Controlled Oral Word Association Test Research Articles

Editors' note: Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease

In “Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease,” authors Brodsky et al. aimed to compare motor and nonmotor outcomes at 6 months of asleep deep brain stimulation (DBS) for Parkinson disease (PD) using intraoperative imaging guidance to confirm electrode placement vs awake DBS using microelectrode recording to confirm electrode placement. They found that asleep DBS for PD was associated with improved motor outcomes over 6 months, on par with, or better than, awake DBS, and was superior with regard to speech fluency and quality of life. In the accompanying editorial, Drs. Aziz and Hariz point out that microelectrode recording (MER) should be reserved as a tool for scientific research on basal ganglia neuronal activity. The authors explain that well-visualized targets, such as the subthalamic nucleus and internal globus pallidus (GPi), can also be done while the patient is fully asleep and without MER. Commenting on the Brodsky et al. article, Dr. Sidiropoulos requests comparison between image-guided DBS surgery and MER-guided surgery and questions why the asleep group was more shifted towards GPi as a target compared to the awake cohort. Commenting on the editorial, Dr. Sidiropoulos also suggests that accurate thalamic targeting for tremor using image-guided techniques is more challenging. Dr. Aziz, author of the editorial, agrees that the subdivisions of the thalamus are not so clearly visualized. He explains, however, that using image-guided approaches is emerging and thalamic targets can be extrapolated from visualization of the red nucleus and the posterior subthalamic area. Dr. Troster also commented on the article. He asks for several clarifications regarding verbal fluency scores data, correlation between verbal fluency scores and 39-item Parkinson's Disease Questionnaire (PDQ-39) cognition and communication scores, and the effect on the Dementia Rating Scale (DRS). Brodsky et al. explain that Controlled Oral Word Association Test (COWAT) standard scores were used and that the longitudinal mixed-effects models were evaluated and confirmed previous findings. They clarify that statistical analysis of the correlation between the COWAT speech fluency scores and the cognition and communication subscores of the PDQ-39 was not performed, but that the improvement in both cohorts was significant. Finally, they explain that while the DRS is influenced by speech fluency, there were enough other factors in the DRS that counterbalanced the improvement in speech that was seen in the asleep DBS group. In “Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease,” authors Brodsky et al. aimed to compare motor and nonmotor outcomes at 6 months of asleep deep brain stimulation (DBS) for Parkinson disease (PD) using intraoperative imaging guidance to confirm electrode placement vs awake DBS using microelectrode recording to confirm electrode placement. They found that asleep DBS for PD was associated with improved motor outcomes over 6 months, on par with, or better than, awake DBS, and was superior with regard to speech fluency and quality of life.

Author response: Clinical outcomes of asleep vs awake deep brain stimulation for Parkinson disease.

We thank Dr. Tröster for the thoughtful comments on our article.1 To clarify, Controlled Oral Word Association Test (COWAT) scores were standard scores instead of raw word counts, reflected in the means and SDs pre and post deep brain stimulation (DBS) for categorical fluency (awake pre-DBS: 47.95 ± 7.28, awake post-DBS: 42.94 ± 10.45; asleep pre-DBS: 97.61 ± 17.1, asleep post-DBS: 96.95 ± 15.5) and phonemic fluency (awake pre-DBS: 47.95 ± 7.28, awake post-DBS: 42.94 ± 10.45; asleep pre-DBS: 97.61 ± 17.1, asleep post-DBS: 96.95 ± 15.5).

