Relative associations of behavioral and physiological risks for cardiometabolic disease with cognition in bipolar disorder during mid and later-life: findings from the UK biobank.

BACKGROUND: Cardiometabolic disease risk factors are disproportionately prevalent in bipolar disorder (BD) and are associated with cognitive impairment. It is, however, unknown which health risk factors for cardiometabolic disease are relevant to cognition in BD. This study aimed to identify the cardiometabolic disease risk factors that are the most important correlates of cognitive impairment in BD; and to examine whether the nature of the relationships vary between mid and later life. METHODS: Data from the UK Biobank were available for 966 participants with BD, aged between 40 and 69 years. Individual cardiometabolic disease risk factors were initially regressed onto a global cognition score in separate models for the following risk factor domains; (1) health risk behaviors (physical activity, sedentary behavior, smoking, and sleep) and (2) physiological risk factors, stratified into (2a) anthropometric and clinical risk (handgrip strength, body composition, and blood pressure), and (2b) cardiometabolic disease risk biomarkers (CRP, lipid profile, and HbA1c). A final combined multivariate regression model for global cognition was then fitted, including only the predictor variables that were significantly associated with cognition in the previous models. RESULTS: In the final combined model, lower mentally active and higher passive sedentary behavior, higher levels of physical activity, inadequate sleep duration, higher systolic and lower diastolic blood pressure, and lower handgrip strength were associated with worse global cognition. CONCLUSIONS: Health risk behaviors, as well as blood pressure and muscular strength, are associated with cognitive function in BD, whereas other traditional physiological cardiometabolic disease risk factors are not.

Efficacy and safety of established and off-label ADHD drug therapies for cognitive impairment or attention-deficit hyperactivity disorder symptoms in bipolar disorder: A systematic review by the ISBD Targeting Cognition Task Force.

BACKGROUND: Abnormalities in dopamine and norepinephrine signaling are implicated in cognitive impairments in bipolar disorder (BD) and attention-deficit hyperactivity disorder (ADHD). This systematic review by the ISBD Targeting Cognition Task Force therefore aimed to investigate the possible benefits on cognition and/or ADHD symptoms and safety of established and off-label ADHD therapies in BD. METHODS: We included studies of ADHD medications in BD patients, which involved cognitive and/or safety measures. We followed the procedures of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement. Searches were conducted on PubMed, Embase and PsycINFO from inception until June 2023. Two authors reviewed the studies independently using the Revised Cochrane Collaboration's Risk of Bias tool for Randomized trials. RESULTS: Seventeen studies were identified (N = 2136), investigating armodafinil (k = 4, N = 1581), methylphenidate (k = 4, N = 84), bupropion (k = 4, n = 249), clonidine (k = 1, n = 70), lisdexamphetamine (k = 1, n = 25), mixed amphetamine salts (k = 1, n = 30), or modafinil (k = 2, n = 97). Three studies investigated cognition, four ADHD symptoms, and 10 the safety. Three studies found treatment-related ADHD symptom reduction: two involved methylphenidate and one amphetamine salts. One study found a trend towards pro-cognitive effects of modafinil on some cognitive domains. No increased risk of (hypo)mania was observed. Five studies had low risk of bias, eleven a moderate risk, and one a serious risk of bias. CONCLUSIONS: Methylphenidate or mixed amphetamine salts may improve ADHD symptoms in BD. However, there is limited evidence regarding the effectiveness on cognition. The medications produced no increased mania risk when used alongside mood stabilizers. Further robust studies are needed to assess cognition in BD patients receiving psychostimulant treatment alongside mood stabilizers.

Exploring the cognitive profiles related to unimodal auditory versus multisensory hallucinations in schizophrenia-spectrum disorders.

INTRODUCTION: Hallucinations can be experienced across multiple sensory modalities, but psychiatric studies investigating the cognitive mechanisms of hallucinations have been somewhat restricted to the auditory domain. This study explored the cognitive profiles of individuals experiencing multisensory hallucinations (MH) in schizophrenia-spectrum disorders (SSD) and compared these to those experiencing unimodal auditory hallucinations (AH) or no hallucinations (NH). METHODS: Participants included SSD patients (n = 119) stratified by current hallucination status (NH, AH, MH) and nonclinical controls (NCs; n = 113). Group performance was compared across several cognitive domains: speed of processing, attention, working memory, verbal learning, visual learning, reasoning and problem-solving, social cognition, and inhibition. RESULTS: The clinical groups performed worse than NCs but differences between the clinical groups were not evident across most cognitive domains. Exploratory analyses revealed that the MH group was more impaired on the visual learning task compared to the NH (but not AH) group. CONCLUSIONS: Preliminary results suggest that impaired visual learning may be related to MH. This could be attributed to the presence of visual hallucinations (VH), or greater psychopathology, in this group. However, replication is needed, as well as the investigation of other potential cognitive mechanisms of MH.