The Prevalence of Depression in Dementia Syndrome.

BACKGROUND: It is estimated that up to 90% of patients with dementia are affected by behavioral and psychiatric symptoms during the course of the disease. The aim of this study was to investigate the prevalence of depression in dementia and mild cognitive impairment (MCI), the use of benzodiazepines and antidepressants among them and the impact of former education on their cognitive decline. SUBJECTS AND METHODS: In the study we have enrolled 100 patients with clinical diagnoses of either MCI or dementia, as was established by a single cognitive neurology subspecialist. All patients were assessed during their regular outpatient follow-ups in the University Clinical Center Zagreb, Croatia, in the period between November 2019 and March 2020. Using the patients' medical history the demographic data, disease characteristics, history of other diseases, use of medications, Mini-Mental State Examination (MMSE) and the data on radiological brain examinations were obtained. The statistical tests were used depending on the distribution of variables. RESULTS: In total, there were 34 patients diagnosed with dementia and 66 diagnosed with MCI. The diagnosis of depression before the onset of dementia or MCI was established in 11% and it has developed in further 20% after cognitive deterioration, which represents an increase of 81.81%. The total prevalence of depression in the study group is thus 31%.The proportion of patients taking benzodiazepines was 26% and antidepressants 17%.The MMSE scores were significantly lower in patients with Alzheimer's disease than in patients with vascular MCI or dementia. Generally, MMSE values correlated significantly with the duration of education. CONCLUSIONS: Depression is a frequent accompanying disease of dementia that aggravates already complex clinical picture and greatly diminishes the quality of life of the patient. It is important to monitor changes in a patient's cognitive decline and presence of psychiatric symptoms in order to give medical professionals a better chance to alleviate the complex issues that arise during the management of this specter of diseases.

Epidemiology of Pharmacological Treatment of Multiple Sclerosis in Croatia.

Treatment of multiple sclerosis has been a dynamic field lately, with many new and emerging treatment options. In this study, we investigate the use of disease modifying therapies (DMTs) for multiple sclerosis in Croatia. The data on DMT use was provided by the Agency for Medicinal Products and Medical Devices of Croatia (HALMED). The data from 2005 to 2016 was available. Consumption of DMTs (in DDD/1000/day) has been increasing by 9% annually on average since 2005. In the same period, the annual cost for those drugs has been increasing by 14.6% annually on average. The consumption of IFN-beta 1-a has been increasing by a much steeper rate than IFN-beta 1-b. Until 2010 the consumption of glatiramer acetate has been negligible, with a steep increase between 2011 and 2014, and a steady rate of consumption since. Recently, several new DMTs became available, namely dimethyl fumarate, teriflunomide and fingolimod. Natalizumab became available after 2010, and its consumption has been growing steadily, but its consumption figures are exceeded by alemtuzumab. New DMTs are not as readily available in Croatia as they are in some countries. However, there is a continuous increase in the number of prescriptions, along with growing costs in pharmacological treatment of multiple sclerosis, and this can be expected to become even more pronounced in the following years, due to the abundance of new therapeutic options that are steadily becoming available.

The Effects of Electroconvulsive Therapy Augmentation of Antipsychotic Treatment on Cognitive Functions in Patients With Treatment-Resistant Schizophrenia.

