Ninoslav Mimica

Platelet serotonin concentration and monoamine oxidase type B activity in female patients in early, middle and late phase of Alzheimer's disease

Alzheimers disease (AD) is a progressive, neurodegenerative disorder with unclear aetiology. Cognitive impairment in AD might be associated with altered serotonergic system. The aim of the study was to determine platelet serotonin (5-HT) concentrations and platelet monoamine oxidase type B (MAO-B) activity in patients with different severity of AD. Platelet 5-HT concentrations and MAO-B activity were determined spectrofluorimetrically in 74 female patients with AD (NINCDS-ADRDA, DSM-IV-TR criteria), subdivided according to the Mini Mental State Examination (MMSE) scores in three groups with a) 23 patients in early (MMSE scores 19-24), b) 23 patients in middle (MMSE 10-18), and c) 28 patients in late (MMSE 0-9) phase of AD, and in 49 age-matched healthy women. Platelet 5-HT concentrations and MAO-B activity were similar between all patients with AD and healthy subjects, but were significantly lower in patients in the late phase of AD than in other phases of AD, and in healthy controls. The significant correlations were found between MMSE scores and platelet 5-HT concentrations, MAO-B activity and age. Lower platelet 5-HT concentration and MAO-B activity in the late phase of AD suggested that these markers might indicate severity and/or clinical progress of AD.

Brain derived neurotrophic factor Val66Met polymorphism and psychotic symptoms in Alzheimer's disease

OBJECTIVE Alzheimers disease (AD) is an irreversible, progressive neurodegenerative disorder with a high prevalence. Since behavioral disturbances, such as psychotic symptoms, represent a key feature of AD, genes related to dopamine, serotonin and brain derived neurotrophic factor (BDNF), are considered as candidate genes for AD. BDNF is a neurotrophin that regulates neurodevelopment, neuroplasticity, and neuronal functions. BDNF is involved in the etiopathogenesis of psychiatric and neurodegenerative disorders. A single base pair polymorphism (BDNF Val66Met) was reported to be associated with AD and/or schizophrenia, as well as other psychoses, although some studies failed to replicate these findings. The aim of the study was to evaluate the association between BDNF Val66Met variants and AD, as well as onset of AD or presence of psychotic symptoms in AD. METHOD BDNF Val66Met was analyzed in 211 patients with AD and in 402 aged healthy control subjects. All subjects were ethnically homogenous Caucasians from Croatia, and were subdivided according to the gender, onset of AD, and presence of psychotic symptoms. A χ(2) test, with Bonferroni correction and standardized residuals were used to evaluate the data. RESULTS Distribution of the BDNF Val66Met genotypes differed significantly between male and female AD patients with or without psychotic symptoms. This difference was due to the significant contribution of the Met/Val genotype and the combined Met/Met and Met/Val genotypes between psychotic and non-psychotic symptoms in male, but not in female patients with AD. The frequency of the gene variants of the BDNF Val66Met did not differ significantly among male and female patients with AD and control subjects, or between male and female patients with early or late onset AD. There were significant sex related differences in age, duration of illness and scores of dementia between patients with AD. CONCLUSION Our male patients were younger, had shorter duration of illness, and had less severe dementia and higher cognitive performance than female AD patients. The gene variants of the BDNF Val66Met polymorphism were significantly associated with the presence of psychotic symptoms in male, but not in female patients with AD. The results had adequate statistical power to suggest that BDNF Val66Met was not related to susceptibility to AD or the onset of AD, but that presence of one or two Met alleles of BDNF Val66Met polymorphism might present a risk factor for psychosis in AD.

The Reliability and Validity of the Mini-Mental State Examination in the Elderly Croatian Population

Aim: The aim of this study was standardization and validation of the Mini-Mental State Examination (MMSE) in the general Croatian aging population. Methods: Three-hundred and forty-four participants underwent the MMSE test, 217 cognitively healthy subjects without neurological and psychiatric disorders and 127 patients with mild cognitive impairment (MCI) or dementia. Results: The optimal cutoff point for screening of the general Croatian population (cognitively healthy vs. MCI and dementia) is 26/27; in the Croatian population aged ≥65 years, the cutoff point is 24/25, whereas for screening of highly educated persons (≥14 years of education) aged ≥65 years a higher cutoff point should be used (26/27). Conclusions: MMSE results when standardized and validated in a certain population might better contribute to recognition of the individuals at risk that should be directed to dementia outpatient clinics.

