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Background: Clinical diagnosis in primary progressive aphasia (PPA) is challenging. Recently, emphasis has been placed on the importance of screening evaluation. Three different screening tests that use different strategies based on the assessment of language (Mini-Linguistic State Examination, MLSE) or different cognitive domains (Addenbrooke's Cognitive Examination, ACE-III and Dépistage Cognitif de Québec, DCQ) have been proposed and independently validated. These tests aim to detect PPA and classify into the three main variants (non-fluent (nfvPPA), semantic (svPPA) and logopenic (lvPPA))., Objective: This study aims to evaluate and compare the diagnostic capacity of these three instruments in PPA., Methods: A cross-sectional study including 43 patients with PPA (nfvPPA ( n  = 19), svPPA ( n  = 8), and lvPPA ( n  = 16)) and 21 cognitively unimpaired controls was conducted. Clinical diagnoses were established based on an extensive multidisciplinary assessment including neuropsychological assessment, fluorodeoxyglucose-positron emission tomography, MRI, and cerebrospinal fluid biomarkers. Both PPA patients and controls completed the three tests (MLSE, ACE-III, and DCQ)., Results: Internal consistency was excellent for the three tests. The area under the curve for the diagnosis of PPA was 0.950 for MLSE, 0.953 for ACE-III, and 0.933 for DCQ. Correlations between the three tests were high. The MLSE, ACE-III, and DCQ tests obtained adequate levels of discrimination between the variants of PPA, with accuracies between 76-79%., Conclusions: This study confirms the validity of ACE-III, MLSE, and DCQ for the diagnosis of PPA and its variants. This suggests that detailed assessment of linguistic characteristics (MLSE) and non-linguistic features (DCQ, ACE-III) are relevant for the diagnosis and classification of PPA., Competing Interests: Declaration of conflicting interestsJordi A Matias-Guiu is an Associate Editor of this journal but was not involved in the peer-review process of this article nor had access to any information regarding its peer-review. The other authors have no conflict of interest to report. Data availabilityThe dataset is available from the corresponding author upon reasonable request.

Object decision (OD) test is one subtest of the Birmingham Object Recognition Battery (BORB). It is useful for differential diagnosis among several neurodegenerative diseases. However, normative data provided with this battery count on very few subjects and do not control for the effect of age, which limits interpretability. The purpose of Study 1 was to provide normative data for the OD test of the BORB (version A-hard). The objectives of Study 2 were to establish the diagnostic validity of this task and predictive validity of the normative data in the case of the semantic variant of primary progressive aphasia (svPPA) and Alzheimer's disease (AD).Based on multiple linear regressions, equations to calculate Z-scores corrected for age were provided for 130 participants aged from 47 to 89 years. Performance of 20 healthy participants was compared to that of 14 individuals with svPPA and 18 with AD. After controlling for confounders, participants with svPPA had a lower total score than controls and AD participants. AD participants had a poorer performance than controls only when chimeric objects were considered. Among those with a deficit on the total score of the test, 94% (17/18, including 12 with svPPA) were correctly identified as having a pathological condition (svPPA or AD). This test could help refine differential diagnosis between svPPA and AD patients, especially before the deficits of episodic memory show up.