OBJECTIVES: Treatment-resistant schizophrenia (TRS) continues to be a challenge in modern psychiatry. Most of these patients have severe neurocognitive deficits. Electroconvulsive therapy (ECT) has proved effective and safe in the treatment of TRS, but because of potential neurocognitive adverse effects, it is associated with many controversies. The aim of this prospective, open study was to evaluate the effects of ECT augmentation of antipsychotics on cognitive functions in patients with TRS. METHODS: Overall, 31 inpatients with TRS were included, 16 men, with an average (SD) age of 34.1 (11.187) years. The evaluation of clinical symptoms and global impression, as well as verbal memory, visual memory, working memory, psychomotor speed, verbal fluency, and executive functioning, was conducted before and after the completion of ECT treatment. RESULTS: We ran a series of paired-samples t tests, and the Bonferroni adjustment for multiple comparisons reduced the significance level to P = 0.004. The neurocognitive domains that demonstrated statistically significant improvement were immediate and delayed verbal memory, and executive functioning, whereas statistical trend was observed for visual memory and psychomotor speed. None of the neurocognitive functions exhibited significant deterioration after the ECT treatment. Electroconvulsive therapy was effective in reducing general symptoms of schizophrenia, resulting in more than 30% decrease in the overall symptom severity measured by the Positive and Negative Syndrome Scale. CONCLUSIONS: Notwithstanding some limitations of this study, the combination of ECT and antipsychotics has improved several neurocognitive domains, without evidence of worsening of any cognitive functions.

Epidemiological Characteristics of Dementia Treatment in Croatia.

BACKGROUND: In spite of the increase in the number of patients with dementia in countries with older population, basic epidemiologic data are still scarce. The objective of this paper is to investigate pharmacoepidemiological characteristics of treatment of dementia in Croatia, and to present them in the context of certain epidemiological characteristics that illustrate the growing pressure this disease exerts on the healthcare system. SUBJECTS AND METHODS: Data on medication utilization were taken from Croatian Health Insurance Fund (HZZO) and Agency for Medicinal Products and Medical Devices of Croatia (HALMED). Data on the number of hospital stays were supplied by Croatian Institute of Public Health (HZJZ). Internal data on the number of outpatient examinations from the Clinical hospital "Sveti Duh" were used as well. RESULTS: In the observed period (2012-2014), 4568 patients were treated with anti-dementia medications, of which 1275 (32%) with donepezil, and 2753 (68%) with memantine. According to HALMED, the utilization of those medications is constantly increasing, and has increased manifold from 2005 to 2014. The estimate of the proportion of treated patients with dementia aged 60 years and over is around 9.2%. The number of dementia-related hospital stays is also increasing, and has increased by 9.6% in the last 5-year period, compared to the preceding 5-year period. The number of outpatient examinations in Clinical Hospital "Sveti Duh" grew from 351 in 2007 to 1151 in 2015 (January 1(st) - October 26(th)). CONCLUSION: The strain this condition exerts on the healthcare system is increasing yearly. In spite of the large increase in the medication utilization over the previous years, the proportion of treated patients is still small, and further increase in their use is to be expected. It is necessary to monitor this in the years ahead.

Comparison of Sleep Disturbances in Post-Traumatic Stress Disorder and Depression Patients

The aim of this study was to explore differences in the intensity of depressiveness, sleep disturbances and sleepiness between post-traumatic stress disorder (PTSD) patients and patients with depression. A total of 170 patients were examined, including 120 PTSD patients and 50 patients with depression. All participants completed the Beck Depression Inventory, Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. The results showed difference in the subjective assessment of sleep quality between the war veterans with PTSD and civilians with depression, without significant differences between them in the level of depressiveness and sleepiness. Considering the fact that insomnia can occur as an early, covert sign of both PTSD and depression and that differences in the intensity of sleep disturbances between the groups were established, the use of these and similar instruments for the assessment of sleep quality can be useful in distinguishing patients with PTSD and depression, treatment of their sleep disturbances, and prevention of more severe symptoms in both diagnostic categories.

Isolated and persistent cognitive dysfunction in a patient with acute disseminated encephalomyelitis.

