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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., Graphical Abstract Graphical abstract

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.

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 9.2 mg/L was associated with depressive symptoms at day 8 (OR: 2.06, 95%CI: 1.30–3.28, P 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

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.

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.

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&rsquo, 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&ndash, 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&ndash, 2.87, p = 0.001), and 12 months post-stroke (OR = 1.61, 95% CI 1.14&ndash, 2.48, p = 0.009). PSD was also an independent risk factor for death three (OR = 5.68, 95% CI 1.58&ndash, 20.37, p = 0.008) and 12 months after stroke (OR = 4.53, 95% CI 2.06&ndash, 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.

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.

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.

Physical activity (PA) is a factor that may have an influence on the symptoms of Parkinson&rsquo, 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 &plusmn, 9.2 years with a Hoehn&ndash, Yahr scale score &le, 4 and a Mini Mental State Examination (MMSE) score &ge, 24 were examined. For the study&rsquo, s purposes, the authors analyzed age, sex, education, history of PD, dopaminergic treatment, the severity of PD symptoms using Unified Parkinson&rsquo, s Disease Rating Scale (UPDRS), and Hoehn&ndash, 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 &lt, 0.01), the significant predictor was starting therapy with the dopamine agonist (DA) (&beta, = 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, 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&rsquo, 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.

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.

Neuropsychiatric symptoms can be interrelated to delirium. We aimed to investigate an association between pre-stroke neuropsychiatric symptoms and the risk of delirium in stroke patients. We included 606 patients (median age: 73, 53% female) with stroke or transient ischemic attack admitted within 48 hours from symptoms onset. We assessed delirium on a daily basis during the first 7 days of hospitalization. To make diagnosis of delirium we used DSM-5 criteria. We used Neuropsychiatric Inventory to assess neuropsychiatric symptoms occurring within 4 weeks prior to stroke. We diagnosed delirium in 28.2% of patients. On univariate analysis, higher score of pre-stroke depression (OR: 1.58, 95% CI: 1.04–2.40, P = 0.03), apathy (OR: 2.23, 95% CI: 1.44–3.45, P

Background It is known that YKL-40- a marker of glial inflammation, and VILIP-1- a marker of neuronal injury, reflect functional and structural changes in AD brains, although there is limited data concerning their potential influence on blood-brain barrier (BBB) homeostasis. Objective Therefore, the aim of our study was to investigate the relationship between markers of inflammation and degeneration in the central nervous system (CNS) of patients with AD and mild cognitive impairment (MCI) as well as immunological response in CNS and BBB function. Methods Cerebrospinal fluid (CSF) concentrations of proteins tested were determined in 45 AD patients, 18 MCI subjects, and 23 non-demented controls using ELISA method. Results CSF concentrations of YKL-40 were significantly higher in MCI and AD patients, whereas CSF levels of VILIP-1 were statistically higher in the AD group as compared to the subjects without cognitive deficits. Elevated concentrations of YKL-40 correlated significantly with increased albumin quotient and decreased Aβ42/40 ratio in AD patients and with IgG quotient in the total study group. We did not find a relationship between VILIP-1 and immunological parameters reflecting BBB dysfunction and humoral immune response. Conclusion Our findings indicate that YKL-40 may contribute to decreased stability and increased permeability of BBB in AD patients. It is assumed that YKL-40 is implicated in the development of brain barriers, although its precise mechanism of action in the BBB disruption remains unrevealed. Further studies on larger groups of patients are required to confirm our hypothesis.

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.

Background Hereditary spastic paraplegia is a large group of degenerative, neurological disorders characterized by progressive lower limb spasticity and weakness. The disease was investigated precisely but still clinicians often make incorrect or late diagnosis. Our aim was to investigate the genetic background and clinical phenotype of spastic paraplegia in large Polish family. Case presentation A 37 years old woman presented with 4-year history of walking difficulties. On neurological examination, she had signs of upper motor lesion in lower extremities. She denied sphincter dysfunction and her cognition was normal. Her family history was positive for individuals with gait problems. The initial diagnosis was familial spastic paraplegia. Genetic testing identified a novel mutation in SPAST gene. All available family members were examined and had genetic testing. The same mutation in SPAST gene was identified in other affected family members. All patients caring the mutation presented with different phenotypes. Conclusion This study presents a family with spastic paraplegia due to a novel mutation c.1390G›T(p.Glu464Term) in SPAST gene. Affected individuals showed a range of phenotypes that varied in their severity. This case report demonstrates, the signs of hereditary spastic paraplegia can be often misdiagnosed with other diseases. Therefore genetic testing should always be considered in patients with lower limb spasticity and positive family history in order to help to establish the correct diagnosis.

