Stefanie Klug

Awareness of memory deficits in subjective cognitive decline, mild cognitive impairment, Alzheimer's disease and Parkinson's disease

BACKGROUND Impaired awareness of memory deficits has been recognized as a common phenomenon in Alzheimers disease (AD) and research is now increasingly focusing on awareness in groups at risk for future dementia. This study aimed to determine whether levels of awareness differ among healthy elderly people and patients with subjective cognitive decline (SCD), amnestic and non-amnestic subtypes of mild cognitive impairment (aMCI, naMCI), Alzheimers disease (AD) and Parkinsons disease (PD), to explore correlates of awareness and to establish frequencies of memory over- and underestimation within each diagnostic group. METHODS 756 consecutive outpatients of a memory clinic and 211 healthy controls underwent thorough neuropsychological testing. Impairment of awareness was measured as the difference between subjective memory appraisals (16-item questionnaire on current memory-related problems in everyday life) and objective memory performance (15-item delayed recall task). Subgroups of over- and underestimators were classified using percentile ranks of controls. RESULTS At group level, awareness significantly decreased along the naMCI→aMCI→AD continuum, with naMCI patients showing a tendency towards overestimation of memory dysfunction. PD patients showed accurate self-appraisals as long as memory function was largely unaffected. However, there was a considerable between-group overlap in awareness scores. Furthermore, different correlates of awareness were observed depending on the diagnostic group. In general, unawareness seems to be associated with decreased cognitive performance in various domains (especially memory), higher age and lower levels of depression and self-reported functional impairment. CONCLUSION Impaired awareness is an important symptom in aMCI. Yet, given the considerable variability in awareness scores, longitudinal studies are required to evaluate their predictive power.

Health-Related Quality of Life in Patients with Subjective Cognitive Decline and Mild Cognitive Impairment and its Relation to Activities of Daily Living.

BACKGROUND Health related quality of life (HRQOL) is an important issue in the context of dementia care. OBJECTIVES The purpose of this study was to investigate HRQOL in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI) and its relation to Activity of Daily Living (ADL). METHODS In this cross sectional study, four experimental groups (each n = 98), controls, SCD, naMCI and aMCI, were compared. For data collection, neuropsychological methods (NTBV) and psychological questionnaires (SF-36 and B-ADL) were used. Multivariate analysis of variance was calculated to detect differences in HRQOL between groups. Correlations between HRQOL and ADL were explored. RESULTS The dimensions of HRQOL showed mainly consistent differences between the control and the SCD group and MCI subgroups. In almost every dimension of HRQOL, the control group scored higher than subjects with SCD, naMCI, or aMCI. The controls showed low to moderate negative correlations between HQROL and B-ADL in some dimensions of the HRQOL. In the SCD group, low negative correlations with ADL were observed in some HRQOL scales. Low to moderate correlations were found between each scale of the SF-36 and the B-ADL in both MCI subtypes. We found gender differences in HRQOL. CONCLUSION In conclusion, we could demonstrate that patients with SCD report reduced quality of life. This knowledge is important to get a better understanding of the individuals with SCD and may pave the way for the development of early intervention.

Subjective memory complaints, depressive symptoms and cognition in Parkinson's disease patients

The goal of this study was to establish the prevalence of subjective memory complaints (SMCs) and depressive symptoms (DS)s and their relation to cognitive functioning in patients with Parkinsons disease (PD).

Activities of Daily Living and Depressive Symptoms in Patients with Subjective Cognitive Decline, Mild Cognitive Impairment, and Alzheimer's Disease.

BACKGROUND Subjective cognitive decline (SCD) may be an early indicator for an increased risk of dementia. The exact definition of SCD remains unclear and has recently become a major research interest. OBJECTIVES To determine impairments in activities of daily living (ADL) and depressive symptoms in elderly individuals with SCD, mild cognitive impairment (MCI), and Alzheimers disease (AD). METHODS We included 752 consecutive patients suffering from SCD, non-amnestic (naMCI) or amnestic MCI (aMCI), AD, and 343 healthy controls into this prospective cohort study. A neuropsychological test battery, B-ADL and BDI-II was performed. RESULTS SCD patients showed a decreased performance in ADL compared to controls. Performance in ADL declined concurrently with cognitive abilities along the controls-SCD-naMCI-aMCI-AD continuum. Individuals with cognitive complains, no matter if SCD, MCI, or AD patients, reported more often depressive symptoms compared to healthy controls without complaints. Within all five cognitive subgroups, patients with depressive symptoms reported more difficulties in ADL in comparison to patients without depressive symptoms. Adjusting for depressive symptoms, there was no significant group difference between the control versus the SCD group (OR 1.1, CI 0.6-1.7). CONCLUSIONS SCD is a heterogeneous clinical condition. Specific features such as slightly impaired ADL and depressive symptoms are associated with SCD. Clinical markers may serve as an indicator for preclinical AD and in combination with biomarkers guide to an early diagnosis of a progressive neurodegenerative disease.

