Subtle Cognitive Differences Research Articles

Caregiver Experiences, Healthcare Provider Perspectives and Child Outcomes with Virtual Care in a Neonatal Neurodevelopmental Follow-Up Clinic: A Mixed-Methods Study

Background: Caregiver and healthcare provider perspectives of virtual care have not been explored in depth in the literature for neonatal follow-up clinics. Our objective was to evaluate caregivers’ and healthcare providers’ perspectives and compare neurodevelopmental outcomes of preterm neonates before and after implementing virtual care during the SARS-CoV-2 pandemic. Methods: Semi-structured interviews were conducted with families and healthcare providers, designed and analyzed using phenomenological qualitative methods. A retrospective cohort study was conducted to evaluate and compare neurodevelopmental characteristics of two preterm cohorts, one before (“in-person”) and after (“virtual”) virtual care. Results: Three themes were identified: increased confidence in in-person assessments, adequate delivery of information using virtual platforms and a preference for specialized care through the neonatal follow-up clinic. A total of 252 infants born preterm, 104 infants in the in-person group and 148 infants in the virtual group, were included in the study. The adjusted odds ratio (aOR) of cerebral palsy was lower when virtual care was used compared to in-person assessments (aOR = 0.11, 95% CI 0.01–0.98) while the adjusted odds of cognitive delay measured by in-person standardized testing were higher (aOR = 2.78, 95% CI 1.25–6.19). Conclusions: Caregivers and healthcare providers prefer in-person assessments for comprehensive developmental support. It may be more challenging to detect subtle cognitive differences using caregiver-reported measures. Cerebral palsy may be missed when assessments are completed virtually.

Application of the Preclinical Alzheimer’s Cognitive Composite for tracking progression in cognitively unimpaired older adults with known Amyloid status: A 24‐month Interim Analysis of the Chariot‐Pro cohort

AbstractBackgroundThe ongoing CHARIOT‐PRO Substudy aims to estimate the rate of cognitive change in the early Alzheimer’s pathological continuum, comparing individuals with and without baseline biomarker evidence of amyloid deposition, over a 4.5yr follow up. We previously reported subtle cognitive differences between the two groups at baseline. Here we extend follow‐up to 24m.MethodCognitively unimpaired individuals aged 60–85 years, in good general health and with global Clinical Dementia Rating (CDR) scale = 0, underwent amyloid assessment via PET or lumbar puncture; approximately equal numbers of amyloid positive (A+) and amyloid negative (A‐) individuals were enrolled. This report focuses on the preclinical Alzheimer’s cognitive composite (PACC) total score and the CDR, performed at baseline and at M12 and M24. Subtle deficit at baseline was defined as PACC scores below the 15th percentile of A‐ individuals. The A+ and A‐ groups were compared on rate of progression to CDR > 0 and annualized change from baseline in PACC. Individuals with and without progression at any point in the CDR were compared with respect to PACC baseline and change scores.ResultA+ participants had lower PACC scores at baseline (‐0.39 (2.56) vs 0.40 (2.71), p = 0.001). There was a trend for less improvement at M24 (0.29 (2.1) vs 0.62 (1.76), p = 0.068). More A+ than A‐ participants progressed to CDR = 0.5 (Figure 1; Kaplan‐Meier survival 84.6% vs 93.1%, respectively, p = 0.004). Those with subtle deficit at baseline were more likely to progress to CDR = 0.5 (14.1% vs 5.9%, OR = 2.63, p = 0.008). Participants with progression to CDR = 0.5 at any time had lower PACC scores at baseline (‐1.30 (2.72) vs 0.24 (2.59), p < 0.0005) and greater decline at M24 (‐0.30 (2.20) vs 0.55 (1.88), p = 0.014).ConclusionIn A+ individuals, a greater decline in mean PACC scores trended towards significance at 24m, a larger proportion had change in CDR, and CDR progression was associated with declining PACC. In addition, low baseline PACC predicted subsequent increase from CDR = 0. These findings provide further evidence that the PACC has sufficient sensitivity to measure subtle cognitive deficits and serve as an indicator of progression on the early Alzheimer’s pathological continuum.

