The Role of Silence in Verbal Fluency Tasks - A New Approach for the Detection of Mild Cognitive Impairment.

OBJECTIVE: Most recordings of verbal fluency tasks include substantial amounts of task-irrelevant content that could provide clinically valuable information for the detection of mild cognitive impairment (MCI). We developed a method for the analysis of verbal fluency, focusing not on the task-relevant words but on the silent segments, the hesitations, and the irrelevant utterances found in the voice recordings. METHODS: Phonemic ('k', 't', 'a') and semantic (animals, food items, actions) verbal fluency data were collected from healthy control (HC; n = 25; Mage = 67.32) and MCI (n = 25; Mage = 71.72) participants. After manual annotation of the voice samples, 10 temporal parameters were computed based on the silent and the task-irrelevant segments. Traditional fluency measures, based on word count (correct words, errors, repetitions) were also employed in order to compare the outcome of the two methods. RESULTS: Two silence-based parameters (the number of silent pauses and the average length of silent pauses) and the average word transition time differed significantly between the two groups in the case of all three semantic fluency tasks. Subsequent receiver operating characteristic (ROC) analysis showed that these three temporal parameters had classification abilities similar to the traditional measure of counting correct words. CONCLUSION: In our approach for verbal fluency analysis, silence-related parameters displayed classification ability similar to the most widely used traditional fluency measure. Based on these results, an automated tool using voiced-unvoiced segmentation may be developed enabling swift and cost-effective verbal fluency-based MCI screening.

Temporal Speech Parameters Detect Mild Cognitive Impairment in Different Languages: Validation and Comparison of the Speech-GAP Test® in English and Hungarian.

BACKGROUND: The development of automatic speech recognition (ASR) technology allows the analysis of temporal (time-based) speech parameters characteristic of mild cognitive impairment (MCI). However, no information has been available on whether the analysis of spontaneous speech can be used with the same efficiency in different language environments. OBJECTIVE: The main goal of this international pilot study is to address the question of whether the Speech-Gap Test® (S-GAP Test®), previously tested in the Hungarian language, is appropriate for and applicable to the recognition of MCI in other languages such as English. METHODS: After an initial screening of 88 individuals, English-speaking (n = 33) and Hungarianspeaking (n = 33) participants were classified as having MCI or as healthy controls (HC) based on Petersen's criteria. The speech of each participant was recorded via a spontaneous speech task. Fifteen temporal parameters were determined and calculated through ASR. RESULTS: Seven temporal parameters in the English-speaking sample and 5 in the Hungarian-speaking sample showed significant differences between the MCI and the HC groups. Receiver operating characteristics (ROC) analysis clearly distinguished the English-speaking MCI cases from the HC group based on speech tempo and articulation tempo with 100% sensitivity, and on three more temporal parameters with high sensitivity (85.7%). In the Hungarian-speaking sample, the ROC analysis showed similar sensitivity rates (92.3%). CONCLUSION: The results of this study in different native-speaking populations suggest that changes in acoustic parameters detected by the S-GAP Test® might be present across different languages.

Temporal Speech Parameters Indicate Early Cognitive Decline in Elderly Patients With Type 2 Diabetes Mellitus.

INTRODUCTION: The earliest signs of cognitive decline include deficits in temporal (time-based) speech characteristics. Type 2 diabetes mellitus (T2DM) patients are more prone to mild cognitive impairment (MCI). The aim of this study was to compare the temporal speech characteristics of elderly (above 50 y) T2DM patients with age-matched nondiabetic subjects. MATERIALS AND METHODS: A total of 160 individuals were screened, 100 of whom were eligible (T2DM: n=51; nondiabetic: n=49). Participants were classified either as having healthy cognition (HC) or showing signs of MCI. Speech recordings were collected through a phone call. Based on automatic speech recognition, 15 temporal parameters were calculated. RESULTS: The HC with T2DM group showed significantly shorter utterance length, higher duration rate of silent pause and total pause, and higher average duration of silent pause and total pause compared with the HC without T2DM group. Regarding the MCI participants, parameters were similar between the T2DM and the nondiabetic subgroups. CONCLUSIONS: Temporal speech characteristics of T2DM patients showed early signs of altered cognitive functioning, whereas neuropsychological tests did not detect deterioration. This method is useful for identifying the T2DM patients most at risk for manifest MCI, and could serve as a remote cognitive screening tool.

