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.

Bridging the Research Gap between Live Collections in Zoos and Preserved Collections in Natural History Museums.

Zoos and natural history museums are both collections-based institutions with important missions in biodiversity research and education. Animals in zoos are a repository and living record of the world's biodiversity, whereas natural history museums are a permanent historical record of snapshots of biodiversity in time. Surprisingly, despite significant overlap in institutional missions, formal partnerships between these institution types are infrequent. Life history information, pedigrees, and medical records maintained at zoos should be seen as complementary to historical records of morphology, genetics, and distribution kept at museums. Through examining both institution types, we synthesize the benefits and challenges of cross-institutional exchanges and propose actions to increase the dialog between zoos and museums. With a growing recognition of the importance of collections to the advancement of scientific research and discovery, a transformational impact could be made with long-term investments in connecting the institutions that are caretakers of living and preserved animals.

Use of Alzheimer's Disease Cerebrospinal Fluid Biomarkers in A Tertiary Care Memory Clinic.

INTRODUCTION: Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers are promising tools to help identify the underlying pathology of neurocognitive disorders. In this manuscript, we report our experience with AD CSF biomarkers in 262 consecutive patients in a tertiary care memory clinic. METHODS: We retrospectively reviewed 262 consecutive patients who underwent lumbar puncture (LP) and CSF measurement of AD biomarkers (Aß1-42, total tau or t-tau, and p-tau181). We studied the safety of the procedure and its impact on patient's diagnosis and management. RESULTS: The LP allowed to identify underlying AD pathology in 72 of the 121 patients (59%) with early onset amnestic mild cognitive impairment (aMCI) with a high probability of progression to AD; to distinguish the behavioral/dysexecutive variant of AD from the behavioral variant of frontotemporal dementia (bvFTD) in 25 of the 45 patients (55%) with an atypical neurobehavioral profile; to identify AD as the underlying pathology in 15 of the 27 patients (55%) with atypical or unclassifiable primary progressive aphasia (PPA); and to distinguish AD from other disorders in 9 of the 29 patients (31%) with psychiatric differential diagnoses and 19 of the 40 patients (47%) with lesional differential diagnoses (normal pressure hydrocephalus, encephalitis, prion disease, etc.). No major complications occurred following the LP. INTERPRETATION: Our results suggest that CSF analysis is a safe and effective diagnostic tool in select patients with neurocognitive disorders. We advocate for a wider use of this biomarker in tertiary care memory clinics in Canada.

Validation of the Dépistage Cognitif de Québec in the Oldest Old.

OBJECTIVE: We aimed to validate the Dépistage Cognitif de Québec (DCQ; www.dcqtest.org), a new cognitive screening tool for atypical degenerative syndromes, in the oldest old. METHODS: The DCQ was developed by expert behavioural neurologists and clinical neuropsychologists based on updated criteria for Alzheimer's disease, primary progressive aphasia, and behavioural variant frontotemporal dementia. It targets five relevant cognitive domains: Memory, Visuospatial, Executive, Language, and Behaviour. Validation was performed using a prospective community-based sample consisting of 53 healthy French-speaking Canadian volunteers aged between 80 and 94 years old. Normative data were derived from participants with no history of cognitive difficulties and a Montreal Cognitive Assessment (MoCA) score ≥ 24. RESULTS: The mean DCQ total score (out of 100) was 84.65 (SD = 6.33). Pearson's correlation coefficient showed a moderate, but significant, correlation (r = 0.36, p < .01) with the MoCA. Normative data shown in percentiles were stratified by age and education for DCQ total score and for each of the five cognitive domains. CONCLUSIONS: This study suggests that the DCQ is a valid cognitive screening test in the oldest old. It is proposed that the DCQ can help early identification of atypical degenerative syndromes.

The Behavioral/Dysexecutive Variant of Alzheimer's Disease: A Case Series with Clinical, Neuropsychological, and FDG-PET Characterization.