A-123 Problem Solving and Mental Workload in Binge and Non-Binge Drinking College Students

Abstract Objective: Chronic sustained alcohol abuse is known to impact cognitive functioning. We examined potential differences in problem solving ability and mental workload in a more short-term population, binge-drinking college students. Method: Binge-drinking (BD) (n = 129) and non-binge-drinking (NBD) (n = 163) college students completed a computerized test of problem solving, a 3-disk and 4-disk version of the Tower of Hanoi (TOH). After each TOH session, they also completed an assessment of mental workload via the NASA-Task Load Index (NASA-TLX). Mental workload was defined as the Mental Demand subscale of the NASA-TLX. Results: No significant group difference was found in mean number of moves to complete the TOH in either the 3-disk version or 4-disk version. For mental workload, no difference was evident for the 3-disk TOH (BD M = 28.81, SD = 21.05 vs NBD M = 27.09, SD = 21.59, p = 0.497), but there was a difference for the 4-disk TOH condition (BD M = 47.22, SD = 21.86 vs NBD M = 41.84, SD = 22.94, p = 0.044). Conclusion(s): While no group differences in test performance were evident, there was a difference in mental workload on the more difficult TOH condition. We propose that mental workload, which is not normally considered in neuropsychology, might be a valuable tool in assessment of cognitive status, especially when there are subtle cognitive differences. In this case, even with similar test performance, cognitive status might not necessarily be the same between the two groups, with the BD group showing greater mental workload.

Effects of long‐term marijuana use include cognitive deficits in midlife

Subtle cognitive deficits and structural brain differences are seen in cannabis users, but a new study has found that long‐term cannabis use is associated with permanent brain deficits.

Long‐term cannabis use may cause cognitive deficits in midlife

Subtle cognitive deficits and structural brain differences are seen in cannabis users, but a study published in the May issue of The American Journal of Psychiatry has found that long‐term cannabis use is associated with permanent brain deficits.

Identifying Mild Cognitive Impairment by Using Human–Robot Interactions

Background: Mild cognitive impairment (MCI), which is common in older adults, is a risk factor for dementia. Rapidly growing health care demand associated with global population aging has spurred the development of new digital tools for the assessment of cognitive performance in older adults. Objective: To overcome methodological drawbacks of previous studies (e.g., use of potentially imprecise screening tools that fail to include patients with MCI), this study investigated the feasibility of assessing multiple cognitive functions in older adults with and without MCI by using a social robot. Methods: This study included 33 older adults with or without MCI and 33 healthy young adults. We examined the utility of five robotic cognitive tests focused on language, episodic memory, prospective memory, and aspects of executive function to classify age-associated cognitive changes versus MCI. Standardized neuropsychological tests were collected to validate robotic test performance. Results: The assessment was well received by all participants. Robotic tests assessing delayed episodic memory, prospective memory, and aspects of executive function were optimal for differentiating between older adults with and without MCI, whereas the global cognitive test (i.e., Mini-Mental State Examination) failed to capture such subtle cognitive differences among older adults. Furthermore, robot-administered tests demonstrated sound ability to predict the results of standardized cognitive tests, even after adjustment for demographic variables and global cognitive status. Conclusion: Overall, our results suggest the human–robot interaction approach is feasible for MCI identification. Incorporating additional cognitive test measures might improve the stability and reliability of such robot-assisted MCI diagnoses.

