Neuropsychological Profiles in Genetic Frontotemporal Dementia: A Meta-Analysis and Systematic Review.

Characterization of cognitive profiles across genetic FTD gene mutations is crucial for the identification of sensitive endpoints for clinical trials targeting specific pathologies. However, no systematic overview of the literature describing cognitive profiles in different FTD gene mutations has been made thus far. We performed a meta-analysis and systematic review to characterize cognitive profiles across the different FTD gene mutations and clinical disease stages of familial frontotemporal dementia (FTD).

Impairments in knowledge of social norms in presymptomatic, prodromal, and symptomatic frontotemporal dementia.

Introduction: We aimed to assess the knowledge of social norms in patients with behavioral variant frontotemporal dementia (bvFTD) with the Dutch version of the Social Norms Questionnaire (SNQ-NL).

Methods: The SNQ-NL was administered in 34 patients with bvFTD, 20 prodromal mutation carriers, 76 presymptomatic mutation carriers, and 56 controls. Group differences and correlations with other neuropsychological tests and gray matter volume were examined.

Occupational differences in a Dutch sample of patients with primary progressive aphasia, behavioral variant frontotemporal dementia, and Alzheimer's dementia.

Background: Cognitive reserve is a potential mechanism to cope with brain damage as a result of dementia, which can be defined by indirect proxies, including education level, leisure time activities, and occupational attainment. In this study we explored the association between dementia diagnosis and type of occupation in a retrospective Dutch outpatient memory clinic sample of patients with primary progressive aphasia (PPA), behavioral variant frontotemporal dementia (bvFTD), and Alzheimer's Dementia (AD).

Methods: We included data from 427 patients (bvFTD  = 87, PPA  = 148, AD  = 192) and compared the frequency of occupations (11 categories) between patients and data from the Dutch census using Pearson tests and we calculated odds ratios (OR) by means of multinomial logistic regression analyses.

Distinctive cell-free DNA methylation characterizes presymptomatic genetic frontotemporal dementia.

Objective: Methylation of plasma cell-free DNA (cfDNA) has potential as a marker of brain damage in neurodegenerative diseases such as frontotemporal dementia (FTD). Here, we study methylation of cfDNA in presymptomatic and symptomatic carriers of genetic FTD pathogenic variants, next to healthy controls.

Methods: cfDNA was isolated from cross-sectional plasma of 10 presymptomatic carriers (4 C9orf72, 4 GRN, and 2 MAPT), 10 symptomatic carriers (4 C9orf72, 4 GRN, and 2 MAPT), and 9 healthy controls.

Clinical Value of Longitudinal Serum Neurofilament Light Chain in Prodromal Genetic Frontotemporal Dementia.

Background And Objectives: Elevated serum neurofilament light chain (NfL) is used to identify carriers of genetic frontotemporal dementia (FTD) pathogenic variants approaching prodromal conversion. Yet, the magnitude and timeline of NfL increase are still unclear. Here, we investigated the predictive and early diagnostic value of longitudinal serum NfL for the prodromal conversion in genetic FTD.

Longitudinal changes in qualitative aspects of semantic fluency in presymptomatic and prodromal genetic frontotemporal dementia.

Background: The semantic fluency test is one of the most widely used neuropsychological tests in dementia diagnosis. Research utilizing the qualitative, psycholinguistic information embedded in its output is currently underexplored in presymptomatic and prodromal genetic FTD.

Methods: Presymptomatic MAPT (n = 20) and GRN (n = 43) mutation carriers, and controls (n = 55) underwent up to 6 years of neuropsychological assessment, including the semantic fluency test.

The Benson Complex Figure Test detects deficits in visuoconstruction and visual memory in symptomatic familial frontotemporal dementia: A GENFI study.

Objective: Sensitive cognitive markers are still needed for frontotemporal dementia (FTD). The Benson Complex Figure Test (BCFT) is an interesting candidate test, as it assesses visuospatial, visual memory, and executive abilities, allowing the detection of multiple mechanisms of cognitive impairment. To investigate differences in BCFT Copy, Recall and Recognition in presymptomatic and symptomatic FTD mutation carriers, and to explore its cognitive and neuroimaging correlates.

