Paired Associate Learning Test Research Articles

T49. SOCIODEMOGRAPHIC AND LIFESTYLE FACTORS ASSOCIATED WITH GOOD PERFORMANCE IN PAIRED ASSOCIATES LEARNING TEST IN PATIENTS WITH SCHIZOPHRENIA

BackgroundSchizophrenia patients have been found to have long lasting, clinical state independent impairments in intellectual abilities as well as in specific cognitive domains of which visual learning and memory are central to our current study.The main aim of this study was to investigate the sociodemographic and lifestyle factors associated with good visual learning and memory in patients with schizophrenia in a sample of patients.MethodsThe basic population for this study consists of Finnish SUPER study on genetic mechanisms of psychotic disorders (SUPER), part of the Stanley Global Neuropsychiatric Genomics Initiative. The Northern Finland Birth Cohort 1966 (NFBC 1966) functioned as a reference group to define good cognitive performance.The Finnish SUPER study on genetic mechanisms of psychotic disorders is a part of the international Stanley Global Neuropsychiatric Genomics Initiative. The objective of the study is to understand the genetic and biological background of psychotic disorders.The participants of the present study were patients with clinical diagnosis of schizophrenia who were born between 1950–1979 (N=1,907). The reference group of members of the NFBC 1966 consisted 5,506 individuals aged 46–47 years.Paired Associates Learning (PAL) was used both in SUPER and NFBC 1966 studies. PAL test measures visual memory and new learning. We used the primary outcome variable of ‘total errors adjusted’ (TEA) which assesses learning over repeated attempts. Lower than the mean score of TEA of NFBC 1966 was used as cut-off for good performance in PAL test. SUPER participants with good performance in the PAL test were compared to other SUPER participants.Participants in SUPER study were interviewed and filled in a questionnaire about general mental wellbeing, subjective health and lifestyle factor. The association of following sociodemographic and lifestyle factors were investigated: education, age, marital status, self-rated memory, psychotropic medication use, alcohol consumption and cigarette smoking.ResultsOf the SUPER participants, 129 (6,9 %) performed at least on the level on which 50% of the participants of the NFBC 1966 performed. Of SUPER participant males 5,9 % and of the females 8,1 % performed on this level.Performing above the NFBC 1966 50% level in the PAL test was associated with higher educational level and higher use of alcohol in males, and with higher educational level and being married in females.DiscussionIn previous studies age, education, duration of illness, severity of symptoms have been found to count for some of the overall impairments found in schizophrenia. We found a subgroup of schizophrenia patients with good visual learning and memory and sociodemographic and lifestyle factors that were associated with good performance. In our study education and marital status in women and alcohol use in men was associated with better performance in PAL test.

Age‐related Changes in Systemic Circulation Promote Vascular Maladaptation and Impair Vascular Reactivity in Retinal and Brain Circulation in Older Adults

IntroductionNormal brain function requires appropriate provision of oxygen, glucose, and other nutrients. This requirement is fulfilled through continuous adjustment of cerebral blood flow (CBF), the process also known as neurovascular coupling (NVC). Therefore, impairment of the resting CBF or impairment of NVC in the brain may be responsible for the development of vascular cognitive deficits in aging. A novel method, Dynamic Retinal Vessel Analysis (DVA) allows evaluation of NVC responses in the retinal circulation in response to photoreceptor stimulation. Considering that human retina shares similar embryologic origins with the central nervous system, this approach may provide a novel and non‐invasive tool to screen subjects at risk for development of vascular cognitive impairment. In this study, we hypothesize that examination of retinal vessels may provide a proxy measure of the microcirculatory health of the brain. We test whether the arterio‐venous ratio (AVR) and NVC measured in the retina correlate with age, cognitive function, central and cerebrovascular hemodynamics.MethodsFor our study, we enrolled 44 healthy adults 23–86 years of age. DVA and static vessel analysis was performed using a mydriatic retinal camera to determine retinal NVC and AVR. Transcranial Doppler Sonography (TCD) was used to assess resting CBF velocity and pulsatility in the middle cerebral artery (MCA). Pulse Waveform Analysis was used to measure central hemodynamic pressures. and stiffness (augmentation index, AIx) was calculated from these results. Cognitive performance was assessed using Cambridge Neuropsychological Cognitive Test Automated Battery (CANTAB), specifically, Paired Associates Learning (PAL) and Delayed Matching to Sample (DMS) tests. Spearman’s correlation between variables was used for statistical analysis.ResultsRetinal NVC showed negative (rho=−0.48, p=0.02), and MCA pulsatility showed positive (rho=0.69, p<0.01) correlation with aortic pulse pressure. Neither of these vascular parameters correlated with central arterial stiffness (AIx). Older age was associated with decreased cognitive performance: total errors on PAL test (PALTEA28, rho=0.49, p<0.01),mean latency to the correct response during DMS (DMSMLAD, rho=0.46, p<0.01), and correct responses in DMS (DMSPC rho=−0.43, p<0.01). AVR correlated negatively with PALTEA28 (rho=−0.48, p<0.01) and positively with DMSPC (rho=0.64, p<0.01), retinal arteriolar dilation correlated negatively with DMSMLAD (rho=−0.32, p=0.04).ConclusionsOur results demonstrate that age‐related changes in the macrocirculation lead to the maladaptation and decreased reactivity of retinal microcirculation. The association between retinal‐, and brain hemodynamics, together with cognitive performance suggests that the retinal microcirculation may reflect the health of the cerebral microcirculation.

