Efficacy of acetylcholinesterase inhibitors in the logopenic variant of primary progressive aphasia.

INTRODUCTION: For over twenty-five years, cholinesterase inhibitors (ChEIs) have been the main symptomatic treatment for Alzheimer's disease (AD). Several meta-analyses have supported their efficacy in various neurocognitive, functional, and behavioral aspects of amnestic AD. Over 86% of cases of the language variant AD are caused by a similar pathologic process than AD, yet no study has examined the efficacy of ChEIs in this AD variant. We aimed to explore the efficacy of ChEIs in the treatment of language AD by comparing their evolution on the MMSE to that of treated amnestic AD patients. METHODS: A retrospective chart review was performed in forty-five patients with language AD and fifty-two patients with amnestic AD. Both groups were similar regarding age, level of education, and onset of symptoms. Drug history, MMSE scores, functional and neuropsychiatric symptoms were collected on several time points before and after the introduction of ChEIs. Data was analysed using ANOVA and a generalized linear mixed model. RESULTS: Patients with language AD showed a similar trajectory of decline than amnestic AD patients on serial MMSEs up to twenty-four months after the introduction of ChEIs. In language AD patients, ChEIs had a significant impact on activities of daily life (ADLs), but not instrumental activities of daily living (IADLs), and neuropsychiatric symptoms remained stable over time. CONCLUSION: This study provides preliminary evidence for efficacy of ChEIs in patients with language AD and suggests similar benefits to those seen in amnestic AD patients, hence reassuring patients and their physicians.

Frequency and Longitudinal Course of Behavioral and Neuropsychiatric Symptoms in Participants With Genetic Frontotemporal Dementia.

BACKGROUND AND OBJECTIVES: Behavioral and neuropsychiatric symptoms are frequent in patients with genetic frontotemporal dementia (FTD). We aimed to describe behavioral and neuropsychiatric phenotypes in genetic FTD, quantify their temporal association, and investigate their regional association with brain atrophy. METHODS: We analyzed data of pathogenic variant carriers in the chromosome 9 open reading frame 72 (c9orf72), progranulin (GRN), or microtubule-associated protein tau (MAPT) gene from the Genetic Frontotemporal dementia Initiative cohort study that enrolls both symptomatic pathogenic variant carriers and first-degree relatives of known carriers. Principal component analysis was performed to identify behavioral and neuropsychiatric clusters that were compared with respect to frequency and severity between groups. Associations between neuropsychiatric clusters and MRI-assessed atrophy were determined using voxel-based morphometry. We applied linear mixed effects and generalized linear mixed effects models to assess the longitudinal course of symptoms. RESULTS: A total of 522 participants were included: 221 c9orf72 (138 presymptomatic), 213 GRN (157 presymptomatic), and 88 MAPT (62 presymptomatic) pathogenic variant carriers. Principal component analysis revealed 5 phenotypic clusters (67.6% of variance), labeled diverse behavioral, affective, psychotic, euphoric/hypersexual, and tactile hallucinations phenotype. In participants presenting behavioral or neuropsychiatric symptoms, affective symptoms were most frequent across groups (83.6%-88.1%), followed by diverse behavioral symptoms (68.4%-77.9%). In c9orf72 and GRN pathogenic variant carriers, psychotic symptoms (32.0% and 19.4%, respectively) were more frequent than euphoric/hypersexual symptoms (28.7% and 14.2%, respectively), which was the other way around in MAPT pathogenic variant carriers (28.6% and 23.8%). Although diverse behavioral symptoms were associated with gray and white matter frontotemporal atrophy, only a small atrophy cluster in the right thalamus was associated with psychotic symptoms. Euphoric/hypersexual symptoms were associated with atrophy in mesial temporal lobes, basal forebrain structures, and the striatum (p < 0.05). Estimated time to symptom onset, genetic group, education, and sex influenced behavioral and neuropsychiatric symptoms (p < 0.05). Particularly, in c9orf72 pathogenic variant carriers, psychotic symptoms may be starting decades before recognition of onset of illness. DISCUSSION: We identified multiple clusters of behavioral and neuropsychiatric symptoms in participants with genetic FTD that relate to distinct cerebral atrophy patterns. Their severity depends on time, affected gene, sex, and education. These clinical-genetic associations can guide diagnostic evaluations and the design of clinical trials for new disease-modifying and preventive treatments.