CORPUS CALLOSUM VOLUME AND EXECUTIVE FUNCTION: A POTENTIAL EARLY MARKER OF COGNITIVE DECLINE

Several lines of evidence suggest corpus callosum (CC) atrophy in mild cognitive impairment (MCI) and Alzheimer's Disease(AD). While MCI patients have anterior CC atrophy, AD patients have both anterior and posterior atrophy, suggesting progressive atrophy of CC in the course of AD. However, the relation between CC volume and cognitive measures in middle aged individuals without AD is not well-examined. Here, we therefore extend our earlier observations on the relation between CC regional volumes and executive functions in middle-aged individuals (50-65years). 61 healthy volunteers (female=31, age=64.09±8.06, years of education=16.90±4.00) participated in the Tata Longitudinal Study of Aging at Bangalore, India. Of these, a subset of 37 individuals were 50-65 years of age (female=21, age=58.56±4.21, years of education=17.02±4.52). All participants underwent neuropsychological testing and Magnetic Resonance Imaging (MRI) scans as per the Alzheimer's Disease Neuroimaging Initiative (ADNI) protocol. CC volumes were acquired for each individual using Freesurfer Software (http://surfer.nmr.mgh.harvard.edu/). Pearson's correlation analysis was conducted to examine the relation between CC volume and executive functions. Executive functions were tested using Controlled Oral Word Association Test (COWAT), digit span, Stroop test and Trail Making Test (TMT). At baseline (entire group), there was a significant positive correlation between COWAT-A score (higher the score, better the performance) and anterior CC-(r=0.561, p=0.001), central CC-(r=0.403,p=0.022) and posterior CC-(r=0.397,p=0.025) volumes. A significant negative correlation was seen between TMT-A Time (greater the time, poorer the performance) and mid-anterior CC-(r=-0.506,p=0.003), central CC-(r=-0.468,p=0.007), posterior CC-(r=-0.458,p=0.008), mid-posterior CC-(r=-0.424,p=0.016) and anterior CC-(r=-0.399,p=0.024) volumes; Stroop-B interference time and mid-posterior CC volume(r=-0.399,p=0.024); and Stroop-C interference time and mid-posterior CC-(r=-0.487,p=0.005), central CC-(r=-0.467,p=0.007), mid-anterior CC-(r=-0.409,p=0.020) and posterior CC-(r=-0.358,p=0.045) volumes. These findings are mirrored in the middle-aged subset, where there was a significant positive correlation between COWAT-A score and anterior CC-(r=0.558,p=0.007) and posterior CC-(r=0.479,p=0.024) volumes; and a significant negative correlation between TMT-A Time and mid-anterior CC-(r=-0.625,p=0.002), central CC-(r=-0.509,p=0.016), posterior CC-(r=-0.497,p=0.019) and anterior CC-(r=-0.469,p=0.028) volumes. Our findings indicate a significant association between CC volume and executive function. Findings suggest that those with lesser CC volume have lower executive function performance. These relationships observable in middle-age (50-65 years), indicate that CC atrophy is a potential early marker of cognitive decline. Longitudinal observations of these individuals will inform whether CC volumes are early markers of cognitive decline.

What is the prevalence of cognitive impairment in lupus and which instruments are used to measure it? A systematic review and meta-analysis.

To systematically review the literature on the prevalence of Cognitive Dysfunction (CD) in SLE patients in studies that used a specified neuropsychological instrument. This review was prepared with a protocol following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis-Protocols statement. Literature search in Ovid Medline, Embase, and Psyc INFO for articles on CD in adult SLE patients was conducted. Included studies were critically appraised (Newcastle-Ottawa Evaluation Scale) and the Pooled Prevalence (PP) of CD was studied for all instruments. The association between demographics and CD, the risk of CD in SLE compared to healthy subjects and patients with RA, and the course of CD over time were studied narratively whenever sufficient information was available. Of 8054 references, 670 were selected for detailed review and 78 were included in the final analysis. Comprehensive Battery (CB) was utilized in 35 studies in 2463 SLE patients and PP was 38% (95%; CI: 33-43%). The CD prevalence was higher in NPSLE [PP 39% (95% CI: 24-55%]. Automated Neuropsychological Assessment Metric (ANAM) was utilized in 7 studies in 438 patients (PP of CD 26% (95% CI: 12-42%). Other less frequently utilized tools were the Modified Mini-Mental State Exam (MMSE), Montreal Cognitive Assessment (MoCA), Controlled Oral Word Association Test (COWAT) and The Hopkins Verbal Learning Test-Revised (HVLT-R) and subjective tools and others. The relative risk for CD in SLE was greater when compared to RA and to healthy individuals; RR being 1.80 and 2.80, respectively. Information on demographics and its association with CD was very heterogeneous among studies. Patients with lupus have a high prevalence of CD. The delay in diagnosis of CD is complex; although caregivers and patients express concerns about cognitive function, testing for CD often imposes administrative and cost burdens. There is an unmet need to identify the best screening, diagnostic metrics of CD. The assessment of cognitive function over time, and the association of demographics with CD, will require further research.

