) and aggression (OR = 3.39, 95%CI 1.48-7.73, p = 0.004) at the hospital, for anxiety 3 months post-stroke (OR = 2.83, 95%CI 1.25-6.39, p = 0.012), and for apathy at the hospital (OR = 4.82, 95%CI 2.25-10.47, p < 0.001), after 3 (OR = 3.84, 95%CI 1.31-11.21, p = 0.014) and 12 months (OR = 4.95, 95%CI 1.68-14.54, p = 0.004) post stroke. CONCLUSIONS: The results of this study confirm, that mental health problems are very frequent complications of stroke. Delirium in the acute phase of stroke influences mental health of patients. This effect is especially significant in the first months post-stroke and vanishes with time, which suggests that in-hospital delirium might not be a damaging occurrence in most measures of mental health problems from a long-term perspective.

What Determines Spontaneous Physical Activity in Patients with Parkinson's Disease?

Physical activity (PA) is a factor that may have an influence on the symptoms of Parkinson's disease (PD). The aim of this study was to identify the potential determinants of spontaneous PA in a PD patient group. A total of 134 PD patients aged 65.2 ± 9.2 years with a Hoehn-Yahr scale score ≤4 and a Mini Mental State Examination (MMSE) score ≥24 were examined. For the study's purposes, the authors analyzed age, sex, education, history of PD, dopaminergic treatment, the severity of PD symptoms using Unified Parkinson's Disease Rating Scale (UPDRS), and Hoehn-Yahr scale. Additionally, all participants were evaluated through a set of scales for specific neuropsychiatric symptoms including depression, anxiety, apathy, fatigue, and sleep disorders. A linear regression analysis was used with backward elimination. In the total explanatory model, for 12% of the variability in activity (R2 = 0.125; F(16.133) = 2.185; p < 0.01), the significant predictor was starting therapy with the dopamine agonist (DA) (ß= 0.420; t= 4.068; p = 0.000), which was associated with a longer duration of moderate PA. In the total explanatory model, for more than 13% of the variance in time spent sitting (R2 = 0.135; F(16.130) = 2.267; p < 0.01), the significant predictors were secondary education and the results of the UPDRS. The patients with secondary and vocational education, those starting treatment with DA and those with a less severe degree of Parkinson's symptoms (UPDRS), spent less time sitting in a day. It is possible to identify determinants of spontaneous PA. It may elucidate consequences in terms of influence on modifiable conditions of PA and the proper approach to patients with unmodifiable PA factors.

C-reactive protein and post-stroke depressive symptoms.

Our study aimed to explore the association between serum C-reactive protein (CRP) and post-stroke depressive symptoms. We prospectively recruited 572 patients with ischemic stroke or transient ischemic attack in whom serum CRP level was measured within 48 h after stroke onset. Depressive symptoms were assessed at day 8 and 3 months after stroke in 405 and 306 patients, respectively. Patients with greater depressive symptoms at day 8 and patients with greater depressive symptoms 3 months after stroke had higher CRP level (median: 7.9 vs 4.3 mg/L, P < 0.01 and 6.7 vs 3.4 mg/L, P = 0.01, respectively). In the univariate analysis, CRP > 9.2 mg/L was associated with depressive symptoms at day 8 (OR: 2.06, 95%CI: 1.30-3.28, P < 0.01) and CRP > 4.3 mg/L was associated with depressive symptoms 3 months after stroke (OR: 1.79, 95%CI: 1.06-3.02, P = 0.03). In the multivariate analysis, higher CRP level was related to depressive symptoms at day 8 (OR: 2.23, 95%CI: 1.28-3.90, P < 0.01), but not depressive symptoms 3 months after stroke (OR: 1.13, 95%CI: 0.59-2.17, P = 0.71). In conclusion, higher levels of CRP are associated with greater depressive symptoms at day 8 after stroke, but their effects on depressive symptoms 3 months after stroke are less significant.