Caroline Skirrow

Background New disease modifying treatments for Alzheimer’s Disease (AD) require confirmation of amyloid biomarkers and evidence of clinical and/or cognitive AD symptoms. Blood tests for AD biomarkers are poised to enter routine care. However, at‐risk individuals with positive biomarkers vary in their level of cognitive impairment, raising the need...

Background Scalable, efficient methods are needed to enroll diverse populations of older adults into AD observational studies and clinical trials. We evaluated preliminary feasibility of a novel, digital, culturally informed approach to recruit and screen participants for the Alzheimer’s Disease Neuroimaging Initiative (ADNI4). Methods Digital adv...

Background Storyteller, a brief self‐administered test that uses speech analysis to measure cognitive functioning, has demonstrated ability to predict Mild Cognitive Impairment (MCI) and mild Alzheimer’s disease (AD). The test is being implemented globally in Sponsor clinical trials, ADNI, and Sites for pre‐screening and will be used across heterog...

Introduction Normative cognitive data can distinguish impairment from healthy cognitive function and pathological decline from normal ageing. Traditional methods for deriving normative data typically require extremely large samples of healthy participants, stratifying test variation by pre-specified age groups and key demographic features (age, sex...

INTRODUCTION Speech‐based testing shows promise for sensitive and scalable objective screening for Alzheimer's disease (AD), but research to date offers limited evidence of generalizability. METHODS Data were taken from the AMYPRED (Amyloid Prediction in Early Stage Alzheimer's Disease from Acoustic and Linguistic Patterns of Speech) studies (N =...

INTRODUCTION We evaluated preliminary feasibility of a digital, culturally‐informed approach to recruit and screen participants for the Alzheimer's Disease Neuroimaging Initiative (ADNI4). METHODS Participants were recruited using digital advertising and completed digital surveys (e.g., demographics, medical exclusion criteria, 12‐item Everyday Co...

Background Changes in speech occur in early‐stage Alzheimer’s disease. A range of approaches have been used for eliciting and automatically analysing speech, but limited research has directly compared these methods. Method Participants from the AMYPRED‐UK (NCT04828122) and AMYPRED‐US (NCT04928976) studies completed four speech‐elicitation tasks: t...

Background Changes in speech occur in early‐stage Alzheimer’s disease. A range of approaches have been used for eliciting and automatically analysing speech, but limited research has directly compared these methods. Method Participants from the AMYPRED‐UK (NCT04828122) and AMYPRED‐US (NCT04928976) studies completed four speech‐elicitation tasks: t...

Anxiety and depression are associated with a range of impairments in cognitive functioning. Understanding the nature of these deficits may identify targets for intervention and prevent functional decline. We used observational and genetic methods to investigate the relationship of anxiety and depression with three cognitive domains: emotion recogni...

Introduction Biomarkers of mental effort may help to identify subtle cognitive impairments in the absence of task performance deficits. Here, we aim to detect mental effort on a verbal task, using automated voice analysis and machine learning. Methods Audio data from the digit span backwards task were recorded and scored with automated speech reco...

BACKGROUND Cognitive symptoms are an underrecognized aspect of depression that are often untreated. High-frequency cognitive assessment holds promise for improving disease and treatment monitoring. Although we have previously found it feasible to remotely assess cognition and mood in this capacity further work is needed to ascertain the optimal met...

Background Cognitive symptoms are an underrecognized aspect of depression that are often untreated. High-frequency cognitive assessment holds promise for improving disease and treatment monitoring. Although we have previously found it feasible to remotely assess cognition and mood in this capacity, further work is needed to ascertain the optimal me...

BACKGROUND Normative cognitive data can distinguish impairment from healthy cognitive function and pathological decline from normal ageing. Traditional methods for deriving normative data typically require extremely large samples of healthy participants, stratifying test variation by pre-specified age groups and key demographic features (age, sex,...

Vocal and linguistic changes in Alzheimer’s dementia have been documented. The current study assesses whether a fully automated speech‐based artificial intelligence (AI) system can detect early clinical impairment and amyloid positivity, which characterise the earliest stages of Alzheimer’s disease (AD). Two studies were completed in the UK and USA...