Posttraumatic stress disorder and platelet serotonin measures

The role of serotonin (5HT) in the pathophysiology of posttraumatic stress disorder (PTSD) has been suggested by the overlap in clinical symptoms between PTSD and psychiatric conditions in which a serotonin dysfunction is implicated, as well as by the therapeutic efficiency of 5HT-related drugs (antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors) in alleviating symptoms in PTSD. In the present study, the blood platelet, which has been proposed as a peripheral model for the central serotonergic neurons, has been used to search for alterations in 5HT mechanisms in PTSD. Platelet serotonin level and kinetics of serotonin transporter and monoamine oxidase (MAO-B) were assessed in 63 combat-related PTSD patients and 43 sex and age-matched control subjects. A significant reduction in maximal velocity of platelet MAO-B (approx. 30%), with no changes in the enzyme affinity was observed in our patient sample. Conversely, no alterations in kinetic parameters (V(max), K(m)) of platelet serotonin transporter, as well as in platelet 5HT level, were found in the PTSD group.

An essay on human and elements, multielement profiles, and depression

The recent development of the analytical techniques offers the unprecedented possibility to study simultaneously concentration of dozens of elements in the same biological matrix sample of 0.5–1.0 g (multielement profiles). The first part of this essay entitled “Think globally… An outline of trace elements in health and disease” aims to introduce the reader to the fascinating field of elements, there importance to our nutrition, their essentiality, deficiency, toxicity and bioavailability to the body and their overall role in health and disease, including the genetic metabolic impairments. In the second part of the essay entitled “… and act locally. The multielement profile of depression” we aimed to show the potential of such a hair multielement profile analysis for the study of human depression in a randomized, double blind, prospective, observational, cross-sectional, clinical, epidemiological, and analytical study. The preliminary results of this ongoing study lead us to put forward the hypothesis that the metabolic origin of depression may be due to some “energostat” failure, probably located in the thalamus, and activated by several essential element deficiencies.

Genotype-independent decrease in plasma dopamine beta-hydroxylase activity in Alzheimer's disease

The noradrenergic system is involved in the etiology and progression of Alzheimers disease (AD) but its role is still unclear. Dopamine beta-hydroxylase (DBH) as a catecholamine-synthesizing enzyme plays a central role in noradrenaline (NA) synthesis and turnover. Plasma DBH (pDBH) activity shows wide inheritable interindividual variability that is under genetic control. The aim of this study was to determine pDBH activity, DBH (C-970T; rs1611115) and DBH (C1603T; rs6271) gene polymorphisms in 207 patients with AD and in 90 healthy age-matched controls. Plasma DBH activity was lower, particularly in the early stage of AD, compared to values in middle and late stages of the disease, as well as to control values. Two-way ANOVA revealed significant effect of both diagnosis and DBH (C-970T) or DBH (C1603T) genotypes on pDBH activity, but without significant diagnosis×genotype interaction. No association was found between AD and DBH C-970T (OR=1.08, 95% CI 1.13-4.37; p=0.779) and C1603T (OR=0.89; 95% CI 0.36-2.20; p=0.814) genotypes controlled for age, gender, and ApoE4 allele. The decrease in pDBH activity, found in early phase of AD suggests that alterations in DBH activity represent a compensatory mechanism for the loss of noradrenergic neurons, and that treatment with selective NA reuptake inhibitors may be indicated in early stages of AD to compensate for loss of noradrenergic activity in the locus coeruleus.

The Frontal Assessment Battery in the Differential Diagnosis of Dementia

Aim: The Frontal Assessment Battery (FAB) has been used in different clinical settings as a valuable quick bedside test for executive dysfunction. The aim of the study was to evaluate clinical utility of the FAB for differential diagnosis of Alzheimer disease (AD), subcortical vascular cognitive impairment (scVCI), and frontotemporal lobar degeneration (FTLD). Methods: Scores of the total FAB test and subtests were compared between consecutive series of 37 patients with AD, 31 patients with scVCI, 13 patients with FTLD, and 29 cognitively healthy individuals. Results: There was no statistically significant difference in the total FAB scores among the groups of patients with dementia. When comparing subtest scores, patients with FTLD had significantly lower scores on the lexical fluency subtest compared to the patients with AD (P < .001) or scVCI (P < .001); patients with scVCI had significantly lower scores on the motor series subtest compared to patients with FTLD (P = .02) and AD (P = .035) and on conflicting instructions subtest compared to patients with AD (P = .033). Conclusion: Some FAB subtests might enhance diagnostic accuracy taking into account clinical history and other tests of executive function.