Long Non-Coding RNA Profile in Genetic Symptomatic and Presymptomatic Frontotemporal Dementia: A GENFI Study.

Background: Long non-coding RNAs (lncRNAs) play crucial roles in gene regulation and are implicated in neurodegenerative diseases, including frontotemporal dementia (FTD). However, their expression patterns and potential as biomarkers in genetic FTD involving Chromosome 9 Open Reading Frame (C9ORF72), Microtubule Associated Protein Tau (MAPT), and Progranulin (GRN) genes are not well understood. Objective: This study aimed to profile the expression levels of lncRNAs in peripheral blood mononuclear cells collected within the GENetic Frontotemporal dementia Initiative (GENFI). Methods: Fifty-three lncRNAs were analyzed with the OpenArray Custom panel, in 131 patients with mutations in C9ORF72, MAPT, and GRN, including 68 symptomatic mutation carriers (SMC) and 63 presymptomatic mutation carriers (PMC), compared with 40 non-carrier controls (NC). Results: Thirty-eight lncRNAs were detectable; the relative expression of NEAT1 and NORAD was significantly higher in C9ORF72 SMC as compared with NC. GAS5 expression was instead significantly lower in the GRN group versus NC. MAPT carriers showed no significant deregulations. No significant differences were observed in PMC. Disease duration did not correlate with lncRNA expression. Conclusions: NEAT1 and NORAD are upregulated in C9ORF72 SMC and GAS5 levels are downregulated in GRN SMC, underlining lncRNAs' relevance in FTD and their potential for biomarker development. Further validation and mechanistic studies are crucial for clinical implications.

Inflammatory plasma profile in genetic symptomatic and presymptomatic Frontotemporal Dementia - A GENFI study.

BACKGROUND: Inflammation has been proposed as a crucial player in neurodegeneration, including Frontotemporal Dementia (FTD). A few studies on sporadic FTD lead to inconclusive results, whereas large studies on genetic FTD are lacking. The aim of this study is to determine cytokine and chemokine plasma circulating levels in a large cohort of genetic FTD, collected within the GENetic Frontotemporal dementia Initiative (GENFI). METHODS: Mesoscale technology was used to analyse levels of 30 inflammatory factors in 434 plasma samples, including 94 Symptomatic Mutation carriers [(SMC); 15 with mutations in Microtubule Associated Protein Tau (MAPT) 34 in Progranulin (GRN) and 45 in Chromosome 9 Open Reading Frame (C9ORF)72], 168 Presymptomatic Mutation Carriers (PMC; 34 MAPT, 70 GRN and 64 C9ORF72) and 173 Non-carrier Controls (NC)]. RESULTS: The following cytokines were significantly upregulated (P<0.05) in MAPT and GRN SMC versus NC: Tumor Necrosis Factor (TNF)α, Interleukin (IL)-7, IL-15, IL-16, IL-17A. Moreover, only in GRN SMC, additional factors were upregulated, including: IL-1ß, IL-6, IL-10, IL-12/IL-23p40, eotaxin, eotaxin-3, Interferon γ-induced Protein (IP-10), Monocyte Chemotactic Protein (MCP)4. On the contrary, IL-1α levels were decreased in SMC compared with NC. Significantly decreased levels of this cytokine were also found in PMC, independent of the type of mutation. In SMC, no correlations between disease duration and cytokine and chemokine levels were found. Considering NfL and GFAP levels, as expected, significant increases were observed in SMC as compared to NC. These differences in mean values remain significant even when stratifying symptomatic patients by the mutated gene (P<0.0001). Considering instead the levels of NfL, GFAP, and the altered inflammatory molecules, no significant correlations emerged. CONCLUSION: We showed that inflammatory proteins are upregulated in MAPT and GRN SMC, with some specific factors altered in GRN only, whereas no changes were seen in C9ORF72 carriers. Notably, only IL-1α levels were decreased in both SMC and PMC, independent of the type of causal mutation, suggesting common modifications occurring in the preclinical phase of the disease.