Development and pilot data for an app‐based cognitive assessment for detecting memory and executive functioning changes in aging and pre‐clinical AD

AbstractBackgroundMobile, valid and engaging cognitive assessments are essential for detecting and tracking change in research participants and patients at risk for Alzheimer’s Disease and Related Dementias (ADRDs). This pilot study aims to determine the feasibility and psychometric properties of app‐based memory and executive functioning tasks included in the mobile cognitive app performance platform (mCAPP), to detect cognitive changes associated with aging and preclinical Alzheimer’s Disease (AD).MethodThe mCAPP includes three gamified tasks: (1) a memory task that includes learning and matching hidden card pairs and incorporates increasing memory load, pattern separation features (lure vs. non‐lure), and spatial memory (2) a stroop‐like task (“brick drop”) with speeded word and color identification and response inhibition components and (3) a digit‐symbol coding‐like task (“space imposters”) with increasing pairs and incidental learning components. The cohort is also assessed with the NACC UDS3 or T‐Cog neuropsychological battery within six months of the mCAPP testing. Participants included nine older adults (44% female; age=73.9±5.4, years of education=16.6±2.3; 77% Caucasian) with normal cognition who are enrolled in the Penn ADRC cohort. In addition to in‐lab testing, a cohort of participants will also use the mCAPP at home for two weeks and remotely collected data will be presented.ResultOn the brick drop task, performance was significantly slower and less accurate on the inhibition task compared to the word and color identification tasks (p<.05). On the space imposters task, increased reaction time and decreased accuracy was observed as the number of digit‐symbol pairs increased, but the difference was not significant. Correlations with UDS 3.0 measures showed significant relationships between the brick drop word/color identification and trail making test A (TMTA) and category fluency (p<.05) as well as between the response inhibition task and category fluency and olfactory function (p<.05). The space imposters task correlated with the TMTA (p<.05). Data will also be presented on home‐based collection of all three mCAPP tasks.ConclusionThis pilot study shows feasibility and validity of app‐based tests of executive functioning and will also examine detection of subtle cognitive differences associated with preclinical AD through burst testing, home‐based data collection and on all three mCAPP measures.

Specific Abnormalities in White Matter Pathways as Interface to Small Vessels Disease and Cognition in Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Individuals.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by leukoencephalopathy leading to cognitive impairment. Subtle cognitive deficits can be observed early in the course of the disease, before the occurrence of the first stroke. Therefore, markers that can predict disease progression at this early stage, when interventions are likely to alter disease course, are needed. We aimed to examine the biological cascade of microstructural and macrostructural white matter (WM) abnormalities underlying cognitive deficits in CADASIL. Methods: We examined 20 nondemented CADASIL mutation carriers and 23 noncarriers who underwent neuropsychological evaluation and magnetic resonance imaging. Using probabilistic tractography of key WM tracts, we examined group differences in diffusivity measures and WM hyperintensity volume. Successive mediation models examined whether tract-specific WM abnormalities mediated subtle cognitive differences between CADASIL mutation carriers and noncarriers. Results: The largest effect size differentiating the two groups was observed for left superior longitudinal fasciculus-temporal (SLFt) diffusivity (Cohen's f = 0.49). No group differences were observed with a global diffusion measure. These specific microstructural differences in the SLFt were associated with higher WM hyperintensities burden, and subtle executive deficits in CADASIL mutation carriers. Discussion: Worse diffusivity in the left SLFt is related to greater severity of small vessel disease and worse executive functioning in the asymptomatic stage of the disease. Worse diffusivity of the left SLFt may potentially hold promise as an indicator of disease progression. Impact statement Diffusion tensor imaging outperforms conventional imaging of subcortical small vessel disease as a potential marker of future disease progression. Here we identified the left superior longitudinal temporal fasciculus as a critical white matter fiber bundle, of which worse diffusivity can link presence of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy mutations to greater severity of small vessel disease and worse executive functioning in asymptomatic stages of the disease. This tract may hold promise and deserves further examination as an early indicator of disease progression.

Improving neurocognitive testing using computational psychiatry—A systematic review for ADHD.

