Clinical Assessment of Judgment in Adults and the Elderly: Development and Validation of the Three Domains of Judgment Test-Clinical Version (3DJT-CV).

(1) Background: This article discusses the first two phases of development and validation of the Three Domains of Judgment Test (3DJT). This computer-based tool, co-constructed with users and capable of being administered remotely, aims to assess the three main domains of judgment (practical, moral, and social) and learn from the psychometric weaknesses of tests currently used in clinical practice. (2) Method: First, we presented the 3DJT to experts in cognition, who evaluated the tool as a whole as well as the content validity, relevance, and acceptability of 72 scenarios. Second, an improved version was administered to 70 subjects without cognitive impairment to select scenarios with the best psychometric properties in order to build a future clinically short version of the test. (3) Results: Fifty-six scenarios were retained following expert evaluation. Results support the idea that the improved version has good internal consistency, and the concurrent validity primer shows that 3DJT is a good measure of judgment. Furthermore, the improved version was found to have a significant number of scenarios with good psychometric properties to prepare a clinical version of the test. (4) Conclusion: The 3DJT is an interesting alternative tool for assessing judgment. However, more studies are needed for its implementation in a clinical context.

Longitudinal Cognitive Changes in Genetic Frontotemporal Dementia Within the GENFI Cohort.

BACKGROUND AND OBJECTIVES: Disease-modifying therapeutic trials for genetic frontotemporal dementia (FTD) are underway, but sensitive cognitive outcome measures are lacking. The aim of this study was to identify such cognitive tests in early stage FTD by investigating cognitive decline in a large cohort of genetic FTD pathogenic variant carriers and by investigating whether gene-specific differences are moderated by disease stage (asymptomatic, prodromal, and symptomatic). METHODS: C9orf72, GRN, and MAPT pathogenic variant carriers as well as controls underwent a yearly neuropsychological assessment covering 8 cognitive domains as part of the Genetic FTD Initiative, a prospective multicenter cohort study. Pathogenic variant carriers were stratified according to disease stage using the global Clinical Dementia Rating (CDR) plus National Alzheimer's Coordinating Center (NACC) FTLD score (0, 0.5, or ≥1). Linear mixed-effects models were used to investigate differences between genetic groups and disease stages as well as the 3-way interaction between time, genetic group, and disease stage. RESULTS: A total of 207 C9orf72, 206 GRN, and 86 MAPT pathogenic variant carriers and 255 controls were included. C9orf72 pathogenic variant carriers performed lower on attention, executive function, and verbal fluency from CDR plus NACC FTLD 0 onwards, with relatively minimal decline over time regardless of the CDR plus NACC FTLD score (i.e., disease progression). The cognitive profile in MAPT pathogenic variant carriers was characterized by lower memory performance at CDR plus NACC FTLD 0.5, with decline over time in language from the CDR plus NACC FTLD 0.5 stage onwards, and executive dysfunction rapidly developing at CDR plus NACC FTLD ≥1. GRN pathogenic variant carriers declined on verbal fluency and visuoconstruction in the CDR plus NACC FTLD 0.5 stage, with progressive decline in other cognitive domains starting at CDR plus NACC FTLD ≥1. DISCUSSION: We confirmed cognitive decline in the asymptomatic and prodromal stage of genetic FTD. Specifically, tests for attention, executive function, language, and memory showed clear differences between genetic groups and controls at baseline, but the speed of change over time differed depending on genetic group and disease stage. This confirms the value of neuropsychological assessment in tracking clinical onset and progression and could inform clinical trials in selecting sensitive end points for measuring treatment effects as well as characterizing the best time window for starting treatment.

A modified Camel and Cactus Test detects presymptomatic semantic impairment in genetic frontotemporal dementia within the GENFI cohort.