Linguistic factors associated with phonemic fluency performance in a sample of bilingual Hispanic undergraduate students

ABSTRACTResearch has demonstrated that bilingualism impacts neuropsychological performance, but the findings on its effects on verbal fluency have been mixed. This study compared the verbal fluency performance of non-Hispanic White monolingual speakers with a Hispanic bilingual population. Ninety-nine Spanish-English bilingual Hispanic and thirty English-speaking monolingual non-Hispanic White undergraduates completed the Controlled Oral Word Association Test (COWAT). Students also completed a general cognitive and English reading measure. Bilingual students completed an in-depth language questionnaire to gauge language dominance, age of acquisition of second language (AoA), and first language learned. Results revealed that both language dominance and AoA influence phonemic fluency performance in bilingual Hispanics. English-dominant and balanced bilingual students performed similarly to monolingual students. Spanish-dominant bilingual students scored lower than monolinguals or the other bilingual groups. Bilingual students with early AoA (<7 years) performed on par with monolingual students. Late AoA bilinguals performed significantly lower than early AoA bilinguals. Results illustrate the clinical importance of obtaining a full linguistic history of bilingual clients in order to accurately interpret verbal fluency performance, as this is essential for proper diagnoses and treatments.

Cognitive Changes with Omega-3 Polyunsaturated Fatty Acids in Non-Demented Older Adults with Low Omega-3 Index.

To investigate the changes in specific domains of cognitive function in older adults reporting subjective memory complaints with a low omega-3 index receiving omega 3 polyunsaturated fatty acid (n-3 PUFA) supplementation or placebo. This is a secondary exploratory analysis of the Multidomain Alzheimer Preventive Trial (MAPT) using subjects randomized to the n-3 PUFA supplementation or placebo group. French community dwellers aged 70 or over reporting subjective memory complaints, but free from clinical dementia. A subgroup of MAPT subjects in the lowest quartile of omega-3 index distribution with baseline values ≤ 4.83 % (n = 183). The n-3 PUFA supplementation group consumed a daily dose of DHA (800 mg) and EPA (a maximum amount of 225 mg) for 3 years. The placebo group received identical capsules comprising liquid paraffin oil. Linear mixed-model repeated-measures analyses were used including baseline, 6, 12, 24 and 36-month follow-up data to assess between-group differences in the change in eight cognitive tests over 36 months. There was less decline on the Controlled Oral Word Association Test (COWAT) in the n-3 PUFA supplementation group compared to placebo (p = 0.009; between group mean difference over 36 months, 2.3; 95% CI, 0.6,4.0). No significant differences for any of the other cognitive tests were found, including other tests of executive functioning, although, numerically all results were in favour of the n-3 PUFA supplementation. We found some evidence that n-3 PUFAs might be beneficial for the maintenance of executive functioning in older adults at risk of dementia with low omega-3 index, but this exploratory finding requires further confirmation. A larger specifically designed randomised controlled trial could be merited.

Neurocognitive function testing and health related quality of life in stage IV lung cancer patients with and without brain metastases.

2073 Background: Survival in stage IV lung cancer (S4LC) patients (pts) continues to improve, highlighting the importance of assessing health related quality of life (HRQoL). Lung cancer, involvement with brain metastases (BM), and systemic or brain-specific treatment can all impact neurocognitive function (NCF) and HRQoL. We evaluated the relationship between NCF and HRQoL in S4LC pts by BM status. Methods: S4LC pts with BM (BM+) were frequency distributionally-matched to pts without BM (NBM). NCF was measured using the Hopkins Verbal Learning Test – Revised (HVLT-R), the Controlled Oral Word Association Test (COWAT) and Trail Making Tests (TMT-A/B); scores were correlated with health utility score (HUS) data from EQ5D-3L surveys (Pearson Coefficient, R). Results: BM+ (n = 54) and matched NBM (n = 40) pts had similar demographics. The overall median age was 61years; 59% were female; of 89% that were adenocarcinomas, half had EGFR/ALK alterations; mean time since diagnosis was 2.6 years; mean time since BM were diagnosed in BM+ pts was 0.5 years. Mean HUS (mHUS) were similar between groups: 0.77 for BM+ vs. 0.78 for NBM; p = 0.86. However, pts with stable BM had higher HUS than those with progressive BM (mHUS: 0.80 vs 0.69; p = 0.045). Of BM+ pts, 44% had received whole brain radiation (WBRT). Correlations of NCF and HUS specific for BM+ pts were observed for several HLVT scores, including Total Recall (TR), which was correlated with HUS in BM+ (R = 0.35, p = 0.01) but not in NBM (R = 0.04, p = 0.84) and Recognition Discrimination Index (BM+: R = 0.32, p = 0.03 vs NBM: R = 0.13, p = 0.51). In contrast, TMT-A/B NCF test results had slightly stronger associations with HUS in NBM pts. COWAT was least associated with HUS in BM+ or NBM pts. In BM+ pts treated vs untreated with WBRT, HLVT scores were better in untreated patients (TR, p &lt; 0.0001; delayed recall, p = 0.006; retention, p = 0.089), associations not seen with either TMT-A/B or COWAT. Mutation status had no bearing on these associations. Conclusions: NCF impacts HUS in S4LC pts and should be considered in treatment planning. HVLT scores are useful to assess specifically the impact of BM and WBRT in S4LC pts, and is reflected in associations with HRQoL.

