Formal analysis, An overall score 0 indicates no cognitive impairment, a 0.5 score indicates mild cognitive impairment, whilst scores of 1–3 indicate mild to severe stages of dementia [23]. However, an anonymised minimal dataset is made available on request to appropriate researchers. eCollection 2020. Lower scores (probabilities or distances) are associated with MCI. Table 5 shows the results of 10-fold cross-validation and predictive weights or importances of the CERAD variables in Linear SVM and Random Forest Models separating aMCI from deficit or nondeficit schizophrenia. Patients with deficit schizophrenia had significantly lower MMSE, WLM, WL True Recall and WL Recognition than aMCI patients, while WL False Recall was significantly higher in deficit schizophrenia than in aMCI. The results of multiple analyses were p-corrected for false discovery rate [26]. Word List Memory (WLM) measures verbal episodic memory or immediate working memory for verbal information. All data were analyzed using IBM SPSS windows version 24, Statistica 12, MaesStat and MATLAB. e0197004. Previous reports show that semantic memory tests and immediate recall are impaired in MCI as compared with controls [10]. Yes Table 3 First row, shows the model-generated estimated marginal means of the z-values obtained by multivariate GLM analyses after adjustment for age, education and sex. Clesse C, Salime S, Dumand I, Concetta-Ciciarelli SB, Lavenir S, Kacemi K, Heckel-Chalet P, Sissung F, Poinsignon A, Simon A, Decker M, Batt M. Front Psychiatry. 2019 Jul;23(7):840-850. doi: 10.1080/13607863.2018.1501668. Your memories of all those specific events and experiences are examples of episodic memory. In other studies, WLM and WL Recognition tests distinguished MCI patients from healthy controls [11,13]. Egocentric Navigation Abilities Predict Episodic Memory Performance. The rate of incorrect predictions was 20.0% in the training sample, 13.3% in the testing sample and 20.0% in the holdout sample. Random Forest predicted class probabilities and Linear SVM distances to decision boundary for mild cognitive impairment (MCI) versus deficit schizophrenia. Front Hum Neurosci. Approval for the study was obtained from the Institutional Review Board of the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, which is in compliance with the International Guideline for Human Research protection as required by the Declaration of Helsinki, The Belmont Report, CIOMS Guideline and International Conference on Harmonization in Good Clinical Practice (ICH-GCP). In the training sample, the rate of incorrect predictions was 23.9% and this was lower in the testing (18.2%) sample, while the holdout sample showed 25.8% incorrect predictions. Basing on a word list, the verbal learning test (VLT) is a popular method of episodic memory detection; the VLT’s index of “delayed recall” is considered the most sensitive measure for the early diagnosis of AD. https://doi.org/10.1371/journal.pone.0197004, Editor: Stephen D. Ginsberg, Nathan S Kline Institute, UNITED STATES, Received: February 12, 2018; Accepted: April 24, 2018; Published: May 15, 2018. Changes in Tryptophan Catabolite (TRYCAT) Pathway Patterning Are Associated with Mild Impairments in Declarative Memory in Schizophrenia and Deficits in Semantic and Episodic Memory Coupled with Increased False-Memory Creation in Deficit Schizophrenia. Yes Tests for between-subject effects were subsequently used to define the univariate effects of the significant explanatory variables on the dependent variables. The MMSE was significantly lower in deficit schizophrenia than in the other three groups, whilst MMSE was also lower in aMCI than in controls, but not nondeficit schizophrenia patients. Following a 30-min delay, the participant is required to recall List A, following Individuals with aMCI visited our dementia clinic to investigate their subjective memory complaints. In patients with schizophrenia and aMCI no significant associations were detected between age and the CERAD tests. The latter were recruited from community senior club members, normal elderly caregivers, senior Red Cross volunteers and individuals who visited the Health Check Up Clinic, Bangkok, Thailand. We also excluded aMCI and schizophrenia patients with major immune-inflammatory disorders including diabetes mellitus type 1, systemic lupus erythematosus, inflammatory bowel disease and chronic obstructive pulmonary disease. Diagnosis had a significant effects on the 6 CERAD measurements (F = 5.66, df = 15/638, p<0.001, partial eta-squared = 0.109), while also age (F = 5.01, df = 5/231, p<0.001, partial eta-squared = 0.098), education (F = 23.56, df = 3/231, p<0.001, partial eta-squared = 0.338), and gender (F = 4.77, df = 5/231, p<0.001, partial eta-squared = 0.094) had significant effects. https://doi.org/10.1371/journal.pone.0197004.t002. Hierarchical binary logistic