Impaired semantic knowledge is a characteristic feature of some forms of frontotemporal dementia (FTD), particularly the sporadic disorder semantic dementia. Less is known about semantic cognition in the genetic forms of FTD caused by mutations in the genes MAPT, C9orf72, and GRN. We developed a modified version of the Camel and Cactus Test (mCCT) to investigate the presence of semantic difficulties in a large genetic FTD cohort from the Genetic FTD Initiative (GENFI) study. Six-hundred-forty-four participants were tested with the mCCT including 67 MAPT mutation carriers (15 symptomatic, and 52 in the presymptomatic period), 165 GRN mutation carriers (33 symptomatic, 132 presymptomatic), and 164 C9orf72 mutation carriers (56 symptomatic, 108 presymptomatic) and 248 mutation-negative members of FTD families who acted as a control group. The presymptomatic mutation carriers were further split into those early and late in the presymptomatic period (more than vs. within 10 years of expected symptom onset). Groups were compared using a linear regression model, adjusting for age and education, with bootstrapping. Performance on the mCCT had a weak negative correlation with age (rho = -0.20) and a weak positive correlation with education (rho = 0.13), with an overall abnormal score (below the 5th percentile of the control population) being below 27 out of a total of 32. All three of the symptomatic mutation groups scored significantly lower than controls: MAPT mean 22.3 (standard deviation 8.0), GRN 24.4 (7.2), C9orf72 23.6 (6.5) and controls 30.2 (1.6). However, in the presymptomatic groups, only the late MAPT and late C9orf72 mutation groups scored lower than controls (28.8 (2.2) and 28.9 (2.5) respectively). Performance on the mCCT correlated strongly with temporal lobe volume in the symptomatic MAPT mutation group (rho > 0.80). In the C9orf72 group, mCCT score correlated with both bilateral temporal lobe volume (rho > 0.31) and bilateral frontal lobe volume (rho > 0.29), whilst in the GRN group mCCT score correlated only with left frontal lobe volume (rho = 0.48). This study provides evidence for presymptomatic impaired semantic knowledge in genetic FTD. The different neuroanatomical associations of the mCCT score may represent distinct cognitive processes causing deficits in different groups: loss of core semantic knowledge associated with temporal lobe atrophy (particularly in the MAPT group), and impaired executive control of semantic information associated with frontal lobe atrophy. Further studies will be helpful to address the longitudinal change in mCCT performance and the exact time at which presymptomatic impairment occurs.

Thirty Days without a Bite: Wernicke's Encephalopathy in a Patient with Paranoid Schizophrenia.

Wernicke's Encephalopathy (WE) is a preventable neurologic condition characterized by altered mental status, ophthalmoplegia, and ataxia. Although historically associated with alcoholism, a few authors have described WE in patients with non-alcohol related psychiatric disorders. We report herein the case of a 36-year-old young man with paranoid schizophrenia who was brought to hospital for confusion and difficulties with his vision. His roommate said he had gone about thirty days without eating '…because he was on a slimming cure'. History and physical examination suggested WE as a result of isolation and poor diet leading to nutritional deficiency. This was confirmed by brain magnetic resonance imaging showing classic thalamic, mammillary bodies and brainstem lesions. Of note, his cognitive profile was far more heterogeneous than what had classically been described in the literature and involved both cortical and subcortical pathology, generating memory but also significant executive deficits. Intravenous treatment with thiamine was given and our patient showed mild improvements in visual acuity and nystagmus. However, persistent cognitive and physical disabilities consistent with Korsakoff syndrome remained, and he now lives in a supervised home. This case illustrates the tragic consequences of nutritional deficiencies in a patient with paranoid schizophrenia. The threshold to suspect WE in schizophrenic patients should be lowered and in doubt prophylactic parenteral thiamine should be administered.

True and false memories in adolescents with psychosis: evidence for impaired recollection and familiarity.

INTRODUCTION: Psychotic patients are impaired on recall and recognition of studied items (true memory) and typically make more false recall (intrusions) and false recognition than controls, reflecting greater susceptibility to false memory. The functional mechanisms underlying these deficits are poorly understood. The aim of this study was to examine recollection and familiarity in true and false memory in psychotic adolescents without long-term exposure to medication and repeated hospitalisations. METHODS: Seventeen adolescents with psychosis and 17 matched controls were tested on a DRM false memory paradigm combined with a remember (R)/know (K)/guess (G) procedure. Recall and recognition of targets (studied words), critical lures (associated words) and unrelated distractors were measured. Between-group comparisons were made using t-tests and mixed ANOVAs. Independent estimates for recollection and familiarity were also calculated. RESULTS: True memory was impaired in patients. Similar rates of false memory for critical lures were found in both groups. False memory for unrelated distractors was increased in patients. Contrary to controls, who attributed more R and K responses to targets than lures, patients attributed similar proportions of R and K responses to targets and lures. Furthermore, patients attributed more K responses than controls to all distractors. CONCLUSIONS: These findings suggest a deficit in recollection- and familiarity-based memory in psychotic adolescents as well as reliance on preserved gist or meaning-based memory to support poor item-specific memory.