INTRODUCTION: It is well known that some patients with Alz-heimer's disease (AD) have atypical, nonamnestic presentations. While logopenic aphasia and posterior cortical atrophy are well-characterized atypical variants of AD, the behavioral/dysexecutive variant remains a controversial entity, lacking consensus regarding its distinctive clinical and imaging features. METHODS: We present a case series of 8 patients with biomarker confirmation of AD (cerebrospinal fluid [CSF] analysis or amyloid positron emission tomography [PET]) and a progressive frontal syndrome, defined as prominent behavioral and/or executive deficits at initial presentation. We characterize the cohort based on clinical features, cognitive performance in 4 domains (memory, visuospatial, executive, and language) as well as behavior on the Dépistage Cognitif de Québec (DCQ), and regional brain metabolism using 18F-fluorodeoxyglucose PET (FDG-PET). We compare these features with 8 age-matched patients diagnosed with the behavioral variant of frontotemporal dementia (bvFTD) and 37 patients with typical amnestic AD. RESULTS: Patients with the behavioral/dysexecutive variant of AD presented with early-onset (mean age: 59 years old) progressive executive and behavioral problems reminiscent of bvFTD, including disinhibition, loss of social conventions, and hyperorality. Patients scored higher on the Memory Index and lower on the Behavioral Index than patients with amnestic AD on the DCQ, yet they were indistinguishable from patients with bvFTD on each of the cognitive indices. Visual analysis of FDG-PET revealed half of patients with behavioral/dysexecutive AD presented with frontal hypometabolism suggestive of bvFTD and only 3/8 (37.5%) presented significant hypometabolism of the posterior cingulate cortex. Group-level analysis of FDG-PET data revealed that the most hypometabolic regions were the middle temporal, inferior temporal, and angular gyri in behavioral/dysexecutive AD and the inferior frontal gyrus, anterior cingulate cortex, caudate nucleus, and insula in bvFTD. CONCLUSION: The behavioral/dysexecutive variant of AD is a rare, atypical young-onset variant of AD defined clinically by early and prominent impairments in executive and behavioral domains. While behavioral/dysexecutive AD is hardly distinguishable from bvFTD using clinical and cognitive features alone, CSF biomarkers and temporoparietal hypometabolism help predict underlying pathology during life.

Cognitive Profile of the Logopenic Variant of Primary Progressive Aphasia Using the Dépistage Cognitif de Québec.

BACKGROUND/AIMS: The logopenic variant of primary progressive aphasia (lvPPA) is characterized by impaired word-finding and sentence repetition with phonologic errors but spared motor speech and grammar and semantic knowledge. Although its language deficits have been well studied, the full spectrum of cognitive changes in the lvPPA remains to be defined. We aimed to explore the neurocognitive profile of the lvPPA using a newly developed cognitive screening tool for atypical dementias, the Dépistage Cognitif de Québec (DCQ). METHODS: We compared 29 patients with lvPPA to 72 amnestic variant Alzheimer disease (aAD) to 438 healthy control (HC) participants. Performance on the 5 indexes of the DCQ (Memory, Visuospatial, Executive, Language and Behavioral) was compared between the 3 groups. RESULTS: Results showed a significantly lower performance for lvPPA participants in all neurocognitive domains, when compared to HC. When compared to aAD, lvPPA participants had significantly lower scores for language, executive, and visuospatial abilities, but not for memory and behavior. CONCLUSION: Altogether, these findings better define the neurocognitive changes of lvPPA.

Posterior Cingulate Cortex Hypometabolism in Non-Amnestic Variants of Alzheimer's Disease.

BACKGROUND: Hypometabolism of the posterior cingulate cortex (PCC) is an important diagnostic feature of late-onset, amnestic Alzheimer's disease (AD) measured with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). However, it is unclear whether PCC hypometabolism has diagnostic value in young-onset, non-amnestic variants of AD, which exhibit less pathology in the hippocampus and default mode network. OBJECTIVE: Evaluate the prevalence and diagnostic value of PCC hypometabolism in non-amnestic variants of AD. METHODS: We retrospectively identified 60 patients with young-onset, atypical dementia who have undergone a detailed clinical evaluation, FDG-PET, and an amyloid biomarker (amyloid-PET or cerebrospinal fluid analysis). We quantitatively analyzed regional hypometabolism in 70 regions of interest (ROI) using the MIMneuro® software. RESULTS: Based on a cut-off of z-score < -1.5 for significant PCC hypometabolism, the prevalence of PCC hypometabolism in non-amnestic variants of AD was 65% compared to 28% in clinical variants of frontotemporal dementia (FTD). The ROI with the maximal hypometabolism was the dominant middle temporal gyrus in the language variant of AD (mean z score -2.28), middle occipital gyrus in PCA (-3.24), middle temporal gyrus in frontal AD (-2.70), and angular gyrus in corticobasal syndrome due to AD (-2.31). The PCC was not among the 10 most discriminant regions between non-amnestic variants of AD versus clinical variants of FTD. CONCLUSION: We conclude that PCC hypometabolism is not a discriminant feature to distinguish non-amnestic variants of AD from clinical variants of FTD-and should be interpreted with caution in patients with young-onset, non-amnestic dementia.