Distinct cognitive performance and patterns of drug use among early and late onset cocaine users

IntroductionAdolescence is a crucial period for neurodevelopment, but few studies have investigated the impact of early cocaine use on cognitive performance and patterns of substance use. MethodsWe evaluated 103 cocaine dependent inpatients divided in two groups: early-onset users (EOG; n=52), late-onset users (LOG; n=51), and 63 healthy controls. Neuropsychological functioning was evaluated using Digits Forward (DF) and Backward (DB), Trail Making Test (TMT), Stroop Color Word Test (SCWT), Controlled Oral Word Association Test (COWAT), Wisconsin Card Sorting Test (WCST), Rey Osterrieth Complex Figure Test (ROCFT), Frontal Assessment Battery (FAB), and Iowa Gambling Test (IGT). Use of alcohol and other drugs was assessed with the Addiction Severity Index (ASI-6). ResultsAnalyses of covariance controlling for age, IQ and years of education showed that EOG presented worse performance in attention span (DF, p=0.020), working memory (DB, p=0.001), sustained attention (WCST, p=0.030), declarative memory (ROCFT, p=0.031) and general executive functioning (FAB, p=0.003) when compared with the control group. LOG presented impairments on divided attention (TMT, p=0.003) and general executive functioning (FAB, p=0.001) in relation to the control group. EOG presented higher use of cannabis and alcohol than LOG (p≤0.001). ConclusionEarly-onset cocaine users display more pronounced neuropsychological alterations than controls, as well as a greater frequency of polydrug consumption than LOG. The prominent cognitive deficits in EOG probably reflect the deleterious interference of cocaine use with early stages of neurodevelopment. This may be related to more severe clinical characteristics of substance disorder in this subgroup, including polysubstance abuse.

Obese Adolescents Show Reduced Cognitive Processing Speed Compared with Healthy Weight Peers.

Childhood obesity and obesity-associated diabetes and metabolic syndrome (MetS) continue to rise. Obesity has been linked to structural and functional brain abnormalities, particularly in the frontal lobe. One hundred sixty-two adolescents (aged 19.53 ± 1.53 years) underwent medical, neurocognitive, and brain magnetic resonance imaging assessments. Participants were either healthy weight (BMI <25.0 kg/m2 or BMI percentile <85%) or obese (BMI ≥30.0 kg/m2 or BMI percentile ≥95%). We evaluated frontal lobe cognitive functions and the size of the corpus callosum (CC). Groups differed on four measures of processing speed contained in four different cognitive tests, but not on executive function. A confirmatory factor analysis verified that the significant processing speed variables loaded on the same factor. We also found differences between the weight groups on the area of the anterior portion of the CC, but not the overall CC. Only the Controlled Oral Word Association Test (COWAT) was significantly correlated with the area of the anterior portion of the CC. In the obese group, 32.4% met criteria for MetS. No differences were found between obese participants with or without MetS and none of the MetS factors contributed consistently to cognitive performance. Obese adolescents show slower cognitive processing speed while maintaining equivalent performance on executive functioning compared with their healthy weight peers. The group differences in the anterior portion of the CC, responsible for frontal lobe interhemispheric communication, may in part explain our processing speed findings. Future studies should include a longitudinal design and diffusion tensor imaging to examine the integrity of white matter.

P267 Fronto-executive cognitive functioning predicts antidepressant response to transcranial direct current stimulation