Effects of phonological and semantic cuing on encoding and retrieval processes in adolescent psychosis.

The aim of this study was to investigate the effects of cuing on encoding and retrieval processes in adolescent psychosis. Patients and controls were instructed to learn word lists under three conditions: no cue, phonological cue, and semantic cue. Memory performance was measured with free and cued recalls. In free recall, both groups showed higher performance with semantic than with phonological encoding cues, but patients had no advantage from semantic cuing relative to no cue, contrary to controls. Patients' performance improved from free to cued recall, but this was not sufficient to normalize their performance. Impaired strategic processes may lead to encoding and retrieval difficulties in patients.

Shared neurocognitive dysfunctions in young offspring at extreme risk for schizophrenia or bipolar disorder in eastern quebec multigenerational families.

BACKGROUND: Adult patients having schizophrenia (SZ) or bipolar disorder (BP) may have in common neurocognitive deficits. Former evidence suggests impairments in several neuropsychological functions in young offspring at genetic risk for SZ or BP. Moreover, a dose-response relation may exist between the degree of familial loading and cognitive impairments. This study examines the cognitive functioning of high-risk (HR) offspring of parents having schizophrenia (HRSZ) and high-risk offspring of parents having bipolar disorder (HRBP) descending from densely affected kindreds. METHODS: The sample consisted of 45 young offspring (mean age of 17.3 years) born to a parent having SZ or BP descending from large multigenerational families of Eastern Québec that are densely affected by SZ or BP and followed up since 1989. The offspring were administered a lifetime best-estimate diagnostic procedure (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV]) and an extensive standard neuropsychological battery. Raw scores were compared with age- and gender-matched controls. RESULTS: The offspring displayed differences in memory and executive functions when compared with controls. Moderate to large effect sizes (Cohen d) ranging from 0.65 to 1.25 (for IQ and memory) were observed. Several of the cognitive dysfunctions were present in both HRSZ and HRBP, even when considering DSM-IV clinical status. CONCLUSIONS: HRSZ and HRBP shared several aspects of their cognitive impairment. Our data suggest that the extremely high genetic and familial loading of these HRs may have contributed to a quantitatively increased magnitude of the cognitive impairments in both HR subgroups, especially in memory. These offspring at heightened risk present difficulties in processing information that warrant preventive research.

Deficient relational binding processes in adolescents with psychosis: evidence from impaired memory for source and temporal context.

INTRODUCTION: Findings from the literature consistently revealed episodic memory deficits in adolescents with psychosis. However, the nature of the dysfunction remains unclear. Based on a cognitive neuropsychological approach, a theoretically driven paradigm was used to generate valid interpretations about the underlying memory processes impaired in these patients. METHODS: A total of 16 inpatient adolescents with psychosis and 19 individually matched controls were assessed using an experimental task designed to measure memory for source and temporal context of studied words. Retrospective confidence judgements for source and temporal context responses were also assessed. RESULTS: On word recognition, patients had more difficulty than controls discriminating target words from neutral distractors. In addition, patients identified both source and temporal context features of recognised items less often than controls. Confidence judgements analyses revealed that the difference between the proportions of correct and incorrect responses made with high confidence was lower in patients than in controls. In addition, the proportion of high-confident responses that were errors was higher in patients compared to controls. CONCLUSIONS: These findings suggest impaired relational binding processes in adolescents with psychosis, resulting in a difficulty to create unified memory representations. Our findings on retrospective confidence data point to impaired monitoring of retrieved information that may also impair memory performance in these individuals.