Schizophrenia Phenotype Preceding Behavioral Variant Frontotemporal Dementia Related to C9orf72 Repeat Expansion.

Behavioral variant frontotemporal dementia (bvFTD) shares a constellation of clinical features with primary psychiatric disorders. The discovery of new FTD-related genetic mutations has brought attention to this overlap between bvFTD and psychotic disorders. The case reported here raises the question of whether C9orf72 repeat expansion may be involved in neuropsychiatric syndromes beyond the spectrum of neurodegenerative disease. A 61-year-old woman was referred to our memory clinic for behavioral changes and progressive cognitive decline over the last 3 years. Her medical history was significant for schizophrenia since age 36, with an exacerbation of psychotic symptoms at age 55, at which time she slowly worsened, became disorganized and apathetic, and presented new perseverative behaviors. Brain MRI showed mild bilateral frontal and temporal cortical atrophy, and F-fluorodeoxyglucose PET showed bilateral frontal and anterior temporal hypometabolism. Genetic analysis revealed C9orf72 hexanucleotide repeat expansion with more than 80 G4C2 repeats. Recently, FTD due to C9orf72 repeat expansion has been reported to show a high frequency of psychotic presentations. C9orf72 repeat expansion has previously been identified as a rare but possible cause of schizophrenia spectrum disorders. Our case report is characterized by a C9orf72-associated schizophrenia phenotype preceding bvFTD by 2 decades, which might reflect early prodromal neurodegeneration or neurodevelopmental and neurobiological effects of C9orf72 repeat expansion. Analysis of C9orf72 hexanucleotide repeat expansion may be appropriate in patients with schizophrenia spectrum disorders showing new behavioral and/or cognitive changes.

Why We Still Use "Organic Causes": Results From a Survey of Psychiatrists and Residents.

The diagnostic category of "organic disorders" was officially removed from the psychiatric nosology in DSM-IV, published in 1994. Despite this change, physicians continue to use the term "organic causes" to refer to medical and neurological causes of psychiatric symptoms, and it remains part of the ICD-10 classification. In the context of increasing integration of psychiatric disorders within a medical and neuroscientific framework, the reasons behind the ongoing use of this term (reminiscent of mind-body dualism) have to be clarified. The authors conducted a survey of 391 Canadian psychiatrists and psychiatric residents to understand attitudes and beliefs related to this terminology and then applied qualitative and quantitative analyses. Results showed that the terminology is used by the majority (55.9%) of psychiatrists and residents for two main reasons: out of a habit that begins in residency training and because of the belief that other specialties do not fully understand alternative terminology. The authors found that some psychiatrists are concerned that their patients will not receive adequate investigation unless it is made clear through use of the "organic cause" term that other medical causes of psychiatric symptoms are suspected. Use of the "organic cause" term was predicted by being of younger age, performing emergency department calls, and finding alternative terminology difficult to use. These findings highlight the importance of reflecting on and discussing the effect of this terminology used in psychiatry.

The Dépistage Cognitif de Québec: A New Clinician's Tool for Early Recognition of Atypical Dementia.

INTRODUCTION: Early recognition of atypical dementia remains challenging partly because of lack of cognitive screening instruments precisely tailored for this purpose. METHODS: We assessed the validity and reliability of the Dépistage Cognitif de Québec (DCQ; www.dcqtest.org), a newly developed cognitive screening test, to detect atypical dementia using a multicenter cohort of 628 participants. Sensitivity and specificity were compared to the Montreal Cognitive Assessment (MoCA). A predictive diagnostic algorithm for atypical dementia was determined using classification tree analysis. RESULTS: The DCQ showed excellent psychometric properties. It was significantly more accurate than the MoCA to detect atypical dementia. All correlations between DCQ indexes and standard neuropsychological measures were significant. A statistical model distinguished typical from atypical dementia with a predictive power of 79%. DISCUSSION: The DCQ is a better tool to detect atypical dementia than standard cognitive screening tests. Expanding the clinician's tool kit with the DCQ could reduce missed/delayed identification of atypical dementia and accelerate therapeutic intervention.

