Anikó Égerházi

Automated Neuropsychological Test Battery (CANTAB) in mild cognitive impairment and in Alzheimer's disease

Neuropsychological deficits, such as poor episodic memory, are consistent features of mild cognitive impairment and also that of early stage of dementia. The aim of the present study was to detect cognitive dysfunction among patients with Alzheimers disease or with mild cognitive impairment (MCI), which refers to a transitional state between the cognition of normal aeging and mild dementia regarded as a high-risk condition for the development of clinically probable Alzheimers disease (AD). Computerized tests of memory, attention and executive functions were studied in groups of AD subjects (n=15) and MCI subjects (n=25). On all measures, the performance of the AD group was significantly weaker compared to healthy individuals or to the MCI group. The performance of both the AD and MCI patients in the Paired Associate Learning test was significantly impaired, which may suggest that MCI patients are already in the early stages of the disease.

Serum paraoxonase activity changes in patients with Alzheimer's disease and vascular dementia

Abstract The prevalence of Alzheimers disease (AD) and vascular dementia (VAD) increases with aging of the population. The role of lipoproteins in the pathogenesis of AD is unclear: apoE2 offers protection and apoE3 is neutral, while apoE4 promotes the development of the disease.Recently, several studies have confirmed the role of oxidative stress in the pathogenesis of AD and VAD. HDL-associated paraoxonase is one of the antioxidative enzymes that may reduce LDL oxidation. In our study, we investigated the lipid parameters of the sera and the serum paraoxonase activity in patients with AD and VAD.Lipid parameters were determined by an autoanalyzer in 30 AD patients, 40 VAD patients and 40 healthy, age-matched control (C) subjects. Paraoxonase activity was measured spectrophotometrically using paraoxon as the substrate. The phenotypic distribution of paraoxonase was determined by the dual substrate method, using paraoxon and phenylacetate as substrates.In our results, we found that most of the patients with AD had the apoE4 isoform, consistent with other studies. In the VAD and AD patients we found significantly higher total-cholesterol compared to the control group (C: 4.71 ± 0.89, VAD: 6.3 ± 0.8, AD: 6.52 ± 0.7 mmol/l; p < 0.01) and LDL-cholesterol levels (C: 2.6 ± 0.6, VAD: 3.96 ± 0.8, AD: 3.84 ± 0.6 mmol/l; p < 0.001). The HDL-associated antioxidant, paraoxonase activity did not differ significantly in the patient groups, but compared to the healthy control subjects, paraoxonase activity was significantly lower in both of the patient groups (C: 188 ± 55 U/l; AD: 131 ± 37, VAD: 151 ± 50 l; p < 0.05).Our results suggest that the defect in HDL-associated antioxidant capacity plays a role in the pathogenesis of Alzheimers disease and vascular dementia.

Nε(γ-glutamyl)lysine in cerebrospinal fluid marks Alzheimer type and vascular dementia

Ne(γ-glutamyl)lysine isodipeptide is released from the breakdown of proteins cross-linked by transglutaminase enzymes. Transglutaminase activation is a marker of apoptosis and elevated isodipeptide concentrations in body fluids might correlate with the intensity of apoptotic cell turnover. The concentration of Ne(γ-glutamyl)lysine was measured in the cerebrospinal fluid (CSF) of patients with probable Alzheimer’s disease (n = 14) and vascular type dementia (n = 11) and compared with not demented surgical controls (n = 17). Baseline levels of 26–62 nM/l (mean 37.9 ± 8.7 SD) free isodipeptide were detected in control patients. CSF isodipeptide levels showed significant elevation in vascular (mean 95.6 ± 45.1 SD) as well as Alzheimer patients (176.6 ± 77.1 SD). Isodipeptide concentrations above 120 nM/l were 72% specific and 77% sensitive to Alzheimer’s dementia, although the difference between the two dementias was statistically insignificant (p > 0.05). Determination of CSF Ne(γ-glutamyl)lysine isodipeptide concentration offers a novel method for measurement of neurodegeneration in primary and mixed dementias.