Depressive Symptoms are the Main Predictor for Subjective Sleep Quality in Patients with Mild Cognitive Impairment--A Controlled Study.

Objective Controlled data on predictors of subjective sleep quality in patients with memory complaints are sparse. To improve the amount of comprehensive data on this topic, we assessed factors associated with subjective sleep quality in patients from our memory clinic and healthy individuals. Methods Between February 2012 and August 2014 patients with mild cognitive impairment (MCI) and subjective cognitive decline (SCD) from our memory clinic and healthy controls were recruited. Apart from a detailed neuropsychological assessment, the subjective sleep quality, daytime sleepiness and depressive symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS) and the Beck Depression Inventory (BDI-II). Results One hundred fifty eight consecutive patients (132 (84%) MCI patients and 26 (16%) SCD patients) and 75 healthy controls were included in the study. Pairwise comparison of PSQI scores showed that non-amnestic MCI (naMCI) patients (5.4±3.5) had significantly higher PSQI scores than controls (4.3±2.8, p = .003) Pairwise comparison of PSQI subscores showed that naMCI patients (1.1±0.4) had significantly more “sleep disturbances” than controls (0.9±0.5, p=.003). Amnestic MCI (aMCI) (0.8±1.2, p = .006) and naMCI patients (0.7±1.2, p = .002) used “sleep medication” significantly more often than controls (0.1±0.6) Both, aMCI (11.5±8.6, p<.001) and naMCI (11.5±8.6, p<.001) patients showed significantly higher BDI-II scores than healthy controls (6.1±5.3). Linear regression analysis showed that the subjective sleep quality was predicted by depressive symptoms in aMCI (p<.0001) and naMCI (p<.0001) patients as well as controls (p<.0001). This means, that more depressive symptoms worsened subjective sleep quality. In aMCI patients we also found a significant interaction between depressive symptoms and global cognitive function (p = .002) Discussion Depressive symptoms were the main predictor of subjective sleep quality in MCI patients and controls, but not in SCD patients. Better global cognitive function ameliorated the negative effect of depressive symptoms on the subjective sleep quality in aMCI patients.

Facial emotion recognition in patients with subjective cognitive decline and mild cognitive impairment

BACKGROUND Deficits in facial emotion recognition (FER) have been shown to substantially impair several aspects in everyday life of affected individuals (e.g. social functioning). Presently, we aim at assessing differences in emotion recognition performance in three patient groups suffering from mild forms of cognitive impairment compared to healthy controls. METHODS Performance on a concise emotion recognition test battery (VERT-K) of 68 patients with subjective cognitive decline (SCD), 44 non-amnestic (non-aMCI), and 25 amnestic patients (aMCI) with mild cognitive impairment (MCI) was compared with an age-equivalent sample of 138 healthy controls all of which were recruited within the framework of the Vienna Conversion to Dementia Study. Additionally, patients and controls underwent individual assessment using a comprehensive neuropsychological test battery examining attention, executive functioning, language, and memory (NTBV), the Beck Depression Inventory (BDI), and a measure of premorbid IQ (WST). RESULTS Type of diagnosis showed a significant effect on emotion recognition performance, indicating progressively deteriorating results as severity of diagnosis increased. Between-groups effect sizes were substantial, showing non-trivial effects in all comparisons (Cohens ds from -0.30 to -0.83) except for SCD versus controls. Moreover, emotion recognition performance was higher in women and positively associated with premorbid IQ. CONCLUSIONS Our findings indicate substantial effects of progressive neurological damage on emotion recognition in patients. Importantly, emotion recognition deficits were observable in non-amnestic patients as well, thus conceivably suggesting associations between decreased recognition performance and global cognitive decline. Premorbid IQ appears to act as protective factor yielding lesser deficits in patients showing higher IQs.

