Touchscreen-based finger tapping: Repeatability and configuration effects on tapping performance

Parkinson’s disease (PD) is a progressive neurodegenerative disease that affects almost 2% of the population above the age of 65. To better quantify the effects of new medications, fast and objective methods are needed. Touchscreen-based tapping tasks are simple yet effective tools for quantifying drug effects on PD-related motor symptoms, especially bradykinesia. However, there is no consensus on the optimal task set-up. The present study compares four tapping tasks in 14 healthy participants. In alternate finger tapping (AFT), tapping occurred with the index and middle finger with 2.5 cm between targets, whereas in alternate side tapping (AST) the index finger with 20 cm between targets was used. Both configurations were tested with or without the presence of a visual cue. Moreover, for each tapping task, within- and between-day repeatability and (potential) sensitivity of the calculated parameters were assessed. Visual cueing reduced tapping speed and rhythm, and improved accuracy. This effect was most pronounced for AST. On average, AST had a lower tapping speed with impaired accuracy and improved rhythm compared to AFT. Of all parameters, the total number of taps and mean spatial error had the highest repeatability and sensitivity. The findings suggest against the use of visual cueing because it is crucial that parameters can vary freely to accurately capture medication effects. The choice for AFT or AST depends on the research question, as these tasks assess different aspects of movement. These results encourage further validation of non-cued AFT and AST in PD patients.

Role of real-world evidence studies in cardiology

The introduction of evidence-based medicine into practical healthcare provides physicians with the opportunity to use treatment approaches, which have been proven to be effective in randomized controlled trials. In this case, it is necessary to consider using the medication in a particular patient in accordance with the design of clinical trials and strictly follow the instructions. Drugs should be critically selected with focus on quality of available efficacy and safety data obtained in the population closest to a patient. In addition, clinicians should regularly review the available data with particular regard to its quality. The advantages, disadvantages, limitations and methodological problems of observational studies should be carefully considered during the interpretation of results. At the same time, the compliance of the results of real-world evidence studies with registration trial data indicates a high reproducibility of medication effects.

Arm swing responsiveness to dopaminergic medication in Parkinson’s disease depends on task complexity

The evidence of the responsiveness of dopaminergic medication on gait in patients with Parkinson’s disease is contradicting. This could be due to differences in complexity of the context gait was in performed. This study analysed the effect of dopaminergic medication on arm swing, an important movement during walking, in different contexts. Forty-five patients with Parkinson’s disease were measured when walking at preferred speed, fast speed, and dual-tasking conditions in both OFF and ON medication states. At preferred, and even more at fast speed, arm swing improved with medication. However, during dual-tasking, there were only small or even negative effects of medication on arm swing. Assuming that dual-task walking most closely reflects real-life situations, the results suggest that the effect of dopaminergic medication on mobility-relevant movements, such as arm swing, might be small in everyday conditions. This should motivate further studies to look at medication effects on mobility in Parkinson’s disease, as it could have highly relevant implications for Parkinson’s disease treatment and counselling.

A-2 Mean Arterial Pressure Effects on Hippocampal Volume by Alzheimer’s Disease Risk

Objective Extant literature demonstrates increased risk of Alzheimer’s Disease (ad) and hippocampal degeneration with hypertension. Less is known about blood pressure (BP) and APOE4 effects, and their interaction on hippocampal volume. We hypothesized that the effects of elevated mean arterial pressure (MAP) on hippocampal volume would be stronger among those with at least one APOE4 allele. We further hypothesized that MAP effects would be stronger in an ad group than either mild cognitive impairment (MCI) or control groups, and stronger in MCI than controls. Methods Participants (N = 965; 46.4% female; 92.9% White; 56.7% MCI, 18.3% ad) were selected from the ad Neuroimaging Initiative database. Inclusion criteria: complete demographics, diagnostic evaluation, APOE genotyping (46.6.% APOE4 positive), BP measurements (mean MAP = 94.55mmg3 (SD = 10.41)), and MRI. Hippocampal volume was quantified using FreeSurfer 5.3 (bilateral mean = 6844.51 mm3 (SD = 1191.68)). The sample age was 72.84 (SD = 7.55) with 16.02 (SD = 2.77) years of education on average. Results Although MAP and APOE4 each significantly accounted for variance in bilateral and each hippocampal volume using a hierarchical multiple quadratic regression, the interaction of MAP and APOE4 did not (see Table). Similarly, while MAP and diagnostic group were each found to significantly account for variance in hippocampal volumes, their interactions did not. Conclusions Results are consistent with previous findings that higher BP negatively impacts hippocampal volume. However, interaction hypotheses were not supported. Therefore, APOE4 and MAP may represent independent mechanisms in ad pathology. However, antihypertensive medication effects, which may mitigate hippocampal atrophy, were not assessed. Future investigations might control medication effects and investigate homogenous versus heterogeneous APOE variants.