Computational models, in conjunction with (neuro)cognitive tests, are increasingly used to understand the cognitive characteristics of participants with attention-deficit/hyperactivity disorder (ADHD). We reviewed 50 studies from a broad range of cognitive tests for ADHD to synthesize findings and to summarize the new insights provided by three commonly applied computational models (i.e., diffusion decision models, absolute accumulator models, ex-Gaussian distribution models). Four areas are discussed to improve the utility of (neuro)cognitive testing for ADHD: (a) the requirements for appropriate application of the computational models; (b) the consideration of sample characteristics and neurophysiological measures; (c) the integration of findings from cognitive psychology into the literature of cognitive testing to reconcile mixed evidence; and (d) future directions for the study of ADHD endophenotypes. We illustrate how computational models refine our understanding of cognitive concepts (slow processing speed, inhibition failures) presumed to characterize ADHD. We also show that considering sample characteristics and integrating findings from computational models and neurophysiological measures provide evidence for ADHD endophenotype-specific cognitive characteristics. However, studying the cognitive characteristics of ADHD endophenotypes often lies beyond the scope of existing research for three reasons: some cognitive tests lack sensitivity to detect clinical characteristics; analysis methods do not allow the study of subtle cognitive differences; and the precategorization of participants restricts the study of symptom severity on a continuous spectrum. We provide recommendations for cognitive testing, computational modeling, and integrating electrophysiological measures to produce more valuable tools in research and clinical practice (above and beyond the research domain of ADHD). (PsycInfo Database Record (c) 2021 APA, all rights reserved).

What you “mean” is not what I “mean”: Categorization of verbs by Germans and Koreans using the semantic differential

Although there are different approaches to classifying verb categories, the approaches are often not consistent with the results of experimental studies investigating the neurocognitive reality of the categories. One proposal for addressing these inconsistencies is embodiment theory, which states that verbs can be categorized based on accompanying sensorimotor mental simulations. Despite numerous studies on this topic, it remains unclear whether verbs can actually be categorized by means of these sensorimotor simulations and whether these categories are crosslingual.In this study, verbs were examined using the semantic differential in 106 native German and Korean speakers. The aim was to determine with which semantic dimensions each verb can be described and whether verb subcategories can be defined.We were able to show that every verb has an individual semantic profile and that subcategories of verbs exist. For the German and Korean participants, most of the verb categories were comparable and therefore mostly crosslingual. However, there were also distinct subcategories of verbs which can probably be correlated with subtle cognitive and experience-based differences between the participating groups. We conclude from this research that it is problematic to use a single verb classification system for the German and Korean languages.

The preclinical amyloid sensitive composite to determine subtle cognitive differences in preclinical Alzheimer\u2019s disease

Recently, the focus of Alzheimer’s disease (AD) research has shifted from the clinical stage to the preclinical stage. We, therefore, aimed to develop a cognitive composite score that can detect the subtle cognitive differences between the amyloid positive (Aβ+) and negative (Aβ−) status in cognitively normal (CN) participants. A total of 423 CN participants with Aβ positron emission tomography images were recruited. The multiple-indicators multiple-causes model found the latent mean difference between the Aβ+ and Aβ− groups in the domains of verbal memory, visual memory, and executive functions. The multivariate analysis of covariance (MANCOVA) showed that the Aβ+ group performed worse in tests related to the verbal and visual delayed recall, semantic verbal fluency, and inhibition of cognitive inference within the three cognitive domains. The Preclinical Amyloid Sensitive Composite (PASC) model we developed using the result of MANCOVA and the MMSE presented a good fit with the data. The accuracy of the PASC score when applied with age, sex, education, and APOE ε4 for distinguishing between Aβ+ and Aβ− was adequate (AUC = 0.764; 95% CI = 0.667–0.860) in the external validation set (N = 179). We conclude that the PASC can eventually contribute to facilitating more prevention trials in preclinical AD.