Telltale silence: temporal speech parameters discriminate between prodromal dementia and mild Alzheimer's disease.

This study presents a novel approach for the early detection of mild cognitive impairment (MCI) and mild Alzheimer's disease (mAD) in the elderly. Participants were 25 elderly controls (C), 25 clinically diagnosed MCI and 25 mAD patients, included after a clinical diagnosis validated by CT or MRI and cognitive tests. Our linguistic protocol involved three connected speech tasks that stimulate different memory systems, which were recorded, then analyzed linguistically by using the PRAAT software. The temporal speech-related parameters successfully differentiate MCI from mAD and C, such as speech rate, number and length of pauses, the rate of pause and signal. Parameters pauses/duration and silent pauses/duration linearly decreased among the groups, in other words, the percentage of pauses in the total duration of speech continuously grows as dementia progresses. Thus, the proposed approach may be an effective tool for screening MCI and mAD.

Dementia in Hungary: General practitioners' routines and perspectives regarding early recognition.

Background: Undetected dementia in primary care is a global problem. Since general practitioners (GPs) act as the first step in the identification process, examining their routines could help us to enhance the currently low recognition rates.Objectives: The study aimed to explore, for the first time in Hungary, the dementia identification practices and views of GPs.Methods: In the context of an extensive, national survey (February-November 2014) 8% of all practicing GPs in Hungary (n = 402) filled in a self-administered questionnaire. The questions (single, multiple-choice, Likert-type) analysed in the present study explored GPs' methods and views regarding dementia identification and their ideas about the optimal circumstances of case-finding.Results: The vast majority of responding GPs (97%) agreed that the early recognition of dementia would enhance both the patients' and their relatives' well-being. When examining the possibility of dementia, most GPs (91%) relied on asking the patients general questions and only a quarter of them (24%) used formal tests, even though they were mostly satisfied with both the Clock Drawing Test (69%) and the Mini-Mental State Examination (65%). Longer consultation time was chosen as the most important facet of improvement needed for better identification of dementia in primary care (81%). Half of the GPs (49%) estimated dementia recognition rate to be lower than 30% in their practice.Conclusions: Hungarian GPs were aware of the benefits of early recognition, but the shortage of consultation time in primary care was found to be a major constraint on efficient case-finding.

Cognitive Functioning and Psychological Well-being in Breast Cancer Patients on Endocrine Therapy.

BACKGROUND/AIM: Anti-cancer therapies may deteriorate cognitive functioning, affective functioning and psychological well-being. MATERIALS AND METHODS: In this prospective longitudinal pilot study, premenopausal and postmenopausal patients received adjuvant endocrine therapy (ET) (tamoxifen with or without LHRH analog or aromatase inhibitor) or were observed only (control group). At baseline testing and 6, 12 and 24 months thereafter, cognitive, depression and anxiety tests and quality of life (QOL) measurements were performed. RESULTS: Overall, 46 cases were evaluated. None of the studied cognitive parameters differed between the subgroups or changed by time. No differences were found regarding anxiety, depression or QOL measures either. Baseline cognitive test and QOL results were in association with later anxiety and depression. CONCLUSION: No cognitive impairment was found during the two years of ET. Baseline cognitive scores and QOL dimensions proved good predictors of later anxiety and depression.

Application of BisANS fluorescent dye for developing a novel protein assay.

In many biology- and chemistry-related research fields and experiments the quantification of the peptide and/or protein concentration in samples are essential. Every research environment has unique requirements, e.g. metal ions, incubation times, photostability, pH, protease inhibitors, chelators, detergents, etc. A new protein assay may be adequate in different experiments beyond or instead of the well-known standard protocols (e.g. Qubit, Bradford or bicinchoninic acid) in related conceptions. Based on our previous studies, we developed a novel protein assay applying the 4,4'-Dianilino-1,1'-binaphthyl-5,5'-disulfonic acid dipotassium salt (BisANS) fluorescent dye. This molecule has several advantageous properties related to protein detection: good solubility in water, high photostability at adequate pH, quick interaction kinetics (within seconds) with proteins and no exclusionary sensitivity to the chelator, detergent and inhibitor ingredients. The protocol described in this work is highly sensitive in a large spectrum to detect protein (100-fold diluted samples) concentrations (from 0.28 up to more than 100 µg/mL). The BisANS protein assay is valid and applicable for quantification of the amount of protein in different biological and/or chemical samples.