Introduction Transcranial direct current stimulation (tDCS) is a promising new treatment for depression, however, clinical trials to-date indicate variable efficacy, thereby raising the need to identify inter-individual predictors of response. Objective In the current study we aimed to investigate pre-treatment neurocognitive performance as a predictor of antidepressant response to tDCS. Materials and methods Data was pooled from five clinical trials, including two randomised controlled trials (RCTs), which investigated the antidepressant effects of anodal tDCS (1–2 mA) administered to the prefrontal cortex for 20 min over a course of between 10 and 20 sessions. Data from 71 cases was included in the analysis. Mood was assessed before and after an acute course of treatment using the Montgomery-Asberg Depression Rating Scale. The following neurocognitive tests were administered prior to treatment: Simple and choice reaction time, the Symbol Digit Modalities Test (SDMT), Rey Auditory Verbal Memory Task (RAVLT), Digit Span, and the Controlled Oral Word Association Test (COWAT). Results Better pre-treatment fronto-executive functioning, as indicated by SDMT and COWAT performance, predicted antidepressant response to tDCS after controlling for confounds. A cognitive composite which comprised from both SDMT and COWAT performance independently predicted better antidepressant response in an adjusted model (β = −.35, p = .001). Higher depressive severity at pre-treatment was a negative predictor of antidepressant response (β = .36, p = .001). Conclusions Pre-treatment fronto-executive functioning on measures subserved by the left prefrontal cortex, the site of stimulation, is a predictor of response for tDCS treatment for depression. This study highlights the importance of inter-individual neurobiological differences in mediating tDCS antidepressant effects.

The impact of neurocognitive function on health utility scores (HUS) in Stage 4 (S4) lung cancer patients (pts) with and without brain metastases (BrM).

225 Background: As targeted therapies for S4LC pts have improved survival, the impact of health-related quality of life (HRQoL) in these pts grows in importance. In pts with BrM, loss of NCF may affect HRQoL significantly. We evaluated the relationship between NCF and HUS as a measure of HRQoL in S4LC pts. Methods: Self-reported HUS data from EQ5D-3L were obtained cross-sectionally from S4LC pts with (BrM) or without BrM (non-BrM). NCF was measured using the Hopkins Verbal Learning Test – Revised (HVLT-R), the Controlled Oral Word Association Test (COWAT) and Trail Making Tests (TMT-A/B). NCF scores were correlated with HUS (Pearson Coefficient, R). Results: BrM (n = 54) and non-BrM (n = 40) patients had similar demographics- overall median age was 61 (range 33-89) years; 59% were female; 45% had EGFR/ALK alterations; BrM pts were treated with whole brain (n = 20), stereotactic radiation (n = 19), both (n = 6), or sole use of systemic agents (n = 6); 3 were observed; 7 had BrM resection. Overall HUS were similar between BrM and non-BrM groups (mean HUS (mHUS): 0.77 vs. 0.78; p = 0.86). However, pts with stable brain disease had higher HUS than those with progressive brain disease (mHUS: 0.80 (n = 36) vs 0.69 (n = 17); p = 0.045). There was a trend towards lower HUS in symptomatic vs. asymptomatic BrM (mHUS: 0.70 (n = 10) vs. 0.78 (n = 43); p = 0.07). Multiple correlations between NCF scores and HUS were found. HLVT-Total Recall correlated with HUS in BrM but not non-BrM (R=0.35, p = 0.01; vs. non- R=0.04, p = 0.84 respectively) as did the HLVT-Recognition (BrM: R=0.32, p = 0.03 vs. non-BrM: R=0.13, p = 0.51). In contrast, TMT-A/B were associated with HUS in both BrM (p = 0.03, 0.06) and non-BrM pts (p = 0.001, 0.03). COWAT was associated with HUS only when all pts were analyzed together (p = 0.04). Conclusions: In S4LC pts, HUS were correlated with multiple measures of NCF. The impact of uncontrolled brain disease and poor NCF on HUS demonstrates that this measure has clinical utility, with important HRQoL implications as metastatic lung cancer pts live longer.

Measurement of Peripheral Vision Reaction Time Identifies White Matter Disruption in Patients with Mild Traumatic Brain Injury.

This study examined whether peripheral vision reaction time (PVRT) in patients with mild traumatic brain injury (mTBI) correlated with white matter abnormalities in centroaxial structures and impairments in neuropsychological testing. Within 24 h after mTBI, crossed reaction times (CRT), uncrossed reaction times (URT), and crossed-uncrossed difference (CUD) were measured in 23 patients using a laptop computer that displayed visual stimuli predominantly to either the left or the right visual field of the retina. The CUD is a surrogate marker of the interhemispheric transfer time (ITT). Within 7 days after the injury, patients received a diffusion tensor-MRI (DTI) scan and a battery of neuropsychological tests. Nine uninjured control subjects received similar testing. Patients 18-50 years of age were included if they had a post-resuscitation Glasgow Coma Scale >13 and an injury mechanism compatible with mTBI. Healthy controls were either age- and gender-matched family members of the TBI patients or healthy volunteers. CUD deficits >2 standard deviations (SD) were seen in 40.9% of patients. The CUD of injured patients correlated with mean diffusivity (MD) (p < 0.001, ρ = -0.811) in the posterior corpus callosum. Patients could be stratified on the basis of CUD on the Stroop 1, Controlled Oral Word Association Test (COWAT), and the obsessive-compulsive component of the Basic Symptom Inventory tests. These studies suggest that the PVRT indirectly measures white matter integrity in the posterior corpus callosum, a brain region frequently damaged by mTBI.