Validation of the Dépistage Cognitif de Québec: A New Cognitive Screening Tool for Atypical Dementias.

OBJECTIVE: This study aimed to validate and provide normative data for the Dépistage Cognitif de Québec (DCQ; www.dcqtest.org), a new cognitive screening tool for atypical dementias. METHOD: The DCQ was developed by expert behavioral neurologists and clinical neuropsychologists based on updated criteria for Alzheimer's disease, primary progressive aphasia, and behavioral variant frontotemporal dementia. It targets five relevant domains: Memory, Visuospatial, Executive, Language, and Behavior. Validation was performed in a population-based sample of 410 healthy French-speaking Canadians aged between 50 and 89 years old. Normative data were derived from a subsample of 285 participants. RESULTS: Mean DCQ total score (out of 100) was 89.17 (SD = 7.36). Pearson's correlation coefficient showed a strong and significant correlation (r = .71, p < .001) with the Montreal Cognitive Assessment. Internal consistency for the cognitive domains assessed by Cronbach's alpha was satisfactory (.74). Test-retest reliability was adequate (Pearson's coefficient = . 70, p < .001) and interrater reliability, excellent (intraclass correlation = .99, p < .001). Normative data shown in percentiles were stratified by age and education. CONCLUSIONS: This study suggests that the DCQ is a valid and reliable cognitive screening test. Application of the DCQ on populations with atypical dementias is underway to derive sensitivity and specificity values for various dementias.

Cognition and anatomy of adult Niemann-Pick disease type C: Insights for the Alzheimer field.

Niemann-Pick disease type C (NPC) is a rare lysosomal storage disorder causing an intracellular lipid trafficking defect and varying damage to the spleen, liver, and central nervous system. The adult form, representing approximately 20% of the cases, is associated with progressive cognitive decline. Intriguingly, brains of adult NPC patients exhibit neurofibrillary tangles, a characteristic hallmark of Alzheimer's disease (AD). However, the cognitive, psychiatric, and neuropathological features of adult NPC and their relation to AD have yet to be explored. We systematically reviewed the literature on adult NPC with a particular focus on cognitive and neuroanatomical abnormalities. The careful study of cognition in adult NPC allows drawing critical insights in our understanding of the pathophysiology of AD as well as normal cognition.

Risk Factors, Neuroanatomical Correlates, and Outcome of Neuropsychiatric Symptoms in Alzheimer's Disease.

BACKGROUND: An integrative model of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) is lacking. OBJECTIVE: In this study, we investigated the risk factors, anatomy, biology, and outcomes of NPS in AD. METHODS: 181 subjects were included from the Alzheimer's Disease Neuroimaging Study (ADNI). NPS were assessed with the Neuropsychiatric Inventory Questionnaire at baseline and 6 months. NPI >3 was used as a threshold for NPS positivity. Three NPS courses were characterized: 1) minimal/absent (negative at 0 and 6 months, n = 77); 2) fluctuating (positive only at one time point, n = 53); 3) persistent (positive at both time points, n = 51). We examined the association between NPS course and family history of dementia, personal history of psychiatric disorders, cerebrospinal fluid biomarkers, atrophy patterns, as well as longitudinal cognitive and functional measures at 12 and 24 months (MMSE, CDR-SOB, FAQ). RESULTS: AD subjects with absent, fluctuating, or persistent NPS had similar CSF amyloid-ß and tau levels. AD subjects with minimal/absent NPS had less personal history of psychiatric disorders (35%) than those with fluctuating (57%; p = 0.015) or persistent NPS (47%, not significant). At 24 months, AD subjects with persistent NPS had worse cognitive (MMSE; p = 0.05) and functional (CDR-SOB; p = 0.016) outcomes. Dorsolateral prefrontal atrophy was seen in persistent NPS, but not in fluctuating NPS. CONCLUSIONS: Our results suggest that individuals with personal history of psychiatric disorders might be more vulnerable to develop NPS throughout the course of AD. The worst cognitive and functional outcomes associated with NPS in AD underscores the importance of monitoring NPS early in the disease course.