Episodic Memory and Hippocampal Volume Predict 5-Year Mild Cognitive Impairment Conversion in Healthy Apolipoprotein ε4 Carriers.

The Apolipoprotein (APOE) ε4 allele increases the risk for mild cognitive impairment (MCI) and dementia, but not all carriers develop MCI/dementia. The purpose of this exploratory study was to determine if early and subtle preclinical signs of cognitive dysfunction and medial temporal lobe atrophy are observed in cognitively intact ε4 carriers who subsequently develop MCI. Twenty-nine healthy, cognitively intact ε4 carriers (ε3/ε4 heterozygotes; ages 65-85) underwent neuropsychological testing and MRI-based measurements of medial temporal volumes over a 5-year follow-up interval; data were converted to z-scores based on a non-carrier group consisting of 17 ε3/ε3 homozygotes. At follow-up, 11 ε4 carriers (38%) converted to a diagnosis of MCI. At study entry, the MCI converters had significantly lower scores on the Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT) Trials 1-5, and RAVLT Immediate Recall compared to non-converters. MCI converters also had smaller MRI volumes in the left subiculum than non-converters. Follow-up logistic regressions revealed that left subiculum volumes and RAVLT Trials 1-5 scores were significant predictors of MCI conversion. Results from this exploratory study suggest that ε4 carriers who convert to MCI exhibit subtle cognitive and volumetric differences years prior to diagnosis.

Apolipoprotein E ε4 Allele Is Associated with Reduced Retention of the "Where" Memory Component in Cognitively Intact Older Adults.

The present study investigated the effect of the apolipoprotein E (ApoE) ε4 allele on the four memory components (i.e., who, when, where, and what) among cognitively intact older adults. Participants comprised 47 cognitively intact older adults, who were classified into 2 groups based on the presence or absence of at least 1 ApoE ε4 allele. All participants completed standardized neuropsychological tests, including the Logical Memory subtest of the Wechsler Memory Scale-III with a revised scoring method. The results revealed that recollection for each component followed a pattern of who > what > when = where. Furthermore, a significant group-by-component-by-condition interaction indicated that the presence of the ApoE ε4 allele resulted in a disproportionately detrimental effect on the where component retention in the verbal episodic memory task; this finding was significantly correlated with hippocampal volumes. These results highlighted the importance of evaluating the subcomponents of verbal episodic memory to detect subtle cognitive differences related to ApoE ε4 status, which could help elucidate the mechanism behind the cascades caused by ApoE ε4 in the trajectories of cognitive aging.

Cognition at age 70: Life course predictors and associations with brain pathologies.

ObjectiveTo investigate predictors of performance on a range of cognitive measures including the Preclinical Alzheimer Cognitive Composite (PACC) and test for associations between cognition and dementia biomarkers in Insight 46, a substudy of the Medical Research Council National Survey of Health and Development.MethodsA total of 502 individuals born in the same week in 1946 underwent cognitive assessment at age 69–71 years, including an adapted version of the PACC and a test of nonverbal reasoning. Performance was characterized with respect to sex, childhood cognitive ability, education, and socioeconomic position (SEP). In a subsample of 406 cognitively normal participants, associations were investigated between cognition and β-amyloid (Aβ) positivity (determined from Aβ-PET imaging), whole brain volumes, white matter hyperintensity volumes (WMHV), and APOE ε4.ResultsChildhood cognitive ability was strongly associated with cognitive scores including the PACC more than 60 years later, and there were independent effects of education and SEP. Sex differences were observed on every PACC subtest. In cognitively normal participants, Aβ positivity and WMHV were independently associated with lower PACC scores, and Aβ positivity was associated with poorer nonverbal reasoning. Aβ positivity and WMHV were not associated with sex, childhood cognitive ability, education, or SEP. Normative data for 339 cognitively normal Aβ-negative participants are provided.ConclusionsThis study adds to emerging evidence that subtle cognitive differences associated with Aβ deposition are detectable in older adults, at an age when dementia prevalence is very low. The independent associations of childhood cognitive ability, education, and SEP with cognitive performance at age 70 have implications for interpretation of cognitive data in later life.