We report a case of pathology-proven acute disseminated encephalomyelitis (ADEM) in which the patient's symptoms were solely cognitive. Although cognitive dysfunction is a well-recognized symptom in adults with multiple sclerosis, cognitive assessment of adults with ADEM has rarely been reported. A 35-year-old woman was referred to our center for evaluation of cognitive disturbance and demyelinating lesions seen on brain magnetic resonance imaging (MRI). We performed a neurologic examination, full neuropsychological assessment, brain MRI, blood and cerebrospinal fluid analyses, visual evoked potentials, and brain biopsy. The patient's Mini-Mental State Examination score was 26/30. Cognitive assessment revealed multiple severe dysfunctions, mainly in executive and attention tasks. She scored below the normal range on the Digit Span Forward and Backward Test and the Trail Making Test Part B. The Frontal Assessment Battery showed deficits in mental flexibility, motor programming, and inhibitory control. She also scored in the impaired range on tests of verbal fluency and memory. The brain MRI and biopsy confirmed a diagnosis of ADEM. This case report points to the limitations of relying on clinical presentation, neuroimaging, and current controversial diagnostic criteria in diagnosing ADEM in adults, and highlights the essential role of pathologic evaluation.

Soluble TREM2 Concentrations in the Cerebrospinal Fluid Correlate with the Severity of Neurofibrillary Degeneration, Cognitive Impairment, and Inflammasome Activation in Alzheimer's Disease.

BACKGROUND: Individuals with specific TREM2 gene variants that encode for a Triggering Receptor Expressed on Myeloid cells 2 have a higher prevalence of Alzheimer's disease (AD). By interacting with amyloid and apolipoproteins, the TREM2 receptor regulates the number of myeloid cells, phagocytosis, and the inflammatory response. Higher TREM2 expression has been suggested to protect against AD. However, it is extremely difficult to comprehend TREM2 signaling in the context of AD. Previous results are variable and show distinct effects on diverse pathological changes in AD, differences between soluble and membrane isoform signaling, and inconsistency between animal models and humans. In addition, the relationship between TREM2 and inflammasome activation pathways is not yet entirely understood. OBJECTIVE: This study aimed to determine the relationship between soluble TREM2 (sTREM2) levels in cerebrospinal fluid (CSF) and plasma samples and other indicators of AD pathology. METHODS: Using the Enzyme-Linked Immunosorbent Assay (ELISA), we analyzed 98 samples of AD plasma, 35 samples of plasma from individuals with mild cognitive impairment (MCI), and 11 samples of plasma from healthy controls (HC), as well as 155 samples of AD CSF, 90 samples of MCI CSF, and 50 samples of HC CSF. RESULTS: CSF sTREM2 levels were significantly correlated with neurofibrillary degeneration, cognitive decline, and inflammasome activity in AD patients. In contrast to plasma sTREM2, CSF sTREM2 levels in the AD group were higher than those in the MCI and HC groups. Moreover, concentrations of sTREM2 in CSF were substantially higher in the MCI group than in the HC group, indicating that CSF sTREM2 levels could be used not only to distinguish between HC and AD patients but also as a biomarker to detect earlier changes in the MCI stage. CONCLUSIONS: The results indicate CSF sTREM2 levels reliably predict neurofibrillary degeneration, cognitive decline, and inflammasome activation, and also have a high diagnostic potential for distinguishing diseased from healthy individuals. To add sTREM2 to the list of required AD biomarkers, future studies will need to include a larger number of patients and utilize a standardized methodology.

Serotonin Receptor Gene Polymorphisms Are Associated with Cerebrospinal Fluid, Genetic, and Neuropsychological Biomarkers of Alzheimer's Disease.