Multicenter Validation of an MMSE-MoCA Conversion Table.

BACKGROUND: Accumulating evidence points to the superiority of the MoCA over the MMSE as a cognitive screening tool. To facilitate the transition from the MMSE to the MoCA in clinical and research settings, authors have developed MMSE-MoCA conversion tables. However, it is unknown whether a conversion table generated from Alzheimer's disease (AD) patients would apply to patients with other dementia subtypes like vascular dementia or frontotemporal dementia. Furthermore, the reliability and accuracy of MMSE-MoCA conversion tables has not been properly evaluated. METHOD: We retrospectively examined the MMSE-MoCA relationship in a large multicenter sample gathered from 3 Memory Clinics in Quebec, Canada (1492 patients). We produced an MMSE-MoCA conversion table using the equi-percentile method with log-linear smoothing. We then cross-validated our conversion table with the ADNI dataset (1202 patients) and evaluated its accuracy for future predictions. RESULTS: The MMSE-MoCA conversion table is consistent with previously published tables and has an intra-class correlation of 0.633 with the ADNI sample. However, we found that the MMSE-MoCA relationship is significantly modified by diagnosis (P < .01), with dementia subtypes associated with a dysexecutive syndrome showing a trend towards higher MMSE than other dementia syndromes for a given MoCA score. The large width of 95% confidence interval (CI) for a new prediction suggests questionable reliability for clinical use. CONCLUSION: In this study, we validated a conversion table between MMSE and MoCA using a large multicenter sample. Our results suggest caution in interpreting the tables in heterogeneous clinical populations, as the MMSE-MoCA relationship may be different across dementia subtypes.

Differences in Rate of Cognitive Decline and Caregiver Burden between Alzheimer's Disease and Vascular Dementia: a Retrospective Study.

Few studies have explored the rate of cognitive decline and caregiver burden within the context of a specialized memory clinic. When this was done, the focus was largely on functional decline related to Alzheimer's disease (AD). Our goal was to compare the longitudinal decline of AD patients to those with Vascular Dementia (VaD) on Mini-Mental State Examination (MMSE). We further explored the differential impact on caregiver burden. We retrospectively studied 237 charts from patients seen at our Memory Clinic between 2006 and 2012. The data was collected over 17 years. Cohorts were formed by excluding conditions other than AD and VaD, and including patients who had been assessed at least twice with the MMSE (AD: n = 83; mean age: 67.7 yo; VaD: n = 32; mean age: 73.3yo). A small group of 36 caregivers was surveyed by phone to explore caregiver burden. Results indicated that the natural history of MMSE changes in AD patients differed significantly from that of patients with VaD (F = 10.41, p<0.0014), with AD patients showing more cognitive decline over time. Sadness, stress/anxiety, fatigue, and sleep disorders were reported as the main preoccupations by caregivers and its impact was rated as 'severe' in 50% of cases. Altogether, this study provides further insight into the natural history of cognitive decline in AD and VaD. Future studies should explore the progression of dementing disorders in larger cohorts using prospective methodological designs.

Clinical Utility of Amyloid PET Imaging in the Differential Diagnosis of Atypical Dementias and Its Impact on Caregivers.

