Ethnic differences in the effects of apolipoprotein E ɛ4 and vascular risk factors on accelerated brain aging.

The frequency of the apolipoprotein E ɛ4 allele and vascular risk factors differs among ethnic groups. We aimed to assess the combined effects of apolipoprotein E ɛ4 and vascular risk factors on brain age in Korean and UK cognitively unimpaired populations. We also aimed to determine the differences in the combined effects between the two populations. We enrolled 2314 cognitively unimpaired individuals aged ≥45 years from Korea and 6942 cognitively unimpaired individuals from the UK, who were matched using propensity scores. Brain age was defined using the brain age index. The apolipoprotein E genotype (ɛ4 carriers, ɛ2 carriers and ɛ3/ɛ3 homozygotes) and vascular risk factors (age, hypertension and diabetes) were considered predictors. Apolipoprotein E ɛ4 carriers in the Korean (ß = 0.511, P = 0.012) and UK (ß = 0.302, P = 0.006) groups had higher brain age index values. The adverse effects of the apolipoprotein E genotype on brain age index values increased with age in the Korean group alone (ɛ2 carriers × age, ß = 0.085, P = 0.009; ɛ4 carriers × age, ß = 0.100, P < 0.001). The apolipoprotein E genotype, age and ethnicity showed a three-way interaction with the brain age index (ɛ2 carriers × age × ethnicity, ß = 0.091, P = 0.022; ɛ4 carriers × age × ethnicity, ß = 0.093, P = 0.003). The effects of apolipoprotein E on the brain age index values were more pronounced in individuals with hypertension in the Korean group alone (ɛ4 carriers × hypertension, ß = 0.777, P = 0.038). The apolipoprotein E genotype, age and ethnicity showed a three-way interaction with the brain age index (ɛ4 carriers × hypertension × ethnicity, ß=1.091, P = 0.014). We highlight the ethnic differences in the combined effects of the apolipoprotein E ɛ4 genotype and vascular risk factors on accelerated brain age. These findings emphasize the need for ethnicity-specific strategies to mitigate apolipoprotein E ɛ4-related brain aging in cognitively unimpaired individuals.

Association between exercise habit changes and incident dementia after ischemic stroke.

We aimed to investigate the effects of exercise habit changes on the risk of incident dementia after ischemic stroke using the Korean National Health Insurance Services Database. This study included 223,426 patients with a new diagnosis of ischemic stroke between 2010 and 2016 who underwent two serial ambulatory health checkups. The participants were divided into four categories according to their habit change or regular exercise: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. The primary outcome was new diagnosis of dementia. Multivariate Cox proportional models were used to assess the effects of changes in exercise habits on the risk of incident dementia. After a median of 4.02 years of follow-up, 22,554 (10.09%) dementia cases were observed. After adjusting for covariates, exercise dropouts, new exercisers, and exercise maintainers were significantly associated with a lower risk of incident dementia than persistent non-exercisers (adjusted hazard ratio [aHR] 0.937; 95% confidence interval [CI] 0.905-0.970, aHR 0.876; 95% CI 0.843-0.909, aHR 0.705; 95% CI 0.677-0.734, respectively). The impact of changes in exercise habit was more prominent in the 40-65 years age group. An energy expenditure ≥ 1000 metabolic equivalents of task-min/wk post-stroke, regardless of pre-stroke physical activity status, was mostly associated with a lower risk of each outcome. In this retrospective cohort study, initiating or continuing moderate-to-vigorous exercise after ischemic stroke was associated with a lower risk of dementia development. Further, pre-stroke regular physical activity also reduced the risk of incident dementia. The promotion of exercise in ambulatory stroke patients may reduce their future risk of incident dementia.

Distinct cerebral cortical perfusion patterns in idiopathic normal-pressure hydrocephalus.