Effects of Collagen Hydrolysates on Human Brain Structure and Cognitive Function: A Pilot Clinical Study

This study investigated the effects of collagen hydrolysates (CH) on language cognitive function and brain structure. In this open-label study, 5 g CH was administered once a day for 4 weeks to 30 healthy participants aged 49–63 years. The primary outcome measures were the brain healthcare quotients based on gray matter volume (GM-BHQ) and fractional anisotropy (FA-BHQ). The secondary outcome measures were changes in scores between week 0 and week 4 for word list memory (WLM) and standard verbal paired associate learning (S-PA) tests as well as changes in the physical, mental, and role/social component summary scores of the Short Form-36(SF-36) quality of life instrument. CH ingestion resulted in significant improvements in FA-BHQ (p = 0.0095), a measure of brain structure, as well in scores for the WLM (p = 0.0046) and S-PA (p = 0.0007) tests, which measure cognitive function. There were moderate correlations between the change in WLM score and the change in GM-BHQ (r = 0.4448; Spearman’s rank correlation) and between the change in S-PA score and the change in FA-BHQ (r = 0.4645). Daily ingestion of CH changed brain structure and improved language cognitive function.

Relation between vitamin D level and severity, symptomatology and cognitive dysfunction of major depressive disorder—A sample of Egyptian patients

BackgroundVitamin D helps in the regulation of neurotransmission and neuroprotection. Therefore, vitamin D deficiency might lead to inactivated receptors and may result in depression. AimThe study assessed the relation between serum level of vitamin D and severity, symptomatology and cognitive dysfunction of Major Depressive Disorder (MDD) in a sample of Egyptian patients. MethodsSerum levels of 25-hydroxy vitamin D were measured with electro-chemiluminescence binding assay in 75 patients with MDD. Vitamin D deficiency was described as <20 ng/ml. Patients were recruited from Psychiatry and Addiction Hospital, Kasr Al Ainy outpatient clinic. Patients were subjected to the Structured Clinical Interview for DSM-IV Axis I Disorders(SCID), Hamilton depression scale (HAM-D), Mini- mental status examination (MMSE), Wechsler memory subtests (story A and paired associate learning test (PALT)), Benton visual retention test (BVRT) and Trail B test. Results94.6 % of patients had vitamin D deficiency. There was no significant correlation between levels of vitamin D and severity of depression according to HAM-D. Regarding symptoms of depression, there was a statistically significant difference between levels of vitamin D, being more deficient with genital symptoms: decreased libido and menstrual disturbances. There was no statistically significant correlation between level of vitamin D and cognitive functions. ConclusionMDD was associated with vitamin D deficiency but no statistical significant correlation could be established neither between levels of vitamin D and severity of depression nor between levels of vitamin D and cognitive dysfunction. Vitamin D level was statistically correlated with decreased libido and menstrual disturbances.

Comparative Effect of Local Anesthesia with Lidocaine 2% Versus Topical Anesthesia on Cognitive Function in Ophthalmic Surgery.