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.

Alzheimer's disease (AD) is a neurodegenerative, inevitably progressive disease with a rate of cognitive, functional, and behavioral decline that varies highly from patient to patient. Although several clinical predictors of AD progression have been identified, to our mind in clinical practice there is a lack of a reliable biomarker that enables one to stratify the risk of deterioration. Identification of biomarkers that allow the monitoring of AD progression could change the way physicians and caregivers make treatment decisions. This review summarizes the results of studies on potential biochemical and radiological markers related to AD progression.

BackgroundThe aim of the case study was to describe the profile of cognitive and emotional functioning of a patient with possible progressive supranuclear palsy (PSP) from a longitudinal perspective.Participants and procedureThis study involved an 71-year-old male patient diagnosed with PSP, and 9 matched healthy subjects. Neuro-psychological examination of the patient was performed twice with a 6 month interval. A set of neuropsycho-logical tests was used to assess both cognition and behaviour.ResultsNeuropsychological assessment revealed executive dysfunction dominance (planning deficits, reduced cogni-tive flexibility and abstract thinking, impulsiveness), reduced verbal fluency, psychomotor slowness and prob-lems with memory retrieval from the long-term memory storage in contrast to significantly better recognition of the previously learned information. According to emotional functioning, frontal change of personality was ob-served, with apathy, disinhibition, lack of insights, impulsiveness and “utilization behaviours”.ConclusionsThe profile of emotional and cognitive impairments met the criteria for dementia. There was a progression of deficits at visit two in comparison to visit one. The longitudinal perspective allowed the dynamics of emotional, cognitive and behavioural changes to be described over time: from depression related to initially preserved criticism of the illness to apathy and emotional blunting and behavioural frontal syndrome connected with the systematic loss of insight.

Background and purpose Delirium is a very common neurobehavioral complication after stroke, but its influence on long-term outcome is not well characterized. The objective of the study was to determine the prognostic significance of delirium for functional status, nursing home admission, and mortality in a large cohort of patients with delirium in the acute phase of stroke assessed 3 and 12 months after stroke. Methods All stroke survivors included in PROPOLIS were followed up (n = 682). Outcome data included: discharge destination, recurrence of stroke, cardiovascular complications, functional activity and mobility, nursing home admission, and mortality. Results Patients with delirium were discharged to another hospital or nursing home significantly more often than those presenting without delirium. The 3- and 12-month post-stroke mortality rates were higher in delirious patients (OR 6.41 CI 3.76–10.92; p

Although delirium is the most common neurobehavioral complication after stroke, its motor subtypes-hypoactive, hyperactive, mixed, and none-as well as their risk factors are not well characterized. Motor subtypes influence recognition and prognosis of delirium in hospitalized patients.The aim of this prospective study was to assess the frequency of poststroke delirium subtypes and to describe their predictive models. Consecutive patients with stroke were screened for delirium with the Confusion Assessment Method for the Intensive Care Unit. Delirium was diagnosed according to DSM-5 criteria, and subtypes were classified with the Delirium Motor Subtype Scale-4. Baseline demographic characteristics, biochemistry, stroke-related data, medications, neurological deficits, and premorbid cognitive and functional impairments were assessed.Out of 750 patients (mean age, 71.75 years [SD=13.13]), 203 (27.07%) had delirium: 85 (11.34%) were hypoactive, 77 (10.27%) were mixed hypoactive-hyperactive, 31 (4.13%) were hyperactive, and 10 (1.33%) had an unspecified type. Cognitive impairment at the time of hospital admission and spatial neglect, among other factors, were identified as the best predictors for all motor delirium subtypes.Screening for poststroke delirium is important because the hypoactive subtype bears the worst prognosis and is misdiagnosed the most compared with other subtypes. All identified factors for the predictive models of delirium subtypes are routinely assessed during hospital admission. Their occurrence in patients with stroke should alert the treating physician to the high risk for a particular delirium subtype.