Addition of the FTD Module to the Neuropsychiatric Inventory improves classification of frontotemporal dementia spectrum disorders.

Most neuropsychiatric symptoms (NPS) common in frontotemporal dementia (FTD) are currently not part of the Neuropsychiatric Inventory (NPI). We piloted an FTD Module that included eight extra items to be used in conjunction with the NPI. Caregivers of patients with behavioural variant FTD (n = 49), primary progressive aphasia (PPA; n = 52), Alzheimer's dementia (AD; n = 41), psychiatric disorders (n = 18), presymptomatic mutation carriers (n = 58) and controls (n = 58) completed the NPI and FTD Module.

The ScreeLing: Detecting Semantic, Phonological, and Syntactic Deficits in the Clinical Subtypes of Frontotemporal and Alzheimer's Dementia.

The ScreeLing is a screening instrument developed to assess post-stroke aphasia, via the linguistic levels Syntax, Phonology, and Semantics. It could also be a useful test for the clinical subtypes of frontotemporal dementia (FTD) and Alzheimer's dementia (AD), as specific and often selective disorders are expected. Its ability to differentiate between the clinical subtypes of FTD and AD is, however, still unknown.

Mindfulness-Based Stress Reduction in Pre-symptomatic Genetic Frontotemporal Dementia: A Pilot Study.

Pre-symptomatic frontotemporal dementia (FTD) mutation carriers and first-degree family members that are 50% at-risk for FTD may experience symptoms of anxiety and depression as a result of the ambiguity of when or if symptoms of the disease will manifest. We conducted a pilot study to investigate the use of an online mindfulness-based stress reduction (MBSR) course to reduce symptoms of anxiety and depression in presymptomatic frontotemporal dementia (FTD) mutation carriers and individuals 50% at-risk. Seven known mutation carriers and six individuals 50% at-risk completed a standardized 8-week MBSR course, and filled out pre- and post and two-month follow-up questionnaires.

Longitudinal Cognitive Changes in Genetic Frontotemporal Dementia Within the GENFI Cohort.

Background And Objectives: Disease-modifying therapeutic trials for genetic frontotemporal dementia (FTD) are underway, but sensitive cognitive outcome measures are lacking. The aim of this study was to identify such cognitive tests in early stage FTD by investigating cognitive decline in a large cohort of genetic FTD pathogenic variant carriers and by investigating whether gene-specific differences are moderated by disease stage (asymptomatic, prodromal, and symptomatic).

Methods: , , and pathogenic variant carriers as well as controls underwent a yearly neuropsychological assessment covering 8 cognitive domains as part of the Genetic FTD Initiative, a prospective multicenter cohort study.

Cognitive composites for genetic frontotemporal dementia: GENFI-Cog.

Background: Clinical endpoints for upcoming therapeutic trials in frontotemporal dementia (FTD) are increasingly urgent. Cognitive composite scores are often used as endpoints but are lacking in genetic FTD. We aimed to create cognitive composite scores for genetic frontotemporal dementia (FTD) as well as recommendations for recruitment and duration in clinical trial design.

Short Digital Spatial Memory Test Detects Impairment in Alzheimer's Disease and Mild Cognitive Impairment.

Background: Impairment in navigation abilities and object location memory are often seen in early-stage Alzheimer's Disease (AD), yet these constructs are not included in standard neuropsychological assessment. We investigated the differential ability of a short digital spatial memory test in mild AD dementia and mild cognitive impairment (MCI).

Methods: 21 patients with AD dementia (66.

A data-driven disease progression model of fluid biomarkers in genetic frontotemporal dementia.