BackgroundMultiple clinical trials targeted the assessment of cognitive function following local versus general anesthesia in patients undergoing ophthalmic surgery, but no previous clinical trials have focused on the effect of topical anesthesia on cognitive function.ObjectivesThis study aimed to compare the effect of local anesthesia with lidocaine 2% versus topical anesthesia with Oxybuprocaine (benoxinate hydrochloride 0.4%) on cognitive function in patients undergoing elective cataract surgery.MethodsThis is a prospective randomized clinical trial carried out on 60 patients undergoing elective cataract surgery by phacoemulsification. Thirty patients received local anesthesia with lidocaine 2% and thirty patients received topical anesthesia with Oxybuprocaine (benoxinate hydrochloride 0.4%). Patients’ satisfaction was assessed postoperatively using the Iowa satisfaction with anesthesia scale (ISAS). Cognitive assessment for all patients was done preoperatively and 1 week postoperatively using paired-associate learning test (PALT) and category verbal fluency (VF) test (animal category).ResultsThere was no statistically significant difference between local and topical anesthesia groups in the mean of responses to the 11 statements of ISAS (P = 0.071). Regarding cognitive assessment, there was a statistically significant postoperative decline in the local anesthesia group in both PALT scores (P = 0.005) and VF scores (P = 0.01). In the topical anesthesia group, there was no statistically significant difference between pre- and postoperative PALT scores (P = 0.326) or VF scores (P = 0.199).ConclusionsPostoperative cognitive dysfunction following elective cataract surgeries under local anesthesia can be attributed to the effect of local anesthesia rather than the effect of surgery.

Supplementation With Whey Peptide Rich in β-Lactolin Improves Cognitive Performance in Healthy Older Adults: A Randomized, Double-Blind, Placebo-Controlled Study.

Epidemiological reports showed that consumptions of fermented dairy products are beneficial for cognitive decline in elderly. Our previous preclinical studies have demonstrated that intakes of whey peptide rich in the β-lactolin [β-lactopeptide of glycine-thereonine-tryptophan-tyrosine (GTWY)] improve memory and attention by regulating monoamine system, and clinical study using neuropsychological test suggested that consumptions with GTWY-rich whey peptide enhance cognitive performance associated with the frontal cortex activity. However, corresponding interventional studies in humans are limited. Objectives: to evaluate the effects of the whey peptide on cognitive functions in healthy older adults using a randomized, double-blinded, placebo-controlled trial design. 114 healthy subjects aged 50–75 were supplemented with the whey peptide or placebo for 12 weeks, and changes in cognitive function were assessed using neuropsychological tests at weeks 0, 6, and 12 of the intervention. Neuropsychological tests included assessments for memory functions (subtests from Wechsler memory scale-revised, standard verbal paired-associate learning test, and recognition memory test for faces), assessments for attention (cancelation and detection tests), and assessments for general cognitive functions (repeatable battery for assessments of neuropsychological status). Cerebral blood flow was also assessed using near-infrared spectroscopy (NIRS) after 6 weeks of intervention. This study was registered on the 19 November, 2017 in the database of the University Hospital Medical Information Network (UMIN) prior to enrollment of subjects (Registration No. UMIN000030461: https://www.umin.ac.jp/ctr/index-j.htm). In the whey peptide group, visual paired-associates I and visual cancelation tests were significantly improved compared with those in the placebo group at weeks 6 and 12 of the intervention, respectively. Visuospatial and constructional scores of the repeatable battery for assessments of neuropsychological status and standard verbal paired-associate learning tests (S-PA) also tended to be improved by the intervention at week 12. Daily intakes of GTWY-rich whey peptide show beneficial effects on cognitive performance, especially associative learning memory and control of attention, in healthy older adults and might prevent age-related cognitive declines.

Postoperative cognitive dysfunction and the possible underlying neurodegenerative effect of anaesthesia

Introduction: There is alarming evidence about the involvement of general anaesthesia in the development of postoperative cognitive dysfunction.Aim: To clarify the impact of general anaesthesia on cognitive function and to study the possible effect of general anaesthesia on serum S100B, the marker of neuronal degeneration.Methods: This is a prospective randomised controlled study carried out on 50 patients undergoing elective laparoscopic cholecystectomy under conventional general anaesthesia. Cognitive assessment for selected patients was done preoperative and 1 week postoperative using Paired Associate Learning test (PALT) for assessment of verbal memory and Benton Visual Retention test (BVRT) for assessment of visual memory. Quantitative determination of serum S100B was done for all patients in the basal sample and postoperative sample by applying an enzyme- linked immunoabsorbent assay technique on am automated ELISA platform.Results: Regarding cognitive tests, there was a statistically significant difference between the mean value of preoperative PALT and postoperative PALT (p-value = .012). There was also a statistically significant difference between the mean value of preoperative BVRT and postoperative BVRT (p-value = .011). Regarding S100B, there was a statistically significant difference between preoperative and postoperative serum level (p-value = .002). There was also a statistically significant negative correlation between postoperative S100B serum level and the postoperative scores of both PALT and BVRT.Conclusion: General anaesthesia is incriminated in the development of postoperative verbal and visual memory impairment and in the postoperative increase in serum S100B, the markers of neuronal degeneration.