regression analyses were employed to delineate the significant explanatory variables (CERAD data) which predict aMCI versus deficit schizophrenia and aMCI versus nondeficit schizophrenia. The CDR evaluates 6 domains including memory, orientation, judgement, problem solving, social affairs, home and hobbies and personal care. In particular, responses aloud should impede immediate- but not delayed-recall performance. Automatic architecture training identified the best model with 2 hidden layers with 3 and 2 units in layer 1 and 2, respectively, and with hyperbolic tangent as activation function in layer 1 and identity in hidden layer 2. Conversely, the type of responses should interact with the recall test. The same variables together with lowered WL Recognition were also associated with aMCI versus nondeficit schizophrenia. However, males and females do not differ significantly on working memory and semantic memory tasks. In Random Forest, the importance is calculated based on GINI importances, which measure the average gain in purity of diagnosis classes when that feature is used as criterion to split data points. Participants with schizophrenia and aMCI were recruited at the Department of Psychiatry, King Chulalongkorn Memorial Hospital’s Dementia clinic, Bangkok, Thailand. Table 2 shows that in normal controls, there were significant and inverse associations between age and VFT, BNT and MMSE, but not the other CERAD tests. These 63 normal volunteers had a CDR score of 0 and a MMSE score of at least 24. Language deficits including poor naming performance are early and important diagnostic criteria for MCI [16,34,35]. https://doi.org/10.1371/journal.pone.0197004.t003. COVID-19 is an emerging, rapidly evolving situation. In order to define the correlations between education and the CERAD test scores we have computed the intercorrelation matrix between the two variables in normal controls. Data access requests can be submitted to the Department of Psychiatry Data Access Committee (psych.researchdata@chula.ac.th). Committeri G, Fragueiro A, Campanile MM, Lagatta M, Burles F, Iaria G, Sestieri C, Tosoni A. Miguel Ángel Rivas-Fernández Laboratorio de Neurociencia Cognitiva, Departamento de Psicoloxía Clínica e Psicobioloxía, Universidade de … Mean (SE) z scores of Consortium to Establish a Registry for Alzheimer’s disease…, Fig 3. However, since lower education may be a risk factor for aMCI and deficit schizophrenia (see Discussion) we have examined inter-group differences with (secondary analyses) and without (primary analyses) adjustment for education. It is interesting to note that after considering the effects of BNT in logistic regression analyses, SVM and Random Forest and Neural Networks, WLM was also a significant feature of nondeficit schizophrenia versus aMCI. -, Petersen RC, Negash S. Mild cognitive impairment: an overview. Fig 1 shows the differences in the z values of the VFT, BNT and MMSE test scores in the 4 study groups. Memory decline has been defined as a decrease of at least 1 SD from the mean change score on immediate recall (IR), delayed recall (DR), and retention, based on the AVLT (Dik, Jonker et al. These results show that impairments in episodic memory, immediate working memory and recall are characteristic features of deficit schizophrenia, whilst dysnomia is a feature of aMCI. Results of GLM and logistic regression analyses, linear SVM, Random Forest and Neural Networks agreed that deficit schizophrenia is well-separated from aMCI patients by lowered WLM and MMSE test scores and higher false recall scores, while patients with aMCI show lower BNT scores. Both amnestic mild cognitive impairment (aMCI) and schizophrenia, in particular deficit schizophrenia, are accompanied by cognitive impairments. Neural network importance chart showing…, Fig 4. In our study, increasing age is accompanied by lowered VFT, BNT and MMSE scores, which are also the key features of aMCI, suggesting that accelerated ageing in processes that mediate language and executive-semantic functions play an important role in aMCI. Education was significantly and positively associated with all 4 scores (all p<0.004). However, sometimes these changes occur sooner than anticipated or faster than expected. No, Is the Subject Area "Word recognition" applicable to this article? These differences are inherent to the study sample selection, namely elderly subjects with aMCI (>62 years) and younger schizophrenia subjects in a stable phase of illness. No, Is the Subject Area "Alzheimer's disease" applicable to this article? Fig 2 shows the differences in the z values of the WLM correct1, correct2, correct3 and WLM total in the 4 study groups. https://doi.org/10.1371/journal.pone.0197004.t001. The new DSM-5 diagnosis of mild neurocognitive disorder and its relation to research in mild cognitive impairment. WL True Recall was significantly lower in