Development and psychometric properties of a five-language multiperspective instrument to assess clinical decision making style in the treatment of people with severe mental illness (CDMS)

BackgroundThe aim of this study was to develop and evaluate psychometric properties of the Clinical Decision Making Style (CDMS) scale which measures general preferences for decision making as well as preferences regarding the provision of information to the patient from the perspectives of people with severe mental illness and staff.MethodsA participatory approach was chosen for instrument development which followed 10 sequential steps proposed in a current guideline of good practice for the translation and cultural adaptation of measures. Following item analysis, reliability, validity, and long-term stability of the CDMS were examined using Spearman correlations in a sample of 588 people with severe mental illness and 213 mental health professionals in 6 European countries (Germany, UK, Italy, Denmark, Hungary, and Switzerland).ResultsIn both patient and staff versions, the two CDMS subscales “Participation in Decision Making” and “Information” reliably measure distinct characteristics of decision making. Validity could be demonstrated to some extent, but needs further investigation.ConclusionsTogether with two other five-language patient- and staff-rated measures developed in the CEDAR study (ISRCTN75841675) – “Clinical Decision Making in Routine Care” and “Clinical Decision Making Involvement and Satisfaction” – the CDMS allows empirical investigation of the complex relation between clinical decision making and outcome in the treatment of people with severe mental illness across Europe.

The development and evaluation of a five-language multi-perspective standardised measure: clinical decision-making involvement and satisfaction (CDIS)

BackgroundThe aim of this study was to develop and evaluate a brief quantitative five-language measure of involvement and satisfaction in clinical decision-making (CDIS) – with versions for patients (CDIS-P) and staff (CDIS-S) – for use in mental health services.MethodsAn English CDIS was developed by reviewing existing measures, focus groups, semistructured interviews and piloting. Translations into Danish, German, Hungarian and Italian followed the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Task Force principles of good practice for translation and cultural adaptation. Psychometricevaluation involved testing the measure in secondary mental health services in Aalborg, Debrecen, London, Naples, Ulm and Zurich.ResultsAfter appraising 14 measures, the Control Preference Scale and Satisfaction With Decision-making English-language scales were modified and evaluated in interviews (n = 9), focus groups (n = 22) and piloting (n = 16). Translations were validated through focus groups (n = 38) and piloting (n = 61). A total of 443 service users and 403 paired staff completed CDIS. The Satisfaction sub-scale had internal consistency of 0.89 (0.86-0.89 after item-level deletion) for staff and 0.90 (0.87-0.90) for service users, both continuous and categorical (utility) versions were associated with symptomatology and both staff-rated and service userrated therapeutic alliance (showing convergent validity), and not with social disability (showing divergent validity), and satisfaction predicted staff-rated (OR 2.43, 95%CI 1.54- 3.83 continuous, OR 5.77, 95%CI 1.90-17.53 utility) and service user-rated (OR 2.21, 95%CI 1.51-3.23 continuous, OR 3.13, 95%CI 1.10-8.94 utility) decision implementation two months later. The Involvement sub-scale had appropriate distribution and no floor or ceiling effects, was associated with stage of recovery, functioning and quality of life (staff only) (showing convergent validity), and not with symptomatology or social disability (showing divergent validity), and staff-rated passive involvement by the service user predicted implementation (OR 3.55, 95%CI 1.53-8.24). Relationships remained after adjusting for clustering by staff.ConclusionsCDIS demonstrates adequate internal consistency, no evidence of item redundancy, appropriate distribution, and face, content, convergent, divergent and predictive validity. It can be recommended for research and clinical use. CDIS-P and CDIS-S in all 3 five languages can be downloaded at http://www.cedar-net.eu/instruments.Trial registrationISRCTN75841675.

[The early diagnosis and differential diagnosis of Alzheimer's disease with clinical methods].

Alzheimers disease is a progressive and fatal neurodegenerative disorder in which the novel drugs can slow down the progression in the early phase. Our purpose was to find biological markers, which would detect neuropathology in the prodromal and early phase of Alzheimers disease. Beside the routine diagnostic methods, neuropsychological test, auditory event related potential and special laboratory tests were performed among subjects with Alzheimers disease, vascular dementia, mild cognitive impairment and major depression compared to a healthy control group. Visual Paired Associate Learning was impaired in all patient groups, in major depression it seemed to be reversible. In amnestic mild cognitive impairment and in dementia a longer latency of late component of auditory evoked potential, P300, was found. Reduced paraoxonase activity in the serum and increased Nepsilon(gamma-glutamyl)lysine isodipeptide concentration in the cerebrospinal fluid were detected in both dementia groups. Characteristic changes of Visual Paired Associate Learning and P300 might predict the conversion to Alzheimers disease in mild cognitive impairment. The paraoxonase activity and the isodipeptide concentration can be sensitive markers of the pathomechanism of neurodegeneration. A combined use of the above-mentioned methods can help in the early prediction and diagnosis of Alzheimers disease.