Association study of the ABCA7 rs3752246 polymorphism in Alzheimer's disease.

The ATP-binding cassette, sub-family A, member 7 (ABCA7) gene has been identified as a strong genetic risk locus for Alzheimer's disease (AD). Our case-control study (416 AD patients and 302 controls) provides further data on the rs3752246 polymorphism in AD in the Hungarian population that has not been investigated so far regarding the ABCA7 gene variants. A modest, marginally significant association of the G allele containing genotypes with AD was observed (p = 0.054). In line with the previous results in other populations, the G allele carriers had an increased risk for developing AD considering C/C genotype as reference category.

Hungarian general practitioners' attitude and the role of education in dementia care.

BACKGROUND: Dementia in the elderly constitutes a growing challenge in healthcare worldwide, including Hungary. There is no previous report on the role of general practitioners in the management of dementia. AIM: The purpose of the present study was to investigate the Hungarian general practitioners' attitude toward their patients living with dementia as well as dementia care. Our goal was also to assess their willingness and habits in assessing dementia. Additionally we wanted to explore the role of education about dementia, and its impact on their attitude in dementia management. METHODS: As part of a large survey, a self-administered questionnaire was filled out voluntarily by 402 of general practitioners. According to our preset criteria, 277 surveys were selected for evaluation. Descriptive statistical analysis and Likert-scale analysis were performed. FINDINGS: Half of the doctors (49.8%) indicated that they conducted a test to assess cognitive functions in case of suspicion. Among the respondents who did not assess, 50.0% of physicians cited lack of time as the main reason for not doing so and 14.4% of them had not proper knowledge of testing methods. The respondents most often mentioned feelings toward their patients with dementia, were regret (Likert-scale mean: 3.33), helplessness (3.28) and sadness (3.07). The majority of physicians thought the treatment of dementia was difficult (4.46). Most of the respondents (81.2%) indicated that in the past 2 years they had not participated in any training about dementia. Those practitioners who had participated in some form of education were less likely to feel helpless facing a patient with dementia, and education also determined their approach to dementia care.

Nilvadipine in mild to moderate Alzheimer disease: A randomised controlled trial.

BACKGROUND: This study reports the findings of the first large-scale Phase III investigator-driven clinical trial to slow the rate of cognitive decline in Alzheimer disease with a dihydropyridine (DHP) calcium channel blocker, nilvadipine. Nilvadipine, licensed to treat hypertension, reduces amyloid production, increases regional cerebral blood flow, and has demonstrated anti-inflammatory and anti-tau activity in preclinical studies, properties that could have disease-modifying effects for Alzheimer disease. We aimed to determine if nilvadipine was effective in slowing cognitive decline in subjects with mild to moderate Alzheimer disease. METHODS AND FINDINGS: NILVAD was an 18-month, randomised, placebo-controlled, double-blind trial that randomised participants between 15 May 2013 and 13 April 2015. The study was conducted at 23 academic centres in nine European countries. Of 577 participants screened, 511 were eligible and were randomised (258 to placebo, 253 to nilvadipine). Participants took a trial treatment capsule once a day after breakfast for 78 weeks. Participants were aged >50 years, meeting National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's disease Criteria (NINCDS-ADRDA) for diagnosis of probable Alzheimer disease, with a Standardised Mini-Mental State Examination (SMMSE) score of ≥12 and <27. Participants were randomly assigned to 8 mg sustained-release nilvadipine or matched placebo. The a priori defined primary outcome was progression on the Alzheimer's Disease Assessment Scale Cognitive Subscale-12 (ADAS-Cog 12) in the modified intention-to-treat (mITT) population (n = 498), with the Clinical Dementia Rating Scale sum of boxes (CDR-sb) as a gated co-primary outcome, eligible to be promoted to primary end point conditional on a significant effect on the ADAS-Cog 12. The analysis set had a mean age of 73 years and was 62% female. Baseline demographic and Alzheimer disease-specific characteristics were similar between treatment groups, with reported mean of 1.7 years since diagnosis and mean SMMSE of 20.4. The prespecified primary analyses failed to show any treatment benefit for nilvadipine on the co-primary outcome (p = 0.465). Decline from baseline in ADAS-Cog 12 on placebo was 0.79 (95% CI, -0.07-1.64) at 13 weeks, 6.41 (5.33-7.49) at 52 weeks, and 9.63 (8.33-10.93) at 78 weeks and on nilvadipine was 0.88 (0.02-1.74) at 13 weeks, 5.75 (4.66-6.85) at 52 weeks, and 9.41 (8.09-10.73) at 78 weeks. Exploratory analyses of the planned secondary outcomes showed no substantial effects, including on the CDR-sb or the Disability Assessment for Dementia. Nilvadipine appeared to be safe and well tolerated. Mortality was similar between groups (3 on nilvadipine, 4 on placebo); higher counts of adverse events (AEs) on nilvadipine (1,129 versus 1,030), and serious adverse events (SAEs; 146 versus 101), were observed. There were 14 withdrawals because of AEs. Major limitations of this study were that subjects had established dementia and the likelihood that non-Alzheimer subjects were included because of the lack of biomarker confirmation of the presence of brain amyloid. CONCLUSIONS: The results do not suggest benefit of nilvadipine as a treatment in a population spanning mild to moderate Alzheimer disease. TRIAL REGISTRATION: Clinicaltrials.gov NCT02017340, EudraCT number 2012-002764-27.