Direct Measures of Medication Effects: Exploring the Scientific Utility of Behavior-Analytic Assessments

The purpose of the current study was to explore the scientific utility of two behavior analytic assessments (i.e., progressive ratio and demand assessments) for psychotropic medication evaluation. For a sample of 23 children with disabilities who were prescribed medication, we conducted a series of generalizability and optimization studies to identify sources of score variance and conditions in which stable estimates of behavior can be obtained. To inform construct validity, we calculated correlations between scores from each assessment and those from a standardized behavior rating scale (Aberrant Behavior Checklist-Second Edition; ABC-2). Results offer initial support for the scientific utility of progressive ratio scores. More research is needed to evaluate sensitivity to change and construct validity of scores from these and other behavior analytic assessments.

Increased Glutamate Plus Glutamine in the Right Middle Cingulate in Early Schizophrenia but Not in Bipolar Psychosis: A Whole Brain 1H-MRS Study

Proton magnetic resonance spectroscopy (1H-MRS) studies have examined glutamatergic abnormalities in schizophrenia and bipolar-I disorders, mostly in single voxels. Though the critical nodes remain unknown, schizophrenia and bipolar-I involve brain networks with broad abnormalities. To provide insight on the biochemical differences that may underlie these networks, the combined glutamine and glutamate signal (Glx) and other metabolites were examined in patients in early psychosis with whole brain 1H-MRS imaging (1H-MRSI). Data were acquired in young schizophrenia subjects (N = 48), bipolar-I subjects (N = 21) and healthy controls (N = 51). Group contrasts for Glx, as well as for N-acetyl aspartate, choline, myo-inositol and creatine, from all voxels that met spectral quality criteria were analyzed in standardized brain space, followed by cluster-corrected level alpha-value (CCLAV ≤ 0.05) analysis. Schizophrenia subjects had higher Glx in the right middle cingulate gyrus (19 voxels, CCLAV = 0.05) than bipolar-I subjects. Healthy controls had intermediate Glx values, though not significant. Schizophrenia subjects also had higher N-acetyl aspartate (three clusters, left occipital, left frontal, right frontal), choline (two clusters, left and right frontal) and myo-inositol (one cluster, left frontal) than bipolar-I, with healthy controls having intermediate values. These increases were likely accounted for by antipsychotic medication effects in the schizophrenia subgroup for N-acetyl aspartate and choline. Likewise, creatine was increased in two clusters in treated vs. antipsychotic-naïve schizophrenia, supporting a medication effect. Conversely, the increments in Glx in right cingulate were not driven by antipsychotic medication exposure. We conclude that increments in Glx in the cingulate may be critical to the pathophysiology of schizophrenia and are consistent with the NMDA hypo-function model. This model however may be more specific to schizophrenia than to psychosis in general. Postmortem and neuromodulation schizophrenia studies focusing on right cingulate, may provide critical mechanistic and therapeutic advancements, respectively.

Mapping modifiable determinants of medication adherence in bipolar disorder (BD) to the theoretical domains framework (TDF): a systematic review

Background Around 40% of people with bipolar disorder (BD) are non-adherent to medication leading to relapse, hospitalisation and increased suicide risk. Limited progress in addressing non-adherence may be partly attributable to insufficient understanding of the modifiable determinants of adherence that require targeting in interventions. We synthesised the modifiable determinants of adherence in BD and map them to the theoretical domains framework (TDF). Method We searched CINAHL, Cochrane Library, Embase, LILACS, Medline, PsychINFO and PubMed until February 2020. We included studies reporting modifiable determinants of adherence in BD. Two reviewers independently screened studies, assessed quality, extracted modifiable determinants and mapped them to TDF. Results We included 57 studies involving 32 894 participants. Determinants reported by patients spanned 11 of the 14 TDF domains compared to six domains represented by clinician/researcher. The TDF domains most commonly represented (% and example) in studies were: ‘Environmental context and resources’ (63%, e.g. experiencing side effects), ‘Beliefs about consequences’ (63%, e.g. beliefs about medication effects), ‘Knowledge’ (40%, e.g. knowledge about disorder), ‘Social influences’ (33%, e.g. support from family/clinicians), ‘Memory, attention and decision processes’ (33%, e.g. forgetfulness), ‘Emotion’ (21%, e.g. fear of addiction) and ‘Intentions’ (21%, e.g. wanting alternative treatment). ‘Intentions’, ‘Memory, attention and decision processes’ and ‘Emotion’ domains were only reported by patients but not clinicians. Conclusions Clinicians may be underappreciating the full range of modifiable determinants of adherence and thus not providing adherence support reflective of patients' needs. Reporting of modifiable determinants in behavioural terms facilitates developing theory-based interventions to address non-adherence in BD.