1346-P: Longitudinal Evaluation of Cognitive Functioning in Young Children with Type 1 Diabetes: Persistent Effects on IQ and Vocabulary

Background: Subtle but significant cognitive differences between youth with and without type 1 diabetes (T1D) have been observed and found to be related to chronic hyperglycemia. We report continued follow-up of prospectively acquired cognitive data obtained over 4.5 years in a large cohort of young children with and without T1D. Methods: 181 children with T1D and 90 age-matched nondiabetic controls underwent age-appropriate neuropsychological testing at three time points: baseline, 18 months, and approximately 2.9 years after the second visit (T1D group: 11.2 ± 1.9 y, HbA1c: 8.1 ± 1.0%, diabetes duration 6.4 y at the time of latest evaluation; control group: mean age 11.6 ± 1.7 years). Effects of T1D on cognition were estimated based on longitudinal mixed effects modeling after controlling for parental full-scale IQ. Results: The T1D group continued to show significantly lower scores on Full Scale IQ (Cohen’s d=-0.31, p=0.024), Verbal IQ (d=-0.33, p=0.009), and Vocabulary (d=-0.42, p=0.002) compared to nondiabetic controls at last follow-up. Processing speed, memory and learning were similar between the T1D and the control groups. Within the T1D group, there was a significant inverse relationship between HbA1c at last follow-up and Vocabulary (r=-0.307, p=0.001) as well as between HbA1c and VIQ (r=-0.200, p=0.037), controlling for parental IQ. Conclusion: In this large cohort of children with relatively well-controlled T1D followed for 4.5 years, differences in full-scale and verbal IQ persist over time compared to nondiabetic controls, and effects on vocabulary and verbal IQ are related to glycemic control. These findings further support the importance of optimizing glycemic control during this critical period of brain maturation. Disclosure S.A. Weinzimer: Consultant; Self; Eli Lilly and Company, Sanofi. Consultant; Spouse/Partner; Tandem Diabetes Care. Consultant; Self; Zealand Pharma A/S. Speaker's Bureau; Self; Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Stock/Shareholder; Self; InsuLine Medical Ltd. J.M. Ambrosino: Consultant; Spouse/Partner; Eli Lilly and Company, Sanofi. Consultant; Self; Tandem Diabetes Care. Consultant; Spouse/Partner; Zealand Pharma A/S. Speaker's Bureau; Spouse/Partner; Insulet Corporation, Medtronic, Tandem Diabetes Care. Stock/Shareholder; Spouse/Partner; InsuLine Medical Ltd. A. Cato: None. B. Jo: None. K.A. Englert: Consultant; Self; PicoLife Technologies, LLC. N.H. White: None. A. Arbelaez: None. T. Hershey: Research Support; Spouse/Partner; Sage Pharmaceuticals. L.A. Fox: None. E. Tsalikian: None. M. Tansey: Advisory Panel; Self; Daiichi Sankyo Company, Limited. B.A. Buckingham: Advisory Panel; Self; ConvaTec Inc., Novo Nordisk Inc., Profusa, Inc. Consultant; Self; Medtronic MiniMed, Inc. Research Support; Self; Beta Bionics, ConvaTec Inc., Dexcom, Inc., Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Other Relationship; Self; Insulet Corporation, Tandem Diabetes Care. T. Aye: None. D.M. Wilson: Advisory Panel; Self; Tolerion, Inc. Research Support; Self; Beta Bionics, Dexcom, Inc., Medtronic. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceutical Company Limited. A.L. Reiss: None. N. Mauras: Consultant; Self; Novo Nordisk Inc., PicoLife. Research Support; Self; Medtronic MiniMed, Inc. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development (DIRECNET: U01HD-41906, HD-41908, HD-41915, HD-41918, HD-56526, R01HD-078463, U54HD087011); National Center for Advancing Translational Sciences (UL1TR000448)

What Can Eye Movements Tell Us about Subtle Cognitive Processing Differences in Autism?