Feasibility and acceptability of a videoconference-based cognitive-behavioral intervention for caregivers of individuals living with mild cognitive impairment or early Alzheimer's disease.

Objective: The objective of the current pilot study was to investigate the feasibility and acceptability of a videoconference-based cognitive behavioral (CBT) intervention for caregivers of individuals living with mild cognitive impairment or early Alzheimer's disease. The intervention included psychoeducation on emotions, strategies for management of unhelpful emotions and thoughts, behavioral activation, breathing and relaxation, strategies for communication and information on external resources. Methods: This study used a cross-sectional design with two groups of four caregivers who received an 8-week CBT-based intervention via videoconference. Measures of feasibility and acceptability were collected post-intervention as well as suggestions for improvements. Results: Eight female caregivers were enrolled in the intervention, one participant opted out at the seventh session. Of those who completed the program, all participants reported that it was very easy to participate using the online modality. All participants felt that the intervention was at least partly adapted to their experience and needs as a caregiver. Five out of seven participants (71%) indicated that they felt better and would recommend the intervention to another caregiver. Conclusion: The current study demonstrated that it is feasible and acceptable to use a videoconference CBT-based group intervention with MCI or mild AD female caregivers. Innovation: This is the first videoconference-based cognitive behavioral intervention for caregivers of individuals living with MCI or mild AD.

Impaired glymphatic system in genetic frontotemporal dementia: a GENFI study.

The glymphatic system is an emerging target in neurodegenerative disorders. Here, we investigated the activity of the glymphatic system in genetic frontotemporal dementia with a diffusion-based technique called diffusion tensor image analysis along the perivascular space. We investigated 291 subjects with symptomatic or presymptomatic frontotemporal dementia (112 with chromosome 9 open reading frame 72 [C9orf72] expansion, 119 with granulin [GRN] mutations and 60 with microtubule-associated protein tau [MAPT] mutations) and 83 non-carriers (including 50 young and 33 old non-carriers). We computed the diffusion tensor image analysis along the perivascular space index by calculating diffusivities in the x-, y- and z-axes of the plane of the lateral ventricle body. Clinical stage and blood-based markers were considered. A subset of 180 participants underwent cognitive follow-ups for a total of 640 evaluations. The diffusion tensor image analysis along the perivascular space index was lower in symptomatic frontotemporal dementia (estimated marginal mean ± standard error, 1.21 ± 0.02) than in old non-carriers (1.29 ± 0.03, P = 0.009) and presymptomatic mutation carriers (1.30 ± 0.01, P < 0.001). In mutation carriers, lower diffusion tensor image analysis along the perivascular space was associated with worse disease severity (ß = -1.16, P < 0.001), and a trend towards a significant association between lower diffusion tensor image analysis along the perivascular space and higher plasma neurofilament light chain was reported (ß = -0.28, P = 0.063). Analysis of longitudinal data demonstrated that worsening of disease severity was faster in patients with low diffusion tensor image analysis along the perivascular space at baseline than in those with average (P = 0.009) or high (P = 0.006) diffusion tensor image analysis along the perivascular space index. Using a non-invasive imaging approach as a proxy for glymphatic system function, we demonstrated glymphatic system abnormalities in the symptomatic stages of genetic frontotemporal dementia. Such measures of the glymphatic system may elucidate pathophysiological processes in human frontotemporal dementia and facilitate early phase trials of genetic frontotemporal dementia.

