Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects

Study Overview
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Brief Summary
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This study is being done to learn more about normal thinking and behavior, mild thinking and behavior problems, Frontotemporal Dementia and other forms of dementia in families in which one or more relatives have a mutation associated with Frontotemporal Dementia.

Detailed Description
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This multicenter study will enroll 300 members of familial Frontotemporal Dementia (FTD) families across 8 experienced FTD research centers with a known mutation in MAPT, PGRN, or C9ORF72 (100 mutation carriers with mild dementia or minimally symptomatic yet non-demented, 100 asymptomatic mutation carriers, and 100 clinically normal relatives who are non-mutation carriers) to obtain annual assessments including T1-MRI, FLAIR, diffusion tensor imaging (DTI), ASL perfusion (ASLp), intrinsic connectivity functional MRI (icfMRI), MR spectroscopy (MRS), CSF, blood, and behavioral, neuropsychological and functional assessment, for a total of three assessments per participant. A primary goal of this study is to identify the most robust and reliable methods to track disease progression in familial FTD so that disease-modifying therapeutic trials can be designed appropriately.

Official Title
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Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects

Conditions
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Familial Frontotemporal Dementia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be a member of family with a known mutation in one of the three major FTLD related genes: MAPT, PGRN, or C9ORF72. At least 18 years of age. The predominant phenotype in the kindred must be cognitive/behavioral (ie, kindreds in whom parkinsonism or ALS is the predominant clinical phenotype among affected relatives may be excluded) Have a reliable informant who personally speaks with or sees that subject at least weekly. Subject is sufficiently fluent in English to complete all measures Subject must be willing and able to consent to the protocol and undergo yearly evaluations over 3 years. Subject must be willing and able to undergo neuropsychological testing (at least at baseline visit). Subject must have no contraindication to MRI imaging. Exclusion Criteria Known presence of a structural brain lesion (e.g. tumor, cortical infarct). Presence of another neurologic disorder which could impact findings (eg, multiple sclerosis). Subject is unwilling to return for follow-up yearly, undergo neuropsychological testing and MR imaging. Subject has no reliable informant.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Frontotemporal Dementia - MAPT<br>Frontotemporal Dementia with microtubule associated protein tau (MAPT) mutation | |
| Frontotemporal Dementia - PGRN<br>Frontotemporal Dementia with progranulin (PGRN; also known as granulin or GRN) mutation | |
| Frontotemporal Dementia - C9OR72<br>Frontotemporal Dementia with chromosome 9 open reading frame 72 (C9ORF72) mutation. | |
| Control<br>Member of family with a known mutation in one of the three major FTD related genes: MAPT, PGRN, and C9ORF72. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of decline in traditional measures of clinical (neuropsychological and behavioral composites) function and cortical volume on structural MRI in the symptomatic phase of familial FTD | neuropsychological, clinical/behavioral, neuroimaging measures | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of decline in traditional measures of clinical (neuropsychological and behavioral composites) function and cortical volume on structural MRI in the asymptomatic phase of familial FTD | neuropsychological, clinical/behavioral, neuroimaging measures | 5 years | 
| Value of novel imaging and clinical measures for characterizing asymptomatic familial FTD subjects, and factors predicting clinical rates of progression in each group. | neuropsychological, clinical/behavioral, neuroimaging measures | 5 years | 
| Genetic and biofluid factors that modify rates of clinical and neuroimaging decline in the asymptomatic and symptomatic phases of familial FTD. | genetic and biolfuid factors | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Frontotemporal Dementia, MAPT, PGRN, C9ORF72