A decrease in serotonergic transmission throughout the brain is among the earliest pathological changes in Alzheimer's disease (AD). Serotonergic receptors are also affected in AD. Polymorphisms in genes of serotonin (5HT) receptors have been mostly associated with behavioral and psychological symptoms of dementia (BPSD). In this study, we examined if AD patients carrying different genotypes in 5HTR1B rs13212041, 5HTR2A rs6313 (T102C), 5HTR2C rs3813929 (-759C/T), and 5HTR6 rs1805054 (C267T) polymorphisms have a higher risk of faster disease progression (assessed by neuropsychological testing), are more prone to develop AD-related pathology (reflected by levels of cerebrospinal fluid [CSF] AD biomarkers), or have an association with an apolipoprotein E (APOE) haplotype. This study included 115 patients with AD, 53 patients with mild cognitive impairment (MCI), and 2701 healthy controls. AD biomarkers were determined in the CSF of AD and MCI patients using enzyme-linked immunosorbent assays (ELISA), while polymorphisms were determined using either TaqMan SNP Genotyping Assays or Illumina genotyping platforms. We detected a significant decrease in the CSF amyloid ß1-42 (Aß1-42) and an increase in p-tau181/Aß1-42 ratio in carriers of the T allele in the 5HTR2C rs3813929 (-759C/T) polymorphism. A significantly higher number of APOE ε4 allele carriers was observed among individuals carrying a TT genotype within the 5HTR2A T102C polymorphism, a C allele within the 5HTR1B rs13212041 polymorphism, and a T allele within the 5HTR6 rs1805054 (C267T) polymorphism. Additionally, individuals carrying the C allele within the 5HTR1B rs13212041 polymorphism were significantly more represented among AD patients and had poorer performances on the Rey-Osterrieth test. Carriers of the T allele within the 5HTR6 rs1805054 had poorer performances on the MMSE and ADAS-Cog. As all four analyzed polymorphisms of serotonin receptor genes showed an association with either genetic, CSF, or neuropsychological biomarkers of AD, they deserve further investigation as potential early genetic biomarkers of AD.

Association study of a functional catechol-o-methyltransferase polymorphism and cognitive function in patients with dementia.

A functional catechol-o-methyltransferase (COMT Val158/108Met) polymorphism, a valine (Val) to methionine (Met) substitution, has been associated with cognitive processing in the normal brain, older age, mild cognitive impairment and in various dementias. COMT is involved in the breakdown of dopamine and other catecholamines, especially in the frontal cortex; hence the carriers of Met allele, with the lower enzymatic activity, are expected to perform better on particular neuro-cognitive tests. The study included 46 patients with dementia and 65 healthy older subjects. The neurological status was assessed, using the Mini Mental Status Examination (MMSE), and the batery of different neurological tests. In DNA samples COMT polymorphism was genotyped. Patients with dementia exhibited significant genotype-induced differences in scores for MMSE, Visual Association Test (VAT) duration of numbers test, VAT time of response to numbers test, VAT average response to numbers test and WPLCR/PPLR unanswered. Carriers of Met/Met genotype had significantly lower scores of MMSE, significantly longer time to respond to VAT duration of numbers test, VAT time of response to numbers test and VAT average response to numbers test, and significantly greater number of unanswered questions to WPLCR/PPLR when compared to Met/Val or Val/Val genotypes. Our preliminary data showed significantly impaired performance in several neuro-cognitive tests in carriers of Met/Met genotype in patients with dementia compared to either Met/Val or Val/Val genotype carriers. Although Met/Met genotype with more dopamine available in the frontal cortex should be associated with better neuro-cognitive test results than Met/Val or Val/Val genotype, our data on patients with dementia did not confirm this hypothesis. Further study on larger sample of patients is needed to clarify the role of COMT polymorphism in cognitive functions.

Association of the MAOB rs1799836 Single Nucleotide Polymorphism and APOE ε4 Allele in Alzheimer's Disease.

