Cambridge Neuropsychological Test Automated Battery Research Articles

Safety, pharmacokinetics, and potential neurological interactions of ivermectin, tafenoquine, and chloroquine in Rhesus macaques.

Ivermectin (IVM) could be used for malaria control as treated individuals are lethal to blood-feeding Anopheles, resulting in reduced transmission. Tafenoquine (TQ) is used to clear the liver reservoir of Plasmodium vivax and as a prophylactic treatment in high-risk populations. It has been suggested to use ivermectin and tafenoquine in combination, but the safety of these drugs in combination has not been evaluated. Early derivatives of 8-aminoquinolones (8-AQ) were neurotoxic, and ivermectin is an inhibitor of the P-glycoprotein (P-gp) blood brain barrier (BBB) transporter. Thus, there is concern that co-administration of these drugs could be neurotoxic. This study aimed to evaluate the safety and pharmacokinetic interaction of tafenoquine, ivermectin, and chloroquine (CQ) in Rhesus macaques. No clinical, biochemistry, or hematological outcomes of concern were observed. The Cambridge Neuropsychological Test Automated Battery (CANTAB) was employed to assess potential neurological deficits following drug administration. Some impairment was observed with tafenoquine alone and in the same monkeys with subsequent co-administrations. Co-administration of chloroquine and tafenoquine resulted in increased plasma exposure to tafenoquine. Urine concentrations of the 5,6 orthoquinone TQ metabolite were increased with co-administration of tafenoquine and ivermectin. There was an increase in ivermectin plasma exposure when co-administered with chloroquine. No interaction of tafenoquine on ivermectin was observed in vitro. Chloroquine and trace levels of ivermectin, but not tafenoquine, were observed in the cerebrospinal fluid. The 3''-O-demethyl ivermectin metabolite was observed in macaque plasma but not in urine or cerebrospinal fluid. Overall, the combination of ivermectin, tafenoquine, and chloroquine did not have clinical, neurological, or pharmacological interactions of concern in macaques; therefore, this combination could be considered for evaluation in human trials.

Relationship between cognitive function and functional outcomes in remitted major depression

BackgroundFew studies have focused on functional impairment in depressed patients during symptomatic remission. The exact relationship between cognitive performance and functional outcomes of patients with Major depressive disorder (MDD) remains unclear.MethodsParticipants diagnosed with MDD were included and interviewed at both baseline and follow-up. Cognitive function was assessed during acute episodes using the Cambridge Neuropsychological Test Automated Battery (CANTAB), which targeted attention (Rapid Visual Processing - RVP), visual memory (Pattern Recognition Memory - PRM), and executive function (Intra-Extra Dimensional Set Shift - IED). The 17-item Hamilton Depression Scale (HAMD) was used for symptom assessment. Participants were divided into two groups based on their SDSS (Social Disability Screening Schedule) scores, and the differences between their demographic information, HAMD scores, and baseline CANTAB test results were compared. Logistic regression analysis was used to identify cognitive predictors of social function during symptomatic remission.ResultsAccording to the SDSS score at follow-up, 103 patients were divided into the normal social function group (n = 81,78.6%) and the poor social function group (n = 22, 21.4%) during clinical remission. Participants with poorer social function performed worse in the visual memory (PRM) and executive function tests (IED) at the baseline. Logistic regression analysis suggested that performance on the PRM (95%CI = 0.31–0.93, p = 0.030) and IED (95%CI = 1.01–1.13, p = 0.014) tests, instead of less severe symptoms, significantly contributed to functional outcomes.ConclusionBetter performance in visual memory and executive function during acute episodes may predict better social functional outcomes in individuals with MDD. A potential early intervention to improve social function in individuals with MDD could include the treatments for executive function and visual memory.

Short-term Aronia melanocarpa extract supplementation improves cognitive performance: a randomized, double-blind, placebo-controlled cross-over study in healthy young adults.