Clinical recognition of frontotemporal dementia with right anterior temporal predominance: A multicenter retrospective cohort study.

INTRODUCTION: Although frontotemporal dementia (FTD) with right anterior temporal lobe (RATL) predominance has been recognized, a uniform description of the syndrome is still missing. This multicenter study aims to establish a cohesive clinical phenotype. METHODS: Retrospective clinical data from 18 centers across 12 countries yielded 360 FTD patients with predominant RATL atrophy through initial neuroimaging assessments. RESULTS: Common symptoms included mental rigidity/preoccupations (78%), disinhibition/socially inappropriate behavior (74%), naming/word-finding difficulties (70%), memory deficits (67%), apathy (65%), loss of empathy (65%), and face-recognition deficits (60%). Real-life examples unveiled impairments regarding landmarks, smells, sounds, tastes, and bodily sensations (74%). Cognitive test scores indicated deficits in emotion, people, social interactions, and visual semantics however, lacked objective assessments for mental rigidity and preoccupations. DISCUSSION: This study cumulates the largest RATL cohort unveiling unique RATL symptoms subdued in prior diagnostic guidelines. Our novel approach, combining real-life examples with cognitive tests, offers clinicians a comprehensive toolkit for managing these patients. HIGHLIGHTS: This project is the first international collaboration and largest reported cohort. Further efforts are warranted for precise nomenclature reflecting neural mechanisms. Our results will serve as a clinical guideline for early and accurate diagnoses.

A cross-cultural study of the Montreal Cognitive Assessment for people with hearing impairment.

BACKGROUND: Cognitive screening tools enable the detection of cognitive impairment, facilitate timely intervention, inform clinical care, and allow long-term planning. The Montreal Cognitive Assessment for people with hearing impairment (MoCA-H) was developed as a reliable cognitive screening tool for people with hearing loss. Using the same methodology across four languages, this study examined whether cultural or linguistic factors affect the performance of the MoCA-H. METHODS: The current study investigated the performance of the MoCA-H across English, German, French, and Greek language groups (n = 385) controlling for demographic factors known to affect the performance of the MoCA-H. RESULTS: In a multiple regression model accounting for age, sex, and education, cultural-linguistic group accounted for 6.89% of variance in the total MoCA-H score. Differences between languages in mean score of up to 2.6 points were observed. CONCLUSIONS: Cultural or linguistic factors have a clinically significant impact on the performance of the MoCA-H such that optimal performance cut points for identification of cognitive impairment derived in English-speaking populations are likely inappropriate for use in non-English speaking populations. To ensure reliable identification of cognitive impairment, it is essential that locally appropriate performance cut points are established for each translation of the MoCA-H.

Mini-SEA: Validity and Normative Data for the French-Quebec Population Aged 50 Years and Above.

OBJECTIVE: The mini Social cognition & Emotional Assessment (mini-SEA) is a social cognition battery which assesses theory of mind and emotion recognition. Currently, no psychometrically validated measure of social cognition with adapted normative data exists for the middle-aged and elderly French-Quebec population. This project aims to determine the known-group discriminant validity of a cultural and linguistic adaptation of the mini-SEA between cognitively healthy people, those with mild cognitive impairment (MCI) or living with Alzheimer's Disease (AD). This study also aims to examine the stability of mini-SEA's performance over a 3-4-month time period, as well as to produce normative data for French-Quebec people aged 50 years. Normative data are derived for the full and an abbreviated version of the Faux Pas subtest. METHOD: The sample included 211 French-speaking participants from Quebec (Canada) aged 50 to 89 years. Mini-SEA's performance between a sub-sample of cognitively healthy people (n = 20), those with MCI (n = 20) or with AD (n = 20) was compared. A sub-sample of cognitively healthy people (n = 30) performed the task twice to estimate test-retest reliability. Socio-demographic variables' effects on scores were examined to produce normative data in the form of regression equations or percentile ranks. RESULTS: Significant differences emerged between cognitively healthy people and those with MCI or AD. Moreover, scores were relatively stable over a period of 3 to 4 months. Finally, for the normative data, age, gender, and education were associated with performance on the mini-SEA or its subtests. CONCLUSIONS: This study improves and standardizes social cognition's assessment among French-Quebec individuals, which will help characterize their cognitive profile.