Autism spectrum disorder (ASD) is neurodevelopmental condition principally characterised by impairments in social interaction and communication, and repetitive behaviours and interests. This article reviews the eye movement studies designed to investigate the underlying sampling or processing differences that might account for the principal characteristics of autism. Following a brief summary of a previous review chapter by one of the authors of the current paper, a detailed review of eye movement studies investigating various aspects of processing in autism over the last decade will be presented. The literature will be organised into sections covering different cognitive components, including language and social communication and interaction studies. The aim of the review will be to show how eye movement studies provide a very useful on-line processing measure, allowing us to account for observed differences in behavioural data (accuracy and reaction times). The subtle processing differences that eye movement data reveal in both language and social processing have the potential to impact in the everyday communication domain in autism.

Cognitive functioning in first episode bipolar I disorder patients with and without history of psychosis

BackgroundPsychosis in bipolar I disorder (BDI) has been associated with increased cognitive dysfunction, which may relate to poorer functional outcomes. However, it is not known whether cognition differs between BDI patients with (BDP+) or without (BDP-) history of psychosis early in the disease course, or if it is impacted by the presence of mood congruent (MCP) versus incongruent (MIC) psychotic features. We compare cognition between these groups in BDI patients recently recovered from first episode of mania. MethodsAttention, verbal learning/memory, processing speed and executive functioning were compared between: 1) all BDI patients (n = 73) and healthy controls (HC, n = 45), 2) BDP+ (n = 60) and BDP- (n = 13) patients and 3) MCP (n = 27) and MIC (n = 33) patients. Post-hoc analyses compared all patient groups with HC. ResultsWhile BDI patients performed worse than HC in all domains, there were no significant differences between BDP+ and BDP-, or MCP and MIC, patients. However, BDP+ and MIC groups demonstrated different patterns of impairment compared to HC then did BDP- or MCP. Executive functioning and cognitive flexibility in particular appeared to be a deficit area in BDP+ patients. LimitationsThis study may have been underpowered to detect differences in direct comparison between BDP+ and BDP- patients. ConclusionWhile replication in larger samples is required, these results suggest that subtle cognitive differences between BDP+ and BDP-, and between MIC and MCP, patients may be present shortly after disease onset. These patient subsets may therefore be of interest in examining early intensive strategies to preserve cognition.

DETECTING SUBTLE COGNITIVE IMPAIRMENT ASSOCIATED WITH GENETIC APOE ALZHEIMER’S DISEASE RISK

The apolipoprotein e 4 allele (ApoE4) is a well-known genetic risk factor for Alzheimer's Disease (AD). The DCTclock test administers the standard Clock Drawing Test, both Command and Copy conditions, using a digitizing ballpoint pen and software that captures and analyzes both the final drawing and the entire drawing process. We examined whether the DCTclock test detected subtle cognitive differences in those with and without AD genetic risk. The study sample was 1243 dementia-free Framingham Heart Study participants who were genotyped for ApoE and completed a DCTclock test, both Command and Copy conditions. High AD risk was defined as ApoE4+ (n=266), low risk as ApoE4- (n=949); ApoE 2/4 (n=28) were excluded because of potential E2 protective effects. ApoE risk groups did not differ in age, gender or education, and were compared to DCTclock metrics using the Welch Two Sample t-test. DCTclock metrics were extracted from the drawing process and combined to create composite scales and a total score for the test. Variables of interest in this study included: (1) DCTclock score, a weighted sum of metrics, where metrics with individual significance in this analysis are described in (2) to (7); (2) Drawing Efficiency, a composite score that combines stroke count, total time, drawing size, and pen ink length; (3) Information Processing, a composite score that combines length and distribution of latencies between pen strokes; (4) Average Latency, average latency between pen stroke; (5) Longest Latency, the longest latency between pen strokes (6) Relative Long Latencies, sum of latencies > participant's Average Latency; (7) Long Latency Count, number of latencies > average age group mean. When compared to the ApoE4- group, those with ApoE4+ had: significantly worse DCTclock Score (p=0.02); for Command condition, lower Drawing Efficiency (p=0.01) and longer Average Latency (p= 0.04); for Copy condition, worse Information Processing (p=0.04), and higher Longest Latency (p=0.02), Relative Long Latencies (p=0.04), and Long Latency Count (p=0.03). ApoE4+ individuals had worse DCTclock metrics compared to those who were ApoE4-. These results suggest the DCTclock can detect subtle cognitive impairment in people who are at higher AD genetic risk but asymptomatic for disease.