Introduction: Artificial intelligence (AI) systems leveraging speech and language changes could support timely detection of Alzheimer's disease (AD). Methods: The AMYPRED study (NCT04828122) recruited 133 subjects with an established amyloid beta (Aβ) biomarker (66 Aβ+, 67 Aβ-) and clinical status (71 cognitively unimpaired [CU], 62 mild cogniti...

Early detection of Alzheimer’s disease is required to identify patients suitable for disease-modifying medications and to improve access to non-pharmacological preventative interventions. Prior research shows detectable changes in speech in Alzheimer’s dementia and its clinical precursors. The current study assesses whether a fully automated speech...

Background ADHD in adults is a common and debilitating neurodevelopmental mental health condition. Yet, diagnosis, clinical management and monitoring are frequently constrained by scarce resources, low capacity in specialist services and limited awareness or training in both primary and secondary care. As a result, many people with ADHD experience...

Background Story recall is a simple and sensitive cognitive test that is commonly used to measure changes in episodic memory function in early Alzheimer disease (AD). Recent advances in digital technology and natural language processing methods make this test a candidate for automated administration and scoring. Multiple parallel test stimuli are r...

Introduction The diagnosis of neurodegenerative and psychiatric disorders (NPDs) in primary care can suffer from inefficiencies resulting in misdiagnoses and delayed diagnosis, limiting effective treatment options. The development of speech and language-based profiling biomarkers could aid in achieving earlier motor diagnosis for PD for instance, o...

Introduction Neurodegenerative and psychiatric disorders (NPDs) confer a huge health burden, which is set to increase as populations age. New, remotely delivered diagnostic assessments that can detect early stage NPDs by profiling speech could enable earlier intervention and fewer missed diagnoses. The feasibility of collecting speech data remotely...

Background Changes in speech, language, and episodic and semantic memory are documented in Alzheimer’s disease (AD) years before routine diagnosis. Aims Develop an Artificial Intelligence (AI) system detecting amyloid-confirmed prodromal and preclinical AD from speech collected remotely via participants’ smartphones. Method A convenience sample o...

INTRODUCTION: Longitudinal data is key to identifying cognitive decline and treatment response in Alzheimer's disease (AD). METHODS: The Automatic Story Recall Task (ASRT) is a novel, fully automated test that can be self-administered remotely. In this longitudinal case-control observational study, 151 participants (mean age: 69.99 (range 54-82), 7...

Background: Understanding the nature of cognitive deficits in anxiety and depression may identify intervention targets and help prevent functional decline. This study used observational and genetic methods to investigate the association of anxiety and depression with emotion recognition, response inhibition, and working memory, in young adulthood....

The ability of remote research tools to collect granular, high-frequency data on symptoms and digital biomarkers is an important strength because it circumvents many limitations of traditional clinical trials and improves the ability to capture clinically relevant data. This approach allows researchers to capture more robust baselines and derive no...

Attention-deficit/hyperactive disorder (ADHD) is characterized by symptoms which are dynamic in nature: states of hyperactivity, inattention and impulsivity as core symptoms, and emotion dysregulation as associated feature. Although tremendous work has been done to investigate between-subject differences (how patients with ADHD differ from healthy...

Background: Psychosis-like experiences (PLEs) are common and associated with mental health problems and poorer cognitive function. There is limited longitudinal research examining associations between cognition and PLEs in early adulthood. Aims: We investigated the association of PLEs with different domains of cognitive function, using cross-sectio...

Background: Despite evidence-based national guidelines for ADHD in the United Kingdom (UK), ADHD is under-identified, under-diagnosed, and under-treated. Many seeking help for ADHD face prejudice, long waiting lists, and patchy or unavailable services, and are turning to service-user support groups and/or private healthcare for help. Methods: A gro...

Background Emotional dysregulation (ED) is a core diagnostic symptom in borderline personality disorder (BPD) and an associated feature of attention-deficit/hyperactivity disorder (ADHD). We aimed to investigate differences in dynamical indices of ED in daily life in ADHD and BPD. Methods We used experience sampling method (ESM) and multilevel mod...

Background Although studies have examined the association between tobacco and cannabis use in adolescence with subsequent cognitive functioning, study designs are usually not able to distinguish correlation from causation. Methods Separate patterns of tobacco and cannabis use were derived using longitudinal latent class analysis based on measures...