Efficacy of LSVT LOUD® on Phonatory Control and Voice Quality in Patients with Primary Progressive Apraxia of Speech: Case Studies.

Primary progressive apraxia of speech (PPAOS) is a neurodegenerative syndrome characterized by the progressive and initially isolated or predominant onset of difficulties in the planning/programming of movements necessary for speech production and can be accompanied by dysarthria. To date, no study has used an evidence-based treatment to address phonation control in patients with PPAOS. The aim of this study was to evaluate the feasibility and efficacy of LSVT LOUD® as a treatment for phonatory control in speakers with PPAOS. Three speakers with PPAOS received LSVT LOUD® therapy, and changes in phonatory control, voice quality and prosody were measured immediately, and one, four and eight weeks after the end of the treatment. Overall, the results suggest that the treatment is feasible and could improve voice quality, intensity, and control in some patients with PPAOS. The generalization of the results is also discussed.

Distinct spatial contributions of amyloid pathology and cerebral small vessel disease to hippocampal morphology.

INTRODUCTION: Cerebral small vessel disease (SVD) and amyloid beta (Aß) pathology frequently co-exist. The impact of concurrent pathology on the pattern of hippocampal atrophy, a key substrate of memory impacted early and extensively in dementia, remains poorly understood. METHODS: In a unique cohort of mixed Alzheimer's disease and moderate-severe SVD, we examined whether total and regional neuroimaging measures of SVD, white matter hyperintensities (WMH), and Aß, as assessed by 18F-AV45 positron emission tomography, exert additive or synergistic effects on hippocampal volume and shape. RESULTS: Frontal WMH, occipital WMH, and Aß were independently associated with smaller hippocampal volume. Frontal WMH had a spatially distinct impact on hippocampal shape relative to Aß. In contrast, hippocampal shape alterations associated with occipital WMH spatially overlapped with Aß-vulnerable subregions. DISCUSSION: Hippocampal degeneration is differentially sensitive to SVD and Aß pathology. The pattern of hippocampal atrophy could serve as a disease-specific biomarker, and thus guide clinical diagnosis and individualized treatment strategies for mixed dementia.

Longitudinal cerebral perfusion in presymptomatic genetic frontotemporal dementia: GENFI results.

INTRODUCTION: Effective longitudinal biomarkers that track disease progression are needed to characterize the presymptomatic phase of genetic frontotemporal dementia (FTD). We investigate the utility of cerebral perfusion as one such biomarker in presymptomatic FTD mutation carriers. METHODS: We investigated longitudinal profiles of cerebral perfusion using arterial spin labeling magnetic resonance imaging in 42 C9orf72, 70 GRN, and 31 MAPT presymptomatic carriers and 158 non-carrier controls. Linear mixed effects models assessed perfusion up to 5 years after baseline assessment. RESULTS: Perfusion decline was evident in all three presymptomatic groups in global gray matter. Each group also featured its own regional pattern of hypoperfusion over time, with the left thalamus common to all groups. Frontal lobe regions featured lower perfusion in those who symptomatically converted versus asymptomatic carriers past their expected age of disease onset. DISCUSSION: Cerebral perfusion is a potential biomarker for assessing genetic FTD and its genetic subgroups prior to symptom onset. HIGHLIGHTS: Gray matter perfusion declines in at-risk genetic frontotemporal dementia (FTD). Regional perfusion decline differs between at-risk genetic FTD subgroups . Hypoperfusion in the left thalamus is common across all presymptomatic groups. Converters exhibit greater right frontal hypoperfusion than non-converters past their expected conversion date. Cerebral hypoperfusion is a potential early biomarker of genetic FTD.