The aims of the study are to evaluate idiopathic normal-pressure hydrocephalus (INPH)-related cerebral blood flow (CBF) abnormalities and to investigate their relation to cortical thickness in INPH patients. We investigated cortical CBF utilizing surface-based early-phase 18 F-florbetaben (E-FBB) PET analysis in two groups: INPH patients and healthy controls. All 39 INPH patients and 20 healthy controls were imaged with MRI, including three-dimensional volumetric images, for automated surface-based cortical thickness analysis across the entire brain. A subgroup with 37 participants (22 INPH patients and 15 healthy controls) that also underwent 18 F-fluorodeoxyglucose (FDG) PET imaging was further analyzed. Compared with age- and gender-matched healthy controls, INPH patients showed statistically significant hyperperfusion in the high convexity of the frontal and parietal cortical regions. Importantly, within the INPH group, increased perfusion correlated with cortical thickening in these regions. Additionally, significant hypoperfusion mainly in the ventrolateral frontal cortex, supramarginal gyrus, and temporal cortical regions was observed in the INPH group relative to the control group. However, this hypoperfusion was not associated with cortical thinning. A subgroup analysis of participants that also underwent FDG PET imaging showed that increased (or decreased) cerebral perfusion was associated with increased (or decreased) glucose metabolism in INPH. A distinctive regional relationship between cerebral cortical perfusion and cortical thickness was shown in INPH patients. Our findings suggest distinct pathophysiologic mechanisms of hyperperfusion and hypoperfusion in INPH patients.

Risk of dementia according to the smoking habit change after ischemic stroke: a nationwide population-based cohort study.

There is a paucity of research regarding the association between the risk of incident dementia and changes in smoking habits in the acute ischemic stroke population. We aimed to investigate the effects of smoking habit change on the risk of incident dementia in an ischemic stroke population using data from the Korean National Health Insurance Services Database. This nationwide population-based cohort study included 197,853 patients with ischemic stroke. The patients were divided into never smokers, former smokers, smoking quitters, sustained smokers, and new smokers, based on the 2-year change in smoking status between the two consecutive health examinations before and after the index stroke. The patients were followed up from the index date to 2018 to assess the development of dementia. Dementia was further categorized into Alzheimer's, vascular, and other types of dementia according to the International Classification of Diseases, Tenth Revision diagnosis. Multivariable Cox proportional hazards models were used to assess the association between changes in smoking habits and the risk of dementia. After a median of 4.04 years of follow-up, 19,595 (9.9%) dementia cases were observed. Among them, 15,189 (7.7%) were diagnosed with Alzheimer's disease dementia and 2719 (1.4%) were diagnosed with vascular dementia. After adjusting for covariates, including age, sex, alcohol intake habits, cigarette pack-year, regular physical activity, income, history of hypertension, diabetes mellitus, dyslipidemia, and chronic kidney disease, new smokers, sustained smokers, and smoking quitters were significantly associated with a higher risk of all-cause dementia than never smokers (adjusted hazard ratio [aHR] 1.395, 95% confidence interval [CI] 1.254-1.552; aHR 1.324, 95% CI 1.236-1.418; and aHR 1.170, 95% CI 1.074-1.275, respectively). Similar trends were observed for both Alzheimer's dementia and vascular dementia, but the association between new smokers and vascular dementia was not significant. The impact of smoking habit change was more prominent in the 40-65-year-old group. New and sustained smokers had a substantially higher risk of incident dementia after ischemic stroke than never smokers. Smoking quitters also had an elevated risk of incident dementia, but the detrimental effects were lower than those in new and sustained smokers.

Performance of the plasma Aß42/Aß40 ratio, measured with a novel HPLC-MS/MS method, as a biomarker of amyloid PET status in a DPUK-KOREAN cohort.

BACKGROUND: We assessed the feasibility of plasma Aß42/Aß40 determined using a novel liquid chromatography-mass spectrometry method (LC-MS) as a useful biomarker of PET status in a Korean cohort from the DPUK Study. METHODS: A total of 580 participants belonging to six groups, Alzheimer's disease dementia (ADD, n = 134), amnestic mild cognitive impairment (aMCI, n = 212), old controls (OC, n = 149), young controls (YC, n = 15), subcortical vascular cognitive impairment (SVCI, n = 58), and cerebral amyloid angiopathy (CAA, n = 12), were included in this study. Plasma Aß40 and Aß42 were quantitated using a new antibody-free, LC-MS, which drastically reduced the sample preparation time and cost. We performed receiver operating characteristic (ROC) analysis to develop the cutoff of Aß42/Aß40 and investigated its performance predicting centiloid-based PET positivity (PET+). RESULTS: Plasma Aß42/Aß40 were lower for PET+ individuals in ADD, aMCI, OC, and SVCI (p < 0.001), but not in CAA (p = 0.133). In the group of YC, OC, aMCI, and ADD groups, plasma Aß42/Aß40 predicted PET+ with an area under the ROC curve (AUC) of 0.814 at a cutoff of 0.2576. When adding age, APOE4, and diagnosis, the AUC significantly improved to 0.912. CONCLUSION: Plasma Aß42/Aß40, as measured by this novel LC-MS method, showed good discriminating performance based on PET positivity.