Test-retest reliability is essential to the development and validation of psychometric tools. Here we respond to the article by Karlsen et al. (Applied Neuropsychology: Adult, 2020), reporting test-retest reliability on the Cambridge Neuropsychological Test Automated Battery (CANTAB), with results that are in keeping with prior research on CANTAB a...

UNSTRUCTURED In recent years, there has been a surge in using online platforms and personal devices to administer brief clinical assessments, in natural settings, and at regular intervals or in response to acute changes (e.g., in mood or behaviour). The SARS-CoV-2 pandemic has accelerated interest in remote testing for clinical research programmes,...

Background: There is evidence to suggest that the broad discrepancy in the ratio of males to females with diagnosed ADHD is due, at least in part, to lack of recognition and/or referral bias in females. Studies suggest that females with ADHD present with differences in their profile of symptoms, comorbidity and associated functioning compared with...

Background and Aims There have been few longitudinal studies of association between alcohol use and cognitive functioning in young people. We aimed to examine whether alcohol use is a causal risk factor for deficient cognitive functioning in young adults. Design Linear regression was used to examine the relationship between longitudinal latent cla...

Background: Although studies have examined the association between tobacco and cannabis use in adolescence with subsequent cognitive functioning, study designs are usually not able to distinguish correlation from causation. Methods: First, separate patterns of tobacco and cannabis use were derived using longitudinal latent class analysis based on m...

BACKGROUND Computerised assessments already confer advantages for deriving accurate and reliable measures of cognitive function, including test standardisation, accuracy of response recordings and automated scoring. Web-based cognitive assessment could improve accessibility and flexibility of research and clinical assessment, widen participation an...

Background: Computerized assessments are already used to derive accurate and reliable measures of cognitive function. Web-based cognitive assessment could improve the accessibility and flexibility of research and clinical assessment, widen participation, and promote research recruitment while simultaneously reducing costs. However, differences in...

Background and Aims: There have been few prospective studies of association between alcohol use and cognitive functioning in young people. We aim to examine whether alcohol use is a risk factor for deficient cognitive functioning in young adults. Design: Longitudinal latent class analysis was used to derive patterns of binge drinking. Linear regres...

Objective Intelligence quotient (IQ) outcomes after pediatric epilepsy surgery show significant individual variation. Clinical factors such as seizure cessation or antiepileptic medication discontinuation have been implicated, but do not fully account for the heterogeneity seen. Less is known about the impact of neurobiological factors, such as bra...

Mindwandering_and_ADHD_SupplementaryMaterial_JAD – Supplemental material for Validation of the Mind Excessively Wandering Scale and the Relationship of Mind Wandering to Impairment in Adult ADHD

BACKGROUND Cognitive symptoms are common in major depressive disorder, and may help to identify patients that need treatment or who are not experiencing adequate treatment response. Digital tools to provide real time data assessing cognitive function could help to support patients treatment and remediation of cognitive and mood symptoms. OBJECTIVE...

Background: Cognitive symptoms are common in major depressive disorder and may help to identify patients who need treatment or who are not experiencing adequate treatment response. Digital tools providing real-time data assessing cognitive function could help support patient treatment and remediation of cognitive and mood symptoms. Objective: Th...

Introduction Normative cognitive data can help to distinguish pathological decline from normal aging. This study presents normative data from the Cambridge Neuropsychological Test Automated Battery, using linear regression and nonlinear quantile regression approaches. Methods Heinz Nixdorf Recall study participants completed Cambridge Neuropsychol...

Objective: This study investigates excessive mind wandering (MW) in adult ADHD using a new scale: the Mind Excessively Wandering Scale (MEWS). Method: Data from two studies of adult ADHD was used in assessing the psychometric properties of the MEWS. Case-control differences in MW, the association with ADHD symptoms, and the contribution to function...

Childhood-onset epilepsy is associated with educational underattainment and underemployment. In some children, surgical intervention may be offered as treatment for medication-resistant seizures. Successful treatment may halt seizure-related cognitive and academic deterioration, providing opportunity for greater success in school and work. This cha...

Here we examine the evidence for long-term changes in cognitive functions after epilepsy surgery in studies published mostly since 2010. Specifi cally, we looked for evidence of developmental “catch-up” as indicated by an increase in IQ scores in comparison with preoperative values. About half of the studies report signifi cant increase in IQ score...