Hair iodine for human iodine status assessment.

BACKGROUND Today, human iodine deficiency is, after iron, the most common nutritional deficiency in developed European and underdeveloped third world countries. A current biological indicator of iodine status is urinary iodine, which reflects very recent iodine exposure; a long-term indicator of iodine status remains to be identified. METHODS We analyzed hair iodine in a prospective, observational, cross-sectional, and exploratory study involving 870 apparently healthy Croatians (270 men and 600 women). Hair iodine was analyzed with inductively coupled plasma mass spectrometry. RESULTS The hair iodine median was 0.499 μg/g, and was 0.482 and 0.508 μg/g for men and women respectively, suggesting no sex-related difference. We studied hair iodine uptake by analyzing the logistic sigmoid saturation curve of the median derivatives to assess iodine deficiency, adequacy, and excess. We estimated overt iodine deficiency to occur when hair iodine concentration was below 0.1-0.15 μg/g. Then there was a saturation range interval of about 0.1-2.0 μg/g where the deposition of iodine in the hair was linearly increasing (R(2)=0.994). Eventually, the sigmoid curve became saturated at about 2.0 μg/g and upward, suggesting excessive iodine exposure. CONCLUSION Hair appears to be a valuable and robust biological indicator tissue for assessing long-term iodine status. We propose that an adequate iodine status corresponds with hair iodine uptake saturation of 0.565-0.739 μg/g (55-65%).

Catatonic schizophrenia in Croatia

Abstract A representative sample of schizophrenic subjects was collected for epidemiological and clinical follow-up in 1972 from the pool of 8069 patients registered in the Croatian Psychotics Case Register (CPCR). This sample comprised 402 patients (207 males and 195 females), who were followed up until 1990/91. The diagnosis of schizophrenia, catatonic type according to ICD-8 (V/295.2), was made in 59 cases (14.7 %; 28 males, 31 females) at least once in the course of the follow-up. This study presents data concerning the diagnostic instability of the catatonic subtype during the long-term follow-up. As subtype diagnoses were frequently changed over the course of illness, at the end of the follow-up, the diagnosis of catatonic schizophrenia was only confirmed in 11 (18.6 %) cases. Positive family history of psychosis was found in 44.1 % of catatonic patients, a percent significantly greater than the corresponding figure for all non-catatonic schizophrenic subtypes combined (20.1 %). This study provides preliminary evidence that the catatonic subtype of schizophrenia is a separate diagnostic entity with a high familial loading.

Alzheimer’s disease and type 2 diabetes: the association study of polymorphisms in tumor necrosis factor-alpha and apolipoprotein E genes

Type 2 diabetes (T2D) and Alzheimer’s disease (AD) are two progressive disorders with high prevalence worldwide. Polymorphisms in tumor necrosis factor-alpha (TNF-α) and apolipoprotein E (ApoE) genes might be associated with both T2D and AD, representing possible genetic markers for the development of the AD in subjects with T2D. The aim was to determine ApoE and G-308A TNF-α gene polymorphisms in unrelated Croatian Caucasians: 207 patients with sporadic AD, 196 T2D patients and 456 healthy controls. Patients with AD had higher frequency of ApoE4 allele compared to T2D patients and controls. The significant association, observed between ApoE2 allele and T2D, disappeared after the data were adjusted for age and sex. The genotype or allele frequencies of G-308A TNF-α gene polymorphism were similar among the patients with AD, T2D and healthy controls. In conclusion, these results do not support the hypothesis that the A allele of G-308A TNF-α gene polymorphism is associated either with AD or T2D. Our data confirm the association between the ApoE4 allele and AD, and point out the E2 allele of ApoE gene as the possible risk factor for T2D.