A Key Role for Subiculum-Fornix Connectivity in Recollection in Older Age.

Individual differences in memory during aging are associated with the microstructure of the fornix, a bidirectional tract connecting the hippocampus with the diencephalon, basal forebrain and cortex. To investigate the origin of alterations in fornix microstructure, measurement of hippocampal subfield volumes was combined with diffusion MRI and cognitive evaluation in a new sample of 31 healthy human participants aged 50–89 years. The fornix, uncinate and parahippocampal cingulum were reconstructed using diffusion MRI tractography. Episodic memory was assessed with free and cued verbal recall, visual recognition and paired associate learning tests. Recall performance was associated with fornix microstructure and hippocampal subfield volumes. Subiculum and CA1 volumes remained positively associated with fornix microstructure when controlling for other volumes. Subiculum volume was also associated with fornix microstructure independent of age. Regression analyses showed that subiculum-fornix associations explained more variation in recall than that of CA1-fornix associations. In a multivariable regression model, age and subiculum volume were independent predictors of free recall whilst fornix microstructure and CA1 volume were not. These results suggest that age-related changes in a network that includes the subiculum and fornix are important in cognitive change in healthy aging. These results match anatomical predictions concerning the importance of hippocampal – diencephalic projections for memory.

Examining Validity of the Standardized Verbal Paired Associates Learning Test

本研究では標準言語性対連合学習検査 (S-PA) の標準化に際して収集したデータをもとに, S-PA の正答数と他の神経心理学的検査の成績との関連を分析し, S-PA の併存的妥当性について検討を行った。 S-PA 開発の際に収集した健常者データ 758 名分, および脳損傷例データ 48 名分を分析対象とした。 S-PA との関連をみる他の検査として健常者データに関しては, 言語流暢性検査 (WFT) および WAIS-III の数唱問題と類似問題を分析に用いた。脳損傷例データに関しては WFT および WAIS-III と WMS-R の全検査結果を分析に用いた。分析の結果, S-PA の正答数は WMS-R の言語性記憶指標や言語性対連合の成績と高い相関を示し, 言語性記憶検査として S-PA の併存的妥当性が確認された。一方で S-PA と WMS-R の論理的記憶の成績との相関はやや低く, S-PA は物語の記銘とは異なる側面を測定している検査であると考えられた。また, S-PA の成績には語彙の豊富さや単語の共通点を探す能力, 視覚的イメージの操作や処理の素早さも関連する可能性が示唆された。

Effect of local anesthesia (with lidocaine vs bupivacaine) on cognitive function in patients undergoing elective cataract surgery.

PurposePostoperative cognitive dysfunction has gained much attention over the last years. Multiple clinical trials have attempted to differentiate the effect of local vs general anesthesia on postoperative cognitive function. The aim of this work was to study the effect of local anesthesia with lidocaine vs bupivacaine on cognitive functionPatients and methodsThis was a prospective randomized trial carried out on 61 patients undergoing elective cataract surgery by phacoemulsification under local anesthesia. Twenty-eight patients received lidocaine 2% and 33 patients received bupivacaine 0.5%. Cognitive assessment for all patients was done preoperatively and 1 week postoperatively using paired associate learning test (PALT) and category verbal fluency (VF) test (animal category).ResultsRegarding cognitive assessment of patients in lidocaine group, there was a statistically significant difference between the mean value of preoperative PALT and postoperative PALT (P-value =0.004), and between the mean value of preoperative VF and postoperative VF (P-value =0.002). As for bupivacaine group, there was a statistically significant difference between the mean value of preoperative PALT and postoperative PALT (P-value =0.021), and between the mean value of preoperative VF and postoperative VF (P-value =0.037). On comparing lidocaine and bupivacaine groups in pre and postoperative PALT & VF scores, there was no statistically significant difference between both groupsConclusionBoth lidocaine and bupivacaine caused postoperative cognitive impairment. Lidocaine was found to have a worse effect on cognitive function than bupivacaine, but the difference was not statistically significant.