Evidence on the potential beneficial effects of anthocyanin-rich foods and supplements on cognitive performance is mainly based on acute or long-term studies in older adults. However, short-term studies focusing on a younger population are lacking. Therefore, short-term effects of Aronia melanocarpa extract (AME) supplementation on cognitive performance were investigated in healthy young adults. Potential underlying mechanisms were also addressed. A randomized, double-blind, placebo-controlled cross-over study was performed involving 35 apparently healthy young adults. Participants consumed AME (180mg anthocyanins/day) or a placebo for 1week, separated by at least 2weeks of wash-out. Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Furthermore, arterial stiffness (carotid-to-femoral pulse wave velocity), retinal microvascular calibers (fundus photography), and serum brain-derived neurotrophic factor (BDNF) concentrations were measured at baseline and after 1week. Participants had a mean age of 25 ± 4years and an average BMI of 23.4 ± 2.7kg/m2. Compliance was excellent and the study product was well-tolerated. As compared to placebo, movement time was significantly reduced by 4.8% within the five-choice reaction time test after 1week of AME supplementation (intervention effect: -12ms; p < 0.05). Memory and executive function did however not change. Serum BDNF concentrations were significantly higher after AME supplementation as compared to placebo (+ 5.7%; intervention effect: 1.8ng/mL; p < 0.05). However, arterial stiffness and retinal microvascular calibers were not affected. Short-term AME supplementation beneficially affected cognitive performance as attention and psychomotor speed improved. Serum BDNF concentrations were increased, but vascular function markers were not affected. The study was registered on Clinical Trials under NCT03793777 on January 4th, 2019.

A Comparative Evaluation of Error Processing Performance and its Relationship with Cognitive Function in Patients with Alzheimer's Disease, Individuals with Mild Cognitive Impairment, and Normal Controls Using the Event-Related Potentials.

Some pathological changes occur in patients with Alzheimer's disease (AD) prior to the onset of clinical symptoms. In the present study, we aimed to investigate the potential of event-related potential (ERP) components in error processing performance as a neuromarker of mild cognitive impairment (MCI) and transition to AD and their relation with cognitive functions. We conducted an evaluation of 16 patients diagnosed with AD, 16 patients with MCI, and 15 normal controls using three subtests from the Cambridge Neuropsychological Testing Automated Battery (CANTAB). The ERP components of error processing were extracted and compared among the three groups using a modified version of the Eriksen flanker task. Additionally, we assessed the correlation between the cognitive results and the ERP components. Significant differences were observed among the three groups in terms of providing correct responses following errors and the amplitude of error-related negativity (ERN). These differences were also significant between all paired groups. Regarding other ERP components of error processing and the peak latency of ERN, no significant differences were observed among the three groups. The findings revealed that the spatial working memory and new learning were correlated with the amplitude of ERN. In the context of error processing performance, both the accuracy of responses following an error and the amplitude of ERN can be considered as indicators of MCI and its progression to AD. The present findings do not support the use of other error processing components as differential markers in the three groups.

An exploratory, randomised, crossover study to investigate the effect of nicotine on cognitive function in healthy adult smokers who use an electronic cigarette after a period of smoking abstinence

BackgroundAs well as being associated with serious negative health outcomes, smoking has been reported to have an array of physiological and psychological effects, including effects on mood and cognitive function. Post-cessation, loss of such effects (including temporary deficits in cognitive function) have been cited as reasons for resumption of smoking. The effects of e-cigarettes and nicotine delivered by e-cigarettes on these functions have not been widely researched but may play a role in the effectiveness of e-cigarettes as a satisfactory alternative to combustible cigarettes for people who smoke, and in encouraging individuals who would otherwise continue to smoke, to transition to e-cigarettes.MethodsThe study was an exploratory, randomised, partially-blinded, single-centre, five-arm crossover trial that recruited 40 healthy male and female people who smoke. At 5 study sessions, following a 12-h period of nicotine abstinence, participants were randomly assigned to use either a combustible cigarette, an e-cigarette of three varying nicotine strengths (18 mg/mL, 12 mg/mL or 0 mg/mL respectively) or observe a no product usage session. Participants completed pre- and post-product usage assessments to examine the product usage effect on cognitive performance (using the Cambridge Neuropsychological Test Automated Battery (CANTAB)), subjective mood and smoking urges.ResultsA significant improvement in sustained attention task performance was observed following use of both the nicotine containing e-cigarettes and combustible cigarette compared to no product use. Additionally, there were no significant differences between the nicotine containing products, indicating that nicotine use enhanced sustained attention regardless of delivery format. Nicotine containing e-cigarette and combustible cigarette use also significantly improved overall mood of participants compared to no product use, with no significant differences observed between the nicotine containing products. Nicotine containing e-cigarette and combustible cigarette use significantly reduced smoking urges compared to no product use, though combustible cigarette use elicited the greatest reduction in smoking urges.ConclusionsOverall, the nicotine containing products improved sustained attention and mood while reducing smoking urges, with the studied e-cigarettes having comparable effects to combustible cigarettes across the assessed cognitive parameters and mood measures. These results demonstrate the potential role of e-cigarettes to provide an acceptable alternative for combustible cigarettes among people who would otherwise continue to smoke.Trial registration ISRCTN (identifier: ISRCTN35376793).

