Diagnostic accuracy of research criteria for prodromal frontotemporal dementia.

BACKGROUND: The Genetic Frontotemporal Initiative Staging Group has proposed clinical criteria for the diagnosis of prodromal frontotemporal dementia (FTD), termed mild cognitive and/or behavioral and/or motor impairment (MCBMI). The objective of the study was to validate the proposed research criteria for MCBMI-FTD in a cohort of genetically confirmed FTD cases against healthy controls. METHODS: A total of 398 participants were enrolled, 117 of whom were carriers of an FTD pathogenic variant with mild clinical symptoms, while 281 were non-carrier family members (healthy controls (HC)). A subgroup of patients underwent blood neurofilament light (NfL) levels and anterior cingulate atrophy assessment. RESULTS: The core clinical criteria correctly classified MCBMI vs HC with an AUC of 0.79 (p < 0.001), while the addition of either blood NfL or anterior cingulate atrophy significantly increased the AUC to 0.84 and 0.82, respectively (p < 0.001). The addition of both markers further increased the AUC to 0.90 (p < 0.001). CONCLUSIONS: The proposed MCBMI criteria showed very good classification accuracy for identifying the prodromal stage of FTD.

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.

Amyloid-PET of the white matter: Relationship to free water, fiber integrity, and cognition in patients with dementia and small vessel disease.

White matter (WM) injury is frequently observed along with dementia. Positron emission tomography with amyloid-ligands (Aß-PET) recently gained interest for detecting WM injury. Yet, little is understood about the origin of the altered Aß-PET signal in WM regions. Here, we investigated the relative contributions of diffusion MRI-based microstructural alterations, including free water and tissue-specific properties, to Aß-PET in WM and to cognition. We included a unique cohort of 115 participants covering the spectrum of low-to-severe white matter hyperintensity (WMH) burden and cognitively normal to dementia. We applied a bi-tensor diffusion-MRI model that differentiates between (i) the extracellular WM compartment (represented via free water), and (ii) the fiber-specific compartment (via free water-adjusted fractional anisotropy [FA]). We observed that, in regions of WMH, a decrease in Aß-PET related most closely to higher free water and higher WMH volume. In contrast, in normal-appearing WM, an increase in Aß-PET related more closely to higher cortical Aß (together with lower free water-adjusted FA). In relation to cognitive impairment, we observed a closer relationship with higher free water than with either free water-adjusted FA or WM PET. Our findings support free water and Aß-PET as markers of WM abnormalities in patients with mixed dementia, and contribute to a better understanding of processes giving rise to the WM PET signal.

Specificity of Entorhinal Atrophy MRI Scale in Predicting Alzheimer's Disease Conversion.

We compared entorhinal cortex atrophy (ERICA) score vs. medial temporal atrophy (MTA) score's ability to predict conversion from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD) using magnetic resonance imaging (MRI). We hypothesized that ERICA would show higher specificity. Data from 61 aMCI patients were analyzed. Positive ERICA was associated with AD conversion with a sensitivity of 56% (95% CI: 30-80%) and a specificity of 78% (63-89%) vs. 69% (41-89%) SE and 60% (44-74%) SP for the MTA. Results suggest that ERICA is superior to MTA in predicting conversion from aMCI to AD in a small sample of participants.

Vascular burden and cognition: Mediating roles of neurodegeneration and amyloid PET.

It remains unclear to what extent cerebrovascular burden relates to amyloid beta (Aß) deposition, neurodegeneration, and cognitive dysfunction in mixed disease populations with small vessel disease and Alzheimer's disease (AD) pathology. In 120 subjects, we investigated the association of vascular burden (white matter hyperintensity [WMH] volumes) with cognition. Using mediation analyses, we tested the indirect effects of WMH on cognition via Aß deposition (18 F-AV45 positron emission tomography [PET]) and neurodegeneration (cortical thickness or 18 F fluorodeoxyglucose PET) in AD signature regions. We observed that increased total WMH volume was associated with poorer performance in all tested cognitive domains, with the strongest effects observed for semantic fluency. These relationships were mediated mainly via cortical thinning, particularly of the temporal lobe, and to a lesser extent serially mediated via Aß and cortical thinning of AD signature regions. WMH volumes differentially impacted cognition depending on lobar location and Aß status. In summary, our study suggests mainly an amyloid-independent pathway in which vascular burden affects cognitive function via localized neurodegeneration. HIGHLIGHTS: Alzheimer's disease often co-exists with vascular pathology. We studied a unique cohort enriched for high white matter hyperintensities (WMH). High WMH related to cognitive impairment of semantic fluency and executive function. This relationship was mediated via temporo-parietal atrophy rather than metabolism. This relationship was, to lesser extent, serially mediated via amyloid beta and atrophy.