„Uwspólnione” tworzenie sensu w interakcji dziecka z dorosłym

This article demonstrates the results of the educational project “stimulating children’s thinking” carried out in some primary schools in a metropolitan environment (Lodz, Poland). The aim of the study was to identify the ways of understanding the concept of community by 9–10-year old children. In the didactical intervention operations designed, the research data came from participated observation, focus interview, and children’s production analysis (graphical visualization, pairedassociate learning tasks and tests of unfinished tasks). Based on my research, I see the need for triggering the cognitive activity of pupils in conditions that ensure the development of conceptual systems. Moreover, the findings suggest the need of broader understanding of educational environments in Polish educational culture.

T2 Relaxometry and Diffusion Tensor Indices of the Hippocampus and Entorhinal Cortex Improve Sensitivity and Specificity of MRI to Detect Amnestic Mild Cognitive Impairment and Alzheimer's Disease Dementia.

Quantitative T2 and diffusion MRI indices inform about tissue state and microstructure, both of which may be affected by pathology before tissue atrophy. To evaluate the capability of both volumetric and quantitative MRI (qMRI) of the hippocampus and entorhinal cortex (EC) for classification of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD). Retrospective cross-sectional study. Consecutive cohorts of healthy age-matched controls (n = 62), aMCI patients (n = 25), and ADD patients (n = 14). 3T using T1-weighted imaging, T2-weighted imaging, T2 relaxometry and diffusion tensor imaging (DTI). Montreal Cognitive Assessment and paired associate learning tests for cognitive state. Hippocampal subfield volumes by the automated segmentation of hippocampal subfields system from structural brain images. T2 relaxation time and DTI indices quantified for hippocampal subfields. The fraction of voxels with high T2 values (>20 ms above subfield median) was calculated and regionalized for hippocampus and EC. Support vector machine and receiver operating characteristic analyses from cognitive and MRI data. qMRI classified aMCI and ADD with excellent sensitivity (79.0% and 94.5%, respectively) and specificity (85.6% and 86.1%, respectively), superior to volumes alone (70.0% and 84.5% for respective sensitivities; 82.2 and 91.1 for respective specificities) and similar to cognitive tests (61.7% and 87.5% for respective sensitivities; 88.2% and 90.7% for respective specificities). Regions of high T2 are dispersed throughout each hippocampal subfield in aMCI and ADD with higher concentration than controls, and was most pronounced in the EC. No other individual qMRI marker than EC volume can separate aMCI from ADD, however. DATA CONCLUSION: qMRI markers of hippocampal and entorhinal tissue states are sensitive and specific classifiers of aMCI and ADD. They may serve as markers of a neurodegenerative state preceding volume loss. 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2019;49:445-455.

Assessment of Cognitive Impairment in a Mouse Model of High-Fat Diet-Induced Metabolic Stress with Touchscreen-Based Automated Battery System.

Obesity-related metabolic disorders can affect not only systemic health but also brain function. Recent studies have elucidated that amyloid beta deposition cannot satisfactorily explain the development of Alzheimer's disease (AD) and that dysregulation of glucose metabolism is a critical factor for the sporadic onset of non-genetic AD. Identifying the pathophysiology of AD due to changes in brain metabolism is crucial; however, it is limited in measuring changes in brain cognitive function due to metabolic changes in animal models. The touchscreen-based automated battery system, which is more accurate and less invasive than conventional behavioral test tools, is used to assess the cognition of mice with dysregulated metabolism. This system was introduced in humans to evaluate cognitive function and was recently back-translated in monkeys and rodents. We used outbred ICR mice fed on high-fat diet (HFD) and performed the paired associates learning (PAL) test to detect their visual memory and new learning ability loss as well as to assess memory impairment. The behavioral performance of the HFD mice was weaker than that of normal mice in the training but was not significantly associated with motivation. In the PAL test, the average number of trials completed and proportion of correct touches was significantly lower in HFD mice than in normal diet-fed mice. Our results reveal that HFD-induced metabolic dysregulation has detrimental effects on operant learning according to the percentage of correct responses in PAL. These findings establish that HFD-induced metabolic stress may have an effect in accelerating AD-like pathogenesis.