Convergent and criterion validity of the CogState computerized brief battery cognitive assessment in women with and without breast cancer

Objective: Computerized tests have increasingly garnered interest for assessing cognitive functioning due to their potential logistical and financial advantages over traditional ‘pencil and-paper’ neuropsychological tests. However, psychometric information is necessary to guide decisions about their clinical and research utility with varied populations. We explored the convergent construct validity and criterion validity of the CogState computerized tests in breast cancer survivors, a group known to present with mostly mild, subtle cognitive dysfunction. Method: Fifty-three post-menopausal women (26 breast cancer survivors, 27 healthy controls) completed the CogState Brief Battery tests with passed performance checks, conceptually matched traditional neuropsychological tests, and a self-report measure of daily functioning, the Functional Activities Questionnaire. Results: Significant positive correlations were found between the CogState Brief Battery tests and traditional neuropsychological tests, although the traditional tests specifically hypothesized to correlate with CogState tests did not reach statistical significance. Analysis of Covariance results showed preliminary support for criterion validity, as the patient and control groups differed on the traditional test of working memory (Digits Backwards, p = .01), with a trend towards significance for the CogState test of working memory (One Back, p = .02), controlled for age, race, and mood. Conclusions: The results provide preliminary support for further research to determine if the CogState tests are viable as screening tools to detect subtle cognitive differences between breast cancer survivors and healthy women. Our study was limited by the low base rate of cognitive impairment and small sample size. We recommend further research employing sufficiently powered sample sizes and a longitudinal, repeated measures study design.

Longitudinal Evaluation of Cognitive Functioning in Young Children with Type 1 Diabetes over 18 Months.

Decrements in cognitive function may already be evident in young children with type 1 diabetes (T1D). Here we report prospectively acquired cognitive results over 18 months in a large cohort of young children with and without T1D. A total of 144 children with T1D (mean HbA1c: 7.9%) and 70 age-matched healthy controls (mean age both groups 8.5 years; median diabetes duration 3.9 years; mean age of onset 4.1 years) underwent neuropsychological testing at baseline and after 18-months of follow-up. We hypothesized that group differences observed at baseline would be more pronounced after 18 months, particularly in those T1D patients with greatest exposure to glycemic extremes. Cognitive domain scores did not differ between groups at the 18 month testing session and did not change differently between groups over the follow-up period. However, within the T1D group, a history of diabetic ketoacidosis (DKA) was correlated with lower Verbal IQ and greater hyperglycemia exposure (HbA1c area under the curve) was inversely correlated to executive functions test performance. In addition, those with a history of both types of exposure performed most poorly on measures of executive function. The subtle cognitive differences between T1D children and nondiabetic controls observed at baseline were not observed 18 months later. Within the T1D group, as at baseline, relationships between cognition (Verbal IQ and executive functions) and glycemic variables (chronic hyperglycemia and DKA history) were evident. Continued longitudinal study of this T1D cohort and their carefully matched healthy comparison group is planned.