Association of antidepressant and benzodiazepine use, and anticholinergic burden with cognitive performance in schizophrenia

Schizophrenia is characterized by cognitive impairment affecting everyday functioning. Earlier research has hypothesized that antidepressants may associate with better cognitive functioning, but results are mixed. This study explored the association between antidepressant use and cognitive performance in terms of reaction time and visual learning in a clinical sample. In addition, we examined benzodiazepine use and anticholinergic burden. Study participants were drawn from the SUPER-Finland cohort, collected among patients with psychotic illnesses in 2016–2018 throughout Finland (n = 10,410). The analysis included adults with a schizophrenia diagnosis (F20) and results from a cognitive assessment (n = 3365). Information about medications and psychosocial factors were gathered through questionnaire and interview. Cognitive performance was assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) with two subtests measuring reaction time and visual learning. Almost 36 % of participants used at least one antidepressant. The use of antidepressants in general was not associated with performance in the reaction time and visual learning tasks. However, the use of SNRI antidepressants was associated with a faster reaction time. Benzodiazepine use and a higher anticholinergic burden were associated with poorer performance in both tests. The results strengthen earlier findings that there is no association between antidepressant use in general and cognitive performance in schizophrenia. However, the association of SNRI medications with a faster reaction time warrants further research. Moreover, the results suggest that more attention should be paid to the anticholinergic burden of the medications used by patients with schizophrenia, as well as avoiding continuous benzodiazepine use.

Sex-differential patterns of neuropsychological functioning in adults with attention-deficit/hyperactivity disorder

BackgroundThe sex-differential prevalence of attention-deficit/hyperactivity disorder (ADHD) varies across the lifespan, but little is known about sex differences in executive functions in adults with ADHD. MethodsWe assessed 261 adults, aged 18–40 years, diagnosed with ADHD (170 males [assigned at birth], aged 25.81 ± 5.49; 91 females, aged 27.76 ± 5.42) and 308 neurotypical adults (176 males, aged 24.62 ± 5.14; 132 female, aged 25.37 ± 5.42) via psychiatric interviews to confirm ADHD and other psychiatric diagnoses. They were assessed by the Cambridge Neuropsychological Testing Automated Battery (CANTAB) on Reaction Time (arousal/processing speed), Rapid Visual Information Processing (sustained attention), Spatial Span (spatial memory), Spatial Working Memory, Intradimentional/Extradimensional Shift (set-shifting), and Stocking of Cambridge (spatial planning). The primary analyses were adjusted for age, full-scale IQ, and co-occurring psychiatric conditions. ResultsAdults with ADHD had various co-occurring psychiatric conditions without sex differences in ADHD-neurotypical differences. Both adult males and females with ADHD performed poorer in all CANTAB tasks than same-sex neurotypical adults. Significant sex-moderating effects were observed in neuropsychological performance, including greater ADHD-neurotypical differences in arousal for females than males and in location memory for spatial tasks in males than females. ConclusionThere were no sex-moderating effects in the presence of co-occurring psychiatric conditions in adult ADHD. However, there were sex-moderating effects on how ADHD related to neuropsychological functioning in adulthood. ADHD was associated with more challenges in arousal/processing speed in females and more challenges in strategy use or inhibition in spatial memory in males.

Effects of the active botanical blend "WKUP GT" on attention and cognitive functions after lunch in healthy volunteers.

"WKUP GT", a low caffeine beverage consisting of carob, Guarana, Green Tea and Elderberry extracts was studied on attention and cognitive functions post-lunch in a pilot randomized double blind placebo controlled trial. Thirty healthy volunteers were included in a crossover design trial, presenting five beverages randomly assigned to the following groups: placebo, "WKUP GT" (single, double or triple doses), or "caffeine" as an active control. Hemodynamic measurements were assessed as safety outcomes. The Cambridge Neuropsychological Test Automated Battery (CANTAB), was used to evaluate the patients when beverages were consumed 30 and 120min after lunch (respectively Delta30 and Delta120 considering baseline). Drinking "caffeine" or "WKUP GT" after lunch, showed significant improvement (p<0.05) in rapid visual information processing compared to placebo (Delta120 of "caffeine", "WKUP" single and double). In addition, improvement in Multitasking Test (Delta30 for "WKUP" double, and Delta120 for "caffeine" and "WKUP" triple compared to placebo) was observed. "WKUP" triple also showed significant improvement for "memory" when compared to placebo (Delta120). Compared to "caffeine", WKUP GT did not increase systolic blood pressure. "WKUP GT" showed improvements for attention, memory, psychomotor and executive function tasks after lunch without increase in pulse rate.