Effects of perinatal undernutrition on social transmission of food preference in adult male Wistar rats

Nutrition plays a fundamental role in learning and memory, and early experimental undernutrition interferes with brain memory processes. Social transmission of food preference (STFP) is a natural olfactory paired-associate learning test that has not been used to assess the effects of early undernutrition on memory consolidation. Male Wistar rats were randomly divided into two groups: control and early undernourished. The underfed rats received different percentages of a balanced diet during gestation. After birth, pups were underfed by alternating every 12 h between two lactating dams, one with ligated nipples. Weaning occurred on PD 25 followed by an ad lib diet until PD 90. Demonstrator rats were given powdered food mixed with cinnamon, followed by a 30-min interaction with an underfed observer. Thereafter, the observer had two choices of food: cinnamon or cocoa. During the food preference test, control and underfed OBS rats preferred the food containing cinnamon. Through social interaction, the UG OBS rats showed latency for head contacts and oral-nasal investigation was higher in the underfed rats; only head contacts and oral-nasal investigation frequency was lower; with the duration lower, but oral-nasal investigation duration was higher (p < 0.05). In the preference phase, the OBS underfed rat latencies for both stimuli were prolonged, the frequency lower only for cocoa, and the duration lower for cinnamon but higher for cocoa (p < 0.05). Findings suggested that early undernutrition interfered with the attentive social transmission to take a decision during the preference phase, but not with the short-term memory consolidation of social food preference.

Differential effects of a computerized cognitive stimulation program on older adults with mild cognitive impairment according to the severity of white matter hyperintensities.

ObjectiveThis study aimed to explore whether a computerized cognitive stimulation program (CCS) induced differential effects in older adults with mild cognitive impairment (MCI) according to the severity of white matter hyperintensities (WMH), which are associated with cognitive impairment and increased risk of progression to Alzheimer’s disease because of the damage they cause to cortical and subcortical networks.Patients and methodsTwenty-nine MCI patients with no or little WMH (MCI-non-WMH) and 22 MCI patients with moderate or severe WMH (MCI-WMH) attended a 24-session CCS program (two sessions per week for a duration of 3 months) focused on executive functions, attention, and processing speed. Cognitive and psychosocial assessments were performed at baseline, postintervention, and 3 months after the intervention.ResultsBoth groups improved on several cognitive measures after the intervention. However, the MCI-non-WMH group improved on a higher number of cognitive measures than the MCI-WMH group. At postintervention assessment, CCS had a more beneficial effect on the MCI-non-WMH group than on the MCI-WMH group with regard to improving categorical fluency (4.6±6.8 vs 0.4±6.4; effect size=0.37; p=0.002). During the 3-month follow-up assessment, significantly higher score improvements were observed in the MCI-non-WMH group for the paired-associate learning test (6.4±3 vs 4.7±3.5 points; effect size=0.43; p=0.005) as well as categorical fluency (3.8±7.8 vs −0.7±6 points; effect size=0.55; p=0.0003).ConclusionsThese findings suggest that WMH severity was related to cognitive improvement induced by a CCS program and highlight the importance of considering WMH in interventional studies on subjects with MCI.

The Mismeasurement of Mind: Life-Span Changes in Paired-Associate-Learning Scores Reflect the “Cost” of Learning, Not Cognitive Decline

The age-related declines observed in scores on paired-associate-learning (PAL) tests are widely taken as support for the idea that human cognitive capacities decline across the life span. In a computational simulation, we showed that the patterns of change in PAL scores are actually predicted by the models that formalize the associative learning process in other areas of behavioral and neuroscientific research. These models also predict that manipulating language exposure can reproduce the experience-related performance differences erroneously attributed to age-related decline in age-matched adults. Consistent with this, results showed that older bilinguals outperformed native speakers in a German PAL test, an advantage that increased with age. These analyses and results show that age-related PAL performance changes reflect the predictable effects of learning on the associability of test items, and indicate that failing to control for these effects is distorting the understanding of cognitive and brain development in adulthood.