Several CSF and blood biomarkers for genetic frontotemporal dementia have been proposed, including those reflecting neuroaxonal loss (neurofilament light chain and phosphorylated neurofilament heavy chain), synapse dysfunction [neuronal pentraxin 2 (NPTX2)], astrogliosis (glial fibrillary acidic protein) and complement activation (C1q, C3b). Determining the sequence in which biomarkers become abnormal over the course of disease could facilitate disease staging and help identify mutation carriers with prodromal or early-stage frontotemporal dementia, which is especially important as pharmaceutical trials emerge. We aimed to model the sequence of biomarker abnormalities in presymptomatic and symptomatic genetic frontotemporal dementia using cross-sectional data from the Genetic Frontotemporal dementia Initiative (GENFI), a longitudinal cohort study.

Impairment of episodic memory in genetic frontotemporal dementia: A GENFI study.

Introduction: We aimed to assess episodic memory in genetic frontotemporal dementia (FTD) with the Free and Cued Selective Reminding Test (FCSRT).

Methods: The FCSRT was administered in 417 presymptomatic and symptomatic mutation carriers (181 chromosome 9 open reading frame 72 [], 163 progranulin [], and 73 microtubule-associated protein tau []) and 290 controls. Group differences and correlations with other neuropsychological tests were examined.

Classification using fractional anisotropy predicts conversion in genetic frontotemporal dementia, a proof of concept.

Frontotemporal dementia is a highly heritable and devastating neurodegenerative disease. About 10-20% of all frontotemporal dementia is caused by known pathogenic mutations, but a reliable tool to predict clinical conversion in mutation carriers is lacking. In this retrospective proof-of-concept case-control study, we investigate whether MRI-based and cognition-based classifiers can predict which mutation carriers from genetic frontotemporal dementia families will develop symptoms ('convert') within 4 years.

Emotion recognition of morphed facial expressions in presymptomatic and symptomatic frontotemporal dementia, and Alzheimer's dementia.

Background: The emotion recognition task (ERT) was developed to overcome shortcomings of static emotion recognition paradigms, by identifying more subtle deficits in emotion recognition across different intensity levels. In this study, we used the ERT to investigate emotion recognition deficits across the frontotemporal (FTD) and Alzheimer's Dementia (AD) spectrum.

Methods: With the ERT, we assessed the recognition of facial emotional expressions (anger-disgust-fear-happiness-sadness-surprise) across four intensities (40-60-80-100%) in patients with behavioural variant FTD (bvFTD; n = 32), and AD (n = 32), presymptomatic FTD mutation carriers (n = 47) and controls (n = 49).

Serum neurofilament light chain in genetic frontotemporal dementia: a longitudinal, multicentre cohort study.

Background: Neurofilament light chain (NfL) is a promising blood biomarker in genetic frontotemporal dementia, with elevated concentrations in symptomatic carriers of mutations in GRN, C9orf72, and MAPT. A better understanding of NfL dynamics is essential for upcoming therapeutic trials. We aimed to study longitudinal NfL trajectories in people with presymptomatic and symptomatic genetic frontotemporal dementia.

Bias Introduced by Multiple Head Coils in MRI Research: An 8 Channel and 32 Channel Coil Comparison.

Neuroimaging MRI data in scientific research is increasingly pooled, but the reliability of such studies may be hampered by the use of different hardware elements. This might introduce bias, for example when cross-sectional studies pool data acquired with different head coils, or when longitudinal clinical studies change head coils halfway. In the present study, we aimed to estimate this possible bias introduced by using different head coils to create awareness and to avoid misinterpretation of results.

Gray and white matter changes in presymptomatic genetic frontotemporal dementia: a longitudinal MRI study.

In genetic frontotemporal dementia, cross-sectional studies have identified profiles of presymptomatic neuroanatomical loss for C9orf72 repeat expansion, MAPT, and GRN mutations. In this study, we characterize longitudinal gray matter (GM) and white matter (WM) brain changes in presymptomatic frontotemporal dementia. We included healthy carriers of C9orf72 repeat expansion (n = 12), MAPT (n = 15), GRN (n = 33) mutations, and related noncarriers (n = 53), that underwent magnetic resonance imaging at baseline and 2-year follow-up.