Cortical neuroanatomical changes related to specific neuropsychological deficits in subcortical vascular cognitive impairment.

OBJECTIVE: Neuropsychological test-specific neural substrates in subcortical vascular cognitive impairment (SVCI) are expected to differ from those in Alzheimer's disease-related cognitive impairment (ADCI) but the details are unclear. To determine neural substrates related to cerebral small vessel disease, we investigated the correlations between cognitive dysfunctions measured by standardized neuropsychological tests and cortical thickness in a large sample of participants with amyloid negative (Aß (-)) SVCI. METHODS: One hundred ninety-eight participants with Aß (-) SVCI were recruited from the memory clinic between November 2007 to August 2018. To acquire neural substrates, we performed linear regression using the scores of each neuropsychological test as a predictor, cortical thickness as an outcome, and age, sex, education years, intracranial volume and white matter hyperintensity (WMH) as confounders. RESULTS: Poor performances in each neuropsychological test were associated with cortical atrophy in certain brain regions regardless of WMH. Especially, not the medial temporal but the frontal and posterior cingulate regions with cortical atrophy were mainly associated with memory impairment. Poor performance in animal fluency was more likely to be associated with cortical atrophy in the left hemisphere, while poor performance in the visuospatial memory test was more likely to be associated with cortical atrophy in the right hemisphere. CONCLUSIONS: Our findings suggested that cortical atrophy was an important factor of cognitive impairment in Aß (-) SVCI regardless of WMH. Furthermore, our findings might give clinicians a better understanding of specific neural substrates of neuropsychological deficits in patients with SVCI.

Sex differences in the association between the APOEε4 allele and hearing impairment: A longitudinal memory clinic study.

BACKGROUND: The APOEε4 allele and hearing impairment are risk factors for dementia. Cross-sectional studies have shown controversial findings regarding the relationship between APOEε4 and hearing impairment. These may be explained by reported sex differences in the association between APOEε4 and some Alzheimer's disease biomarkers. We aimed to investigate APOEε4 and hearing impairment in a longitudinal setting considering the modifying effects of sex on APOEε4. METHODS: In total, 1810 subjects with APOE genotype at Ilsan Hospital memory clinics were linked to the longitudinal National Health Insurance Service database with International Statistical Classification of Diseases and Related Health Problems 10th revision (ICD-10) diagnosis codes of hearing impairment. After excluding cases with prevalent hearing impairment and incomplete records, 1092 subjects were analyzed for the period January 2004-July 2019. We used Cox proportional hazard models with or without adjustment for education, hypertension, diabetes, and cognitive function. Effect modification was analyzed by sex stratification and by adding APOEε4 by sex interaction terms. RESULTS: Hearing impairment did not differ between APOEε4 carriers and non-carriers. Sex-stratification analysis with an unadjusted model showed men with APOEε4 developed more hearing impairment than men without (HR 1.90, 95% CI 1.20-3.01), but women did not. The results remained similar in covariate-adjusted models. The interaction between APOEε4 and sex was also significant regardless of adjustment. CONCLUSIONS: Our longitudinal analyses suggested male memory clinic visitors with APOEε4 allele were more likely to develop hearing impairment than those without the genotype. This group may benefit more from regular monitoring and preventive measures for hearing impairment.

Transversus abdominis plane block for lumboperitoneal shunt surgery in idiopathic normal pressure hydrocephalus: a case report.

The transversus abdominis plane (TAP) block is an ideal pain control method used in surgeries that require abdominal wall incisions through the injection of an anesthetic solution into the plane between the internal oblique muscle and transversus abdominis muscle. Herein, we report an 83-year-old man who was diagnosed with idiopathic normal pressure hydrocephalus (iNPH) and underwent lumboperitoneal shunt surgery (LPS). The TAP block was performed before LPS, and the numerical rating scale for pain was 0 at day 1 after the surgery. The patient was discharged early at day 3 after surgery despite the patient being extremely old, as he reported quick relief from the postoperative abdominal pain. The TAP block can hence be considered for use before LPS in elderly patients with iNPH.

Clinical significance of vitamin D in idiopathic normal pressure hydrocephalus.