A Speech Recognition-based Solution for the Automatic Detection of Mild Cognitive Impairment from Spontaneous Speech.

BACKGROUND: Even today the reliable diagnosis of the prodromal stages of Alzheimer's disease (AD) remains a great challenge. Our research focuses on the earliest detectable indicators of cognitive decline in mild cognitive impairment (MCI). Since the presence of language impairment has been reported even in the mild stage of AD, the aim of this study is to develop a sensitive neuropsychological screening method which is based on the analysis of spontaneous speech production during performing a memory task. In the future, this can form the basis of an Internet-based interactive screening software for the recognition of MCI. METHODS: Participants were 38 healthy controls and 48 clinically diagnosed MCI patients. The provoked spontaneous speech by asking the patients to recall the content of 2 short black and white films (one direct, one delayed), and by answering one question. Acoustic parameters (hesitation ratio, speech tempo, length and number of silent and filled pauses, length of utterance) were extracted from the recorded speech signals, first manually (using the Praat software), and then automatically, with an automatic speech recognition (ASR) based tool. First, the extracted parameters were statistically analyzed. Then we applied machine learning algorithms to see whether the MCI and the control group can be discriminated automatically based on the acoustic features. RESULTS: The statistical analysis showed significant differences for most of the acoustic parameters (speech tempo, articulation rate, silent pause, hesitation ratio, length of utterance, pause-per-utterance ratio). The most significant differences between the two groups were found in the speech tempo in the delayed recall task, and in the number of pauses for the question-answering task. The fully automated version of the analysis process - that is, using the ASR-based features in combination with machine learning - was able to separate the two classes with an F1-score of 78.8%. CONCLUSION: The temporal analysis of spontaneous speech can be exploited in implementing a new, automatic detection-based tool for screening MCI for the community.

ABCA1 rs2230805 and rs2230806 common gene variants are associated with Alzheimer's disease.

The ATP-binding cassette, sub-family A, member 1 gene (ABCA1) is a relevant positional and functional candidate gene for Alzheimer's disease (AD). A case-control association study of genetic variations covering the ABCA1 locus was performed in relation to AD risk in a Hungarian sample. Five single nucleotide polymorphisms (rs2422493: C-477T, rs2740483: G-17C, rs2230805: G474A/L158L, rs2230806: G656A/R219K and rs2066718: G2311A/V771M) were genotyped in 431 AD patients and 302 cognitively healthy, elderly controls. In single marker analysis, significant associations were found in the case of rs2230805 and rs2230806 polymorphisms: the minor A allele containing genotypes for both polymorphisms were more frequent in the control compared to the AD group. Haplotype analysis revealed that rs2230805, rs2230806 and rs2066718 polymorphisms created a linkage disequilibrium (LD) block with a strong LD between rs2230805 and rs2230806 polymorphisms. In the haplotype risk association tests, A-A-G haplotype of the rs2230805-rs2230806-rs2066718 polymorphisms was found to be nominally significantly more frequent in the control group. After correcting p values for multiple testing, only the effects of the rs2230805 and rs2230806 polymorphisms remained significant in the recessive model suggesting a modest protective effect of their minor alleles in AD, which should be interpreted with considerable caution, until further studies elucidate their role in AD pathology.