Development of a sensitive trial-ready poly(GP) CSF biomarker assay for C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis.

OBJECTIVE: A GGGGCC repeat expansion in the C9orf72 gene is the most common cause of genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). As potential therapies targeting the repeat expansion are now entering clinical trials, sensitive biomarker assays of target engagement are urgently required. Our objective was to develop such an assay. METHODS: We used the single molecule array (Simoa) platform to develop an immunoassay for measuring poly(GP) dipeptide repeat proteins (DPRs) generated by the C9orf72 repeat expansion in cerebrospinal fluid (CSF) of people with C9orf72-associated FTD/ALS. RESULTS AND CONCLUSIONS: We show the assay to be highly sensitive and robust, passing extensive qualification criteria including low intraplate and interplate variability, a high precision and accuracy in measuring both calibrators and samples, dilutional parallelism, tolerance to sample and standard freeze-thaw and no haemoglobin interference. We used this assay to measure poly(GP) in CSF samples collected through the Genetic FTD Initiative (N=40 C9orf72 and 15 controls). We found it had 100% specificity and 100% sensitivity and a large window for detecting target engagement, as the C9orf72 CSF sample with the lowest poly(GP) signal had eightfold higher signal than controls and on average values from C9orf72 samples were 38-fold higher than controls, which all fell below the lower limit of quantification of the assay. These data indicate that a Simoa-based poly(GP) DPR assay is suitable for use in clinical trials to determine target engagement of therapeutics aimed at reducing C9orf72 repeat-containing transcripts.

Tau positron emission tomography, cerebrospinal fluid and plasma biomarkers of neurodegeneration, and neurocognitive testing: an exploratory study of participants with myotonic dystrophy type 1.

OBJECTIVE: To investigate Tau pathology using multimodal biomarkers of neurodegeneration and neurocognition in participants with myotonic dystrophy type 1 (DM1). METHODS: We recruited twelve participants with DM1 and, for comparison, two participants with Alzheimer's Disease (AD). Participants underwent cognitive screening and social cognition testing using the Dépistage Cognitif de Québec (DCQ), among other tests. Biomarkers included Tau PET with [18F]-AV-1451, CSF (Aß, Tau, phospho-Tau), and plasma (Aß, Tau, Nf-L, GFAP) studies. RESULTS: Of the twelve DM1 participants, seven completed the full protocol (Neurocognition 11/12; PET 7/12, CSF 9/12, plasma 12/12). Three DM1 participants were cognitively impaired (CI). On average, CI DM1 participants had lower scores on the DCQ compared to cognitively unimpaired (CU) DM1 participants (75.5/100 vs. 91.4/100) and were older (54 vs. 44 years old) but did not differ in years of education (11.3 vs. 11.1). The majority (6/7) of DM1 participants had no appreciable PET signal. Only one of the CI participants presented with elevated Tau PET SUVR in bilateral medial temporal lobes. This participant was the eldest and most cognitively impaired, and had the lowest CSF Aß 1-42 and the highest CSF Tau levels, all suggestive of co-existing AD. CSF Tau and phospho-Tau levels were higher in the 3 CI compared to CU DM1 participants, but with a mean value lower than that typically observed in AD. Nf-L and GFAP were elevated in most DM1 participants (9/11 and 8/11, respectively). Finally, CSF phospho-Tau was significantly correlated with plasma Nf-L concentrations. CONCLUSIONS AND RELEVANCE: We observed heterogenous cognitive and biomarker profiles in individuals with DM1. While some participants presented with abnormal PET and/or CSF Tau, these patterns were highly variable and only present in a small subset. Although DM1 may indeed represent a non-AD Tauopathy, the Tau-PET tracer used in this study was unable to detect an in vivo Tau DM1 signature in this small cohort. Interestingly, most DM1 participants presented with elevated plasma Nf-L and GFAP levels, suggestive of other, possibly related, central brain alterations which motivate further research. This pioneering study provides novel insights towards the potential relationship between biomarkers and neurocognitive deficits commonly seen in DM1.

