GENetic Fronto Temporal Dementia Initiative in Lille

The purposes of this study is :

• to improve characterization of symptomatic FTD patients or presymptomatic subjects at risk of genetic FTD
• to develop markers indicative of the optimal time to start disease-modifying therapy, based on the proximity to clinical onset.
• to develop markers of disease progression that can be used as outcome measures.
• to derive sample size estimates for clinical trials.

Participants will include those affected with the disorder as well as at-risk members of families (both mutation carriers and non-carrier first-degree relatives who will serve as a control group).

All participants will be assessed longitudinally with a set of clinical, neuropsychiatric, cognitive, imaging and biosample protocols.

Inclusion criteria

• The participant must be 18 years old or older.
• The participant must be a member of a family with a known pathogenic mutation in the GRN or MAPT genes, or with a pathogenic expansion in the C9orf72 gene :

• An affected member is one who has been clinically diagnosed by a neurologist as having frontotemporal dementia or a disorder in the FTD spectrum.
• An at-risk member is one who is a first-degree relative of a family member affected with the disease.
• Pathogenicity of a GRN or MAPT mutation is defined by those included within the GENFI list of FTD mutation. If a novel mutation is discovered that is likely to be pathogenic and has not yet been included within the FTD mutation database then the GENFI Genetics Core will decide on inclusion. Please send an email to the GENFI Trials Team at [email protected].
• A pathogenic C9orf72 expansion is defined as greater than 30 repeats. Intermediate expansions are not considered pathogenic.
• Participants from one of the small number of families around the world in which 2 (or more) pathogenic mutations have been found should not be included in GENFI.
• If the participant is demented or cognitively impaired there must be an available caregiver that can escort them.
• The participant must have an identified informant.
• The participant must be fluent in the language of their country of assessment.
• The participant accepts that genetic analysis will be carried out on his/her blood samples, and that no results will be available neither for the investigator nor for the participant.

Exclusion criteria

• Participant has another medical or psychiatric illness that would interfere in completing assessments.
• Contraindications to FDG-PET (allergy to FDG…)
• Participant is pregnant.