Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects

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.

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.