Introduction: Apolipoprotein E (APOE) epsilon 4 is the major genetic risk factor for Alzheimer's disease (AD), but its prevalence is unclear because earlier studies did not require biomarker evidence of amyloid beta(A beta) pathology. Methods: We included 3451 A beta+ subjects (853 AD-type dementia, 1810 mild cognitive impairment, and 788 cognitively normal). Generalized estimating equation models were used to assess APOE epsilon 4 prevalence in relation to age, sex, education, and geographical location. Results: The APOE epsilon 4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal, and it decreased with advancing age in A beta+ cognitively normal and A beta+ mild cognitive impairment (P

Delirium is the most common and serious neurobehavioral complication in acute hospital admissions. Some patients develop signs of delirium but do not meet all diagnostic criteria. Stroke is a major risk factor for delirium. The aim of this prospective study was to build a predictive model for delirium and subsyndromal post-stroke delirium. Patients with stroke were screened for delirium during the first 7 days after admission. Delirium was diagnosed according to DSM-V criteria. Baseline demographic, biochemical, stroke-related data, medications used, neurological deficit, and premorbid cognitive and functional impairment were assessed. 750 consecutive stroke patients (71.75 ± 13.13 years) were recruited; 203 (27.07%) had delirium. In predictive model for delirium MoCA score and white blood count on admission, neglect, vision deficits, physical impairment, and higher comorbidity prior to stroke had the highest predictive value. Subsyndromal delirium was diagnosed in 60 patients. MoCA score and potassium level on admission, and urinary tract infection during hospitalization had the highest predictive value for its development. Delirium occurs in one-fourth of admissions due to stroke; subsyndromal delirium is less prevalent and affects less than one per ten patients. The hyperactive form is the most rare type of delirium. The factors best predicting delirium are easily assessed in everyday practice and their co-occurrence in patients with stroke should alert the treating physician of high risk of delirium.

Contains fulltext : 190311.pdf (Publisher’s version ) (Closed access) Importance: Cerebral amyloid-beta aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials. Objective: To investigate whether amyloid-beta aggregation is associated with cognitive functioning in persons without dementia. Design, Setting, and Participants: This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017. Main Outcomes and Measures: Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score

In stroke patients higher levels of plasma fibrinogen are associated with increased risk of unfavourable functional outcome and short-term mortality. The aim of our study was to determine the relationship between plasma fibrinogen level and long-term risk of death in ischemic stroke patients. Seven hundred thirty six patients (median age 71; 47.1 % men) admitted to the stroke unit within 24 h after stroke were included. Plasma fibrinogen level was measured on day 1 of hospitalisation. Hyperfibrinogenemia was defined as plasma fibrinogen concentration >3.5 g/L. The maximal follow-up period was 84 months. Hyperfibrinogenemia was found in 25.0 % of patients. On multivariate logistic regression analysis, after adjustment for age, stroke severity, atrial fibrillation, smoking, white blood cell count, fever, in-hospital pneumonia and hyperglycemia, hyperfibrinogenemia was associated with increased case fatality (HR 1.71, 95 % CI 1.29–2.26, P

Background: Acetylcholinesterase inhibitors (AChEIs) are the treatment of choice for patients with Alzheimer’s disease (AD). However, their efficacy is moderate and differs from patient to patient. Recent studies suggest that the Q192R variant of the paraoxonase 1 gene (PON1) might affect individual susceptibility to these drugs. Methods: We investigated the influence of 3 single nucleotide polymorphisms (SNPs) in PON1 (rs 662, rs 854560, rs 705381) and the APOE common polymorphism in 101 Polish patients with late-onset AD in response to treatment with AChEIs. Results: No significant differences were observed between carriers and non-carriers of the PON1 SNPs or the APOE common polymorphism in terms of treatment response. These results did not change after stratification of APOE status. Conclusion: Our results suggest that both the investigated PON1 and APOE common SNPs do not influence treatment response to AChEIs in patients with AD.