P362 Longitudinal antibody response to SARS-CoV-2 infection and antibody responses to COVID-19 vaccination in Inflammatory Bowel Disease patients receiving biologics

Background Given that IBD patients were excluded from COVID-19 vaccine trials, there is a lack of vaccine efficacy data in this population. In this study, we evaluated longitudinal serological responses to SARS-CoV-2 infection as well as to COVID-19 vaccination in IBD patients. Methods We collected clinical data and sera from IBD patients enrolled in an observational SARS-CoV-2 sero-surveillance study at our large hospital center in New York City during routine infusions and clinic visits. To distinguish between infection and vaccination, sera was collected prior to vaccination where possible, and all sera was tested for both antibodies to SARS-CoV-2-specific RBD, the target of current available vaccines in the U.S., and nucleocapsid proteins. Results Our results reveal waning antibody titres in 13 of 16 (81%) patients infected with SARS-CoV-2 over a course of 6-7 months. Of 48 vaccinated patients, 16 patients completed vaccine schedules with two doses, and all 16 (100%) achieved seroconversion above the threshold required for convalescent plasma donation. Conclusion While antibody responses to infection in IBD patients have questionable stability, completion of the COVID-19 vaccine series in IBD patients results in robust serological responses. To our knowledge is the first data confirming adequate serological responses to COVID-19 vaccination in IBD patients with and without biologic medications. Studies are needed to assess adequacy of dosing schedules, medication effects, measurement of cell-mediated responses, durability of immune responses, and clinical efficacy of COVID-19 vaccines in IBD patients.

339 Long-term Perception of Medication Effectiveness in Subjects Receiving Lemborexant for up to 12 Months

Introduction The Patient Global Impression–Insomnia version (PGI-I) is a self-report instrument used to evaluate a patient’s perception of the effects of their insomnia medication on their sleep relative to starting treatment. The PGI-I includes 3 items related to medication effects (helped/worsened sleep; decreased/increased time to fall asleep; and increased/decreased total sleep; responses include: 1=positive, 2=neutral, 3=negative) and 1 item related to perceived appropriateness of study medication strength (responses include: 1=too strong, 2=just right, 3=too weak). In Study E2006-G000-303 (Study 303; SUNRISE-2; NCT02952820), significantly greater percentages of subjects reported a positive impact of the dual orexin receptor antagonist lemborexant (LEM) versus placebo (PBO) at 1, 3, and 6mo for each of the PGI-I items related to medication effects. PGI-I results at 9 and 12mo are presented here for subjects that received continuous treatment with LEM for up to 12mo. Methods Study 303 was a 12-mo, randomized, double-blind, PBO-controlled (first 6mo [Period 1]), phase 3 study. Subjects were aged ≥18y with insomnia disorder. During Period 1, subjects received PBO (n=318) or LEM (5mg, [LEM5], n=316; 10mg, [LEM10], n=315). During Period 2 (second 6mo), LEM subjects continued their assigned dose while PBO subjects were rerandomized to LEM5 or LEM10 (reported separately). Subjects were also administered the PGI-I at months 9 and 12. Results At 9 and 12mo, the majority of LEM5 (9mo, n=241; 12mo, n=205) and LEM10 (9mo, n=211; 12mo, n=192) subjects reported that their study medication “helped” sleep at night (9mo: LEM5=73.4%; LEM10=76.3%; 12mo: LEM5=74.6%; LEM10=77.6%), reduced time to fall asleep (9mo: LEM5=79.3%, LEM10=78.2%; 12mo: LEM5=76.6%, LEM10=80.2%), and increased total sleep time (9mo: LEM5=62.2%, LEM10=73.0%; 12mo: LEM5=62.4%; LEM10=65.1%). Also, at both 9 and 12mo, the majority of subjects in the LEM5 and LEM10 groups, responded that treatment strength was “just right” (9mo: LEM5=60.6%, LEM10=62.1%; 12mo: LEM5=63.4%; LEM10=60.4%). LEM was well tolerated. Most adverse events were mild or moderate. Conclusion The majority of subjects receiving LEM5 or LEM10 reported a positive medication effect at both 9 and 12mo, sustaining similar positive effects for LEM achieved earlier, during the first 6mo of treatment in Study 303. Support (if any) Eisai Inc.