Extending the phenotypic spectrum assessed by the CDR plus NACC FTLD in genetic frontotemporal dementia.

INTRODUCTION: We aimed to expand the range of the frontotemporal dementia (FTD) phenotypes assessed by the Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD). METHODS: Neuropsychiatric and motor domains were added to the standard CDR plus NACC FTLD generating a new CDR plus NACC FTLD-NM scale. This was assessed in 522 mutation carriers and 310 mutation-negative controls from the Genetic Frontotemporal dementia Initiative (GENFI). RESULTS: The new scale led to higher global severity scores than the CDR plus NACC FTLD: 1.4% of participants were now considered prodromal rather than asymptomatic, while 1.3% were now considered symptomatic rather than asymptomatic or prodromal. No participants with a clinical diagnosis of an FTD spectrum disorder were classified as asymptomatic using the new scales. DISCUSSION: Adding new domains to the CDR plus NACC FTLD leads to a scale that encompasses the wider phenotypic spectrum of FTD with further work needed to validate its use more widely. Highlights: The new Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains neuropsychiatric and motor (CDR plus NACC FTLD-NM) rating scale was significantly positively correlated with the original CDR plus NACC FTLD and negatively correlated with the FTD Rating Scale (FRS).No participants with a clinical diagnosis in the frontotemporal dementia spectrum were classified as asymptomatic with the new CDR plus NACC FTLD-NM rating scale.Individuals had higher global severity scores with the addition of the neuropsychiatric and motor domains.A receiver operating characteristic analysis of symptomatic diagnosis showed nominally higher areas under the curve for the new scales.

The DDQ-30, a new naming-from-definition test: Normative data for the adult French-Quebec population and validation study in mild cognitive impairment and Alzheimer's disease.

Assessing naming abilities is a standard clinical procedure for adults and is usually carried out using picture naming tests. However, the use of picture naming tests can have limitations, as people may have visual impairments that can affect the validity of the measurement. This article introduces the DDQ-30, a new naming-from-definition test for detecting anomia in people with visual-perceptual limitations. The article describes three studies. Study 1 focused on the developmental phase of the DDQ-30. In Study 2, healthy participants and individuals with mild cognitive impairment or Alzheimer's disease were assessed with the DDQ-30 to determine its predictive validity. Study 3 examined a group of adults and older French-speaking Quebecers to obtain normative data. The DDQ-30 effectively differentiated between AD and healthy participants. In addition, normative data were collected on 251 participants aged 50 years and older. Analyses showed that age and educational level were significantly related to performance on the DDQ-30. The DDQ-30 fills an important gap and promises to help clinicians and researchers better detect anomia in people with visual impairment.

NfL reliability across laboratories, stage-dependent diagnostic performance and matrix comparability in genetic FTD: a large GENFI study.

BACKGROUND: Blood neurofilament light chain (NfL) is increasingly considered as a key trial biomarker in genetic frontotemporal dementia (gFTD). We aimed to facilitate the use of NfL in gFTD multicentre trials by testing its (1) reliability across labs; (2) reliability to stratify gFTD disease stages; (3) comparability between blood matrices and (4) stability across recruiting sites. METHODS: Comparative analysis of blood NfL levels in a large gFTD cohort (GENFI) for (1)-(4), with n=344 samples (n=148 presymptomatic, n=11 converter, n=46 symptomatic subjects, with mutations in C9orf72, GRN or MAPT; and n=139 within-family controls), each measured in three different international labs by Simoa HD-1 analyzer. RESULTS: NfL revealed an excellent consistency (intraclass correlation coefficient (ICC) 0.964) and high reliability across the three labs (maximal bias (pg/mL) in Bland-Altman analysis: 1.12±1.20). High concordance of NfL across laboratories was moreover reflected by high areas under the curve for discriminating conversion stage against the (non-converting) presymptomatic stage across all three labs. Serum and plasma NfL were largely comparable (ICC 0.967). The robustness of NfL across 13 recruiting sites was demonstrated by a linear mixed effect model. CONCLUSIONS: Our results underline the suitability of blood NfL in gFTD multicentre trials, including cross-lab reliable stratification of the highly trial-relevant conversion stage, matrix comparability and cross-site robustness.