The effect of transcranial direct current stimulation (tDCS) on cognitive function recovery in patients with depression following electroconvulsive therapy (ECT): protocol for a randomized controlled trial

BackgroundElectroconvulsive therapy (ECT) is a highly effective treatment for depressive disorder. However, the use of ECT is limited by its cognitive side effects (CSEs), and no specific intervention has been developed to address this problem. As transcranial direct current stimulation (tDCS) is a safe and useful tool for improving cognitive function, the main objective of this study was to explore the ability to use tDCS after ECT to ameliorate the cognitive side effects.Methods60 eligible participants will be recruited within two days after completing ECT course and randomly assigned to receive either active or sham stimulation in a blinded, parallel-design trial and continue their usual pharmacotherapy. The tDCS protocol consists of 30-min sessions at 2 mA, 5 times per week for 2 consecutive weeks, applied through 15-cm2 electrodes. An anode will be placed over the left dorsolateral prefrontal cortex (DLPFC), and a cathode will be placed over the right supraorbital cortex. Cognitive function and depressive symptoms will be assessed before the first stimulation (T0), after the final stimulation (T1), 2 weeks after the final stimulation (T2), and 4 weeks after the final stimulation (T3) using the Cambridge Neuropsychological Test Automated Battery (CANTAB).DiscussionWe describe a novel clinical trial to explore whether the administration of tDCS after completing ECT course can accelerates recovery from the CSEs. We hypothesized that the active group would recover faster from the CSEs and be superior to the sham group. If our hypothesis is supported, the use of tDCS could benefit eligible patients who are reluctant to receive ECT and reduce the risk of self-inflicted or suicide due to delays in treatment.Trial registration detailsThe trial protocol is registered with https://www.chictr.org.cn/ under protocol registration number ChiCTR2300071147 (date of registration: 05.06.2023). Recruitment will start in November 2023.

Executive functioning in children with ADHD Investigating the cross-method correlations between performance tests and rating scales.

Replicated evidence shows a weak or non-significant correlation between different methods of evaluating executive functions (EF). The current study investigates the association between rating scales and cognitive tests of EF in a sample of children with ADHD and executive dysfunction. The sample included 139 children (aged 6-13) diagnosed with ADHD and executive dysfunctions. The children completed subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and the Children's Organizational Skills Scale (COSS). Pairwise Spearman correlations were calculated between the composite and separate subscales of cognitive tests and rating scales. In secondary analyses, pairwise Spearman correlations were conducted between all composite scales and subscales, stratified by child sex and child ADHD subtype. The correlation analyses between composite scores yielded no significant correlations. The results when comparing CANTAB TO and BRIEF GE are r=-.095, p=.289, and r=.042, p=.643 when comparing CANTAB TO and COSS TO. The analyses between all composite scales and subscales found one significant negative correlation (r=-.25, p<.01). There are significant cross-method differences when stratified by the ADHD-Inattentive subtype, showing significant negative correlations (moderate) between CANTAB and BRIEF composite (r=-.355, p=.014) and subscales. It is possible that the different methods measure different underlying constructs of EF. It may be relevant to consider the effects of responder bias and differences in ecological validity in both measurement methods. The results found no significant correlations. The expectation in research and clinical settings should not be to find the same results when comparing data from cognitive tests and rating scales. Future research might explore novel approaches to EF testing with a higher level of ecological validity, and designing EF rating scales that capture EF behaviors more so than EF cognition.

Comparing attention, impulsivity, and executive functions between patients with opiate use disorder: Buprenorphine maintenance treatment versus active users, in comparison with healthy controls.

Opioid use disorders (OUDs) affect over 16 million people worldwide, with a particularly high prevalence rate in Asia. OUDs are associated with significant health consequences, including neurocognitive impairment, which affects individuals' ability to make decisions, respond to stressful situations, and regulate behavior. Understanding the specific ways in which OUDs affect cognitive functioning is important in treatment considerations. This study compared the attention, impulsivity, and executive functions of Turkish men with active OUD (n = 40) with those of men in remission from OUD who were on buprenorphine/naloxone maintenance (BMT; n = 41) and with those of a comparison group of healthy controls (HC; n = 43). The Cambridge Neuropsychological Test Automated Battery (CANTAB) was used to assess neurocognitive functioning. Analyses found significant impairment in measures of continuous attention, cognitive impulsivity, motor impulsivity, and executive functions in the two patient groups compared to the control group, but the two patient groups did not differ from each other. The data from this study indicate that individuals with OUD exhibit neurocognitive damage, and those in remission from OUD who receive maintenance treatment do not show improvement in this domain. Neurocognitive damages should be considered in long-term treatment planning of patients with OUD.

