Aleksandra Klimkowicz-Mrowiec

Severity of explicit memory impairment due to Alzheimer's disease improves effectiveness of implicit learning.

BackgroundConsistent evidence from human and experimental animals studies indicates that memory is organized into two relatively independent systems with different functions and brain mechanisms. The explicit memory system, dependent on the hippocampus and adjacent medial temporal lobe structures, refers to conscious knowledge acquisition and intentional recollection of previous experiences. The implicit memory system, dependent on the striatum, refers to learning of complex information without awareness or intention. The functioning of implicit memory can be observed in progressive, gradual improvement across many trials in performance on implicit learning tasks. The influence of explicit memory on implicit memory has not been precisely identified yet. According to data from some studies, explicit memory seems to exhibit no influence on implicit memory,whereas the other studies indicate that explicit memory may inhibit or facilitate implicit memory.ObjectivesThe analysis of performance on implicit learning tasks in patients with different severity of explicit memory impairment due to Alzheimer’s disease allows one to identify the potential influence of the explicit memory system on the implicit memory system.Patients and methods51 patients with explicit memory impairment due to Alzheimer’s disease (AD) and 36 healthy controls were tested. Explicit memory was examined by means of a battery of neuropsychological tests. Implicit habit learning was examined on probabilistic classification task (weather prediction task).ResultsPatients with moderate explicit memory impairment performed the implicit task significantly better than those with mild AD and controls.ConclusionResults of our study support the hypothesis of competition between the implicit and explicit memory systems in humans.

Predictors of Poststroke Dementia: Results of a Hospital-Based Study in Poland

Dementia affects up to 30% of stroke survivors 3 months after stroke. The goal of this study was to determine the risk factors of poststroke dementia (PSD) in a cohort of consecutive stroke patients in Poland. A standard stroke evaluation was conducted on admission in 220 consecutive patients with ischemic/hemorrhagic stroke after excluding 30 (12%) patients with prestroke dementia. After 3 months, the survivors completed a comprehensive neuropsychological examination. The DSM-IV definition was used for diagnosis of dementia. Dementia was diagnosed in 44 (22.6%) patients 3 months after stroke. In logistic regression analysis, age (OR 1.08, 95% CI 1.04–1.14, p < 0.001), diabetes mellitus (OR 2.67, 95% CI 1.06–6.57, p = 0.03) and neurological deficit on admission (OR 0.92, 95% CI 0.89–0.96, p < 0.001) were independently associated with PSD in the Polish hospital-based population.

Paraoxonase 2 Gene C311S Polymorphism Is Associated with a Risk of Large Vessel Disease Stroke 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.

Interleukin-1 Gene -511 CT Polymorphism and the Risk of Alzheimer's Disease in a Polish Population

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.

Influence of rs1080985 single nucleotide polymorphism of the CYP2D6 gene on response to treatment with donepezil in patients with alzheimer’s disease

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.

Fibrin Clot Properties in Acute Stroke What Differs Cerebral Hemorrhage From Cerebral Ischemia

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<0.001). In ICH patients compared with IS patients, only lysis time was shorter by 13% (P<0.001). In the ICH group, neurological deficit correlated significantly (P<0.05) with clot compaction, and the rate of increase in D-dimers released from clots, whereas initial hematoma volume correlated with lag phase of fibrin formation on turbidimetry and compaction (P<0.05). 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.

Interleukin-6 gene -174 C/G and apolipoprotein E gene polymorphisms and the risk of Alzheimer disease in a Polish population

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.

Beta-blockers use and risk of hyperglycemia in acute stroke patients

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.

Paraoxonase Gene Polymorphism and the Risk for Alzheimer’s Disease in the Polish Population

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.

Paraoxonase 1 gene polymorphisms do not influence the response to treatment in Alzheimer's disease.

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.