the three patients groups as compared with controls, lower in deficit schizophrenia as compared with the three other groups but no differences between nondeficit schizophrenia and aMCI. First, time is of the essence when administering tests. Moreover, aMCI patients were included only when the Clinical Dementia Rating Scale (CDR) score was equal to 0.5 and the CDR memory component was 0.5, indicating aMCI. Declarative Memory consists of memory for events (episodic memory) and facts (semantic memory). Memory impairments, especially in episodic memory, are significantly worse in younger patients with deficit schizophrenia as compared with elderly patients with aMCI, while the latter show more dysnomia than patients with schizophrenia. Lower BNT and increased WLM are strongly associated with aMCI versus deficit schizophrenia. 2008;13(1):45–53. RESULTS. Table 3 shows the differences between the 4 study groups in the 5 WL recall and recognition variables and the results of multivariate GLM and post-hoc analyses. 40 healthy volunteers were recruited by word of mouth to match the schizophrenia patients for age, whereas 63 elderly controls were recruited to match the elderly aMCI patients. Patients with schizophrenia and aMCI have a significantly different neurocognitive profile. Mean (SE) z scores of Consortium to Establish a Registry for Alzheimer’s disease…, Fig 4. There was a highly significant effect of diagnostic groups (F = 10.18, df = 15/646, p<0.001) explaining 17.7% of the variance in the data. Episodic memory must … code spatiotemporal relations: The What-Where-When test. Neural correlates of autobiographical memory in amnestic Mild Cognitive Impairment. Copyright: © 2018 Kanchanatawan et al. Neural network importance charts show that deficit and nondeficit schizophrenia are best separated from aMCI using total BNT score, while WLM and WL false Recall follow at a distance. https://doi.org/10.1371/journal.pone.0197004.t005. Neural network importance chart showing…, Fig 5. The effects of healthy aging, amnestic mild cognitive impairment, and Alzheimer's disease on recollection and familiarity: a meta-analytic review. A deficit in episodic memory is often observed in aMCI patients who subsequently will develop Alzheimer’s dementia [6]. S1 Fig and S2 Fig show the Random Forest predicted class probabilities and Linear SVM distances to decision boundary for aMCI versus deficit and nondeficit schizophrenia, respectively. Those subjects additionally underwent physical and neurological examination to exclude age-related medical and neurological pathologies. WL False Recall was significantly higher in deficit schizophrenia than in the three other groups and higher in aMCI and nondeficit schizophrenia than in controls. In Linear SVM, the sign of the weights is associated with the diagnostic class, while the magnitude reflects its importance. The aim of the present study was to examine the cognitive differences between aMCI and (non)deficit schizophrenia. Fig 4 shows the impact of the input variables in the neural model as relative and normalized importances. In MCI, however, low memory and MMSE scores are significantly associated with amyloid positivity [42,43], while increased cerebro-spinal fluid amyloid β42 and t-Tau are the best predictors of conversion from MCI to AD [43]. TrueWLRecall: Word List Recall, Delayed, true recall; FalseWLRecall: Word List Recall, Delayed, false recall (WL False Recall); CorrectWLRecognition: WL Recognition Correct Yes response; NoWLRecognition: Word List Recognition Correct No response; WLRecognition: sum of Correctand No WLRecognition. The main finding of this study is that deficit schizophrenia and aMCI show major differences in neurocognitive profiles. Nevertheless, since there were differences in sex ratio between the study groups, we have used sex as a second factor in the secondary analyses. The episodic and semantic memories are information processing systems. Negative symptoms, including alogia, anhedonia, apathy, social withdrawal and incongruous emotional responses, are often chronic and present between acute symptom episodes, a nosological entity named deficit schizophrenia[17]. TrueWLRecall: Word List Recall, Delayed, true recall; FalseWLRecall: Word List Recall, Delayed, false recall (WL False Recall); CorrectWLRecognition: WL Recognition Correct Yes response; NoWLRecognition: Word List Recognition Correct No response; WLRecognition: sum of Correctand No WLRecognition. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. c. the name of the first president of the United States d. how to ride a bike Table 6 also shows the results of MLP Neural networks predicting aMCI and nondeficit schizophrenia using the CERAD scores as input variables. Table 3 (row 2) shows the differences between the 4 study groups in the 4 WLM variables and the results of post-hoc analyses. Moreover, aMCI patients were significantly separated from controls by lower VFT, BNT, MMSE, and WLM test results. here. Memory is commonly reported as a big area of concern for people with epilepsy. WLRecCorrect and WLRec total were significantly lower in deficit schizophrenia than in the three other groups. The schizophrenia patients were in a stable phase of illness and divided into 40 without (nondeficit) and 40 with deficit schizophrenia. Indeed, given the significant associations between age and BNT and MMSE variables (see Table 2) and education and sex (see results of GLM analyses) we also examined whether using CERAD features provide any predictive power in the presence of these confounding variables. Episodic memory has been used as a measure of memory decline. The 4 WLM variables were significantly lower in deficit schizophrenia than in the three other groups and lower in aMCI than in controls, while there were no differences between aMCI and nondeficit schizophrenia. In each case, the end result will be that you cannot recall an event or a piece of information when you need it. Conclusions: There was a highly significant effect of diagnostic groups (F = 11.41, df = 9/577, p<0.001) explaining 12.4% of the variance in the data. Table 6 shows the results of MLP Neural networks predicting aMCI versus deficit schizophrenia (output or target variables) using the CERAD scores as input variables. a) subjective memory complaints, b) abnormal memory for age, c) normal general cognitive function, d) preservation of functional activities, and e) absence of dementia". The aim of the present study was to examine the cognitive differences between aMCI and (non)deficit schizophrenia. Data curation, It is less common to assess implicit memory. Tests were two-tailed and a p-value of 0.05 was used for statistical significance. Nevertheless, to the best of our knowledge no previous studies have shown the validity of the MATRICS in aMCI, while the CERAD is useful to assess episodic and semantic memory impairments (and to a lesser degree also executive functions) in aMCI [10–16] and schizophrenia [18]. Yes Table 4 shows the results of binary logistic regression analysis with aMCI and (non)deficit schizophrenia as dependent variables and the CERAD tests as explanatory variables. NIH The a priori hypothesis was that individuals with (deficit) schizophrenia show greater impairments in episodic and semantic memory scores than patients with aMCI. Consistently, females perform better than males on episodic memory tasks including delayed recall and recognition. BNT total was the dominant determinant, while WL Recognition, WLM and WL True Recall followed at a distance. Shown are the results of Multilayer Perceptron Neural Network analysis with network information, model summary, parameter estimates, and input variable importance. Using the CERAD features to segregate aMCI from deficit schizophrenia resulted in a good 10-fold cross-validation accuracy for Linear SVM as well as Random Forest. Towards this end we recruited 60 participants with aMCI, 40 with deficit and 40 with nondeficit schizophrenia and 103 normal volunteers. VFT24: verbal fluency test; BNT: Modified Boston Naming Test; BNTh: naming of highly frequency objects; BNTm: naming of medium frequency objects; BNTl: naming of low frequency objects; BNTtotal: BNT total score. Memory impairments, especially in episodic memory, are significantly worse in younger patients with deficit schizophrenia as compared with elderly patients with aMCI, while the latter show more dysnomia than patients with schizophrenia. See this image and copyright information in PMC. We excluded aMCI and schizophrenia patients with other major axis-1 DSM-IV-TR diagnoses including schizoaffective disorder, major depression, bipolar disorder, substance use disorders and psycho-organic disorders. No, Is the Subject Area "Support vector machines" applicable to this article? Yes  |  Thus, while memory disturbances are considered to be the main features of aMCI [6], episodic memory tests are even more impaired in younger subjects with deficit schizophrenia than in elderly subjects with aMCI. Epub 2014 Aug 15. Healthy controls were patients’ family and ... delayed recall of List A is assessed, without further presentation of those words. More specifically, the biosignature of memory impairments in (deficit) schizophrenia is highly significantly associated with activation of the tryptophan catabolite (TRYCAT) pathway and increased activity of neurotoxic TRYCATs, including picolinic and xanthurenic acid [18]. Interestingly, a recent review shows that the amyloid cascade is not associated with neurocognitive impairments in schizophrenia [41]. S4 Fig .pdf shows the results of this Multilayer Perceptron Neural Network analysis with network information, model summary, parameter estimates, and input variable importances. WLM correct1, WLM correct2 and