Environmental pollutants PM2.5, PM10, carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3) impair human cognitive functions.

Environmental pollution is an emerging global public health problem across the world and causes serious threats to ecosystems, human health, and the planet. This study is designed to explore the impact of environmental pollution particulate matter PM2.5, PM10, carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone (O3) on cognitive functions in students from schools located in or away from air-polluted areas. In this study, two schools were selected: one was located near a traffic-polluted area (school #1), and the second was in an area away from the traffic-polluted area (school #2). In this study, a total of 300 students were recruited: 150 (75 male and 75 female) students from school #1 located in a traffic-polluted area, and 150 students (75 male and 75 female) from school #2 located away from a traffic polluted area. The overall average age of students was 13.53±1.20 years. The students were selected based on age, gender, health status, height, weight, BMI, ethnicity, and homogenous socio-economic and educational status. The pollutants PM2.5, PM10, CO, NO2, O3, and SO2 were recorded in the surrounding environment. The overall mean concentration of environmental pollutants in school #1 was 35.00±0.65 and in school #2 was 29.95±0.32. The levels of airborne particles were measured, and the cognitive functions were recorded using the Cambridge Neuropsychological Test Automated Battery (CANTAB). The students performed the cognitive functions tasks, including the attention switching task (AST), choice reaction time (CRT), and motor screening task (MOT). The results revealed that the AST-Mean 928.34±182.23 vs. 483.79±146.73 (p=0.001), AST-mean congruent 889.12±197.12 vs. 473.30±120.11 (p=0.001), AST-mean in-congruent 988.98±201.27 vs. 483.87±144.57 (p=0.001), CRT-Mean 721.36±251.72 vs. 418.17±89.71 (p=0.001), and MOT-Mean 995.07±394.37 vs. 526.03±57.83 (p=0.001) were significantly delayed among the students who studied in school located in the traffic polluted area compared to students who studied in school which was located away from the traffic-polluted area. Environmental pollution was significantly higher in motor vehicle-congested areas. Cognitive functions were impaired among the students who were studying in a school located in a polluted area. The results further revealed that the students studying in schools located in environmentally polluted areas have attention, thinking, and decision-making abilities related to cognitive function impairment.

Teleyoga for Patients With Alzheimer's Disease and Chronic Musculoskeletal Pain and Their Caregivers: A Feasibility Study.

Chronic musculoskeletal pain is common in patients with Alzheimer's disease (AD), and there is growing awareness that chronic pain has an impact on the progression of dementia. Yoga has shown promise in treating chronic pain. However, attending in-person yoga can be difficult for AD patients. To assess the feasibility, acceptability and preliminary efficacy of an online yoga (teleyoga) protocol suitable for AD patients with chronic pain, and their caregivers. Patients with comorbid mild AD and chronic musculoskeletal pain (n = 15, 57-95 y/o; 73% Female) and their caregivers (n = 15, 50-75 y/o; 67% Female) received 12-week of teleyoga individually (n = 5 dyads) or in groups (n = 10 dyads). Study measures included standard feasibility metrics, and secondary outcomes included the Brief Pain Inventory-Short Form (BPI-SF), Beck Depression Inventory-II (BDI-II), and cognitive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Caregivers also completed measures of caregiver burden, and quality of life (Short Form Health Survey-36, SF-36). Feasibility measures showed adequate treatment adherence (85.1% in patients and 86.3% in caregivers), acceptability (mean acceptability rating = 3.0 for patients and 3.3 for caregivers, indicating positive approval), recruitment rate (n = 16 dyads within 1-year), retention rate (87%), missing data rate (.03%), and fidelity of treatment delivery (87%). Preliminary efficacy findings in the AD group showed significant reductions in pain severity (BPI-SF mean Δ = -.93, P = .045) and depression (BDI-II; mean Δ = -9.85, P = .005). %). Preliminary efficacy findings in the caregiver group showed significant reductions in depression (BDI-II mean Δ = -6.88, P = .036) and fatigue (SF-36 mean Δ = 9.81, P = .021). Results show that teleyoga is a feasible treatment for patients with comorbid mild AD and chronic musculoskeletal pain. Results also provide preliminary evidence of health benefits of teleyoga for both AD patients and their caregivers.