Interleukin-1 is a potent proinflammatory cytokine involved in the pathophysiology of Alzheimer’s disease (AD). We genotyped IL-1β (–511 C/T) and the apolipoprotein E (APOE) common polymorphisms in a large case-controlled study in a Polish population. We included 332 patients with late-onset AD and 220 controls without any neurological deficit, cognitive complaints and history of neurological diseases, aged ≥ 65 years. The distribution of the IL-1β (–511 C/T) genotypes was similar to that in the controls (AD: C/C = 45.8%, C/T = 44.6%, T/T = 9.6% vs. controls: C/C = 53.9%, C/T = 38.3%, T/T = 7.3%, p > 0.05). Our study confirms previous reports that APOE ε4 is strongly related to the risk of AD (odds ratio = 6.60, 95% confidence interval 4.19–10.41). APOE status did not affect the distribution of the studied IL-1β polymorphism. The IL-1β (–511 C/T) polymorphism is not a risk factor for late-onset AD in a Polish population.

Introduction: In the last decade, the stroke mortality rate in Poland significantly decreased. We hypothesised that stroke severity, the major determinant of outcome, is lowered in Polish stroke patients. Material and methods: We compared the stroke severity in two cohorts of first-ever ischaemic stroke patients admitted within 24 h after stroke onset to the Department of Neurology, Jagiellonian University, Krakow in the years 1994-2000 and 2008-2012. To assess stroke severity we used the National Institute of Health Stroke Scale (NIHSS). We defined mild stroke as an NIHSS score ≤ 4. Results: We included 816 patients hospitalised in the years 1994-2000 and 569 patients hospitalised in the years 2008-2012. NIHSS score on admission was higher in the former (mean: 12.0 ±7.0 vs. 8.0 ±6.0, p < 0.01), and the frequency of mild stroke was higher in the latter (12.7% vs. 41.8%, p < 0.01). Although the frequency of hypertension (67.3% vs. 81.2%, p < 0.01), diabetes mellitus (20.8% vs. 26.4%, p = 0.02) and atrial fibrillation (20.7% vs. 26.2%, p = 0.02) was higher in patients hospitalised in the years 2008- 2012, the systolic and diastolic blood pressure values and the frequency of fasting hyperglycaemia were lower in this cohort. This cohort also less frequently suffered from hypercholesterolaemia (25.4% vs. 16.3%, p < 0.01). Conclusions: Reduced stroke severity is associated with better recognition and control of risk factors and explains the improvement of survival in Polish stroke patients.

Neurologic involvement is well recognized in Systemic Scleroderma and increasingly reported in Localized Scleroderma. MRI brain abnormalities are often associated with symptoms such as seizures or headaches. In some cases they may be clinically silent. We describe a 23 years old female with head, trunk and limbs scleroderma who developed Parry-Romberg Syndrome. Brain MRI showed ipsilateral temporal lobe atrophy without any prominent neurologic symptoms. Neuropsychological examination revealed Mild Cognitive Impairment. During the 7 years of follow up we have noticed progression of face atrophy but no progression of brain atrophy. Cognitive functions have been stable. This case highlight that major MRI brain abnormalities in LS may occur with only subtle clinical manifestation such as Mild Cognitive Impairment.

Delirium is a transient condition characterized by sudden and fluctuating disturbances in cognitive function. The condition can be considered a sign of the brain's vulnerability and diminished resilience to insult. Among the many clinical manifestations are cognitive, psychomotor, and sleep disturbances. Delirium is associated with longer hospital stays, worse functional outcomes, and higher mortality. Although up to 48% of patients who have had a stroke develop delirium, the condition has been studied much less in these patients than in general medicine, surgical, and intensive care patients. Coexisting neurologic deficits in patients with stroke limit the use of screening tools that are widely accepted in other populations. The variability of reported assessment methods highlights the need for delirium screening guidelines in stroke. Further, risk factors that are specific to stroke may play an important role in the etiology of delirium, along with such well-known factors as older age and infections. The delirium literature lacks data on differences in clinical manifestations and course in the various types of stroke. Here we review predisposing factors, diagnostic methods, and biomarkers of delirium in stroke and discuss aspects that need further research.