BACKGROUND: Although recent studies show vitamin D deficiency is associated with cognitive decline, urinary incontinence, and gait instability, there has been no study on the effect of vitamin D on idiopathic normal pressure hydrocephalus (iNPH) characterized by the classic symptom triad of cognitive decline, urinary incontinence, and gait instability. We investigated the clinical significance of vitamin D in patients with iNPH. METHODS: Between 2017 and 2020, 44 patients who underwent ventriculoperitoneal shunt surgery were divided into low (< 15 ng/mL) and high (≥ 15 ng/mL) vitamin D groups according to the concentration of 25(OH)D, an effective indicator of vitamin D status. They were respectively evaluated according to clinical and radiological findings. RESULTS: The low vitamin D group (n = 24) showed lower preoperative cognition compared to the high vitamin D group (n = 20) in terms of Korean-Mini Mental Status Examination (K-MMSE) and iNPH grading scale (iNPHGS) (K-MMSE: 20.5 ± 5.4 versus 24.0 ± 4.5, p = 0.041; iNPHGS cognitive score: 2 ± 0.9 versus 1 ± 0.6, p = 0.025). And the low vitamin D group showed pre- and postoperatively more severe urinary incontinence (preoperative iNPHGS urinary score: 1 ± 1.0 versus 0 ± 0.9, p = 0.012; postoperative iNPHGS urinary score:1 ± 1.0 versus 0 ± 0.9, p = 0.014). The score of narrow high-convexity sulci for the low vitamin D group was lower (low vitamin D group: 1 ± 0.7 versus high vitamin D group: 2 ± 0.4, p = 0.031). CONCLUSION: Lower concentration of vitamin D in iNPH may be related to lower preoperative cognition, pre- and postoperative urinary incontinence, and brain morphological change.

Real-world effectiveness, its predictors and onset of action of cholinesterase inhibitors and memantine in dementia: retrospective health record study.

BACKGROUND: The efficacy of acetylcholinesterase inhibitors and memantine in the symptomatic treatment of Alzheimer's disease is well-established. Randomised trials have shown them to be associated with a reduction in the rate of cognitive decline. AIMS: To investigate the real-world effectiveness of acetylcholinesterase inhibitors and memantine for dementia-causing diseases in the largest UK observational secondary care service data-set to date. METHOD: We extracted mentions of relevant medications and cognitive testing (Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores) from de-identified patient records from two National Health Service (NHS) trusts. The 10-year changes in cognitive performance were modelled using a combination of generalised additive and linear mixed-effects modelling. RESULTS: The initial decline in MMSE and MoCA scores occurs approximately 2 years before medication is initiated. Medication prescription stabilises cognitive performance for the ensuing 2-5 months. The effect is boosted in more cognitively impaired cases at the point of medication prescription and attenuated in those taking antipsychotics. Importantly, patients who are switched between agents at least once do not experience any beneficial cognitive effect from pharmacological treatment. CONCLUSIONS: This study presents one of the largest real-world examination of the efficacy of acetylcholinesterase inhibitors and memantine for symptomatic treatment of dementia. We found evidence that 68% of individuals respond to treatment with a period of cognitive stabilisation before continuing their decline at the pre-treatment rate.

The side effect profile of Clozapine in real world data of three large mental health hospitals.

OBJECTIVE: Mining the data contained within Electronic Health Records (EHRs) can potentially generate a greater understanding of medication effects in the real world, complementing what we know from Randomised control trials (RCTs). We Propose a text mining approach to detect adverse events and medication episodes from the clinical text to enhance our understanding of adverse effects related to Clozapine, the most effective antipsychotic drug for the management of treatment-resistant schizophrenia, but underutilised due to concerns over its side effects. MATERIAL AND METHODS: We used data from de-identified EHRs of three mental health trusts in the UK (>50 million documents, over 500,000 patients, 2835 of which were prescribed Clozapine). We explored the prevalence of 33 adverse effects by age, gender, ethnicity, smoking status and admission type three months before and after the patients started Clozapine treatment. Where possible, we compared the prevalence of adverse effects with those reported in the Side Effects Resource (SIDER). RESULTS: Sedation, fatigue, agitation, dizziness, hypersalivation, weight gain, tachycardia, headache, constipation and confusion were amongst the highest recorded Clozapine adverse effect in the three months following the start of treatment. Higher percentages of all adverse effects were found in the first month of Clozapine therapy. Using a significance level of (p< 0.05) our chi-square tests show a significant association between most of the ADRs and smoking status and hospital admission, and some in gender, ethnicity and age groups in all trusts hospitals. Later we combined the data from the three trusts hospitals to estimate the average effect of ADRs in each monthly interval. In gender and ethnicity, the results show significant association in 7 out of 33 ADRs, smoking status shows significant association in 21 out of 33 ADRs and hospital admission shows the significant association in 30 out of 33 ADRs. CONCLUSION: A better understanding of how drugs work in the real world can complement clinical trials.