ROLE OF THE PAIRED ASSOCIATES LEARNING TASK FROM CANTAB IN THE ASSESSMENT OF INDIVIDUALS WITH SUBJECTIVE COGNITIVE DECLINE AND MCI PATIENTS

The combination of computerized neuropsychological assessment and cerebrospinal fluid (CSF) biomarkers may improve the early diagnosis of Alzheimer's disease (AD) [Soldan et al., 2016]. Cambridge Neuropsychological Test Automated Battery (CANTAB) represents a computerized advanced tool for an in-depth neuropsychological evaluation. In CANTAB, the Paired Associates Learning (PAL) task (total errors and total errors 6-shapes), measuring visuo-spatial associative learning, is altered early in AD course [Junkkila et al., 2012]. We administered PAL in individuals with Subjective Cognitive Decline (SCD) [Jessen et al 2014] and Mild Cognitive Impairment (MCI) [Petersen et al., 2004] who underwent CSF AD biomarkers evaluation. We also explored the capacity of PAL in predicting cognitive decline over time. Seventy-two consecutive patients who referred to our Memory Clinic from 2012 to 2016 for memory complaints underwent a standard neuropsychological evaluation. Forty-one patients were classified as SCD (normal performance) and 31 as MCI (-1.5 SD in memory tests). The neuropsychological assessment also included CANTAB subtests assessing visual memory (pattern recognition memory, PRM), spatial working memory, SWM, and visuo-spatial associative learning, PAL. All patients underwent lumbar puncture to measure CSF AD biomarkers-Aβ1–42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau). The neuropsychological assessment was repeated after 1 year. Out of 72 patients, 26 patients (39%) showed a CSF AD-like profile (16/31, 58%, MCI, 10/41, 24%, SCD). At follow-up, 8/41 (22%) of SCD progressed to MCI, where all but one showed an AD-like profile; 8/31 (25%) of MCI converted to dementia (5 to AD, 3 to other dementias). In SCD group, PAL-total errors fairly discriminated individuals with AD-like CSF profile with respect to those with normal CSF profile (-1.76±1.59 vs -0.65±1.44, p=0.048). Baseline performance on PAL-6 shapes was significantly associated with cognitive worsening as measured by MMSE. These results suggest that PAL test from CANTAB may be a sensitive and reliable neuropsychological measure to identify subjects with subtle cognitive deficits who may deserve CSF analysis for early AD detection.

A Pilot Study of Assessing Cognition in Children with Sickle Cell Disease Using a New Software Package the Cogstate Battery

Introduction17% of children with sickle cell disease (SCD) between the ages of 6 and 16 could have silent infarcts1. Depending on the area of the brain affected silent infarcts can cause problems with attention, coordination, visual-motor speed and executive function. Children with SCD in the UK do not receive routine MRI scans. Subtle defects in cognition can be assessed with neuropsychometric testing which involves multiple tests assessing many areas of cognition. However, testing is limited to those with known neurological deficits due to lack of funding and shortage of specialist staff. There is a need for a robust screening tool for assessment of cognition, which could identify children for further specialist testing.The Cogstate battery is computer-based program that assesses cognition and has been used in several clinical settings, both adult and paediatric2-3. The Cogstate battery is reported to be culturally neutral and is available in several languages. Additionally the Cogstate battery is free from practice effects and so could be used as an annual assessment tool in order to identify any declines as early as possible. The Cogstate battery has not yet been used to assess cognition in children with SCD.Research ObjectivesThe aim of this study was to assess the feasibility of using the Cogstate Battery as a tool for the assessment of cognition in children with SCD. It was hypothesised that the Cogstate battery would be easy to use within this setting and would be acceptable to patients, parents and assessors.MethodsEight clinically well children, aged 10-17 with SCD were recruited through St Mary's Hospital paediatric haematology outpatient clinics. The Cogstate software was downloaded onto a Windows laptop computer and an anonymous profile was created for each child before testing. A battery of 6 tests (Table 1) was created aiming to assess a range of cognitive domains within a reasonable amount of time. Every child completed the battery of tests once, which included a short practice before each test. After testing each patient was asked to give an opinion of how they found the tests. Upon completion of the test the patients' results were uploaded to the Cogstate website which generated a test report and a case report form. A mark was given for each test and a score of over 90 represents normal cognition in the area tested, 81-90 represents mild impairment and below 81 represents impairment. Table 1Tests used in the Cogstate battery and corresponding cognitive domains assessedTest NameCognitive Domain TestedContinuous paired associate learning (CPAL)Paired associate learningDetection (DET)Psychomotor functionGroton maze learning test (ME)Executive functionGroton maze learning test-delayed recall (ME)Delayed recallIdentification (IDN)AttentionOne card learning (OCL)LearningOne-back memory (ONBA)Working memoryResults8 patients completed the battery, taking on average 29 minutes (Table 2). The battery was easy to carry out and although some children reported it as boring, they all finished the tests without distress. The test report generated by the Cogstate website allowed results to be analysed quickly and with ease. An overall score from each test is clearly indicated. The Continuous Paired Associate Learning test was not displayed as part of the test report as there was insufficient normal data to draw conclusions from the results within the age group tested.Table 2Summary Report of 8 patients testedPatientIDDET(Psychomotor function)IDN(Attention)OCL(Learning)ONBS(Processing speed)ONBA(Working memory)ME(Executive function & delayed recall)00018775827883990002106105949011799000396101959511798000476769481949300058684988189890006981049797941110007949091831018600089188108909695ConclusionThe Cogstate battery is a feasible tool for paediatric SCD patients and can be undertaken in a clinic setting. This feasibility study will help design a prospective, comparative study of cognition in children with SCD using the Cogstate battery and conventional neuropsychometric assessment and once validated, would be a useful tool to assess cognition and institute timely educational and medical intervention.