Background Between 10 % to 48 % of patients develop delirium in acute phase of stroke. Delirium determinants and its association with other neuropsychiatric disturbances in stroke are poorly understood. The wildly accepted predictive model of post-stroke delirium is still lacking. Methods/design This is a prospective, observational, single-center study in patients with acute phase of stroke. We aim to include 750 patients ≥18 years with acute stroke or transient ischemic attack admitted to the stroke unit within 48 hours after stroke onset. The goals of the study are: 1) to determine frequency of delirium and subsyndromal delirium in Polish stroke patients within 7 days after admission to the hospital; 2) to determine factors associated with incidence, severity and duration of delirium and subsyndromal delirium and to create a predictive model for post-stroke delirium; 3) to determine the association between delirium and its cognitive, psychiatric, behavioral and functional short and long-term consequences; 4) to validate scales used for delirium diagnosis in stroke population. Patients will be screened for delirium on daily basis. The diagnosis of delirium will be based on DSM-V criteria. Abbreviated version of Confusion Assessment Method and Confusion Assessment Method for the Intensive Care Unit will be used for delirium and sub-delirium screening. Severity of delirium symptoms will be assessed by Delirium Rating Scale Revised 98 and Cognitive Test for Delirium. Patients who survive will undergo extensive neuropsychological, neuropsychiatric and functional assessment 3 and 12 months after the stroke. Discussion This study is designed to provide information on clinical manifestation, diagnostic methods and determinants of delirium spectrum disorders in acute stroke phase and their short and long-term consequences. Collected information allow us to create a predictive model for post-stroke delirium.

Introduction: Mutations in the gene for presenilin 1 ( PSEN-1) cause familial, early-onset Alzheimer’s disease (EOAD). Diagnosis of EOAD is often a challenge because of the high frequency of atypical presentations. Clinical manifestation of EOAD may vary depending on underlying mutation; specific genetic mutations influence development of specific clinical phenotypes; however, intrafamilial phenotypic heterogeneity has also been noted in some pedigrees. Case presentation: We report a case of a 36-year-old woman presenting with progressive behavioral disturbances, dementia, involuntary movements, pyramidal signs, epilepsy, and a family history of early-onset dementia accompanied by involuntary movements. On genetic testing, the mutation at codon 424 (Leu→Arg) in PSEN-1 gene was identified. Conclusion: Our case describes a new phenotype of a known mutation of PSEN-1 at codon 424.

Background and purpose Spontaneous intracerebral haemorrhage (ICH) is the most fatal form of stroke with the highest morbidity and disability rate of all stroke types. Recent data suggest that the genetic background has a sizeable and mostly undiscovered effect on the brain haemorrhage risk. Since the coagulation system is crucial to ICH pathology, we studied the significance of the FGA Thr312Ala polymorphism in two European populations. Materials and methods We genotyped 550 and 224 controls as well as 261 and 242 stroke patients in Polish and Greek populations, respectively. The ICH diagnosis was confirmed by computed tomography. The FGA Thr312Ala polymorphism was analysed using real-time polymorphism chain reaction. Results Both crude and multivariable regression analyses showed that the studied polymorphism is a protective factor in the Polish population under the dominant and additive models of inheritance. Those results did not replicate in the Greek population. The meta-analysis of results from the Polish and the Greek populations proved that FGA Thr312Ala polymorphism affects the risk of ICH in the dominant model of inheritance. Conclusions The FGA Thr312Ala polymorphism affects a risk for ICH in the Polish but not in the Greek population. An advanced meta-analysis of well-designed studies with a significant number of cases might provide useful information of novel polymorphisms, including the FGA Thr312Ala polymorphism, and their role in ICH pathology.

Background and purpose Recent genome-wide association studies have indicated 3 new susceptibility loci for Alzheimer disease (AD): complement receptor 1 (CR1), clusterin (CLU), and the phosphatidylinositol-binding clathrin assembly protein (PICALM). We investigated the influence of the rs6656401 single nucleotide polymorphisms (SNP) of the CR1 gene, the rs3851179 SNP of the PICALM gene, and the rs11136000 SNP of the CLU gene on risk of AD in a Polish population. Material and methods In 253 Caucasian AD patients and 240 controls, analyses identifying the rs6656401, rs3851179 and rs11136000 SNPs and APOE common polymorphisms were performed. Results No significant differences were observed in the distribution of the rs6656401 of CR1, rs3851179 of PICALM and rs11136000 of CLU SNPs between AD patients and controls. The APOE ɛ4 common polymorphism was strongly related to the risk of AD. Conclusion Our results suggest that investigated SNPs are not associated with AD in a Polish population.

