The goal of this observational study is to investigate the role of neuroinflammation in frontotemporal lobar degeneration (FTLD). The main aims of this study are: 1. To elucidate the role and timing of neuroinflammation in FTLD by using a combination of clinical measures, 7T MRI, and CSF biomarkers; 2. To differentiate FTLD-TDP and FTLD-tau during life using biomarkers for neuroinflammation; 3. To identify biomarkers to predict and monitor disease progression in FTLD; Secondary aim: 1\. To explore the role of brain clearance in the disease process of FTLD. Participants will undergo 7T MRI scans, blood and CSF collection, clinical, neurological, and neuropsychological evaluation.
At baseline, the study will involve the following procedures: clinical assessment including neurological and neuropsychological investigation, blood sampling, and a voluntarily lumbar puncture on the first day at the Erasmus MC University Medical Center, (EMC) and two sessions of 7T MRI scanning on the second day at the Leiden University Medical Center (LUMC). After one year, clinical assessment and blood analyses will be repeated in the EMC to assess disease progression. The aim is to include 25 patients with probable or definite FTLD-tau, 25 patients with probable or definite FTLD-TDP, 50 healthy individuals with 50% risk to carry a mutation in MAPT or GRN, or the C9orf72 HRE. If necessary for age matching, 10 additional healthy subjects without increased risk of FTLD will be included.
Study Type
OBSERVATIONAL
Enrollment
110
MRI-scanning of the brain using a 7T MRI scanner
CSF collection via lumbar puncture
Blood is collected by doing a blood withdrawal
Tests for memory, language, attention, executive functions, praxis, social cognition, visuoconstructive skills
Medical history, neurological assessment, neuropsychiatric inventory
Leiden University Medical Center
Leiden, Netherlands
Erasmus MC
Rotterdam, Netherlands
MR Spectroscopy in the lateral anterior cingulate cortex
MR Spectroscopy data analysis in a single volume of interest in the lateral anterior cingulate cortex to assess changes in metabolites related to neurodegeneration and neuroinflammation. The analysis in LCModel will give us metabolite concentrations for total N-acetyl-aspertate (tNAA), glutamate (Glu), myo-inositol (mI), and total choline compound (tCho).
Time frame: At baseline
Diffusion weighted MR spectroscopy in the lateral anterior cingulate cortex
Diffusion weighted MR Spectroscopy data analysis in a single volume of interest in the lateral anterior cingulate cortex to assess changes in the apparent diffusion coefficients of specific metabolites related to neurodegeneration and neuroinflammation. The analysis done in LCModel will give us metabolite apparent diffusion coefficients for total N-acetyl-aspertate (tNAA), glutamate (Glu), myo-inositol (mI), and total choline compound (tCho).
Time frame: At baseline
Quantitative susceptibility mapping for iron localization and quantification
Cross-sectional MR analysis to determine iron accumulation in the brain. The analysis will be performed with the SEPIA toolbox to obtain quantitative susceptibility values in various brain regions.
Time frame: At baseline
Neurodegeneration biomarkers in blood
Biomarkers for neurodegeneration (neurofilament light chain (NFL), total tau) in blood.
Time frame: At baseline
Neurodegeneration biomarkers in CSF
Biomarkers for neurodegeneration (neurofilament light chain (NFL), total tau) in CSF.
Time frame: At baseline
Neuroinflammation biomarkers in CSF
Biomarkers for neuroinflammation (YKL-40, TREM-1, TREM-2, IL-1, IL-6, TNF-α, GFAP, CHIT1) in CSF.
Time frame: At baseline
Iron accumulation biomarkers in blood
Biomarkers for iron accumulation ( ferritin, and iron) in blood.
Time frame: At baseline
Iron acccumulation biomarkers in CSF
Biomarkers for iron accumulation (transferritin, ferritin, and iron) in CSF.
Time frame: At baseline
Clinical and neuropsycological evaluation: Clinical dementia rating scale
Cognitive and neuropsychological assessments for clinical dementia rating scale (CDR) to assess the cognitive functioning of the participant. The CDR is a combination score including multiple neuropsychological functioning on multiple domains (memory, language, attention, executive function, praxis, social cognition, and visuoconstructive skills) and clinical evaluation. A score of 0 means not impaired or no symptoms, a score of 0.5 means prodromal, and a score of 1 and higher (up to 3) reflects a symptomatic individual.
Time frame: At baseline and 1 year follow-up
Clinical and neuropsycological evaluation: Montreal Cognitive Assessment
Cognitive and neuropsychological assessments for Montreal Cognitive Assessment (MoCA) to assess the cognitive functioning of the participant. A total score of 30 can be obtained. A higher score reflects a better performance. The cut-off point for a normal score is 26. A score lower than 26 reflects impairments or one or more cognitive domains.
Time frame: At baseline and 1 year follow-up
Clinical evaluation: Parkinson's Disease Rating Score
Neurological examination for Unified Parkinson's Disease rating score (UPDRS). The score will be between 0 and 260, with a lower score indicating no symptoms and a total score of 260 indicating all symptoms.
Time frame: At baseline and 1 year follow-up
Clinical evaluation: Neuropsychiatric assessment
Neuropsychiatric examination with the neuropsychiatric inventory (NPI) to assess psychiatric symptoms. The NPI has a total score range of \[0, 144\], with a higher score indicating more neuropsychiatric symptoms. A NPI score higher than 0 indicates the presence of one or more symptoms, a score of 4 or higher indicates moderate symptoms.
Time frame: At baseline and 1 year follow-up
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