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Background: Cognitive impairment is common in multiple sclerosis (MS) but not adequately monitored by Expanded Disability Status Scale assessment. The Audio Recorded Cognitive Screen (ARCS) and Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) are easy-to-use tools to assess cognitive function in clinical practice., Objective: To compare the sensitivity of ARCS to BICAMS and their relative predictive value for employment status., Methods: MS patients and healthy controls were assessed using the ARCS and the BICAMS consecutively. Receiver Operating Characteristic (ROC) curve analyses were used to compare the two tests. A step-wise, logistic regression analysis was used to identify the cognitive test(s) that best predicted employment status and quality of life., Results: Total ARCS, memory and attention domain scores were moderately correlated with all BICAMS tests (r = 0.3-0.5; P ≤ 0.05). Total ARCS predicts cognitive impairment with good sensitivity and specificity relative to the BICAMS tests (AUC = 0.8; P = 0.00045). Total ARCS detects higher levels of impairment than BICAMS in MS patients (44% versus 21%). The memory domain of the ARCS and the BVMT-R were the best predictors of employment status (OR = 1.12 and 1.14, P < 0.05)., Conclusion: BICAMS and ARCS have comparable sensitivity for cognitive impairment in MS. Memory assessment from either tests is the best predictor of employment status; however, the BICAMS is a better predictor of work productivity., (Crown Copyright © 2020. Published by Elsevier B.V. All rights reserved.)

Background: Monitoring for cognitive deficits during a course of electroconvulsive therapy (ECT) is recommended, but cognitive assessment can be time consuming. The Audio Recorded Cognitive Screen (ARCS) is a cognitive test instrument with good psychometric properties that places minimal demands on clinicians' time, but until now, it has not been formally evaluated for monitoring cognition in the context of ECT treatment., Objectives: This study aimed to assess the feasibility/utility of using the ARCS in the assessment of depressed patients undergoing ECT., Methods: Depressed patients undergoing ECT were tested with the ARCS and a comparison instrument, the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), in counterbalance order immediately before any ECT and after the sixth ECT treatment episode. Apathy (Apathy Scale) and depression (Profile of Mood states Short Form) were measured on both occasions. Analyses compared performances on the 2 cognitive instruments and examined for associations with the measures of apathy or depression., Results: Twenty-eight individuals (9 male, 19 female) aged 19 to 84 years underwent testing. Performances on the total ARCS were similar to those on the total RBANS, and both showed decline from baseline to follow-up. The total ARCS and RBANS measures correlated well (r = 0.75, P < 0.001). Neither apathy nor depression scores were significantly associated with scores on either the RBANS or ARCS., Conclusions: The ARCS was acceptable and convenient in the assessment of cognition in patients undergoing treatment with ECT. In light of its practical advantages, further evaluation of the ARCS for detecting cognitive impairment and tracking cognitive changes during ECT seems warranted.

Background: Cognitive impairment is a common complication of multiple sclerosis, even in early stage disease, with significant impacts on life quality and social interaction. However, its detection is highly test-dependent., Objective: To validate a recently described screening tool, the ARCS, for detecting cognitive impairment in a multiple sclerosis population., Methods: The ARCS administers tests of executive function, memory, visual spatial construction and language via an audio device to unsupervised patients who write their responses for later scoring. Some 127 patients with a wide variety of disease course and severity were assessed by ARCS, of whom 87 also completed the Paced Auditory Serial Addition Test (PASAT) and 45 underwent formal ('gold standard') neuropsychological testing., Results: Compared with PASAT, we found that the ARCS showed better sensitivity (86% versus 68%) at equivalent specificity (71%) for detection of impairment in any cognitive domain, and superiority in the detection of memory and executive impairments. Acceptance and completion rates for the ARCS were as good or better than for the PASAT., Conclusions: ARCS is sensitive, well-tolerated, easy to administer and facilitates comprehensive cognitive assessment in less than 5 min of clinician time. It has several advantages over the PASAT for detecting cognitive impairment in patients with multiple sclerosis.

Objective: To describe and characterise the Audio Recorded Cognitive Screen (ARCS), a novel instrument that uses an audio device to administer selected neuropsychological tests to unsupervised individuals who write their responses in a special booklet for later scoring., Methods: The ARCS was administered to 733 individuals, comprising 550 from a normative community sample (mean age=59.14, range 18-84 years), 101 clinic patients and a separate validation sample of 82 community controls, who, together with the patients, underwent detailed neuropsychological assessments. These data were examined for the influence of demographic variables on ARCS performance, to establish normal performance and develop scoring routines, and to characterise the structure, reliability and validity of the instrument., Results: Age, gender and education influenced ARCS performance. ARCS tests were generally reliable and correlated well with corresponding conventional neuropsychological tests. Factor analyses indicated that the ARCS measures executive functioning/attention, memory, language, verbal fluency and visuospatial functioning. The ARCS discriminated well between normal (n=82), impaired (n=33) and demented (n=25) individuals, and significantly better than did the Mini Mental State Examination (MMSE), including on a single, demographically adjusted, global QuickARCS score obtainable in about 3 min of the clinician's time. Receiver Operating Characteristic analyses confirmed the superiority of the ARCS over MMSE as a screen for mild dementia (AUC 0.98, 99% CI 0.95 to 1.00) or cognitive impairment (AUC 0.90, 99% CI 0.83 to 0.97)., Conclusions: The ARCS has good validity and reliability, has a sound normative base and measures functioning in multiple cognitive domains while imposing minimal time demands upon the clinician.

Objective: To contrast subjective and objective measures of neuropsychological health in F-111 aircraft Deseal/Reseal maintenance personnel, against two appropriate comparison groups., Methods: Exposed and comparison participants completed a postal questionnaire which included a validated memory questionnaire and additional questions relating to possible cognitive symptoms. They also underwent a comprehensive neuropsychological assessment and screening for a past or current disturbance of mood. Multiple linear or logistic regression was conducted for each outcome using exposure group and potential confounders as explanatory variables., Results: There was a strong and consistent excess of self-reported cognitive problems among the exposed group relative to the comparison groups including a 2.8-4.3-fold increase in self-reported symptoms of forgetfulness, loss of concentration and difficulty finding the right word. On detailed neuropsychological testing, the exposed group performed significantly worse than comparisons on tests of psychomotor speed, executive functioning, and new learning/memory. These findings could not be accounted for by disturbances of mood or other potential confounders., Conclusions: There was a strong and consistent increase in self-reported cognitive problems among the exposed, and small but significant exposure-specific differences on objective tests of cognitive functioning. The findings are consistent with the development of adverse neuropsychiatric changes related to occupational exposure to solvents.

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32,070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.

General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health- and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N=53,949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P=3.93 × 10(-9), MIR2113; rs17522122, P=2.55 × 10(-8), AKAP6; rs10119, P=5.67 × 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P=1 × 10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N=6617) and the Health and Retirement Study (N=5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e.=5%) and 28% (s.e.=7%), respectively. Using polygenic prediction analysis, ~1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N=5487; P=1.5 × 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.