Serotonin1A-receptor-dependent signaling proteins in mouse hippocampus

The serotonin(1A) receptor (5-HT(1A) R) knock-out mouse (KO) is a widely used animal model for anxiety and cognitive function and regulation of signaling cascades by this receptor has been reported. We aimed to determine individual representatives of signaling cascades in order to screen 5-HT(1A) R-dependent signaling proteins (SPs). Hippocampal proteins from wild type and 5-HT(1A) R KO mice were extracted, run on two-dimensional gel electrophoresis, proteins were identified by MALDI and nano-ESI-LC-MS/MS and SPs were quantified by specific software. Nucleoside diphosphate kinase A (NDK A, synonym: nm23), Dual specificity mitogen-activated protein kinase kinase 1 (MAPKK1, synonym: MEK), Serine/threonine-protein phosphatase PP1-gamma catalytic subunit (PP-1G), Septin-5, were reduced in the KO mice. Novel phosphorylation sites at T386 on MAPKK1 and at S225 and Y265 on Septin-5 were observed. MAPKK1 and PP-1G are known 5-HT(1A) R-dependent signaling compounds and are in agreement with receptor knock-out and septin-5 is involved in serotonin transport, although regulation by 5-HT(1A) R has not been reported. 5-HT(1A) R - dependent levels for NDK A have not been demonstrated so far and we herewith propose a role for NDK A in 5-HT(1A) R signaling. Reduced SP levels along with findings of two novel phosphorylation sites may be relevant for interpretation of previous and the design of future studies on this receptor system.

Visuo-constructional functions in patients with mild cognitive impairment, Alzheimer’s disease, and Parkinson’s disease

SummaryBackgroundSeveral recently proposed criteria for assessing cognitive disorder require measuring the cognitive domain of visuo-constructional function. The aims of the present study were to develop a new test (Vienna Visuo-constructional Test—VVT) measuring visuo-constructional functions and to determine the reliability and validity of the VVT in patients with mild cognitive impairment (MCI), Parkinson’s disease (PD), and Alzheimer’s disease (AD). We further examined age and sex effects and the psychometric quality of the VVT.MethodsThe study included 76 healthy controls and 103 patients who were referred to the Department of Neurology, Medical University of Vienna for neurocognitive assessment. An administering and scoring system for the VVT was developed.ResultsInternal consistency (Cronbach’s alpha) was found to range from 0.82 for the healthy control group to 0.93 for the total patient group. There was no sex effect, but age had a negative effect on VVT performance. The VVT successfully differentiated healthy controls from MCI patients, AD patients, and PD patients, respectively.ConclusionThe VVT shows satisfactory validity and reliability and can be administered easily in clinical practice. It constitutes a new measure that can successfully be used to identify visuo-constructional problems in patients with cognitive dysfunction.ZusammenfassungHintergrundMehrere kürzlich vorgeschlagenen Klassifikationsschemeta zur Beurteilung kognitiver Störung fordern die Erfassung der kognitiven Domäne „visuo-konstruktive Funktionen“. Das Ziel der vorliegenden Studie war die Entwicklung eines neuen Tests (Vienna Visuo-Constructional Test—VVT) zur Messung visuo-konstruktiver Funktionen. Mithilfe der VVT wurden bei Patienten mit leichter kognitiver Beeinträchtigung (MCI), Parkinson-Krankheit (PD) und Alzheimer (AD) die visuo-konstruktiven Fähigkeiten untersucht. Des Weiteren wurden Alters- und Geschlechtseffekte und die psychometrische Qualität des VVT bestimmt.MethodenDie Studie umfasste 76 gesunde Kontrollpersonen und 103 Patienten, die sich an der Universitätsklinik für Neurologie, Medizinische Universität Wien einer neurologischen Untersuchung unterzogen. Ein neuartiges Auswertungssystem für die VVT wurde entwickelt.ErgebnisseDie interne Konsistenz (Cronbach Alpha) lag im Bereich von 0,82 für die gesunde Kontrollgruppe und 0,93 für die gesamte Patientengruppe. Es zeigte sich kein Geschlechtereffekt, aber das Alter hatte einen negativen Effekt auf die VVT Leistung. Der VVT konnte erfolgreich zwischen gesunden Kontrollen und MCI-Patienten, Patienten mit AD und PD-Patienten differenzieren.SchlussfolgerungDer VVT zeigte eine zufriedenstellende Gültigkeit und Zuverlässigkeit und kann problemlos in der klinischen Praxis angewendet werden. Es stellt somit ein neues Verfahren dar, um visuell-konstruktive Probleme bei Patienten mit kognitiven Störungen zu identifizieren.