The Dementias Platform UK (DPUK) Data Portal.

The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 individuals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure 'lab' using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 individual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.

Longitudinal evaluation of Tau-P301L transgenic mice reveals no cognitive impairments at 17 months of age.

Introduction: Tau is a microtubule-associated binding protein implicated in neurodegenerative tauopathies, including frontotemporal dementia (FTD) and Alzheimer's disease (AD). These diseases result in the intracellular accumulation of hyperphosphorylated tau in the form of neurofibrillary tangles, the presence of which is associated with cognitive deficits. Methods: We conducted a longitudinal behavioral study to provide a profile of the TgTau(P301L)23027 transgenic mouse in multiple cognitive domains across multiple ages. P301L is the tau mutation most frequently observed in patients with frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17) and this mouse model recapitulates the progressive development of glial and neurofibrillary tangles, and associated cerebral atrophy observed in patients. We examined frontal cortex-dependent executive function and attention with the touchscreen 5-choice serial reaction time test (5-CSRTT) and assessed the function of temporal cortical structures using novel object recognition (OR). Results: Despite using sensitive tasks, there were no apparent changes in executive function, attention, or recognition memory in the transgenic mice from 5 to 17 months of age. Conclusions: This study represents the first comprehensive longitudinal analysis of cognition in the TgTauP301L mouse model and suggests that this model is not ideal for studying early attention and recognition memory impairments associated with tauopathy. However, spatial and object recognition memory impairments were observed during follow-up assessments when the mice were 18 and 21 months, respectively. These impairments are consistent with previous publications, and with a dementia-like phenotype in these mice when aged.

Automatic mining of symptom severity from psychiatric evaluation notes.

OBJECTIVES: As electronic mental health records become more widely available, several approaches have been suggested to automatically extract information from free-text narrative aiming to support epidemiological research and clinical decision-making. In this paper, we explore extraction of explicit mentions of symptom severity from initial psychiatric evaluation records. We use the data provided by the 2016 CEGS N-GRID NLP shared task Track 2, which contains 541 records manually annotated for symptom severity according to the Research Domain Criteria. METHODS: We designed and implemented 3 automatic methods: a knowledge-driven approach relying on local lexicalized rules based on common syntactic patterns in text suggesting positive valence symptoms; a machine learning method using a neural network; and a hybrid approach combining the first 2 methods with a neural network. RESULTS: The results on an unseen evaluation set of 216 psychiatric evaluation records showed a performance of 80.1% for the rule-based method, 73.3% for the machine-learning approach, and 72.0% for the hybrid one. CONCLUSIONS: Although more work is needed to improve the accuracy, the results are encouraging and indicate that automated text mining methods can be used to classify mental health symptom severity from free text psychiatric notes to support epidemiological and clinical research.

Commonly prescribed drugs associate with cognitive function: a cross-sectional study in UK Biobank.

OBJECTIVE: To investigate medications associated with cognitive function. DESIGN: Population-based cross-sectional cohort study. SETTING: UK Biobank. PARTICIPANTS: UK Biobank participants aged 37-73 years who completed cognitive tests at the baseline visit in 2006-2010. MAIN OUTCOME MEASURES: Cognitive test outcomes on verbal-numerical reasoning test (n=165 493), memory test (n=482 766) and reaction time test (n=496 813). RESULTS: Most drugs (262 of 368) were not associated with any cognitive tests after adjusting for age, gender, education, household income, smoking, alcohol status, psychostimulant/nootropic medication use, assessment centre, and concurrent diagnoses and medications. Drugs used for nervous system disorders were associated with poorer cognitive performance (antiepileptics, eg, topiramate breasoning(score) -0.65 (95% CI -1.05 to -0.24), bmemory(score) -1.41 (-1.79 to -1.04); antipsychotics, eg, risperidone breaction time(ms) -33 (-46 to -20), negative values indicate poor cognitive performance and vice versa). Drugs used for non-nervous system conditions also showed significant negative association with cognitive score, including those where such an association might have been predicted (antihypertensives, eg, amlodipine breasoning -0.1 (-0.15 to -0.06), bmemory -0.08 (-0.13 to -0.03), breaction time -3 (-5 to -2); antidiabetics, eg, insulin breaction time -13 (-17 to -10)) and others where such an association was a surprising observation (proton pump inhibitors, eg, omeprazole breasoning -0.11 (-0.15 to -0.06), bmemory -0.08 (-0.12 to -0.04), breaction time -5 (-6 to -3); laxatives, eg, contact laxatives breaction time -13 (-19 to -8)). Finally, only a few medications and health supplements showed association towards a positive effect on cognitive function (anti-inflammatory agents, eg, ibuprofen breasoning 0.05 (0.02 to 0.08), breaction time 4 (3, 5); glucosamine breasoning 0.09 (0.03 to 0.14), breaction time 5 (3 to 6)). CONCLUSIONS: In this large volunteer study, some commonly prescribed medications were associated with poor cognitive performance. Some associations may reflect underlying diseases for which the medications were prescribed, although the analysis controlled for the possible effect of diagnosis. Other drugs, whose association cannot be linked to the effect of any disease, may need vigilance for their implications in clinical practice.