Statin Use and Cognitive Impairment in Patients With Type 1 Diabetes: An Observational Study.

We aimed to assess a wide range of cognitive functions in patients with type 1 diabetes (DM1) compared with healthy control subjects and to evaluate the effects of statins on cognitive functions in DM1 patients. The sample studied consisted of 55 DM1 patients (80.0% with hyperlipidemia, 20% with statin treatment) and 36 age-matched control subjects (77.8% with hyperlipidemia) without diabetes or statin use. Their cognitive functions (attention, memory, and executive functions) were evaluated with the trail making test, controlled oral word association test (COWAT), Rey-Osterrieth complex figure test, brain damage test (diagnosticum für cerebralschädigung, DCS), Wisconsin card sorting test (WCST), and digit span and block design tests from the revised Wechsler adult intelligence scale. Cognitive performance was impaired in DM1 patients when compared with the control group with regard to semantic verbal fluency (COWAT_animals), visual learning (DCS), conceptual-level responses, executive functions (WCST random errors), and WCST trials to complete the first category. Subgroups of DM1 patients distinguished on the basis of statin therapy did not differ with regard to verbal fluency (COWAT_animals), visual learning (DCS), conceptual-level responses, executive functions (WCST random errors), and WCST trials to complete the first category. Multivariate analysis also does not show the impact of statin therapy on cognitive functioning regardless of the duration of education, microangiopathic evidence, the presence of hyperlipidemia, or antihypertensive therapy. We find impairment of cognitive functions in DM1 patients when compared with control subjects without diabetes. However, we show neither the effect of statins nor the significant influence of metabolic control, microangiopathic complications, or the presence of hyperlipidemia on cognitive functions in DM1 patients.

Disparities in Age-Associated Cognitive Decline Between African-American and Caucasian Populations: The Roles of Health Literacy and Education.

To examine health literacy as a mediator of racial disparities in cognitive decline as measured by executive function in elderly adults. Prospective cohort study. Secondary analysis of ElderWalk trial in Boston, Massachusetts. English-speaking African-American and Caucasian individuals in a walking intervention for community-dwelling adults aged 65 and older without dementia at baseline who completed baseline and 12-month evaluations (N = 198). Health literacy was measured using the Short Test of Functional Health Literacy in Adults. Fluid and crystallized cognitive functions were measured at baseline and 12 months using the Trail-Making Test Part B minus Part B (TMT B-A) and the Controlled Oral Word Association Test (COWAT). Associations between health literacy and 12-month cognitive decline were modeled using multivariate linear regression. Participants with higher health literacy and education experienced less cognitive decline than those with limited health literacy according to the TMT B-A (P = .01). After adjusting for covariates, Caucasian participants (n = 63) experienced less decline than African-American participants (n = 135) on TMT B-A (P = .001) and COWAT (P = .001). Adjusting for health literacy led to a 25.3% decrease in the point estimate for racial difference in TMT B-A and a 19.5% decrease in COWAT. Although independently related to cognitive decline, educational attainment did not mediate racial differences. Health literacy is a partial mediator of racial disparities in cognitive decline. These results indicate the need to develop interventions to mitigate cognitive decline that individuals with low heath literacy can use and to modify the healthcare environment to better accommodate this population.

Assessing the criterion validity of four highly abbreviated measures from the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS)

Objective: Cognitive dysfunction is prevalent in multiple sclerosis. As self-reported cognitive functioning is unreliable, brief objective screening measures are needed. Utilizing widely used full-length neuropsychological tests, this study aimed to establish the criterion validity of highly abbreviated versions of the Brief Visuospatial Memory Test – Revised (BVMT-R), Symbol Digit Modalities Test (SDMT), Delis–Kaplan Executive Function System (D-KEFS) Sorting Test, and Controlled Oral Word Association Test (COWAT) in order to begin developing an MS-specific screening battery. Method: Participants from Holy Name Medical Center and the Kessler Foundation were administered one or more of these four measures. Using test-specific criterion to identify impairment at both −1.5 and −2.0 SD, receiver-operating-characteristic (ROC) analyses of BVMT-R Trial 1, Trial 2, and Trial 1 + 2 raw data (N = 286) were run to calculate the classification accuracy of the abbreviated version, as well as the sensitivity and specificity. The same methods were used for SDMT 30-s and 60-s (N = 321), D-KEFS Sorting Free Card Sort 1 (N = 120), and COWAT letters F and A (N = 298). Results: Using these definitions of impairment, each analysis yielded high classification accuracy (89.3 to 94.3%). Conclusions: BVMT-R Trial 1, SDMT 30-s, D-KEFS Free Card Sort 1, and COWAT F possess good criterion validity in detecting impairment on their respective overall measure, capturing much of the same information as the full version. Along with the first two trials of the California Verbal Learning Test – Second Edition (CVLT-II), these five highly abbreviated measures may be used to develop a brief screening battery.