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.

Altered plasma protein profiles in genetic FTD - a GENFI study.

BACKGROUND: Plasma biomarkers reflecting the pathology of frontotemporal dementia would add significant value to clinical practice, to the design and implementation of treatment trials as well as our understanding of disease mechanisms. The aim of this study was to explore the levels of multiple plasma proteins in individuals from families with genetic frontotemporal dementia. METHODS: Blood samples from 693 participants in the GENetic Frontotemporal Dementia Initiative study were analysed using a multiplexed antibody array targeting 158 proteins. RESULTS: We found 13 elevated proteins in symptomatic mutation carriers, when comparing plasma levels from people diagnosed with genetic FTD to healthy non-mutation controls and 10 proteins that were elevated compared to presymptomatic mutation carriers. CONCLUSION: We identified plasma proteins with altered levels in symptomatic mutation carriers compared to non-carrier controls as well as to presymptomatic mutation carriers. Further investigations are needed to elucidate their potential as fluid biomarkers of the disease process.

The impact of phonological short-term memory impairment on verbal repetition in the logopenic variant of primary progressive aphasia.

The logopenic variant of primary progressive aphasia (lvPPA) is characterized mainly by anomia, production of phonological errors, and impairment in repetition of sentences. The functional origin of these language impairments is mainly attributed to the breakdown of phonological short-term memory. The present study examined the effects of phonological short-term memory impairment on language processing in lvPPA. In two studies, 11 participants with lvPPA and 11 healthy control participants were presented with repetition tasks in which the type and length of stimuli and the mode of administration were manipulated. Study 1 aimed to examine the influence of length and lexicality (words vs. pseudowords) on immediate and delayed repetition, whereas Study 2 aimed to examine the influence of length, syntactic complexity (nominalized vs. pronominalized sentences), and serial position on immediate sentence repetition. Study 1 showed that participants' performance with lvPPA was impaired only on immediate repetition of five-syllable pseudowords and on delayed repetition of words and pseudowords. Study 2 showed that participants' performance with lvPPA was impaired in the repetition of nominalized sentences where a recency effect was observed. Repetition of pronominalized sentences was also impaired in the lvPPA group. This study provides additional support for arguments regarding phonological short-term memory as a cause of language impairment in lvPPA. Clinically, the results of the study suggest that instruments for assessing repetition ability in lvPPA should include not only lists of short or long nominalized sentences, but also delayed repetition of words and pseudowords and pronominalized sentences.

Assessing the pool activity level (PAL) checklist for use with people with hearing and vision loss.

BACKGROUND: The PAL is a career-completed assessment that indexes cognitive functional ability to inform individualised support. As hearing and vision loss are prevalent, we assessed the PAL for potential bias with hearing or vision impairment. METHODS: We collected PAL responses for 333 adults aged over 60 years in the UK, France, Canada, Greece and Cyprus. All participants had normal cognition based on self-reported status and normal range scores on a cognitive screening test. Using a Kruskal-Wallis test, we compared PAL item response distributions for people with assessed hearing or vision loss compared to those with normal sensory function. RESULTS: There were no differences in response distributions between hearing or vision impaired groups versus those with normal sensory function on any PAL item. CONCLUSION: The PAL reliably indexes cognitive functional ability and may be used to inform support tailored to individual cognitive level amongst older adults with prevalent hearing and vision impairments.