The continuous performance test (rCPT) for mice: a novel operant touchscreen test of attentional function.

RATIONALE: Continuous performance tests (CPTs) are widely used to assess attentional processes in a variety of disorders including Alzheimer's disease and schizophrenia. Common human CPTs require discrimination of sequentially presented, visually patterned 'target' and 'non-target' stimuli at a single location. OBJECTIVES: The aims of this study were to evaluate the performance of three popular mouse strains on a novel rodent touchscreen test (rCPT) designed to be analogous to common human CPT variants and to investigate the effects of donepezil, a cholinesterase inhibitor and putative cognitive enhancer. METHODS: C57BL/6J, DBA/2J and CD1 mice (n = 15-16/strain) were trained to baseline performance using four rCPT training stages. Then, probe tests assessed the effects of parameter changes on task performance: stimulus size, duration, contrast, probability, inter-trial interval or inclusion of flanker distractors. rCPT performance was also evaluated following acute administration of donepezil (0-3 mg/kg, i.p.). RESULTS: C57BL/6J and DBA/2J mice showed similar acquisition rates and final baseline performance following rCPT training. On probe tests, rCPT performance of both strains was sensitive to alteration of visual and/or attentional demands (stimulus size, duration, contrast, rate, flanker distraction). Relative to C57BL/6J, DBA/2J mice exhibited (1) decreasing sensitivity (d') across the 45-min session, (2) reduced performance on probes where the appearance of stimuli or adjacent areas were changed (size, contrast, flanking distractors) and (3) larger dose- and stimulus duration-dependent changes in performance following donepezil administration. In contrast, CD1 mice failed to acquire rCPT (stage 3) and pairwise visual discrimination tasks. CONCLUSIONS: rCPT is a potentially useful translational tool for assessing attention in mice and for detecting the effects of nootropic drugs.

Trial-unique, delayed nonmatching-to-location (TUNL) touchscreen testing for mice: sensitivity to dorsal hippocampal dysfunction.

RATIONALE: The hippocampus is implicated in many of the cognitive impairments observed in conditions such as Alzheimer's disease (AD) and schizophrenia (SCZ). Often, mice are the species of choice for models of these diseases and the study of the relationship between brain and behaviour more generally. Thus, automated and efficient hippocampal-sensitive cognitive tests for the mouse are important for developing therapeutic targets for these diseases, and understanding brain-behaviour relationships. One promising option is to adapt the touchscreen-based trial-unique nonmatching-to-location (TUNL) task that has been shown to be sensitive to hippocampal dysfunction in the rat. OBJECTIVES: This study aims to adapt the TUNL task for use in mice and to test for hippocampus-dependency of the task. METHODS: TUNL training protocols were altered such that C57BL/6 mice were able to acquire the task. Following acquisition, dysfunction of the dorsal hippocampus (dHp) was induced using a fibre-sparing excitotoxin, and the effects of manipulation of several task parameters were examined. RESULTS: Mice could acquire the TUNL task using training optimised for the mouse (experiments 1). TUNL was found to be sensitive to dHp dysfunction in the mouse (experiments 2, 3 and 4). In addition, we observed that performance of dHp dysfunction group was somewhat consistently lower when sample locations were presented in the centre of the screen. CONCLUSIONS: This study opens up the possibility of testing both mouse and rat models on this flexible and hippocampus-sensitive touchscreen task.