Informant-based tools for assessment and monitoring of cognition, behavior, and function in neurocognitive disorders: Systematic review and report from a CCCDTD5 Working Group.

OBJECTIVE: As part of the fifth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, we assessed the literature on informant-based tools for assessment and monitoring of cognition, behavior, and function in neurocognitive disorders (NCDs) to provide evidence-based recommendations for clinicians and researchers. METHODS: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards guidelines. Publications that validated the informant-based tools or described their key properties were reviewed. Quality of the studies was assessed using the modified Quality Assessment tool for Diagnostic Accuracy Studies. RESULTS: Out of 386 publications identified through systematic search, 34 that described 19 informant-based tools were included in the final review. Most of these tools are backed by good-quality studies and are appropriate to use in clinical care or research. The tools vary in their psychometric properties, domains covered, comprehensiveness, completion time, and ability to detect longitudinal change. Based on these properties, we identify different tools that may be appropriate for primary care, specialized memory clinic, or research settings. We also identify barriers to use of these tools in routine clinical practice. CONCLUSION: There are several good-quality tools available to collect informant-report for assessment and monitoring of cognition, behavior, or function in patients with NCDs. Clinicians and researchers may choose a particular tool based on their specific needs such as domains of interest, desired psychometric properties, and feasibility. Further work is needed to make the tools more user-friendly and to adopt them into routine clinical care.

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.

Research Criteria for the Behavioral Variant of Alzheimer Disease: A Systematic Review and Meta-analysis.

Importance: The behavioral variant of Alzheimer disease (bvAD) is characterized by early and predominant behavioral deficits caused by AD pathology. This AD phenotype is insufficiently understood and lacks standardized clinical criteria, limiting reliability and reproducibility of diagnosis and scientific reporting. Objective: To perform a systematic review and meta-analysis of the bvAD literature and use the outcomes to propose research criteria for this syndrome. Data Sources: A systematic literature search in PubMed/MEDLINE and Web of Science databases (from inception through April 7, 2021) was performed in duplicate. Study Selection: Studies reporting on behavioral, neuropsychological, or neuroimaging features in bvAD and, when available, providing comparisons with typical amnestic-predominant AD (tAD) or behavioral variant frontotemporal dementia (bvFTD). Data Extraction and Synthesis: This analysis involved random-effects meta-analyses on group-level study results of clinical data and systematic review of the neuroimaging literature. The study was performed following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Main Outcomes and Measures: Behavioral symptoms (neuropsychiatric symptoms and bvFTD core clinical criteria), cognitive function (global cognition, episodic memory, and executive functioning), and neuroimaging features (structural magnetic resonance imaging, [18F]fluorodeoxyglucose-positron emission tomography, perfusion single-photon emission computed tomography, amyloid positron emission tomography, and tau positron emission tomography). Results: The search led to the assessment of 83 studies, including 13 suitable for meta-analysis. Data were collected for 591 patients with bvAD. There was moderate to substantial heterogeneity and moderate risk of bias across studies. Cases with bvAD showed more severe behavioral symptoms than tAD (standardized mean difference [SMD], 1.16 [95% CI, 0.74-1.59]; P < .001) and a trend toward less severe behavioral symptoms compared with bvFTD (SMD, -0.22 [95% CI, -0.47 to 0.04]; P = .10). Meta-analyses of cognitive data indicated worse executive performance in bvAD vs tAD (SMD, -1.03 [95% CI, -1.74 to -0.32]; P = .008) but not compared with bvFTD (SMD, -0.61 [95% CI, -1.75 to 0.53]; P = .29). Cases with bvAD showed a nonsignificant difference of worse memory performance compared with bvFTD (SMD, -1.31 [95% CI, -2.75 to 0.14]; P = .08) but did not differ from tAD (SMD, 0.43 [95% CI, -0.46 to 1.33]; P = .34). The neuroimaging literature revealed 2 distinct bvAD neuroimaging phenotypes: an AD-like pattern with relative frontal sparing and a relatively more bvFTD-like pattern characterized by additional anterior involvement, with the AD-like pattern being more prevalent. Conclusions and Relevance: These data indicate that bvAD is clinically most similar to bvFTD, while it shares most pathophysiological features with tAD. Based on these insights, we propose research criteria for bvAD aimed at improving the consistency and reliability of future research and aiding the clinical assessment of this AD phenotype.