BACKGROUND: The dopaminergic system is functionally compromised in Alzheimer's Disease (AD). The activity of Monoamine Oxidase B (MAOB), the enzyme involved in the degradation of dopamine, is increased during AD. Also, increased expression of MAOB occurs in the postmortem hippocampus and neocortex of patients with AD. The MAOB rs1799836 polymorphism modulates MAOB transcription, consequently influencing protein translation and MAOB activity. We recently showed that cerebrospinal fluid levels of amyloid ß1-42 are decreased in patients carrying the A allele in MAOB rs1799836 polymorphism. OBJECTIVE: The present study compares MAOB rs1799836 polymorphism and APOE, the only confirmed genetic risk factor for sporadic AD. METHODS: We included 253 participants, 127 of whom had AD, 57 had mild cognitive impairment, 11 were healthy controls, and 58 suffered from other primary causes of dementia. MAOB and APOE polymorphisms were determined using TaqMan SNP Genotyping Assays. RESULTS: We observed that the frequency of APOE ε4/ε4 homozygotes and APOE ε4 carriers is significantly increased among patients carrying the AA MAOB rs1799836 genotype. CONCLUSION: These results indicate that the MAOB rs1799836 polymorphism is a potential genetic biomarker of AD and a potential target for the treatment of decreased dopaminergic transmission and cognitive deterioration in AD.

Cognitive performance in nondemented nonpsychotic Parkinson disease patients with or without a history of depression prior to the onset of motor symptoms.

In Parkinson disease (PD), cognitive impairment is common, occurs mainly in the form of milder deficits (as opposed to dementia), and commonly coincides with depression. In this cross-sectional study, we evaluated whether depression that existed before the onset of typical motor symptoms (pre-PD depression) reflected on the actual cognitive performance. Nondemented nonpsychotic PD patients with (test, n = 27) and without (control, n = 112) a history of pre-PD depression, caliper-matched for age, education, and disease duration were assessed for motor and nonmotor disease characteristics and in a battery of cognitive tests. Test patients had higher actual depression/anxiety levels. Gradual multivariate and mediation analysis indicated unfavorable effects of pre-PD depression on cognition: a direct effect on mental set shifting/response inhibition (independent of actual depression/ anxiety or other factors); and indirect effects on other cognitive domains mediated through the increased depression/anxiety. Data suggest that pre-PD depression favors poorer cognitive abilities in nondemented patients at a given time after PD has been diagnosed.

IL-1ß, IL-6, IL-10, and TNFα Single Nucleotide Polymorphisms in Human Influence the Susceptibility to Alzheimer's Disease Pathology.

BACKGROUND: Neuroinflammation plays an important role in Alzheimer's disease (AD). During this process, activated microglia release pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1ß, IL-6, and tumor necrosis factor α (TNFα) that participate in neuron damage, but also anti-inflammatory cytokines (such as IL-10), which maintain homeostasis of immune response. Previous studies showed the association of IL-1α -889C/T (rs1800587), IL-1ß-1473G/C (rs1143623), IL-6 -174C/G (rs1800795), IL-10 -1082G/A (rs1800896), and TNFα -308A/G (rs1800629) polymorphisms with AD. OBJECTIVE: We aimed to investigate whether people with certain IL-1α, IL-1ß, IL-6, IL-10, and TNFα genotypes in these polymorphisms are more prone to develop AD-related pathology, reflected by pathological levels of cerebrospinal fluid (CSF) AD biomarkers including amyloid-ß1-42, total tau (t-tau), tau phosphorylated at Thr 181 (p-tau181), Ser 199 (p-tau199), and Thr 231 (p-tau231), and visinin-like protein 1 (VILIP-1). METHODS: The study included 115 AD patients, 53 patients with mild cognitive impairment, and 11 healthy controls. The polymorphisms were determined using real-time polymerase chain reaction. Levels of CSF biomarkers were determined by enzyme-linked immunosorbent assay. RESULTS: A significant increase in p-tau CSF levels was found in patients with the AA IL-10 -1082G/A and GG TNFα -308A/G genotypes, and in carriers of a G allele in IL-1ß -1473C/G and IL-6 -174C/G polymorphisms. t-tau levels were increased in carriers of a G allele in IL-1ß -1473C/G polymorphism. An increase in VILIP-1 levels was observed in patients with CG and GG IL-1ß -1473C/G, GC IL-6 -174C/G, and GG TNFα -308A/G genotype. CONCLUSION: These results suggest that persons carrying certain genotypes in IL10 (-1082G/A), IL1ß (1473C/G), IL6 (-174C/G), and TNFIα (-308A/G) could be more vulnerable to development of neuroinflammation, and consequently of AD.