Content and implementation of clinical decisions in the routine care of people with severe mental illness

Abstract Background: Clinical decision making (CDM) in the treatment of people with severe mental illness relates to a wide range of life domains. Aims: To examine content of CDM in mental health care from the perspectives of service users and staff and to investigate variation in implementation of decisions for differing content. Method: As part of the European multicenter study clinical decision making and outcome in routine care for people with severe mental illness (ISRCTN75841675), 588 service users and their clinicians were asked to identify the decisions made during their last meeting. Decisions were then coded into content categories. Two months later, both parties reported if these decisions had been implemented. Results: Agreement between patients and staff regarding decision making was moderate (κ = 0.21–0.49; p < 0.001). Decisions relating to medication and social issues were most frequently identified. Overall reported level of implementation was 73.5% for patients and 74.7% for staff, and implementation varied by decision content. Conclusions: A variety of relevant decision topics were shown for mental health care. Implementation rates varied in relation to topic and may need different consideration within the therapeutic dyad.

Helping Alliance and Unmet Needs in Routine Care of People With Severe Mental Illness Across Europe: A Prospective Longitudinal Multicenter Study

Abstract The helping alliance (HA) refers to the collaborative bond between patient and therapist, including shared goals and tasks. People with severe mental illness have a complex mixture of clinical and social needs. Using mixed-effects regression, this study examined in 588 people with severe mental illness whether an increase in the HA is associated with fewer unmet needs over time, and whether change in the HA precedes change in unmet needs. It was found that a reduction in unmet needs was slower in patients with higher HA (B = 0.04, p < 0.0001) only for patient-rated measures. Improvement in both patient-rated and staff-rated HA over time was associated with fewer subsequent patient-rated (B = −0.10, p < 0.0001) and staff-rated (B = −0.08, p = 0.0175) unmet needs. With positive changes in the HA preceding fewer unmet needs, findings provide further evidence for a causal relationship between alliance and outcome in the treatment of people with severe mental illness.

Facial emotion recognition deficits and alexithymia in borderline, narcissistic, and histrionic personality disorders

Previous studies that aimed to support emotion recognition deficits and alexithymia in B cluster personality disorders have mainly focused on borderline personality disorder (BPD), and resulted in mixed findings. In our study we examine emotion recognition and alexithymia in patients with histrionic (HPD), narcissistic (NPD) and borderline (BPD) personality disorders compared to each other and healthy controls. Furthermore, the possibility is investigated that it is not the type of PD but the severity of psychopathology which predicts the severity of emotion recognition deficits and alexithymia. Patients with HPD, NPD, BPD and healthy controls (N = 20 for each group) were examined by using the Ekman 60 Faces Test (FEEST) and the Toronto Alexithymia Scale (TAS-20). To measure the extent and severity of psychopathology, the Symptom-Checklist-90 Revised (SCL-90-R) was used. Patient groups performed significantly worse compared to healthy controls on the Ekman test and TAS-20, while we found no significant differences among patient groups in emotion recognition and alexithymia. Furthermore, higher scores on the SCL-90-R predicted poorer emotion recognition performance and higher alexithymic features. The empirical data supports the conclusion that the severity of psychopathology plays an important role in predicting emotion recognition deficits and alexithymia in borderline, narcissistic, and histrionic personality disorders.

A Teszteld a memóriádat (Test Your Memory) magyar változatának validálása

Concerns regarding the projected prevalence of Alzheimers disease (AD) over the next several decades have stimulated a need for the detection of AD in its earliest stages. A self-administered cognitive test (Test Your Memory, TYM) is designed as a short, cognitive screening tool for the detection of AD. Our aim was to validate the Hungarian version of the Test Your Memory (TYM-HUN) test for the detection of AD. The TYM-HUN was applied in case of individuals aged 60 years or more, 50 patients with AD and 50 healthy controls were recruited into the study. We compared the diagnostic utility of the Hungarian version of the TYM in AD with that of the Mini-Mental State Examination (MMSE). The sensitivity and specificity of the TYM-HUN in the detection of Alzheimers disease were determined. The patients with AD scored an average of 15.5/30 on the MMSE and 20.3/50 on the TYM-HUN. The average score achieved by the members of the healthy control group was 27.3/30 on the MMSE and 42.7/50 on the TYM. The total TYM-HUN scores significantly correlated with the MMSE scores (Spearmans rho, r=0.8830; p<0.001). Multivariate logistic regression model demonstrated that a one-point increase in the TYM score reduced the probability of having AD by 36%. The optimal cut-off score on the TYM-HUN was 35/36 along with 94% sensitivity and 94% specificity for the detection of AD. The TYM has a much wider scoring range than the MMSE and is also a suitable screening tool for memory problems, furthermore, it fulfils the requirements of being a short cognitive test for the non-specialists. The TYM-HUN is useful for the detection of Alzheimers disease and can be applied as a screening test in Hungarian memory clinics as well as in primary care settings.