Psychometric Evaluation of the A-NKS: A Diagnostic Instrument to Assess Impairment of Activities of Daily Living in Mild and Major Neurocognitive Disorder According to DSM-5.

BACKGROUND: Activities of daily living (ADL) functioning are important in the diagnosis of neurocognitive disorders (NCD), yet no standardized and validated instrument exist based on international classification systems. OBJECTIVE: We aimed to psychometrically evaluate the differentiated assessment of ADL and instrumental ADL (IADL) impairments due to NCD according to DSM-5 criteria (Instrument für die Erfassung von Alltagsbeeinträchtigungen bei Neurokognitiven Störungen; A-NKS). METHODS: We conducted a pilot study involving 92 participant-informant dyads of participants with mild or major NCDs, cognitively healthy individuals, and an informant, to test acceptability, internal consistency, and convergent validity with similar measures. RESULTS: Both A-NKS versions demonstrated excellent internal consistency (α= 0.95 -0.99) and correlate with other instrumental ADL instruments (participant [informant]: Barthel Index: rs = -0.26, p≤0.05 [rs = -0.30, p≤0.01]; Amsterdam IADL: rs = 0.59, p≤0.01 [rs = 0.48, p≤0.01]; SIDAM ADL: rs = 0.46, p≤0.001 [rs = 0.47, p≤0.001]). Additionally, there are correlations with the scale autonomy of the WHOQOL-OLD (rs = -0.50, p≤0.001 [rs = -0.37, p≤0.001]) and physical, as well as cognitive activities (rs = -0.39, p≤0.001 [rs = -0.50, p≤0.001]). They were well-accepted by participants and informants. CONCLUSIONS: The A-NKS is an instrument with acceptable psychometric properties to assess ADL due to neurodegenerative decline in healthy individuals, and those with mild or major NCD. Further research is needed to confirm reliability and validity and investigate the factor structure.

Differential Diagnosis Between Alzheimer's Disease-Related Depression and Pseudo-Dementia in Depression: A New Indication for Amyloid-ß Imaging?

BACKGROUND: Alzheimer's disease and depression can start with combined cognitive and depressive symptoms [1, 2]. Accurate differential diagnosis is desired to initiate specific treatment. OBJECTIVE: We investigated whether amyloid-ß PET imaging can discriminate both entities. METHODS: This retrospective observational study included 39 patients (20 female, age = 70±11years) with both cognitive and depressive symptoms who underwent amyloid-ß PET imaging and in whom clinical follow-up data was available. Amyloid-ß PET was carried out applying [18F]Florbetaben or [11C]PiB. The PET images were analyzed by standardized visual and relative-quantitative evaluation. Based on clinical follow-up (median of 2.4 years [range 0.3 to 7.0 years, IQR = 3.7 years] after amyloid PET imaging which was not considered in obtaining a definite diagnosis), discrimination ability between AD-related depression and pseudo-dementia in depression/depression with other comorbidities was determined. RESULTS: Visually, all 10 patients with pseudo-dementia in depression and all 15 patients with other depression were rated as amyloid-ß-negative; 2 of 14 patients with AD-related depression were rated amyloid-ß-negative. ROC curve analysis of the unified composite standardized uptake value ratios (cSUVRs) was able to discriminate pseudo-dementia in depression from AD-related depression with high accuracy (AUC = 0.92). Optimal [18F]Florbetaben discrimination cSUVR threshold was 1.34. In congruence with the visual PET analysis, the resulting sensitivity of the relative-quantitative analysis was 86% with a specificity of 100%. CONCLUSION: Amyloid-ß PET can differentiate AD-related depression and pseudo-dementia in depression. Prospective clinical studies are warranted to confirm this result and to potentially broaden the spectrum of clinical applications for amyloid-ß PET imaging.

Psychometric Evaluation of the German Version of the Social Functioning in Dementia Scale (SF-DEM).

BACKGROUND: Dementia is one of the most common and most severe disorder in old age. In addition to cognitive decline and functional impairment, changes in social functioning occur in the course of dementia. Currently, there is no valid instrument in German language to assess social functioning in individuals with dementia. OBJECTIVE: We aim to adapt and psychometrically evaluate a German version of the Social Functioning in Dementia Scale (SF-DEM). METHODS: First, a multi-step and team-based translation process based on the TRAPD model was performed. Second, we interviewed dyads of individuals with mild dementia and caregivers to test the internal consistency, test-retest reliability, interrater reliability, construct validity, and acceptance of the German version of the SF-DEM. RESULTS: The internal consistency of the patient-rated (α= 0.72) and the caregiver-rated (α= 0.76) SF-DEM is at an acceptable level. The interrater reliability was excellent for both versions (patients: ICC = 0.98, CI [0.95-0.99]; caregiver: ICC = 0.95, CI [0.89-0.98]) and the test-retest reliability was moderate (patients: ICC = 0.57, CI [0.26-0.77]; caregiver: ICC = 0.58, CI [0.27-0.78]). Caregiver-rated SF-DEM correlated strong with LSNS-6 (rs = 0.60, p < 0.01), QoL-AD (marriage: rs = 0.61, p < 0.01; friends: rs = 0.51, p = 0.01). In addition, the SF-DEM was accepted by the participants. CONCLUSION: The German SF-DEM is a valid, reliable, and acceptable instrument to assess social functioning in individuals with dementia. Further research should address the psychometric properties in individuals with more severe dementia.