Relationships of Cerebrospinal Fluid Alzheimer's Disease Biomarkers and COMT, DBH, and MAOB Single Nucleotide Polymorphisms.

The noradrenergic and dopaminergic systems are affected in Alzheimer's disease (AD). Polymorphisms in genes encoding enzymes and proteins that are components of these systems can affect products of transcription and translation and lead to altered enzymatic activity and alterations in overall dopamine and noradrenaline levels. Catechol-O-methyltransferase (COMT) and monoamine oxidase B (MAOB) are the enzymes that regulate degradation of dopamine, while dopamine ß-hydroxylase (DBH) is involved in synthesis of noradrenaline. COMT Val158Met (rs4680), DBH rs1611115 (also called -1021C/T or -970C/T), and MAOB rs1799836 (also called A644G) polymorphisms have been previously associated with AD. We assessed whether these polymorphisms are associated with cerebrospinal fluid (CSF) AD biomarkers including total tau (t-tau), phosphorylated tau proteins (p-tau181, p-tau199, and p-tau231), amyloid-ß42 (Aß42), and visinin-like protein 1 (VILIP-1) to test possible relationships of specific genotypes and pathological levels of CSF AD biomarkers. The study included 233 subjects: 115 AD, 53 mild cognitive impairment, 54 subjects with other primary causes of dementia, and 11 healthy controls. Significant decrease in Aß42 levels was found in patients with GG compared to AG COMT Val158Met genotype, while t-tau and p-tau181 levels were increased in patients with AA compared to AG COMT Val158Met genotype. Aß42 levels were also decreased in carriers of A allele in MAO-B rs1799836 polymorphism, while p-tau181 levels were increased in carriers of T allele in DBH rs1611115 polymorphism. These results indicate that COMT Val158Met, DBH rs1611115, and MAOB rs1799836 polymorphisms deserve further investigation as genetic markers of AD.

Education effect on depression and quality of life in nondemented Parkinson's disease patients.

A comparison of nondemented Parkinson's disease patients with lower, intermediate, and higher educational levels indicated an independent association between longer (better) education and less severe depressive difficulties based on the Beck Depression Inventory cognitive-affective items. Well-educated patients also had a better health-related quality of life based on the Parkinson's Disease Questionnaire-39, apparently due to beneficial effects of education on cognitive performance (attention/memory, visuospatial and executive functions) and the degree of depression. More years of education favors milder depressive difficulties and a higher self-perceived life satisfaction in nondemented Parkinson's disease patients.

Nondemented Parkinson disease patients: is cognitive performance associated with depressive difficulties?

BACKGROUND: Poorer cognitive performance in depressed versus nondepressed nondemented Parkinson disease (PD) patients has been suggested. OBJECTIVE: Investigate the relationship between level of depression assessed on a depression-measuring scale and cognitive performance in nondemented PD patients. METHODS: Nondemented idiopathic PD patients (n=110) were evaluated for the level of depression [cognitive-affective items of the Beck's Depression Inventory (BDI)] and performance in a set of tests evaluating cognitive domains typically affected in PD (memory, visuospatial, and executive functions). RESULTS: Multiple regression analysis of BDI scores demonstrated independent association of poorer cognitive performance, more severe parkinsonism, and poorer education with higher BDI scores. The association between poorer cognition and higher BDI scores was conditional on education, that is, was apparent only in less educated patients (<12 y of formal education). CONCLUSIONS: Poorer cognitive performance in nondemented idiopathic PD patients is associated with more severe depressive difficulties. Poorer education is also associated with more severe depression. Education modifies the cognition-depression relationship.