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., (© The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Frontotemporal dementia is a highly heritable neurodegenerative disorder. In about a third of patients, the disease is caused by autosomal dominant genetic mutations usually in one of three genes: progranulin (GRN), microtubule-associated protein tau (MAPT), or chromosome 9 open reading frame 72 (C9orf72). Findings from studies of other genetic dementias have shown neuroimaging and cognitive changes before symptoms onset, and we aimed to identify whether such changes could be shown in frontotemporal dementia., Methods: We recruited participants to this multicentre study who either were known carriers of a pathogenic mutation in GRN, MAPT, or C9orf72, or were at risk of carrying a mutation because a first-degree relative was a known symptomatic carrier. We calculated time to expected onset as the difference between age at assessment and mean age at onset within the family. Participants underwent a standardised clinical assessment and neuropsychological battery. We did MRI and generated cortical and subcortical volumes using a parcellation of the volumetric T1-weighted scan. We used linear mixed-effects models to examine whether the association of neuropsychology and imaging measures with time to expected onset of symptoms differed between mutation carriers and non-carriers., Findings: Between Jan 30, 2012, and Sept 15, 2013, we recruited participants from 11 research sites in the UK, Italy, the Netherlands, Sweden, and Canada. We analysed data from 220 participants: 118 mutation carriers (40 symptomatic and 78 asymptomatic) and 102 non-carriers. For neuropsychology measures, we noted the earliest significant differences between mutation carriers and non-carriers 5 years before expected onset, when differences were significant for all measures except for tests of immediate recall and verbal fluency. We noted the largest Z score differences between carriers and non-carriers 5 years before expected onset in tests of naming (Boston Naming Test -0·7; SE 0·3) and executive function (Trail Making Test Part B, Digit Span backwards, and Digit Symbol Task, all -0·5, SE 0·2). For imaging measures, we noted differences earliest for the insula (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume was 0·80% in mutation carriers and 0·84% in non-carriers; difference -0·04, SE 0·02) followed by the temporal lobe (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume 8·1% in mutation carriers and 8·3% in non-carriers; difference -0·2, SE 0·1)., Interpretation: Structural imaging and cognitive changes can be identified 5-10 years before expected onset of symptoms in asymptomatic adults at risk of genetic frontotemporal dementia. These findings could help to define biomarkers that can stage presymptomatic disease and track disease progression, which will be important for future therapeutic trials., Funding: Centres of Excellence in Neurodegeneration., (Copyright © 2015 Rohrer et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the interrater reliability of the new International Behavioural Variant FTD Criteria Consortium (FTDC) criteria for behavioral variant frontotemporal dementia (bvFTD)., Methods: Twenty standardized clinical case modules were developed for patients with a range of neurodegenerative diagnoses, including bvFTD, primary progressive aphasia (nonfluent, semantic, and logopenic variant), Alzheimer disease, and Lewy body dementia. Eighteen blinded raters reviewed the modules and 1) rated the presence or absence of core diagnostic features for the FTDC criteria, and 2) provided an overall diagnostic rating. Interrater reliability was determined by κ statistics for multiple raters with categorical ratings., Results: The mean κ value for diagnostic agreement was 0.81 for possible bvFTD and 0.82 for probable bvFTD ("almost perfect agreement"). Interrater reliability for 4 of the 6 core features had "substantial" agreement (behavioral disinhibition, perseverative/compulsive, sympathy/empathy, hyperorality; κ = 0.61-0.80), whereas 2 had "moderate" agreement (apathy/inertia, neuropsychological; κ = 0.41-0.6). Clinician years of experience did not significantly influence rater accuracy., Conclusions: The FTDC criteria show promise for improving the diagnostic accuracy and reliability of clinicians and researchers. As disease-altering therapies are developed, accurate differential diagnosis between bvFTD and other neurodegenerative diseases will become increasingly important.

Object decision (OD) test is one subtest of the Birmingham Object Recognition Battery (BORB). It is useful for differential diagnosis among several neurodegenerative diseases. However, normative data provided with this battery count on very few subjects and do not control for the effect of age, which limits interpretability. The purpose of Study 1 was to provide normative data for the OD test of the BORB (version A-hard). The objectives of Study 2 were to establish the diagnostic validity of this task and predictive validity of the normative data in the case of the semantic variant of primary progressive aphasia (svPPA) and Alzheimer's disease (AD).Based on multiple linear regressions, equations to calculate Z-scores corrected for age were provided for 130 participants aged from 47 to 89 years. Performance of 20 healthy participants was compared to that of 14 individuals with svPPA and 18 with AD. After controlling for confounders, participants with svPPA had a lower total score than controls and AD participants. AD participants had a poorer performance than controls only when chimeric objects were considered. Among those with a deficit on the total score of the test, 94% (17/18, including 12 with svPPA) were correctly identified as having a pathological condition (svPPA or AD). This test could help refine differential diagnosis between svPPA and AD patients, especially before the deficits of episodic memory show up. [ABSTRACT FROM AUTHOR]