Evaluation of Intensive vs Standard Blood Pressure Reduction and Association With Cognitive Decline and Dementia: A Systematic Review and Meta-analysis.

Importance: Optimal blood pressure (BP) targets for the prevention of cognitive impairment remain uncertain. Objective: To explore the association of intensive (ie, lower than usual) BP reduction vs standard BP management with the incidence of cognitive decline and dementia in adults with hypertension. Data Sources and Study Selection: A systematic review and meta-analysis of randomized clinical trials that evaluated the association of intensive systolic BP lowering on cognitive outcomes by searching MEDLINE, Embase, CENTRAL, Web of Science, CINAHL, PsycINFO, the International Clinical Trials Registry Platform, and ClinicalTrials.gov from database inception to October 27, 2020. Data Extraction and Synthesis: Data screening and extraction were performed independently by 2 reviewers based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The risk of bias was assessed using the Cochrane risk of bias 2 tool. Random-effects models with the inverse variance method were used for pooled analyses. The presence of potential heterogeneity was evaluated with the I2 index. Main Outcomes and Measures: The primary outcome was cognitive decline. Secondary outcomes included the incidence of dementia, mild cognitive impairment (MCI), cerebrovascular events, serious adverse events, and all-cause mortality. Results: From 7755 citations, we identified 16 publications from 5 trials with 17 396 participants (mean age, 65.7 years [range, 63.0-80.5 years]; 10 562 [60.5%] men) and 2 additional ongoing trials. All 5 concluded trials included in quantitative analyses were considered at unclear to high risk of bias. The mean follow-up duration was 3.3 years (range, 2.0 to 4.7 years). Intensive BP reduction was not significantly associated with global cognitive performance (standardized mean difference, 0.01; 95% CI, -0.04 to 0.06; I2 = 0%; 4 trials; 5246 patients), incidence of dementia (risk ratio [RR], 1.09; 95% CI, 0.32 to 3.67; I2 = 27%; 2 trials; 9444 patients) or incidence of MCI (RR, 0.91; 95% CI, 0.73 to 1.14; I2 = 74%; 2 trials; 10 774 patients) when compared with standard treatment. However, a reduction of cerebrovascular events in the intensive group was found (RR, 0.79; 95% CI, 0.67 to 0.93; I2 = 0%; 5 trials; 17 396 patients) without an increased risk of serious adverse events or mortality. Conclusions and Relevance: In this study, there was no significant association between BP reduction and lower risk of cognitive decline, dementia, or MCI. The certainty of this evidence was rated low because of the limited sample size, the risk of bias of included trials, and the observed statistical heterogeneity. Therefore, current available evidence does not justify the use of lower BP targets for the prevention of cognitive decline and dementia.

Progressive apraxia of speech in Quebec French speakers: A case series.

