The cognitive and behavioral correlates of functional status in patients with frontotemporal dementia: A pilot study

Objective: Frontotemporal dementia (FTD) impinges significantly on cognition, behavior, and everyday functioning. Goal of the present study is the detailed description of behavioral disturbances and functional limitations, as well as the investigation of associations between cognition, behavior, and functional impairment among FTD patients. Given the importance of maintaining a satisfying functional status as long as possible, this study also aims to identify the cognitive correlates of compensatory strategy use in this clinical group.Methods: A total of 13 patients diagnosed with FTD (behavioral variant FTD = 9, non-fluent variant primary progressive aphasia = 3, semantic dementia = 1) were administrated a broad range of neuropsychological tests for the assessment of different cognitive abilities. Behavioral symptomatology and performance on everyday activities were rated with informant-based measures. Descriptive statistics were used for the delineation of behavioral and functional patterns, whereas stepwise multiple regression analyses were performed to identify associations between cognition, behavior, and functional status.Results: Negative symptoms, especially apathy, were found to predominate in the behavior of FTD patients. Instrumental tasks, such as housework and leisure activities, appeared to be the most impaired functional domains. Working memory was the strongest cognitive correlate of performance across various domains of everyday functioning, whereas working memory along with short-term verbal memory accounted for a great proportion of variance in compensatory strategy use. Behavioral disturbances and especially negative symptoms were also found to contribute significantly to functional impairment in FTD.Conclusions: Executive dysfunction, as well as behavioral disturbances contribute significantly to functional disability in FTD. Early interventions tailored at these domains may have the potential to improve functional outcomes and delay the rate of functional decline among FTD patients

Prevalence and determinants of sex-specific dietary supplement use in a greek cohort

We describe the profile of dietary supplement use and its correlates in the Epirus Health Study cohort, which consists of 1237 adults (60.5% women) residing in urban north-west Greece. The association between dietary supplement use and demographic characteristics, lifestyle behaviors, personal medical history and clinical measurements was assessed using logistic regression models, separately for women and men. The overall prevalence of dietary supplement use was 31.4%, and it was higher in women (37.3%) compared to men (22.4%; p-value = 4.2−08). Based on multivariable logistic regression models, dietary supplement use in women was associated with age (positively until middle-age and slightly negatively afterwards), the presence of a chronic health condition (OR = 1.71; 95% CI, 1.18–2.46), lost/removed teeth (OR = 0.52; 95% CI, 0.35–0.78) and diastolic blood pressure (OR per 5 mmHg increase =0.84; 95% CI, 0.73–0.96); body mass index and worse general health status were borderline inversely associated. In men, dietary supplement use was positively associated with being employed (OR = 2.53; 95% CI, 1.21–5.29). A considerable proportion of our sample used dietary supplements, and the associated factors differed between women and men

Evaluation of Excess Significance Bias in Animal Studies of Neurological Diseases

Animal studies generate valuable hypotheses that lead to the conduct of preventive or therapeutic clinical trials. We assessed whether there is evidence for excess statistical significance in results of animal studies on neurological disorders, suggesting biases. We used data from meta-analyses of interventions deposited in Collaborative Approach to Meta-Analysis and Review of Animal Data in Experimental Studies (CAMARADES). The number of observed studies with statistically significant results (O) was compared with the expected number (E), based on the statistical power of each study under different assumptions for the plausible effect size. We assessed 4,445 datasets synthesized in 160 meta-analyses on Alzheimer disease (n = 2), experimental autoimmune encephalomyelitis (n = 34), focal ischemia (n = 16), intracerebral hemorrhage (n = 61), Parkinson disease (n = 45), and spinal cord injury (n = 2). 112 meta-analyses (70%) found nominally (p≤0.05) statistically significant summary fixed effects. Assuming the effect size in the most precise study to be a plausible effect, 919 out of 4,445 nominally significant results were expected versus 1,719 observed (p<10-9). Excess significance was present across all neurological disorders, in all subgroups defined by methodological characteristics, and also according to alternative plausible effects. Asymmetry tests also showed evidence of small-study effects in 74 (46%) meta-analyses. Significantly effective interventions with more than 500 animals, and no hints of bias were seen in eight (5%) meta-analyses. Overall, there are too many animal studies with statistically significant results in the literature of neurological disorders. This observation suggests strong biases, with selective analysis and outcome reporting biases being plausible explanations, and provides novel evidence on how these biases might influence the whole research domain of neurological animal literature. © 2013 Tsilidis et al