Event-related Potentials Improve the Efficiency of Cerebrospinal Fluid Biomarkers for Differential Diagnosis of Alzheimer's Disease.

INTRODUCTION: The pathological process of Alzheimer's disease (AD) in the brain likely begins 20-30 years earlier than the emergence of its first clinical symptoms and symptoms of AD often overlap with the symptoms of other primary causes of dementia. Therefore, it is crucially important to improve early and differential diagnosis of the disease. Event-related potentials (ERP) measured non-invasively by electroencephalography have shown diagnostic potential in AD. AIMS: The aim of this study was to compare the efficiency of P300 and N200 potentials and reaction time (RT) with commonly used protein biomarkers measured in the cerebrospinal fluid (CSF), including amyloid ß peptide (ß1-42), total tau (t-tau), tau protein phosphorylated at threonine 181 (p-tau181), tau protein phosphorylated at serine 199 (p-tau199), tau protein phosphorylated at threonine 231 (p-tau231), and visinin-like protein 1 (VILIP-1) in differential diagnosis of AD in mild cognitive impairment (MCI) and AD patients. SUBJECTS: The study involved 49 AD patients, 28 patients with MCI, 4 healthy control subjects and 16 patients with other primary causes of dementia. RESULTS: ERP (P300RT, N200RT, P300 counting and N200 counting) showed a moderate to strong correlation with protein CSF biomarkers. We confirmed previous observations of moderate to strong correlation between ERP and neuropsychological testing and showed that P300 latency and RT are shortened in AD patients on therapy with acetylcholinesterase inhibitors. Using ERP and RT, a predictive model for determination of AD likelihood in MCI patients was developed, detecting 56.3% of MCI patients with high risk for development of AD in our cohort. MCI patients with pathological levels of Aß1-42 had prolonged P300 latency, indicating that a combination of ERP and CSF protein biomarkers could improve the differential diagnosis of AD in MCI patients. Additionally, the results suggested the potential of P300 latency in differentiating AD and FTD patients. CONCLUSION: Our data provide possible solutions for improvement of differential diagnosis of AD, and reveal that the diagnostic efficiency of CSF protein biomarkers t-tau, p-tau181, p-tau199, p-tau231 and VILIP-1 could be improved by adding ERP in clinical practice.

Evaluation of cerebrospinal fluid phosphorylated tau231 as a biomarker in the differential diagnosis of Alzheimer's disease and vascular dementia.

BACKGROUND: The diagnosis of either Alzheimer's disease (AD) or vascular dementia (VaD) is still largely based on clinical guidelines and exclusion of other diseases that may lead to dementia. AIMS: In this study, we assessed whether the use of sensitive and specific biomarkers such as phosphorylated tau proteins could contribute to an earlier and more accurate diagnosis of AD and VaD, as well as to their differentiation. MATERIAL AND METHODS: A total of 198 patients, of which 152 had AD, 28 VaD, and 18 were healthy controls (HC), were included in the analyses. We analyzed cerebrospinal fluid (CSF) levels of total tau protein (t-tau), tau protein phosphorylated at threonine 231 (p-tau231), and factor score (FS) determined by combination of p-tau231 and Mini-Mental State Examination (MMSE) in patients with AD and VaD, as well as in HC. We tested the diagnostic accuracy of these biomarkers in the CSF and FS (p-tau231, MMSE) in differentiating AD from VaD and HC. RESULTS: Total tau levels were significantly elevated in subjects with AD compared to HC, as well as in VaD subjects compared to HC. DISCUSSION: p-tau231 levels were significantly higher in patients with ADvsHC as well in patients with VaD vsHC. p-tau231 levels did not distinguish AD from VaD patients. Importantly, FS(p-tau231 and MMSE) showed statistically significant differences in the distribution of subjects with AD and VaD. CONCLUSION: These results indicate that FS (p-tau231 and MMSE) has a strong potential to provide an early distinction between AD and VaD.