Recent studies have supported a role for amyloid positron emission tomography (PET) imaging in distinguishing Alzheimer's disease (AD) pathology from other pathological protein accumulations leading to dementia. We investigated the clinical utility of amyloid PET in the differential diagnosis of atypical dementia cases and its impact on caregivers. Using the amyloid tracer 18F-NAV4694, we prospectively scanned 28 patients (mean age 59.3 y, s.d. 5.8; mean MMSE 21.4, s.d. 6.0) with an atypical dementia syndrome. Following a comprehensive diagnostic workup (i.e., history taking, neurological examination, blood tests, neuropsychological evaluation, MRI, and FDG-PET), no certain diagnosis could be arrived at. Amyloid PET was then conducted and classified as positive or negative. Attending physicians were asked to evaluate whether this result led to a change in diagnosis or altered management. They also reported their degree of confidence in the diagnosis. Caregivers were met after disclosure of amyloid PET results and completed a questionnaire/interview to assess the impact of the scan. Our cohort was evenly divided between positive (14/28) and negative (14/28) 18F-NAV4694 cases. Amyloid PET resulted in a diagnostic change in 9/28 cases (32.1%: 17.8% changed from AD to non-AD, 14.3% from non-AD to AD). There was a 44% increase in diagnostic confidence. Altered management occurred in 71.4% (20/28) of cases. Knowledge of amyloid status improved caregivers' outcomes in all domains (anxiety, depression, disease perception, future anticipation, and quality of life). This study suggests a useful additive role for amyloid PET in atypical cases with an unclear diagnosis beyond the extensive workup of a tertiary memory clinic. Amyloid PET increased diagnostic confidence and led to clinically significant alterations in management. The information gained from that test was well received by caregivers and encouraged spending quality time with their loved ones.

Lexical decision with pseudohomophones and reading in the semantic variant of primary progressive aphasia: A double dissociation.

The co-occurrence of semantic impairment and surface dyslexia in the semantic variant of primary progressive aphasia (svPPA) has often been taken as supporting evidence for the central role of semantics in visual word processing. According to connectionist models, semantic access is needed to accurately read irregular words. They also postulate that reliance on semantics is necessary to perform the lexical decision task under certain circumstances (for example, when the stimulus list comprises pseudohomophones). In the present study, we report two svPPA cases: M.F. who presented with surface dyslexia but performed accurately on the lexical decision task with pseudohomophones, and R.L. who showed no surface dyslexia but performed below the normal range on the lexical decision task with pseudohomophones. This double dissociation between reading and lexical decision with pseudohomophones is in line with the dual-route cascaded (DRC) model of reading. According to this model, impairments in visual word processing in svPPA are not necessarily associated with the semantic deficits characterizing this disease. Our findings also call into question the central role given to semantics in visual word processing within the connectionist account.

Clinical Impact of a Second FDG-PET in Atypical/Unclear Dementia Syndromes.

Diagnosis of atypical/unclear dementia is often difficult and this delays treatment initiation. Several authors have shown that beyond standard dementia workup, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) reduces the number of unclear diagnoses, leads to earlier treatment, and has a beneficial impact on families. However, it is not uncommon that the FDG-PET findings are equivocal in this setting. For those cases, a repeat FDG-PET may clarify the diagnosis and prevent treatment delay. We retrospectively assessed the clinical impact of a repeat FDG-PET in 59 patients with atypical/unclear dementia syndromes and inconclusive initial FDG-PET. Changes in primary diagnosis, diagnostic confidence, and management following the second FDG-PET were examined. Conducting a second FDG-PET reduced the number of unclear diagnoses from 80% to 34% , led to diagnostic change in 24% of cases, and treatment modification in 22% of patients. Overall, the clinical impact was higher when initial diagnostic confidence was low and the second FDG-PET repeated ≥12 months after the first one. In tertiary care memory clinic settings, when diagnostic incertitude persists despite extensive evaluation and an equivocal FDG-PET, repeating the FDG-PET 12 months later can greatly clarify the diagnosis and improve management.

Verbal irony comprehension in older adults with amnestic mild cognitive impairment.

OBJECTIVE: The present study examined verbal irony comprehension in 31 aMCI and 33 healthy control (HC) subjects. Although nonliteral language impairments have been evidenced in individuals with amnestic mild cognitive impairment (aMCI) or Alzheimer's disease (AD), verbal irony comprehension remained somewhat underinvestigated in these populations. METHOD: A task measured the capacity to attribute Second-order mental state (i.e., theory of mind; ToM) as well as the ability to distinguish an ironic statement from a lie. Subjects were asked to identify, in a short story, whether the final assertion was a lie or an ironic joke. RESULTS: Our results showed lower performance on a verbal irony comprehension task for aMCI individuals compared with those in the HC group. This pattern of results was related to Second-order ToM and executive functions. CONCLUSION: These findings have implications for the conceptualization of aMCI, and foster investigation of social language comprehension in neurodegenerative diseases such as prodromal AD. Results are discussed in light of actual linguistic theories. The importance of evaluating the role of underlying cognitive processes in verbal irony comprehension is also emphasized.