What is a normal change in memory? n=1 classification of clinically relevant cognitive decline

Background: Clinicians often have to decide whether a person’s reported or measured change in cognition reflects normal aging or clinically-relevant cognitive decline. For most cognitive tests, there is no evidence-based guidance for how much change is ‘normal’ over a given timeframe. This study aimed to statistically determine the limits of clinically-significant memory change among healthy older adults and those with mild cognitive impairment (MCI). Methods: Longitudinal cognitive performance was examined in 21 healthy older adults and 81 individuals with clinically-defined MCI. Participants were assessed on Cantab Paired Associate Learning (PAL), a non-verbal episodic memory test, at baseline, 10 months and 20 months as part of a comprehensive neuropsychological assessment. They were classified as amnestic-MCI if there was a deficit (performance <10th percentile relative to norms) in memory tests (with our without impairment in other cognitive tests), and nonamnestic MCI if deficits were limited to non-memory domains. Over the three assessments, MCI was stable, resolved or progressed to dementia. The performance of control participants was used to determine the normal limits for initial and longitudinal change in performance, against which participants with stable or resolved MCI and those who progressed to dementia could be compared on an individual basis. Results: In healthy controls, PAL showed good stability using Bland-Altmann analysis. Na-MCI, and those with resolved MCI performed at a level comparable to healthy controls on each occasion. Patients with stable a-MCI or AD patients were significantly impaired relative to other groups. This persisted even when controlling for age, education, gender and baseline level of performance. Individual estimates of clinically significant impairment and change were able to reliably detect patients who would subsequently develop dementia, or had stable a-MCI. Conclusions: Repeated assessments with the Cantab PAL test are feasible, show good psychometric properties, and can characterise typical and atypical patterns of change in episodic memory. A repeat assessment of memory at <1 year can reliably inform clinical decisions about the presence or absence of pathological cognitive decline.

The role of the dorsal hippocampus in two versions of the touchscreen automated paired associates learning (PAL) task for mice.

RationaleThe CANTAB object-location paired-associate learning (PAL) test can detect cognitive deficits in schizophrenia and Alzheimer’s disease. A rodent version of touch screen PAL (dPAL) has been developed, but the underlying neural mechanisms are not fully understood. Although there is evidence that inactivation of the hippocampus following training leads to impairments in rats, this has not been tested in mice. Furthermore, it is not known whether acquisition, as opposed to performance, of the rodent version depends on the hippocampus. This is critical as many mouse models may have hippocampal dysfunction prior to the onset of task training.ObjectivesThe objectives of this study are to examine the effects of dorsal hippocampal (dHp) dysfunction on both performance and acquisition of mouse dPAL and to determine if hippocampal task sensitivity could be increased using a newly developed context-disambiguated PAL (cdPAL) paradigm.MethodsIn experiment 1, C57Bl/6 mice received post-acquisition dHp infusions of the GABA agonist muscimol. In experiment 2, C57Bl/6 mice received excitotoxic dHp lesions prior to dPAL/cdPAL acquisition.ResultsPost-acquisition muscimol dose-dependently impaired dPAL and cdPAL performance. Pre-acquisition dHp lesions had only mild effects on both PAL tasks. Behavioural challenges including addition of objects and degradation of the visual stimuli with noise did not reveal any further impairments.ConclusionsdPAL and cdPAL performance is hippocampus-dependent in the mouse, but both tasks can be learned in the absence of a functional dHp.