Cognitive decline and behavioral disturbances in patients with frontotemporal dementia

Social cognition (SC) and executive functions were explored in patients with frontal variant frontotemporal dementia (fv-FTD) in order to understand why behavioural disturbances occur in this disease. An additional purpose was the study of the structure of SC and the role of social cognition in producing effective social behavior. Twenty one patients with fv-FTD and 18 age- and education-matched healthy controls were administered neuropsychological tasks assessing aspects of SC (emotion perception and theory of mind) and executive functions. Behavioural disturbances (both positive and negative symptoms) were assessed using the Frontal Behavioural Inventory (FBI). Fv-FTD patients performed more poorly than their respective control group on theory of mind tasks. Moreover, they had difficulty perceiving the emotion of surprise and the neutral emotional state. Executive dysfunction was also evident particularly on measures of cognitive flexibility and inhibition. Deficits in SC correlated significantly with behavioural disturbances, especially with positive symptoms, but not with “negative behaviours” such as apathy and indifference. Executive dysfunctions played a very crucial role in the clinical picture of fv-FTD. They correlated significantly with both negative and positive behavioural disturbances and contributed significantly to the poor performance of the patients on the theory of mind tasks. Finally, concerning the structure of SC our results are suggestive of a very strong interaction between its subcomponents, namely emotion perception and theory of mind. Moreover, they indicate a very strong correlation between the cognitive subcomponent of SC (theory of mind) and executive functions. Our results highlight the role that specific aspects of SC and executive functions play in the manifestation of FTD symptoms and help to clarify the way in which behavioural disturbances present early in the course of the disorder.Στην παρούσα διατριβή μελετήθηκε η κοινωνική νόηση (ΚΝ) και οι εκτελεστικές λειτουργίες στη μετωπιαία μορφή της μετωποκροταφικής άνοιας (MA), προκειμένου να διερευνηθεί η συνεισφορά πιθανών ελλειμμάτων των συγκεκριμένων γνωστικών λειτουργιών στην εκδήλωση συμπεριφορικών διαταραχών στη νόσο. Ένα δεύτερο στόχο αποτέλεσε η διασαφήνιση της δομής της ΚΝ και του ρόλου της στην εκδήλωση αποτελεσματικής κοινωνικής συμπεριφοράς. Το δείγμα αποτέλεσαν 21 ασθενείς με ΜΑ και 18 υγιείς ενήλικες εξισωμένοι με τους ασθενείς ως προς την ηλικία και το μορφωτικό επίπεδο. Χορηγήθηκαν νευροψυχολογικές δοκιμασίες που εξετάζουν παράγοντες της ΚΝ (αντίληψη συναισθημάτων και Θεωρία του Νου) και εκτελεστικές λειτουργίες. Οι συμπεριφορικές διαταραχές (θετικά και αρνητικά συμπτώματα) εξετάστηκαν με την Κλίμακα Αξιολόγησης Μετωπιαίων Συμπεριφορών (ΚΑΜΣ). Οι ασθενείς με ΜΑ παρουσίασαν εξασθένηση στην αντίληψη της Θεωρίας του Νου, στην αντίληψη του συναισθήματος της έκπληξης αλλά και της ουδέτερης συναισθηματικής κατάστασης. Εκτελεστικές δυσλειτουργίες ήταν εμφανείς κυρίως σε δοκιμασίες γνωστικής ευελιξίας και ικανότητας εφαρμογής ανασταλτικών μηχανισμών. Τα ελλείμματα στην ΚΝ συσχετίστηκαν σημαντικά με τις συμπεριφορικές διαταραχές, κυρίως με τα θετικά συμπτώματα, αλλά όχι με τις «αρνητικές συμπεριφορές», όπως η αδιαφορία και η απάθεια. Οι εκτελεστικές δυσλειτουργίες συνέβαλλαν σημαντικά στην κλινική εικόνα της ΜΑ. Συσχετίστηκαν σημαντικά και με τις αρνητικές και με τις θετικές συμπεριφορικές διαταραχές και συνέβαλλαν στην εξασθένηση στην ικανότητα αντίληψης Θεωρίας του Νου. Τέλος, τα δεδομένα της παρούσας έρευνας παρέχουν ενδείξεις για πολύ ισχυρή σχέση μεταξύ των δύο υποπαραγόντων της ΚΝ, δηλαδή της αντίληψης των συναισθημάτων και της Θεωρίας του Νου. Επιπλέον, υποστηρίζουν μια πολύ ισχυρή σχέση μεταξύ του γνωστικού υποπαράγοντα της ΚΝ, δηλαδή της Θεωρίας του Νου, με τις εκτελεστικές λειτουργίες. Τα πορίσματα της παρούσας διατριβής τονίζουν το ρόλο της ΚΝ και των εκτελεστικών λειτουργιών στην εκδήλωση των συμπτωμάτων της ΜΑ και συμβάλλουν στη διασαφήνιση της κλινικής εικόνας με τις χαρακτηριστικές συμπεριφορικές διαταραχές στα πρώιμα στάδια της νόσου