Pre-treatment letter fluency performance predicts antidepressant response to transcranial direct current stimulation

BackgroundTranscranial direct current stimulation (tDCS) is a promising new treatment for depression, however, clinical trials to-date indicate variable efficacy, thereby raising the need to identify inter-individual predictors of response. In the current study we aimed to investigate pre-treatment neurocognitive performance as a predictor of antidepressant response to tDCS. MethodsData was pooled from five clinical trials, including two randomised controlled trials (RCTs), which investigated the antidepressant effects of anodal tDCS administered to the prefrontal cortex. Data from 57 patients were included in the analysis. Mood was assessed before and after an acute course of treatment using the Montgomery–Åsberg Depression Rating Scale. The following neurocognitive tests were administered prior to treatment: Simple and choice reaction time, the Symbol Digit Modalities Test (SDMT), Rey Auditory Verbal Memory Task (RAVLT), Digit Span, and the Controlled Oral Word Association Test (COWAT). ResultsBetter pre-treatment letter fluency performance measured using the COWAT predicted antidepressant response to tDCS after controlling for confounds. LimitationsSmall sample size and analysis included data from both RCTs and open label studies. ConclusionPre-treatment letter fluency performance, an ability subserved by the left prefrontal cortex, the primary site of stimulation, is a predictor of response for tDCS treatment for depression. This study highlights the importance of inter-individual neurobiological differences in mediating tDCS antidepressant effects.

Effects of Aerobic Exercise Modality on Cognitive Outcomes among Breast Cancer Survivors

Breast cancer has relatively high incidence and high survival rates, demonstrating that there is an ever-increasing population of survivors in the United States. These women frequently suffer from ongoing cognitive dysfunction, which hinders memory, work performance, and ability to complete activities of daily living. Exercise has been shown to improve results on objective cognitive tests in several clinical populations, but this has not been studied among recent breast cancer survivors. PURPOSE: This study was conducted to determine whether aerobic exercise is an effective intervention for improving cognition among recent breast cancer survivors. METHODS: Twenty breast cancer survivors who completed their primary treatment in the past 3 months were randomly assigned to 12 weeks of an aerobic exercise intervention (INT) or a sedentary control group (CON). The intervention group attended moderately intense exercise classes, 3 days each week, while the control group maintained their normal, inactive lifestyle. All participants completed pre/post cognitive testing utilizing the Trail Making Test (TMT-A), Controlled Oral Word Association Test (COWAT), and Design Fluency Trials 1-3 (DF1, DF2, DF3). Data was analyzed with repeated measures ANOVA. RESULTS: Executive function increased in INT vs. CON on scaled scores (SS) from DF1 (CON 11.71±3.5 vs. 10.86±3.0; INT 11.69±4.3 vs. 13.92±3.7, p=0.44). There was also a trend toward greater improvement in INT vs. CON on DF1+DF2 SS (CON 11.29±2.6 vs. 11.57±2.6; INT 12.23±3.4 vs. 14.38±3.4, p=0.178) and on DF1+DF2+DF3 SS (CON 11.43±2.4 vs. 11.86±2.7; INT 12.46±3.3 vs. 13.92±3.3, p=0.364). Education adjusted scores of attention and processing speed on TMT-A did not improve significantly in either group, but showed a slight trend toward greater speed in INT vs. CON (CON 25.12±8.6 vs. 24.39±9.8; INT 25.49±7.5 vs. 22.28±5.5, p=0.459). COWAT scores of verbal fluency did not appear to be affected by aerobic exercise (CON 37.43±14.8 vs. 36.43±15.8; INT 47.69±16.5 vs. 51.46±18.3, p=0.264). CONCLUSIONS: Aerobic exercise can improve several domains of cognitive function in breast cancer survivors when compared to usual care. Given a longer time-frame and larger sample size, these benefits would likely be more pronounced.