Background: Emotional lability (EL), characterized by negative emotional traits and emotional instability, is frequently reported in children and adults with attention deficit hyperactivity disorder (ADHD). However, EL is primarily assessed using retrospective self-report, which is subject to reporting bias and does not consider the potential infl...

Attention-deficit/hyperactivity disorder (ADHD) is associated with cognitive performance and functional brain changes that are sensitive to task conditions, indicating a role for dynamic impairments rather than stable cognitive deficits. Prominent hypotheses consistent with this observation are a failure to optimise brain arousal or activation stat...

The temporal lobes play a prominent role in declarative memory function, including episodic memory (memory for events) and semantic memory (memory for facts and concepts). Surgical resection for medication-resistant and well-localized temporal lobe epilepsy has good prognosis for seizure freedom, but is linked to memory difficulties in adults, espe...

Altered very low-frequency electroencephalographic (VLF-EEG) activity is an endophenotype of ADHD in children and adolescents. We investigated VLF-EEG case-control differences in adult samples and the effects of methylphenidate (MPH). A longitudinal case-control study was conducted examining the effects of MPH on VLF-EEG (.02–0.2 Hz) during a cued...

There is increasing evidence that abnormalities in glutamate signalling may contribute to the pathophysiology of attention-deficit hyperactivity disorder (ADHD). Proton magnetic resonance spectroscopy ([1H]MRS) can be used to measure glutamate, and also its metabolite glutamine, in vivo. However, few studies have investigated glutamate in the brain...

Altered very low-frequency electroencephalographic (VLF-EEG) activity is an endophenotype of ADHD in children and adolescents. We investigated VLF-EEG case-control differences in adult samples and the effects of methylphenidate (MPH). A longitudinal case-control study was conducted examining the effects of MPH on VLF-EEG (.02-0.2Hz) during a cued c...

Emotional lability is recognized as an associated feature of attention-deficit/hyperactivity disorder (ADHD). However, the degree of phenotypic and etiologic overlap between emotional lability and the ADHD dimensions of hyperactivity-impulsivity and inattention remains unclear. The present study examines these associations in a large, community twi...

Background Recent literature on the comparison of machine learning methods has raised questions about the neutrality, unbiasedness and utility of many comparative studies. Reporting of results on favourable datasets and sampling error in the estimated performance measures based on single samples are thought to be the major sources of bias in such c...

Background: Adults with attention-deficit hyperactivity disorder (ADHD) frequently report emotional lability (EL). However, it is not known whether EL may be accounted for by comorbid psychiatric conditions or symptoms. This study evaluates the influence of comorbid clinical symptoms on EL, and investigates the relationship between EL and impairme...

Diagnostic formulations for attention deficit hyperactivity disorder (ADHD) and bipolar disorder (BD) both include symptoms of distractibility, psychomotor agitation and talkativeness, alongside associated emotional features (irritability and emotional lability). Treatment studies suggest the importance of accurate delineation of ADHD and BD. Howev...

ADHD is a common neurodevelopmental disorder that persists into adulthood in around two-thirds of cases. Current operational definitions of ADHD focus on three core domains of inattention, overactivity and impulsivity, yet it is widely recognised that there is a wider range of psychopathology that co-occurs alongside these core symptoms. Among the...

Temporal lobe resection is an established treatment for medication-resistant temporal lobe epilepsy, which in recent years has increasingly been performed in children. However, little is known about the long-term outcome in these children. The aim of this study was to characterize intellectual and psychosocial functioning of children after temporal...

ADHD in adults is frequently associated with unstable or irritable moods reflecting difficulties with emotion regulation. Effect sizes of drug treatments on symptoms that reflect difficulties with emotion regulation, are similar to those on core ADHD symptoms, with co-variation of around 0.8 between the two types of symptoms during the treatment re...

Attention-deficit/hyperactivity disorder (ADHD) is a common and debilitating psychiatric disorder characterized by symptoms of inattention, impulsivity and motor restlessness. Consistently noted alongside these symptoms is mood instability in the form of irritability, volatility, swift changes in mood, hot temper and low frustration tolerance. The...

Some individuals with superior memory, such as the mnemonist Shereshevskii (Luria, 1968), are known to have synaesthesia. However, the extent to which superior memory is a general characteristic of synaesthesia is unknown, as is the precise cognitive mechanism by which synaesthesia affects memory. This study demonstrates that synaesthetes tend to r...