Adiponectin Receptors Are Less Sensitive to Stress in a Transgenic Mouse Model of Alzheimer's Disease.

Background: Adiponectin and leptin are implicated in the initiation and pathomechanism of Alzheimer's disease (AD). The serum concentrations of these adipokines has been extensively studied in AD, however little is known about their receptors in this disease. Objective: We developed a novel approach to examine whether the receptors of adiponectin (AdipoR1 and -R2) and/or leptin (LepR) can contribute to AD pathomechanism. To achieve this, we investigated the effect of both genetic and environmental factors associated with AD on the expression of these receptors. Method: We used C57BL/6J (WT) and APP(swe)/Presen(e9d)1 (AD) mice. Both strains were exposed to restraint stress (RS) daily for 6h over different time periods. Then, we measured the mRNA expression of AdipoR1, AdipoR2 and LepR and the level of AdipoR1 and AdipoR2 proteins in the hippocampal and prefrontal cortical areas of each mouse. Results: We detected brain region specific transcriptomic changes of adiponectin receptors induced by APP and PS1 transgenes. Both acute and chronic RS caused significant elevations in AdipoR1 mRNA expression in the hippocampus of WT mice. In the prefrontal cortex, the mRNA expression of AdipoR1 followed a biphasic course. In AD mice, RS did not promote any changes in the expression of AdipoR1 mRNA and AdipoR1 protein levels. AdipoR2 mRNA in AD animals, however, showed a significant increase in the prefrontal cortex during RS. Regarding AdipoR1 and AdipoR2 mRNA and protein expression, relevant changes could be measured during stress exposure in both brain areas. Furthermore, stress exposed groups exhibited little change in LepR mRNA expression. Conclusion: Our findings indicate that carrying the transgenes associated with AD induces modification in the expression of both adiponectin receptors. In the case of a normal genetic background, these receptors also appear to be sensitive to environmental factors, while in a genetically determined AD model less response to stress stimuli could be observed. The results suggest that modification of adipokine receptors could also be considered in the therapeutic approach to AD.

Relevance of defensin ß-2 and α defensins (HNP1-3) in Alzheimer's disease.

The DEFB4 gene copy numbers were investigated in 206 AD patients and in 250 controls. The levels of the human defensin ß-2 (hBD2) and α-defensins (HNP 1-3) in the sera and in the cerebrospinal fluid (CSF) of the patients and the controls were determined. Higher copy numbers of the DEFB4 gene was observed in AD patients as compared with the controls. The levels of hBD-2 and HNP 1-3 were significantly elevated in the sera and in the CSF of the AD patients These data suggest that both defensin ß-2 and α-defensins have potential role in the development of AD.

Speaking in Alzheimer's Disease, is That an Early Sign? Importance of Changes in Language Abilities in Alzheimer's Disease.

It is known that Alzheimer's disease (AD) influences the temporal characteristics of spontaneous speech. These phonetical changes are present even in mild AD. Based on this, the question arises whether an examination based on language analysis could help the early diagnosis of AD and if so, which language and speech characteristics can identify AD in its early stage. The purpose of this article is to summarize the relation between prodromal and manifest AD and language functions and language domains. Based on our research, we are inclined to claim that AD can be more sensitively detected with the help of a linguistic analysis than with other cognitive examinations. The temporal characteristics of spontaneous speech, such as speech tempo, number of pauses in speech, and their length are sensitive detectors of the early stage of the disease, which enables an early simple linguistic screening for AD. However, knowledge about the unique features of the language problems associated with different dementia variants still has to be improved and refined.

Genetic analysis of the RELN gene: Gender specific association with Alzheimer's disease.