WLM total were significantly lower in all three patient groups as compared with controls, lower in deficit schizophrenia than in the three other study groups, and lower values in nondeficit schizophrenia than in aMCI. Writing – original draft, Roles Aging & Mental Health. Previously, it was shown that education was protective for MCI [47]. Epub 2018 Oct 23. The memory deficit disappeared when memory was specifically probed by asking pointed questions. Yes Thus, schizophrenia is considered to be a neuroprogressive disorder caused by multiple hits causing neuronal disruption, epigenetic changes, and activation of immune-inflammatory and oxidative stress pathways which further impair neuronal functions [41]. Fig 5 shows the relative and normalized importances of the CERAD data contributing to the predictive power of the model. Shown are the model-generated marginal means (SE) of the z-scores of all CERAD tests. Overall, binary logistic regression analyses, Linear SVM and Random Forest (including after adjustment for the confounders were made) agreed that BNT and WLM are the key features segregating aMCI from deficit and nondeficit schizophrenia. Memory research has influenced the development of present-day memory assessment techniques, but not all forms of memory are assessed in the commonly used batteries. Effects on delayed episodic memory were medium in size. One theory is that age-related changes in central pathways make the brain more vulnerable to neurodegenerative processes thereby accelerating detrimental effects of ageing [46]. Overall, the cognitive profile of MCI patients (versus controls) shows more impairments in naming, verbal fluency, verbal memory and recall as compared with controls. Funding: The study was supported by the Asahi Glass Foundation, Chulalongkorn University Centenary Academic Development Project and by Chulalongkorn University, Thai Government Fund GRB_APS_10_57_30_08. 5th ed. These findings indicate that impaired episodic memory is a feature of (non)deficit schizophrenia, whilst dysnomia is a feature of aMCI. Evidence indicates that schizophrenia and in particular deficit schizophrenia are accompanied by objective cognitive deficits as measured using the CERAD[18]. Association AP. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. WLcorrect1: Trial 1 (WLM correct 1); WLcorrect2: Trial 2 (WLM correct 2); WLcorrect3: Trial 3 (WLM correct 3); WLM: Word List Memory, total score. https://doi.org/10.1371/journal.pone.0197004.s002. WLRecCorrect and WLRec total were significantly lower in deficit schizophrenia than in the three other groups and lower in aMCI, but not nondeficit schizophrenia, than in controls. The highly significant differences in cognitive profiles between both (deficit) schizophrenia and aMCI and the significantly greater memory disturbances in younger schizophrenia subjects than in elderly aMCI participants indicate that different pathways underpin both conditions. Memory impairments, especially in episodic memory, are significantly worse in younger patients with deficit schizophrenia as compared with elderly patients with aMCI, while the latter show more dysnomia than patients with schizophrenia. Episodic Memory and Trauma Episodic memory has to do with how you remember specific events, including traumatic memories. Competing Interests: The authors have declared that no competing interests exist. Data curation, 2000). 2003;15(1):257–9. Word List Recall, Delayed, true recall (WL True Recall), which measures the ability to recall (delayed recall) and verbal episodic memory recall. Since the main aim of the study was to analyze the degree of cognitive impairment present in younger schizophrenia patients versus that in aMCI patients (thus elderly individuals) we have carried out GLM analyses without adjustment for age and showed these results in Figures (primary analyses) and with adjustment for age. These findings extend the knowledge that patients with schizophrenia, and especially those with deficit schizophrenia, show reduced independence, poor social functioning, ADL impairments and worse physical health than normal controls [38–40]. HHS Our ability to remember and to recall our past is what links us to our families, our friends and our community.As we age, subtle changes in memory occur naturally as part of the aging process. Epub 2020 Sep 2. However, because the effects on long-term and working memory were qualified by evidence for publication bias, we conclude that the effect of amphetamine and methylphenidate on the examined facets … Imagine that you get a phone call from an old college friend. Schizophrenia is a disabling disorder with a heterogeneous phenotype characterized by many different symptomatic dimensions, including negative, psychotic and neurocognitive symptoms as well as symptoms of depression and anxiety. 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