Background: The Mini-Mental State Examination continues to be used frequently to screen for cognitive impairment in older adults, but it remains unclear how to interpret changes in its score over time to distinguish age-associated cognitive decline from an early degenerative process. We aimed to generate cognitive charts for use in clinical practice for longitudinal evaluation of age-associated cognitive decline.Methods: We used data from the Canadian Study of Health and Aging from 7569 participants aged 65 years or older who completed a Mini-Mental State Examination at baseline, and at 5 and 10 years later to develop a linear regression model for the Mini-Mental State Examination score as a function of age and education. Based on this model, we generated cognitive charts designed to optimize accuracy for distinguishing participants with dementia from healthy controls. We validated our model using a separate data set of 6501 participants from the National Alzheimer's Coordinating Center's Uniform Data Set.Results: For baseline measurement, the cognitive charts had a sensitivity of 80% (95% confidence interval [CI] 75% to 84%) and a specificity of 89% (95% CI 88% to 90%) for distinguishing healthy controls from participants with dementia. Similar sensitivities and specificities were observed for a decline over time greater than 1 percentile zone from the first measurement. Results in the validation sample were comparable, albeit with lower sensitivities. Negative predictive value was 99%.Interpretation: Our innovative model, which factors in age and education, showed validity and diagnostic accuracy for determining whether older patients show abnormal performance on serial Mini-Mental State Examination measurements. Similar to growth curves used in pediatrics, cognitive charts allow longitudinal cognitive evaluation and enable prompt initiation of investigation and treatment when appropriate. [ABSTRACT FROM AUTHOR]

Background: Amnestic mild cognitive impairment (aMCI) and late-life depression (LLD) are associated with increased risk of Alzheimer's disease (AD). This is also true for aMCI with concomitant depressive symptoms (aMCI/D+), but few studies have investigated this syndrome. Objectives: We aimed to clarify the association between cognitive and depressive symptoms in individuals at risk for AD by examining episodic memory for emotional stimuli in aMCI, aMCI/D+, and LLD. Methods: Participants were 34 patients with aMCI, 20 patients with aMCI/D+, 19 patients with LLD, and 28 healthy elderly adults. In an implicit encoding task, participants rated the emotional valence of 12 positive, 12 negative, and 12 neutral words. Immediately and 20 minutes later, participants recalled as many words as possible. They were also asked to identify previously presented words during a yes/no recognition trial. Results: At immediate recall, aMCI participants displayed better recall of emotional words, particularly positive words. aMCI/D+ and control participants displayed better recall of positive and negative words compared to neutral words. LLD participants recalled more negative than neutral words. At delayed recall, emotional words were generally better-remembered than neutral words by all groups. At recognition, all subjects responded more liberally to emotional than to neutral words. Conclusion: We find that the type of emotional information remembered by aMCI patients at immediate recall depends on the presence or absence of depressive symptoms. These findings contribute to identifying sources of heterogeneity in individuals at risk for AD, and suggest that the cognitive profile of aMCI/D+ is different from that of aMCI and LLD. Future studies should systematically consider the presence of depressive symptoms in elderly at-risk individuals. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the comprehension of concrete, abstract and abstract emotional words in semantic variant primary progressive aphasia (svPPA), Alzheimer's disease (AD), and healthy elderly adults (HE) Three groups of participants (9 svPPA, 12 AD, 11 HE) underwent a general neuropsychological assessment, a similarity judgment task, and structural brain MRI. The three types of words were processed similarly in the group of AD participants. In contrast, patients in the svPPA group were significantly more impaired at processing concrete words than abstract words, while comprehension of abstract emotional words was in between. VBM analyses showed that comprehension of concrete words relative to abstract words was significantly correlated with atrophy in the left anterior temporal lobe. These results support the view that concrete words are disproportionately impaired in svPPA, and that concrete and abstract words may rely upon partly dissociable brain regions. [ABSTRACT FROM AUTHOR]