David Bergeron

Multicenter Validation of an MMSE-MoCA Conversion Table

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 Alzheimers 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.

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

ABSTRACT 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.

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.

When students taste their own medicine

In 2010, as more and more medical programmes turned towards mandatory formal peerassisted learning (PAL) to complement their curriculum, 1 we decided to launch a project of our own. We wanted to offer our fellow students optional workshops to give them the opportunity to consolidate their knowledge and to develop their clinical interview and physical examination skills. We founded the Groupe de perfectionnement des habiletés cliniques (GPHC; i.e. the Clinical Skills Acquisition Group), a studentled committee with a mission to organise PAL evening revision workshops. The structure was simple: a small group of between 10 and 12 executive members were placed in charge of developing the pedagogical material and of dealing with workshop logistics. Each semester, we selected and prepared 20 secondor thirdyear medical students to act as peerteachers. We offered our workshops to all who were interested. As it turned out, this studentled formula proved successful: workshops became unexpectedly popular, which led to the diversifi cation and widening of the scope for teaching, and eventually resulted in the collaborative production of pedagogical material. We report here the development of this innovative student initiative over its 5 years of existence and the feedback received from the students who participated in its activities. Although the GPHC ’ s purely optional formula relied on students’ autonomy and motivation, student participation grew steadily from 681 participations at 15 workshops in 2010/11 to 1851 participations at 20 workshops in 2014/15 (Figure 1 ). In an electronic survey, we asked fourthyear medical students what they liked about GPHC workshops and the impact it had on their academic development. We analysed the completed forms using inductive thematic analysis. 2 Convergent themes were concordant with the existing PAL literature: students consistently mentioned both the safe learning environment secured by the absence of evaluation and the cognitive congruence with peerteachers as important We offered our workshops to all who were interested

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

BACKGROUND An integrative model of neuropsychiatric symptoms (NPS) in Alzheimers 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 Alzheimers 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-β 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.

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 Alzheimers 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). Pearsons 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 Cronbachs alpha was satisfactory (.74). Test-retest reliability was adequate (Pearsons 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.

Prevalence of amyloid-β pathology in distinct variants of primary progressive aphasia: Amyloid-β pathology in PPA variants

To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebrospinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants.

Molecular imaging in dementia: Past, present, and future

Molecular imaging techniques using 18F‐fluorodeoxyglucose, amyloid tracers, and, more recently, tau ligands have taken dementia research by storm and undoubtedly improved our understanding of neurodegenerative diseases. The ability to image in vivo the pathological substrates of degenerative diseases and visualize their downstream impact has led to improved models of pathogenesis, better differential diagnosis of atypical conditions, as well as focused subject selection and monitoring of treatment in clinical trials aimed at delaying or preventing the symptomatic phase of Alzheimers disease. In this article, we present the main molecular imaging techniques used in research and practice. We further summarize the key findings brought about by each technique individually and more recently, as adjuncts to each other. Specific limitations of each imaging modality are discussed, as well as recommendations to overcome them. A nonvalidated clinical algorithm is proposed for earlier and more accurate identification of complex/atypical neurodegenerative diseases.

Massive Bitemporal Hemorrhages in Antineutrophil Cytoplasmic Autoantibodies Vasculitis.

ANCA-associated small vessel vasculitides are systemic diseases characterized by inflammation and necrosis of small-sized blood vessels. They are characterized by the presence of antineutrophil cytoplasmic antibodies (ANCAs), which primarily target the kidney, lung, skin and peripheral nervous system. In rare cases, they can affect the central nervous system (CNS) and cause cerebrovascular events. We present a patient with ANCA vasculitis who developed fatal massive bitemporal hemorrhages during the course of immunosuppressive therapy. A 71-year-old man was referred to our tertiary neurological center due to weight loss (10 kg in two months), fatigue, weakness and persistent fever of unknown origin. The patient did not report previous sinusitis, upper airway infection, arthritis or hematuria. Neurological examination only revealed a right foot drop. Laboratory studies showed inflammatory anemia and elevated inflammatory markers. Screening for infectious diseases was negative. Spine MRI indicated a herniated L5-S1 disc. Brain MRI was normal except for a millimetric left occipital ischemic infarct. Whole-body PET scan was conducted to eliminate a neoplastic etiology, but was also negative. Five days after his arrival, the patient developed new weaknesses and paresthesia in the left leg and right hand. Laboratory studies revealed acute renal failure (creatinine 133 μmol/L, hematuria, proteinuria) and elevated c-ANCA counts (1:320). A second MRI of the brain conducted 10 days after the first showed five newmillimetric ischemic foci in the right temporal and left cerebellar regions. In concert with rheumatology, a diagnosis of ANCA vasculitis was made, an immunosuppressive treatment was initiated (high-dose intravenous glucocorticoids), and the patient’s neurological symptoms were stabilized. However, creatinine continued to rise (from 133 to 177 μmol/L in 7 days). A renal biopsy was scheduled to confirm a diagnosis of glomerulonephritis. After five days of induction treatment, tapering oral doses of prednisone were administered. On the first day of prednisone tapering, the patient was found unresponsive in his bed (eyes opened, but unresponsive to simple commands). Head CT showed massive bilateral temporal hemorrhages (see Figure 1). After discussion with the family, the patient was transferred back to his hometown for end-of-life care. Renal biopsy and autopsy could not be performed. Nevertheless, a recent meta-analysis has evaluated the specificity of elevated c-ANCA levels in the serum at 96.3% (CI [94.1-98.5]), which, combined with the high pretest probability of vasculitis (mononeuritis multiplex, acute renal failure, inflammatory anemia, multifocal brain infarcts), made a diagnosis of ANCA vasculitis highly probable even without a gold-standard pathological diagnosis. While it is known that ANCA vasculitis may in some instances involve the CNS, only a few case reports describe the appearance of cerebral hemorrhages, and even fewer a rapid progression toward massive hemorrhages and death. Altogether, our case supports the possibility of cerebral Figure 1: Axial view of a head CT showing massive bitemporal haemorrhages with significant mass effect.

DÉ́PISTAGE COGNITIF DE QUÉBÉC (DCQ): VALIDATION AND NORMATIVE DATA FOR A NOVEL COGNITIVE SCREENING TOOL FOR ATYPICAL DEMENTIAS

Mental State Examination, the original version of the MoCA, and the quality of life scale CASP-19. A multiple regression analysis was performed to verify the influence of age and education and the predictive capacity of the original version of the test on its alternative version. Results: Cronbach’s alpha coefficient was .76. Elimination of any of the items of the 2 version of MoCA never reduces the reliability to below .73. Convergent validity was .65 (p<.001), and divergent validity was .03 (p1⁄40.79). Correlation between the 1 and the 2 version of MoCA was significant and high (r1⁄40.86). There was a negative effect of age (b 1⁄4–0.141, p < 0.01) and a positive effect of education (b 1⁄4–0.549, p < 0.001), but these two effects did not remained significant when the total score of the original form of MoCA was included in the regression model (b1⁄4–0.691, p < 0.001) (Figure1). Conclusions: Our preliminary results showed good psychometrical properties for the 2nd alternative form of the Spanish version and strong relations between forms. Further analyses are required in order to guarantee the use of the alternate Spanish version of the MoCA test in clinical follow-ups and longitudinal studies.