Tau Imaging in Late Traumatic Brain Injury: A [18F]MK-6240 Positron Emission Tomography Study.

Epidemiological studies have identified prior traumatic brain injury (TBI) as a risk factor for developing Alzheimer's disease (AD). Neurofibrillary tangles (NFTs) are common to AD and chronic traumatic encephalopathy following repetitive mild TBI. However, it is unclear if a single TBI is sufficient to cause accumulation of NFTs. We performed a [18F]MK-6240 positron emission tomography (PET) imaging study to assess NFTs in patients who had sustained a single TBI at least 2 years prior to study inclusion. Fourteen TBI patients (49 ± 20 years; 5 M/9 F; 8 moderate-severe, 1 mild-probable, 5 symptomatic-possible TBI) and 40 demographically similar controls (57 ± 19 years; 19 M/21 F) underwent simultaneous [18F]MK-6240 PET and magnetic resonance imaging (MRI) as well as neuropsychological assessment including the Cambridge Neuropsychological Test Automated Battery (CANTAB). A region-based voxelwise partial volume correction was applied, using parcels obtained by FreeSurfer v6.0, and standardized uptake value ratios (SUVR) were calculated relative to the cerebellar gray matter. Group differences were assessed on both a voxel- and a volume-of-interest-based level and correlations of [18F]MK-6240 SUVR with time since injury as well as with clinical outcomes were calculated. Visual assessment of TBI images did not show global or focal increases in tracer uptake in any subject. On a group level, [18F]MK-6240 SUVR was not significantly different in patients versus controls or between subgroups of moderate-severe TBI versus less severe TBI. Within the TBI group, One Touch Stockings problem solving and spatial working memory (executive function), reaction time (attention), and Mini-Mental State Examination (MMSE) (global cognition) were associated with [18F]MK-6240 SUVR. We found no group-based increase of [18F]MK-6240 brain uptake in patients scanned at least 2 years after a single TBI compared with healthy volunteers, which suggests that no NFTs are building up in the first years after a single TBI. Nonetheless, correlations with cognitive outcomes were found that warrant further investigation.

Plasma phosphorylated tau 181 and modifiable risk factors for dementia in a large scale cohort of Australian older adults

AbstractBackgroundUp to 40% of dementia cases could be prevented by addressing modifiable risk factors. Alzheimer’s disease (AD), the most common form of dementia, is preceded by up to decades of silent pathological change providing an ideal window for early detection and intervention. In this study, our objective was to examine the associations between modifiable risk factors and plasma phosphorylated p‐tau 181, a hallmark biomarker of early AD.MethodParticipants were recruited from the Island Study Linking Ageing and Neurodegenerative Disease (ISLAND), a prospective public health initiative in Tasmania, Australia’s southernmost island state. ISLAND participants were invited to complete a set of surveys online: a questionnaire on dementia risk factor adherence, demographic surveys and cognitive tests via the Cambridge Neuropsychological Test Automated Battery (CANTAB); Paired Associates Learning (PAL) and Spatial Working Memory (SWM). At four clinics across the state, participants also provided blood samples for measurement of plasma phosphorylated p‐tau 181 and genotyping for APOE.ResultA total of 738 participants (mean age 65.41 years, mean education 17.36 years, 71.8% female, 26.4% ε4+) took part in the study. We found gender‐specific effects on cognition, whereby identifying as male was associated with significantly lower learning ability (PAL) whilst identifying as female was associated with significantly lower executive function (SWM). In multivariate linear models, increasing alcohol consumption (measured in standard drinks per week) was significantly associated with lower plasma p‐tau 181. In adjusted models, no other modifiable risk factors examined were associated with p‐tau 181. Increasing age, identifying as male and possessing at least one APOE ε4 allele were all associated with higher plasma concentrations of p‐tau 181ConclusionHigher alcohol consumption, higher age, identifying as male and having an APOE ε4 allele were all associated with lower plasma phosphorylated tau 181. This contributes to evidence that both modifiable and non‐modifiable dementia risk factors are related to the biological precedents of AD. These associations were related to gender and genetics, therefore a panel of modifiable and non‐modifiable variables should be included in screening or diagnostic testing for pre‐clinical AD. More research is needed regarding specific alcohol types and biomarkers of AD.