BACKGROUND: The term progressive apraxia of speech (PAOS) is used to describe speakers presenting with isolated or dominant apraxia of speech in the context of a neurodegenerative syndrome, including primary progressive apraxia of speech (PPAOS) and dominant progressive apraxia of speech (DAOS), respectively. Its motor speech profile has been increasingly explored in the last decade, but description remains vague and very English oriented, although the effect of speakers' language on motor speech phenotypes is increasingly recognized. Although some studies suggest that speakers presenting with isolated PAOS (PPAOS) versus dominant PAOS with concomitant aphasia (DAOS) should be differentiated, distinct characteristics of the two presentations are unclear. Furthermore, a careful description of their clinical presentation in languages other than English is required. AIMS: To describe the motor speech characteristics of Quebec French-speaking participants with prominent PAOS and to explore the communication profile of those presenting more specifically with isolated PAOS (PPAOS), and with dominant PAOS and concomitant aphasia (DAOS). METHODS & PROCEDURES: A thorough effort to recruit all speakers presenting with PAOS in the larger population areas of the province of Quebec was conducted over a 3-year span. A total of nine participants with PAOS (pwPAOS; PPAOS = 5, DAOS = 4) underwent a comprehensive language and motor speech assessment, and a cognitive screening. Their performance was compared with 30 matched healthy controls. OUTCOMES & RESULTS: As a group, pwPAOS differed from healthy speakers on all acoustic and perceptual measures. The PPAOS and PAOS subgroups were similar on several measures, but participants from the PPAOS subgroup tended to perform better on articulatory measures and maximum speech rate tasks. CONCLUSIONS & IMPLICATIONS: This study provides an in-depth analysis of motor speech characteristics of PAOS in Quebec French speakers and adds further evidence for the differentiation of PPAOS and DAOS. Combining simple perceptual and acoustic analyses represent a promising approach to distinguish the two variants and identify treatment targets. What this paper adds What is already known on this subject Progressive apraxia of speech (PAOS) is a neurodegenerative syndrome characterized by progressive and initially isolated or dominant apraxia of speech (primary progressive apraxia of speech [PPAOS] and dominant progressive apraxia of speech [DAOS], respectively). Studies mostly report articulatory and prosodic deficits in PAOS, but concomitant deficits such as dysarthria and executive dysfunction are also reported. The description of motor speech skills in PAOS remains vague and English-oriented. Studies suggest that speakers presenting with isolated PAOS vs dominant PAOS with concomitant aphasia should be differentiated, but distinct characteristics of the two presentations are unclear. What this study adds to existing knowledge To the best of the authors' knowledge, this study is the first to report transversal data of Quebec-French participants with PPAOS and DAOS. Moreover, this study is a first step towards identifying potential characteristics that could facilitate the diagnosis of PPAOS and DAOS in Quebec French. It makes a significant contribution to our understanding of progressive apraxia of speech in different cultural languages. What are the potential or actual clinical implications of this work? This study also initiates the search for sensitive tasks for the diagnosis of those speakers (which is an important process), in addition to identifying the core characteristics of PAOS, DAOS, and PPAOS in the development of an assessment battery for this population.

Early symptoms in symptomatic and preclinical genetic frontotemporal lobar degeneration.

OBJECTIVES: The clinical heterogeneity of frontotemporal dementia (FTD) complicates identification of biomarkers for clinical trials that may be sensitive during the prediagnostic stage. It is not known whether cognitive or behavioural changes during the preclinical period are predictive of genetic status or conversion to clinical FTD. The first objective was to evaluate the most frequent initial symptoms in patients with genetic FTD. The second objective was to evaluate whether preclinical mutation carriers demonstrate unique FTD-related symptoms relative to familial mutation non-carriers. METHODS: The current study used data from the Genetic Frontotemporal Dementia Initiative multicentre cohort study collected between 2012 and 2018. Participants included symptomatic carriers (n=185) of a pathogenic mutation in chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN) or microtubule-associated protein tau (MAPT) and their first-degree biological family members (n=588). Symptom endorsement was documented using informant and clinician-rated scales. RESULTS: The most frequently endorsed initial symptoms among symptomatic patients were apathy (23%), disinhibition (18%), memory impairments (12%), decreased fluency (8%) and impaired articulation (5%). Predominant first symptoms were usually discordant between family members. Relative to biologically related non-carriers, preclinical MAPT carriers endorsed worse mood and sleep symptoms, and C9orf72 carriers endorsed marginally greater abnormal behaviours. Preclinical GRN carriers endorsed less mood symptoms compared with non-carriers, and worse everyday skills. CONCLUSION: Preclinical mutation carriers exhibited neuropsychiatric symptoms compared with non-carriers that may be considered as future clinical trial outcomes. Given the heterogeneity in symptoms, the detection of clinical transition to symptomatic FTD may be best captured by composite indices integrating the most common initial symptoms for each genetic group.

Education modulates brain maintenance in presymptomatic frontotemporal dementia.