Association between genetic variants of the reelin (RELN) gene and the risk for developing Alzheimer's disease (AD) was examined in a sample of 432 patients and 308 controls. Single marker and haplotype analyses revealed that the strongly linked rs528528 and rs607755 polymorphisms are associated with AD risk in a gender specific manner. Among men, but not in women the rs528528 T/T and rs607755 A/A genotypes were significantly associated with the susceptibility to AD.

Alterations of membrane protein expression in red blood cells of Alzheimer's disease patients.

Preventive measures, prognosis, or selected therapy in multifactorial maladies, including Alzheimer's disease (AD), require the application of a wide range of diagnostic assays. There is a large unmet need for relatively simple, blood-based biomarkers in this regard. We have recently developed a rapid and reliable flow cytometry and antibody-based method for the quantitative measurement of various red blood cell (RBC) membrane proteins from a drop of blood. Here, we document that the RBC expression of certain membrane proteins, especially that of the GLUT1 transporter and the insulin receptor (INSR), is significantly higher in AD patients than in age-matched healthy subjects. The observed differences may reflect long-term metabolic alterations relevant in the development of AD. These findings may pave the way for a diagnostic application of RBC membrane proteins as relatively stable and easily accessible personalized biomarkers in AD.

Proteomic analysis of cerebrospinal fluid in Alzheimer's disease: wanted dead or alive.

Clinical diagnosis of Alzheimer's disease (AD) relying on symptomatic features has a low specificity, emphasizing the importance of the pragmatic use of neurochemical biomarkers. The most advanced and reliable markers are amyloid-ß (Aß42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF) with relatively high levels of sensitivity, specificity, and diagnostic accuracy. Recent advances within the field of proteomics offer the potential to search for novel biomarkers in CSF by using modern methods, such as microarrays. The purpose of this study was to identify pathognostic proteins in CSF obtained from patients whose clinical AD diagnosis was confirmed by the "core" biomarkers. CSF samples were obtained from 25 AD patients and 25 control individuals. The levels of Aß42, t-tau, and p-tau were measured by ELISA. In the microarray experiments, ultrasensitive slides representing of 653 antigens were used. Apolipoprotein E genotyping was also determined. A decrease of seven CSF proteins in AD were found, four of them (POLG, MGMT, parkin, and ApoD) have a protective function against neuronal death, while the remaining three proteins (PAR-4, granzyme B, Cdk5) trigger multiple pathways facilitating neuronal cell death. Since these proteins from CSF samples could not be identified by western blot, their decreased levels in AD patients were not verified. Our results provide new information of pathognostic importance of POLG and granzyme B in AD. Although the function of MGMT, parkin, ApoD, PAR-4, and Cdk5 was previously known in AD, the findings presented here provide novel evidence of the significance of CSF analysis in the mapping of the AD pathomechanism.

Restraint Stress-Induced Morphological Changes at the Blood-Brain Barrier in Adult Rats.

Stress is well-known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognized in the development of neurodegenerative disorders, such as Alzheimer's disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3, and 21 days) were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occluding, and glucose transporter-1) and astroglia (GFAP). Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, 1-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5, and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes, cognitive and behavioral dysfunctions.

[Frailty syndrome: an old new friend]. / Esendoségszindróma: egy régi új ismeros.

Frailty syndrome is defined as extreme stress vulnerability and decreased potential to adapt. The elderly and chronically ill patients are affected mostly. This condition increases the risk of adverse health outcomes as infections, falls, delirium, institutionalization, progression of comorbidities and mortality. The pathophysiological mechanism is a complex immune and neuroendocrine dysregulation. According to the phenotype model, frailty presents when three of the followings occur: weakness, exhaustion, slowness, weight loss and decreased activity, while cumulative model counts the number of health deficits. Aging, frailty, dementia and depression are independent clinical entities; they may present separately but may also potentiate each other. Hence most of the frailty scales assess the physical, mental and social dimensions as well. Mild or moderate frailty is potentially reversible with an individualised caring plan. Given short, easy-to-use screening tools, risk groups can be identified in the primary care and referred to a specialised team for further treatment. Here the authors summarise the literature of a re-discovered, current clinical phenomena, frailty syndrome, focusing on the practical issues in primary care.