Background and purpose Ischaemic stroke is considered to be multifactorial and interactions between environmental and genetic factors play an important role. Although vascular risk factors are well known, the genetic ones are still undiscovered. In the present study, we assessed the significance of the β-fibrinogen –455G/A gene polymorphism and the risk of ischaemic stroke in a Polish population. Material and methods 426 ischaemic stroke patients classified according to stroke aetiologies (small vessel disease, large vessel disease or cardioembolic stroke) and 234 controls were included in the study. The association of the β-fibrinogen genotypes with ischaemic stroke was tested using logistic regression analysis under dominant, recessive or additive models of inheritance. Results The allele and genotype distributions of the β-fibrinogen –455G/A gene polymorphism did not differ significantly between patients and controls (patients: G – 75%, GG – 56.6%, GA – 36.8%, AA – 6.6%; controls: G – 73.7%, GG – 57.3%, GA – 32.9%, AA – 9.8%; p > 0.05, χ 2 ). In addition, logistic regression analysis adjusted for the known risk factors, i.e. hypertension, ischaemic heart disease, myocardial infarction, hypercholesterolaemia, diabetes mellitus and smoking, did not show a role of the studied polymorphism in ischaemic stroke. Conclusions The β-fibrinogen –455G/A gene polymorphism is not a risk factor for ischaemic stroke in a Polish population.

Aleksandra Klimkowicz-Mrowiec,1 Pawel Wolkow,2 Malgorzata Sado,3 Anna Dziubek,3 Joanna Pera,1 Tomasz Dziedzic,1 Andrzej Szczudlik,1 Agnieszka Slowik1 1Department of Neurology, Jagiellonian University, School of Medicine, Botaniczna, 2Department of Pharmacology, Jagiellonian University, School of Medicine, Grzegórzecka, 3Department of Neurology, University Hospital, Botaniczna, Krakow, Poland Background: Recent data indicate that the rs1080985 single nucleotide polymorphism of the cytochrome P450 (CYP) 2D6 gene may affect the response to treatment with donepezil in patients with Alzheimer's disease. There is also evidence that the common apolipoprotein E (APOE) polymorphism may affect the response to treatment with donepezil in Alzheimer's disease. We investigated the association between response to donepezil and the rs1080985 single nucleotide polymorphism, the minor allele (G) of which was previously reported to be associated with a poor response to this drug in patients with Alzheimer's disease. The common APOE polymorphism was also assessed for its relevance to the outcome of this treatment. Methods: Analysis of CYP2D6 and APOE polymorphisms was undertaken in 88 naive Caucasian patients with Alzheimer's disease. All patients received treatment with donepezil for at least 10 months, and the response to treatment was then assessed according to the National Institute for Health and Clinical Excellence criteria. Results: No significant differences were observed in distribution of the CYP2D6 rs1080985 single nucleotide polymorphism or common APOE polymorphism between responders (68.2%) and nonresponders (31.8%) to treatment with donepezil. Conclusion: Our results suggest that neither the CYP2D6 nor the APOE polymorphism influences the response to treatment with donepezil in a Polish population with Alzheimer’s disease. Keywords: Alzheimer’s disease, CYP2D6, APOE, donepezil, pharmacogenetics, single nucleotide polymorphism

Background and Purpose— Fibrin clot formation is important in acute intracerebral hemorrhage (ICH). We investigated plasma fibrin clot characteristics in acute ICH compared with acute ischemic stroke (IS) and nonstroke conditions. Methods— In the 3 studied groups, we analyzed plasma fibrin clot phenotype and its association with clinical stroke presentation. Results— Compared with controls, in patients with acute strokes, fibrin clots presented with lower clot permeability, longer lysis time, and higher maximum clot absorbance (for all, P P P d -dimers released from clots, whereas initial hematoma volume correlated with lag phase of fibrin formation on turbidimetry and compaction ( P Conclusions— In both types of acute strokes, fibrin clot properties are altered: denser fibrin clots are relatively resistant to lysis. In acute ICH, fibrin clots are more susceptible to tissue plasminogen activator–mediated lysis compared with in IS, which might affect ICH pathogenesis.