OBJECTIVE: Cognitively engaging lifestyles have been associated with reduced risk of conversion to dementia. Multiple mechanisms have been advocated, including increased brain volumes (ie, brain reserve) and reduced disease progression (ie, brain maintenance). In cross-sectional studies of presymptomatic frontotemporal dementia (FTD), higher education has been related to increased grey matter volume. Here, we examine the effect of education on grey matter loss over time. METHODS: Two-hundred twenty-nine subjects at-risk of carrying a pathogenic mutation leading to FTD underwent longitudinal cognitive assessment and T1-weighted MRI at baseline and at 1 year follow-up. The first principal component score of the graph-Laplacian Principal Component Analysis on 112 grey matter region-of-interest volumes was used to summarise the grey matter volume (GMV). The effects of education on cognitive performances and GMV at baseline and on the change between 1 year follow-up and baseline (slope) were tested by Structural Equation Modelling. RESULTS: Highly educated at-risk subjects had better cognition and higher grey matter volume at baseline; moreover, higher educational attainment was associated with slower loss of grey matter over time in mutation carriers. CONCLUSIONS: This longitudinal study demonstrates that even in presence of ongoing pathological processes, education may facilitate both brain reserve and brain maintenance in the presymptomatic phase of genetic FTD.

The contribution of semantic memory to the recognition of basic emotions and emotional valence: Evidence from the semantic variant of primary progressive aphasia.

There is compelling evidence that semantic memory is involved in emotion recognition. However, its contribution to the recognition of emotional valence and basic emotions remains unclear. We compared the performance of 10 participants with the semantic variant of primary progressive aphasia (svPPA), a clinical model of semantic memory impairment, to that of 33 healthy participants using three experimental tasks assessing the recognition of: 1) emotional valence conveyed by photographic scenes, 2) basic emotions conveyed by facial expressions, and 3) basic emotions conveyed by prosody sounds. Individuals with svPPA showed significant deficits in the recognition of emotional valence and basic emotions (except happiness and surprise conveyed by facial expressions). However, the performance of the two groups was comparable when the performance on tests assessing semantic memory was added as a covariate in the analyses. Altogether, these results suggest that semantic memory contributes to the recognition of emotional valence and basic emotions. By examining the recognition of emotional valence and basic emotions in individuals with selective semantic memory loss, our results contribute to the refinement of current theories on the role of semantic memory in emotion recognition.

Comprehension of concrete and abstract words in semantic variant primary progressive aphasia and Alzheimer's disease: A behavioral and neuroimaging study.

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.

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.

Neurofilament light chain: a biomarker for genetic frontotemporal dementia.

OBJECTIVE: To evaluate cerebrospinal fluid (CSF) and serum neurofilament light chain (NfL) levels in genetic frontotemporal dementia (FTD) as a potential biomarker in the presymptomatic stage and during the conversion into the symptomatic stage. Additionally, to correlate NfL levels to clinical and neuroimaging parameters. METHODS: In this multicenter case-control study, we investigated CSF NfL in 174 subjects (48 controls, 40 presymptomatic carriers and 86 patients with microtubule-associated protein tau (MAPT), progranulin (GRN), and chromosome 9 open reading frame 72 (C9orf72) mutations), and serum NfL in 118 subjects (39 controls, 44 presymptomatic carriers, 35 patients). In 55 subjects both CSF and serum was determined. In two subjects CSF was available before and after symptom onset (converters). Additionally, NfL levels were correlated with clinical parameters, survival, and regional brain atrophy. RESULTS: CSF NfL levels in patients (median 6762 pg/mL, interquartile range 3186-9309 pg/mL) were strongly elevated compared with presymptomatic carriers (804 pg/mL, 627-1173 pg/mL, P < 0.001), resulting in a good diagnostic performance to discriminate both groups. Serum NfL correlated highly with CSF NfL (r s = 0.87, P < 0.001) and was similarly elevated in patients. Longitudinal samples in the converters showed a three- to fourfold increase in CSF NfL after disease onset. Additionally, NfL levels in patients correlated with disease severity, brain atrophy, annualized brain atrophy rate and survival. INTERPRETATION: NfL in both serum and CSF has the potential to serve as a biomarker for clinical disease onset and has a prognostic value in genetic FTD.