Telephone based cognitive-behavioral screening for frontotemporal changes in patients with amyotrophic lateral sclerosis (ALS)

Our objective was to establish a valid and reliable battery of measures to evaluate frontotemporal dementia (FTD) in patients with ALS over the telephone. Thirty-one subjects were administered either in-person or by telephone-based screening followed by the opposite mode of testing two weeks later, using a modified version of the UCSF Cognitive Screening Battery. Equivalence testing was performed for in-person and telephone based tests. The standard ALS Cognitive Behavioral Screen (ALS-CBS) showed statistical equivalence at the 5% significance level compared to a revised phone version of the ALS-CBS. In addition, the Controlled Oral Word Association Test (COWAT) and Center for Neurologic Study-Lability Scale (CNS-LS) were also found to be equivalent at the 5% and 10% significance level, respectively. Similarly, the Mini-Mental State Examination (MMSE) and the well-established Telephone Interview for Cognitive Status (TICS) were also statistically equivalent. Equivalence could not be claimed for the ALS-Frontal Behavioral Inventory (ALS-FBI) caregiver interview and the Written Verbal Fluency Index (WVFI). In conclusion, our study suggests that telephone-based versions of the ALS-CBS, COWAT, and CNS-LS may offer clinicians valid tools to detect frontotemporal changes in the ALS population. Development of telephone based cognitive testing for ALS could become an integral resource for population based research in the future.

Agomelatine vs fluoxetine: Efficacy and improvement of cognitive functions in patients with MDD

IntroductionIn major depressive disorder (MDD) neurocognitive functions are impaired. In addition to melatonergic properties of agomelatine, via 5-HT2C antagonism it increases extracellular noradrenaline and dopamine in frontal cortex and may improve the neurocognitive functions of patients with MDD.Aims and objectivesTo investigate the extent of neurocognitive improvement and efficacy of agomelatine and fluoxetine in patients with MDD.Material and methodAgomelatine 25 mg/day (n: 24) and fluoxetine 20 mg/day (n: 24) were administered to drug-naive unipolar, non-psychotic, non-suicidal MDD patients according to DSM-IV. Evaluations were performed just before the treatment and at the sixth week of treatment via administering Hamilton Depression Rating Scale, Rey Auditory Verbal Learning Test, Controlled Oral Word Association Test (COWAT), Digit Span Test (DST), Trail Making Test (TMT-A/B), Stroop Test and Wisconsin Card Sorting Test.ResultsBoth agomelatine and fluoxetine was found to be efficacious for the treatment of MDD (P &lt; 0.05 for both). Further there was no difference between the antidepressant efficacy of two drugs. Both of the drugs improved measured neurocognitive functions (P &lt; 0.05), except scores of DST (P &gt; 0.05) and only fluoxetine improved significantly scores of COWAT (P &lt; 0.05). Only in terms of TMT-B there was significant difference between groups and agomelatine was superior to fluoxetine (P &lt; 0.05).ConclusionAgomelatine and fluoxetine were efficacious in treatment of MDD. Furthermore both of the drugs improved cognitive functions in patients with MDD. Superiority of agomelatine in improvement of executive functioning (TMT-B) is important and therefore it could be an appropriate choice for MDD patients who have pronounced executive disturbances.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Neurocognitive functioning as an intermediary variable between psychopathology and insight in schizophrenia

Based on the neuropsychological deficit model of insight in schizophrenia, we constructed exploratory prediction models for insight, designating neurocognitive measures as the intermediary variables between psychopathology and insight into patients with schizophrenia. The models included the positive, negative, and autistic preoccupation symptoms as primary predictors, and activation symptoms as an intermediary variable for insight. Fifty-six Korean patients, in the acute stage of schizophrenia, completed the Positive and Negative Syndrome Scale, as well as a comprehensive neurocognitive battery of tests at the baseline, 8-weeks, and 1-year follow-ups. Among the neurocognitive measures, the Korean Wechsler Adult Intelligence Scale (K-WAIS) picture arrangement, Controlled Oral Word Association Test (COWAT) perseverative response, and the Continuous Performance Test (CPT) standard error of reaction time showed significant correlations with the symptoms and the insight. When these measures were fitted into the model as intermediaries between the symptoms and the insight, only the perseverative response was found to have a partial mediating effect – both cross-sectionally, and in the 8-week longitudinal change. Overall, the relationship between insight and neurocognitive functioning measures was found to be selective and weak.