Comparing the Classic Paired Associates Learning Task with a new Smartphone‐Based Version of the Task

AbstractBackgroundPAL is a well‐known and trusted task with good sensitivity to deficiencies in memory capabilities as has been shown in hundreds of studies over the past two decades. There has been considerable interest in a smartphone version of PAL that can be used remotely, and Cambridge Cognition has now completed work on the first production version of this task. Here, we show how the task compares with classic PAL, in an online within‐subjects study. PAL may be used in repeated assessments, and one notable feature is that performance tends to improve most strongly between a first and second attempt at the task. We therefore included a first smartphone ‘Familiarisation’ session on Day One, before the Days Two and Three web and smartphone sessions.MethodWe obtained PAL scores from 76 adults (43m, 33f) aged 50+ (M = 56.3, SD = 5.46) using the Prolific online cognitive testing platform for this three‐day crossover‐design study. Participants were divided into two groups. In a first ‘Familiarisation’ session, all participants used their smartphones to complete a PAL assessment, then on Day Two, one group used the web‐based assessment, and the other used smartphone assessment, and on the last day each group changed device from the previous day’s session, as well as a questionnaire about their experience and comparison of the task in different devices.ResultWe found that test‐retest reliability between the tasks was very good (Pearson’s r &gt; .7) between the first (‘Familiarisation’) session and Day Two, and then excellent (Pearson’s r &gt; .8) between mobile and web devices on Day Two and Day Three of the study. Next, when comparing performance across the two groups (web‐first, and smartphone‐first), bias was not significant and numerically a very small 0.2 adjusted error points. A significant improvement was seen between Familiarisation and Day Two, but not second and third, supporting the value of a familiarisation session.ConclusionWe found that the new smartphone version is highly comparable to the classic version of the task, and that familiarisation using PAL on smartphone is effective, generalising across both task versions.

Comparing the Classic Paired Associates Learning Task with a new Smartphone‐Based Version of the Task

AbstractBackgroundPAL is a well‐known and trusted task with good sensitivity to deficiencies in memory capabilities as has been shown in hundreds of studies over the past two decades. There has been considerable interest in a smartphone version of PAL that can be used remotely, and Cambridge Cognition has now completed work on the first production version of this task. Here, we show how the task compares with classic PAL, in an online within‐subjects study. PAL may be used in repeated assessments, and one notable feature is that performance tends to improve most strongly between a first and second attempt at the task. We therefore included a first smartphone ‘Familiarisation’ session on Day One, before the Days Two and Three web and smartphone sessions.MethodWe obtained PAL scores from 76 adults (43m, 33f) aged 50+ (M = 56.3, SD = 5.46) using the Prolific online cognitive testing platform for this three‐day crossover‐design study. Participants were divided into two groups. In a first ‘Familiarisation’ session, all participants used their smartphones to complete a PAL assessment, then on Day Two, one group used the web‐based assessment, and the other used smartphone assessment, and on the last day each group changed device from the previous day’s session, as well as a questionnaire about their experience and comparison of the task in different devices.ResultsWe found that test‐retest reliability between the tasks was very good (Pearson’s r &gt; .7) between the first (‘Familiarisation’) session and Day Two, and then excellent (Pearson’s r &gt; .8) between mobile and web devices on Day Two and Day Three of the study. Next, when comparing performance across the two groups (web‐first, and smartphone‐first), bias was not significant and numerically a very small 0.2 adjusted error points. A significant improvement was seen between Familiarisation and Day Two, but not second and third, supporting the value of a familiarisation session.ConclusionWe found that the new smartphone version is highly comparable to the classic version of the task, and that familiarisation using PAL on smartphone is effective, generalising across both task versions.

Reliability of VPA Learning Over Repeat Exposures Across an Extended Interval Using Automated Remote Method

AbstractBackgroundThe current study examined the test‐retest reliability of a newly developed Learning Over Repeat Exposures (LORE) paradigm using Verbal Paired‐Associates. This LORE paradigm involves the acquisition of a set of 8 verbal paired associates over a 5‐day “burst”. In this investigation, two bursts, separated by a nine‐month interval, were compared to assess the stability of novel learning outcome measures, such as the learning slope (between day 1 and the day of max performance) and first overnight forgetting.MethodAn opportunistically recruited sample of 14 participants (out of an initial pilot study of N = 20) completed the VPA‐LORE task using the Cambridge Cognition ‘NeuroVocalix’ platform, which employs text‐to‐speech and automated speech recognition technology to remotely administer and score the task, enabling its potential use at scale. The task structure consists of an immediate recall following presentation on the first day of a burst, and a single recall attempt followed by a presentation on subsequent days. As with the pilot study, neither floor nor ceiling effects were observed, and performance was in the expected range.ResultThe observed moderate to strong correlations between the two bursts revealed good reliability for the measures examined: learning slope from day 1 to day of max score, r s = .815, first day immediate recall, r s = .736, max pairs learned, r s = .707, and day 1 forgetting r s = .702. In total, participants missed only a few visits, with six missing sessions out of a total of 140 sessions, representing 4.3% of all sessions. The retention of 14 participants from the original pilot study also highlights the feasibility and acceptability of this method.ConclusionThese results suggest that the VPA‐LORE paradigm, delivered via the NeuroVocalix platform, is a stable and reliable assessment tool even when considering extended intervals between bursts and accounting for missing data. The novel learning measures derived from the VPA‐LORE paradigm provide valuable insights into learning processes and could further enhance cognitive assessment. Future research could explore the applicability of the paradigm for clinical populations and longitudinal studies in cognitive assessment.