Association of MAPT haplotype-tagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort.

INTRODUCTION: Alzheimer's disease (AD) is the world leading cause of dementia. Early detection of AD is essential for faster and more efficacious usage of therapeutics and preventive measures. Even though it is well known that one ε4 allele of apolipoprotein E gene increases the risk for sporadic AD five times, and that two ε4 alleles increase the risk 20 times, reliable genetic markers for AD are not yet available. Previous studies have shown that microtubule-associated protein tau (MAPT) gene polymorphisms could be associated with increased risk for AD. METHODS: The present study included 113 AD patients and 53 patients with mild cognitive impairment (MCI), as well as nine healthy controls (HC) and 53 patients with other primary causes of dementia. The study assessed whether six MAPT haplotype-tagging polymorphisms (rs1467967, rs242557, rs3785883, rs2471738, del-In9, and rs7521) and MAPT haplotypes are associated with AD pathology, as measured by cerebrospinal fluid (CSF) AD biomarkers amyloid ß1-42 (Aß1-42 ), total tau (t-tau), tau phosphorylated at epitopes 181 (p-tau181 ), 199 (p-tau199 ), and 231 (p-tau231 ), and visinin-like protein 1 (VILIP-1). RESULTS: Significant increases in t-tau and p-tau CSF levels were found in patients with AG and AA MAPT rs1467967 genotype, CC MAPT rs2471738 genotype and in patients with H1H2 or H2H2 MAPT haplotype. CONCLUSIONS: These results indicate that MAPT haplotype-tagging polymorphisms and MAPT haplotypes should be further tested as potential genetic biomarkers of AD.

A dopamine agonist, pramipexole, and cognitive functions in Parkinson's disease.

The cognitive performance of 55 non-demented idiopathic Parkinson's disease (PD) patients treated with levodopa alone or receiving dopamine agonist pramipexole as add-on therapy to levodopa was evaluated in the present study during 6 months of treatment. Neuropsychological tests were administered two times. In the first assessment to differentiate test sensitive to cognitive changes typical for PD control group was also assessed. After 6 months of treatment PD patients were retested only with tests that differentiate them from control group. Compared to controls PD patients showed inferior performance on Stroop Interference test, Trail Making test, letter fluency and Hooper Visual Organization Test. No statistically significant differences between two groups and first and second neuropsychological assessment were found. Present findings indicate that pramipexole as add-on therapy to levodopa is safe in non-demented PD patients in terms of the effect on cognitive performance.

Effects of melatonin on plasma oxidative stress in rats with streptozotocin induced diabetes.

The aim of this study was to evaluate the effect of single melatonin injection on plasma oxidative stress in rats with streptozotocin induced diabetes. Diabetes was induced after a single intraperitoneal dose of streptozotocin (60 mg/kg), while hyperglycemia was determined 10 days upon injection. Diabetic rats were divided into two groups. In the first group the injection of melatonin was applied intraperitoneally (20 mg/kg), while the second group received physiological solution. Twenty-four hours later the rats were killed and their blood was centrifuged. In the rat plasma the following parameters were evaluated: the glucose level, superoxide radical, lipid peroxidation, reduced glutathione, total antioxidant capacity, antioxidant enzymes and the aldose reductase activity. The injected melatonin decreased the superoxide radical in the rat plasma. Moreover, melatonin increased the total antioxidative capacity and the activity of antioxidative enzymes superoxide dismutase and glutathione peroxidase. These results indicate that melatonin is a strong scavenger, which may diminish negative effects of oxidative stress in diabetic rats 24 hours after its application The findings suggest that melatonin is also a strong antioxidant. It increases the antioxidant enzymes activity, inhibiting the release of superoxide radicals. A high total antioxidative capacity and the lower activity of aldose reductase enlarge melatonin scavenger capacity against reactive oxygen species in diabetic rats.