Background Beta-adrenergic blockade prevents or diminishes stress-induced hyperglycemia in different experimental models. The aim of the study was to determine if the use of beta-blockers before stroke reduces the risk of acute hyperglycemia in stroke patients. Methods We analyzed the data of 603 consecutive patients with acute ischemic stroke and without pre-stroke diagnosis of diabetes mellitus admitted to stroke unit within 24 h after symptoms onset. Results Plasma glucose level on admission (6.0 ± 1.4 vs 6.6 ± 1.9 mmol/L, P = 0.01) and fasting glucose on day 1 (5.2 ± 1.1 vs 5.7 ± 1.1 mmol/L, P = 0.02) were significantly lower in patients treated with beta-blockers before stroke than in those who did not receive such a treatment. On multivariate logistic analysis beta-blockers use before stroke was associated with reduced risk of glucose level on admission ≥7.8 mmol/L (OR: 0.22, 95%CI: 0.07–0.74) and fasting glucose on day 1 ≥ 7.0 mmol/L (OR: 0.21, 95%CI: 0.05–0.91). The risk of fasting hyperglycemia defined as glucose ≥6.1 mmol/L did not differ between groups. Conclusions Beta-blockage before stroke onset may result in lower plasma glucose on admission and prevent early hyperglycemia in patients without pre-stroke diagnosis of diabetes mellitus.

Background: The relationship between different paraoxonase (PON) gene polymorphisms and the risk of Alzheimer’s disease (AD) was studied several times and the results were controversial. Methods: We investigated the association of 4 single-nucleotide polymorphisms (SNPs) of the PON1 (M55L; Q192R; –161C/T) and the PON2 (C311S) genes that were shown to affect the risk of sporadic AD. We studied 360 Caucasian cases with late-onset AD and 354 nondemented controls. Results: No significant differences were observed between the studied PON SNPs and AD risk. The results did not change after stratification of the apolipoprotein E status. Meta-analyses of studies in Caucasians assessing the associations between the PON1 M55L, –161C/T and Q192R SNPs and the risk of AD were performed, and no associations were found. Conclusion: Our results suggest that the studied PON1 and PON2 polymorphisms are not associated with late-onset AD.

Background and purpose Inflammation plays a prominent role in Alzheimer disease (AD) pathogenesis. Interleukin-6 (IL-6), a pro-inflammatory cytokine, and some genetic variations in the IL-6 gene have been reported to be associated with a risk of AD. However, the results of the conducted studies are equivocal. Material and methods We genotyped IL-6 (–174 C/G) and apolipoprotein E gene (APOE) common polymorphisms in a large case-controlled study in a Polish population. We included 361 patients aged ≥ 65 years with AD (mean age 75.8 ± 5.3 years, 232 females [64.3%]) and 200 controls (75.3 ± 7.4 years; 119 females [59.5%]), without any neurological deficit, cognitive complaints or history of neurological diseases. The IL-6 polymorphism was genotyped using TaqMan SNP allelic discrimination by means of an ABI 7900HT (Applied Biosystems, Foster City, CA). Results The distribution of the IL-6 (–174 C/G) genotypes was similar to that in the controls (AD: C/C = 15.79%, C/G = 51.25%, G/G = 32.96% vs. controls: C/C = 21.50%, C/G = 45.50%, G/G = 33.0%, p > 0.05). Our study confirms previous reports that APOE 4 is strongly related to the risk of AD (OR = 6.17; 95% CI: 4.01–9.49). APOE status did not affect the distribution of the studied IL-6 polymorphism. Conclusion IL-6 (–174 C/G) polymorphism is not a risk factor for late onset AD in a Polish population.

Background: Oxidative stress plays a role in atherosclerosis. Human paraoxonase (PON) gene products exhibit antioxidant properties. We studied the significance of the Q192R and M55L polymorphisms of the PON1 gene and the C311S polymorphism of the PON2 gene in different etiologies of ischemic stroke. Methods: One hundred and thirty-six patients with large vessel disease (LVD) stroke, 140 with small vessel disease stroke, 272 with cardioembolic stroke, and their age- and sex-matched controls were included. PON genotypes were evaluated by PCR-RFLP analyses. Results: The distribution of PON1 polymorphisms was similar in each stroke group and in the respective controls. Genotypes with the C allele of the PON2 gene C311S polymorphism were overrepresented in LVD stroke patients as compared with their controls, both in univariate and multivariate (dominant model: OR = 1.58, 95% CI: 1.006–2.48) analyses. Conclusion: The genotype with the C allele of the PON2 gene is a risk factor for LVD stroke in a Polish population.