Exploring the Behaviour, Reliability, and Usability of a new Smartphone Version of Paired Associates Learning

AbstractBackgroundPAL is a well‐known and trusted task with good sensitivity to deficiencies in memory capabilities. There has been considerable interest in a smartphone version of PAL, and Cambridge Cognition has now completed work on smartphone PAL. Parallel work has shown that this new version of PAL is of equivalent difficulty to the existing classic PAL, and this study addresses characteristics of the smartphone version alone, in a well‐powered within‐subjects study designed to assess test‐retest reliability, bias, and the usefulness of a familiarisation session, as well as exploring usability.MethodWe obtained three PAL scores over three consecutive days in 86 (31 m, 55 f) participants aged 55+ (M = 57.6, SD = 5.65) via the Prolific online platform. Each day participants used their own devices to complete the smartphone PAL task. We analysed adjusted error scores up to eight‐box problems, with participants showing extreme score fluctuations (M +/‐ 3xSD) excluded on the basis that the task was not taken under comparable conditions. We analysed test‐retest reliability using Pearson correlations of scores over the three days and analysed the effect of a familiarisation session by looking at mean scores over three days.ResultThere was some attrition of users due to technical issues in the prototype version of the task, but adherence was good, and participants reported high levels of task enjoyment and satisfaction. Test‐retest reliability between familiarisation and Day Two was good, r = .63, and very good between Day Two and Day Three, r = .7. Analysis of mean scores showed that the familiarisation session had a significant effect, with task learning between familiarisation and Day Two significantly greater than between Day Two and Day Three. Participants reported good enjoyment of the task, and overwhelmingly described usability characteristics in positive terms.ConclusionThis study highlights the value of a familiarisation session in reducing learning effects, and, like classic PAL, shows good to very good reliability. Moreover, PAL on a smartphone was well‐liked by these older participants, supporting its use in older populations.

Exploring the Behaviour, Reliability, and Usability of a new Smartphone Version of Paired Associates Learning

AbstractBackgroundPAL is a well‐known and trusted task with good sensitivity to deficiencies in memory capabilities. There has been considerable interest in a smartphone version of PAL, and Cambridge Cognition has now completed work on smartphone PAL. Parallel work has shown that this new version of PAL is of equivalent difficulty to the existing classic PAL, and this study addresses characteristics of the smartphone version alone, in a well‐powered within‐subjects study designed to assess test‐retest reliability, bias, and the usefulness of a familiarisation session, as well as exploring usability.MethodWe obtained three PAL scores over three consecutive days in 86 (31 m, 55 f) participants aged 55+ (M = 57.6, SD = 5.65) via the Prolific online platform. Each day participants used their own devices to complete the smartphone PAL task. We analysed adjusted error scores up to eight‐box problems, with participants showing extreme score fluctuations (M +/‐ 3xSD) excluded on the basis that the task was not taken under comparable conditions. We analysed test‐retest reliability using Pearson correlations of scores over the three days and analysed the effect of a familiarisation session by looking at mean scores over three days.ResultsThere was some attrition of users due to technical issues in the prototype version of the task, but adherence was good, and participants reported high levels of task enjoyment and satisfaction. Test‐retest reliability between familiarisation and Day Two was good, r = .63, and very good between Day Two and Day Three, r = .7. Analysis of mean scores showed that the familiarisation session had a significant effect, with task learning between familiarisation and Day Two significantly greater than between Day Two and Day Three. Participants reported good enjoyment of the task, and overwhelmingly described usability characteristics in positive terms.ConclusionThis study highlights the value of a familiarisation session in reducing learning effects, and, like classic PAL, shows good to very good reliability. Moreover, PAL on a smartphone was well‐liked by these older participants, supporting its use in older populations.