Instruments to Assess Social Functioning in Individuals with Dementia: A Systematic Review.

BACKGROUND: Social functioning is an important parameter for the early detection and diagnosis of dementia, as well as the description of its course and the assessment of intervention effects. Therefore, valid and reliable instruments to measure social functioning in individuals with dementia are needed. OBJECTIVE: We aimed to provide an overview of such instruments including information on feasibility and psychometric properties. METHODS: The review is informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Relevant literature was identified using a pre-specified search string in the databases MEDLINE, PsycINFO, and Web of Science. Information on the characteristics, feasibility, and psychometric properties of the identified instruments were extracted, summarized, and discussed. RESULTS: Out of 5,307 articles, 8 were selected to be included in the study, describing a total of three instruments for measuring social functioning in individuals with dementia: the Nurses' Observation Scale for Geriatric Patients (NOSGER; dimension "social behavior"), the Socioemotional Dysfunction Scale (SDS), and the Social Functioning in Dementia Scale (SF-DEM). The validity of all the three instruments was overall acceptable. Reliability was high for the NOSGER scale "social behavior" and the SF-DEM. Information on the usability of the instruments tended to be scarce. CONCLUSION: There are a few valid and reliable instruments to assess social functioning in individuals with dementia. Further considerations could comprise their feasibility with regard to measuring changes in social functioning over time, in additional target groups, e.g., different types and stages of dementia, and adaptions to different languages and cultural backgrounds.

A multi-centre, randomised, double-blind, placebo-controlled clinical trial of methylphenidate in the initial treatment of acute mania (MEMAP study).

Based on many clinical and preclinical findings the 'vigilance regulation model of mania' postulates that an unstable regulation of wakefulness is a pathogenetic factor in both mania and Attention Deficit Hyperactivity Disorder (ADHD) and induces hyperactivity and sensation seeking as an autoregulatory attempt to stabilize wakefulness. Accordingly, stimulant medications with their vigilance stabilizing properties could have rapid antimanic effects similar to their beneficial effects in ADHD. The MEMAP study - a multi-center, double-blind, placebo-controlled and randomized clinical trial (RCT) - assessed the antimanic efficacy and safety of a 2.5-day treatment with methylphenidate (20-40mg/day). Of 157 screened patients with acute mania, 42 were randomly assigned to receive 20-40mg per day of methylphenidate in one or two applications, or placebo. The primary outcome was the change in Young Mania Rating Scale (YMRS) sum scores from baseline to day 2.5 in the methylphenidate group compared to the placebo group. A group sequential design was chosen to justify early RCT termination based on efficacy or futility at an interim analysis after inclusion of 40 patients. In the interim analysis, the change from baseline in the YMRS total score at day 2.5 was not significantly different between both groups (F(1,37)=0.23; p=0.64). Thus, futility was declared for methylphenidate and the RCT was stopped. In summary, although methylphenidate was well tolerated and safe in the full analysis set, it failed to show efficacy in the treatment of acute mania. TRIAL REGISTRATION: clinicaltrials.gov (URL: http://www.clinicaltrials.gov; registration number: NCT01541605).

Methylphenidate in mania project (MEMAP): study protocol of an international randomised double-blind placebo-controlled study on the initial treatment of acute mania with methylphenidate.

BACKGROUND: Treatment of patients with acute mania remains a considerable medical challenge since onset of action of antimanic medication is delayed for several days. Psychostimulants could have an earlier onset of action. This assumption is based on the 'vigilance regulation model of mania' which postulates that vigilance is unstable in manic patients. Accordingly, vigilance-stabilising psychostimulants could be more useful than conventional treatment in acute mania. We present here the study protocol of a trial intended to study the efficacy and safety of methylphenidate in the initial treatment of acute mania. METHODS/DESIGN: A multi-centre, randomised, double-blind, placebo-controlled clinical trial will be conducted in 88 bipolar inpatients with acute mania. Male and female patients older than 18 years will be randomised to treatment with either methylphenidate (20 to 40 mg/day) or placebo for 2.5 days, given once or twice daily. The main outcome measure is the reduction in the Young Mania Rating Scale (YMRS) after 2.5 days of treatment. Other outcome measures include the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) the Clinical Global Impression-Bipolar Scale (CGI-BP), the Screen for Cognitive Impairment in Psychiatry (SCIP), actigraphy and the EEG-'Vigilance Algorithm Leipzig' (VIGALL). DISCUSSION: A positive study outcome of the proposed study could substantially impact our understanding of the etiopathogenesis of mania and open new treatment perspectives.