Computerized cognitive rehabilitation for treatment of cognitive impairment in multiple sclerosis: an explorative study.

In this explorative study, forty-seven patients with relapsing-remitting multiple sclerosis were randomized to a custom 6-week cognitive rehabilitation intervention (n = 23) using the BrainHQTM web-based platform and to a control group condition (n = 24). Cognitive rehabilitation intervention consisted of two 40-minute sessions per week. All patients were tested with the Brief International Cognitive Assessment for Multiple Sclerosis battery, the Stroop Color-Word Test, and the trail making test, while the Beck Depression Inventory - Fast Screen questionnaire was used as a measure of mood and the cognitive reserve index as a measure of cognitive reserve. We used the reliable change index, to calculate clinically meaningful changes of performance, and to discriminate between responders and non-responders of this intervention. Statistically significant improvement of the group receiving treatment was observed mainly on measures of verbal and non-verbal episodic memory and, to a lesser extent, on reading speed, selective attention/response inhibition, and visual attention. Verbal memory and visual attention improvements remained significant after considering the corrected for multiple comparisons level of significance. According to reliable change index scores, 12/23 (52.2%) of patients in the intervention group presented meaningful improvement in at least one measure (Greek Verbal Learning Test: 26%, Brief Visuospatial Memory Test-Revised: 17.4%, Stroop-Words test: 13%). This explorative study provides evidence that, at least in the short term, cognitive rehabilitation may improve the cognitive performance of multiple sclerosis patients

Correlates of Functional Impairment in Patients with the Behavioral Variant of Frontotemporal Dementia: A PRISMA-Compliant Systematic Review

The behavioral variant of frontotemporal dementia (bvFTD) has a devastating effect on multiple domains of daily living. The purpose of this PRISMA-compliant systematic review is to summarize the most important factors associated with functional impairment in this clinical group by critically analyzing the existing literature spanning the period from 2000 to 2023. To be included in the review, a study had to investigate any kind of correlates of functional status in bvFTD patients, using a previously validated instrument of functional assessment. Out of 40 articles assessed for eligibility, 18 met the inclusion criteria. The anatomical pattern of cerebral atrophy at baseline appeared to be the strongest predictor of the rate of functional decline over time, with the frontal-dominant anatomical subtype being associated with a faster rate of functional impairment. Additionally, executive dysfunction as well as apathy appeared to contribute significantly to functional disability in bvFTD patients. A comparative examination of bvFTD in relation to other clinical subtypes of FTD and other types of dementia in general suggests that it is the predominant atrophy of the frontal lobes along with the subsequent unique combination of cognitive and neuropsychiatric manifestations that account for the pronounced functional limitations observed in these individuals, even from the early stages of the disease

Studying Social Cognition in Patients with Schizophrenia and Patients with Frontotemporal Dementia: Theory of Mind and the Perception of Sarcasm

We investigated social cognition and theory of mind in patients with schizophrenia and in patients with frontotemporal dementia in order to elucidate the cognitive mechanisms involved in the breakdown of these skills in psychiatric and neurological patients. Our tasks included videotaped scenarios of social interactions depicting sincere, sarcastic and paradoxical remarks, as well as lies. We found impaired performance of the schizophrenia group on all theory of mind conditions despite their intact understanding of sincere statements. In contrast, the FTD group performed poorly only when they had to rely on paralinguistic cues indicating sarcasm or lies, and not on paradoxical remarks or sarcasm when given additional verbal cues. Our findings suggest that, while current deficits in social and interpersonal functioning in patients with FTD may reflect a decrement in previously acquired skills, similar deficits in patients with schizophrenia may reflect an altogether inadequately learned process