Frontotemporal Lobar Degeneration (FTLD) is the neuropathological term for a collection of rare neurodegenerative diseases that correspond to four main overlapping clinical syndromes: frontotemporal dementia (FTD), primary progressive aphasia (PPA), corticobasal degeneration syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). The goal of this study is to build a FTLD clinical research consortium to support the development of FTLD therapies for new clinical trials. The consortium, referred to as Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL), will be headquartered at UCSF and will partner with six patient advocacy groups to manage the consortium. Participants will be evaluated at 14 clinical sites throughout North America and a genetics core will genotype all individuals for FTLD associated genes.
Frontotemporal Lobar Degeneration (FTLD) is the neuropathological term for a collection of rare neurodegenerative diseases that correspond to four main overlapping clinical syndromes: frontotemporal dementia (FTD), primary progressive aphasia (PPA), corticobasal degeneration syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). The goal of this study is to build a FTLD clinical research consortium (FTLD CRC) to support the development of FTLD therapies for new clinical trials. The FTLD CRC will be headquartered at UCSF and will partner with six patient advocacy groups to manage the consortium. Patients will be evaluated at 13 clinical sites throughout North America and a genetics core will genotype all individuals for FTLD associated genes. The study will be divided into 2 projects. The first project will be Preparing for Sporadic FTLD Clinical Trials and the second project will be a Longitudinal Assessment of Familial FTLD. Self-registration for an online registry will be available for patients and families with any FTLD syndrome. Eligible participants for research Projects 1 and 2 FTLD will be invited to a CRC site for clinical evaluations. All enrolled participants in both research projects will have a site visit consisting of a neurological exam, medical and family history, cognitive testing, and a blood draw. Participants in Project 1 who have a diagnosis of Progressive Supranuclear Palsy Syndrome will have two additional assessments. A lumbar puncture (LP) will be performed for CSF collection, and an MRI scan of the brain will be done. Participants in Project 2: Longitudinal Assessment of familial FTLD will return for a follow-up visit in 12 months; procedures at the follow-up visit will be identical to those at baseline. Additionally, asymptomatic participants will undergo MRI scans at both visits.
1. Inclusion Criteria:Must meet one of the following research diagnostic criteria for a
Frontotemporal lobar degeneration (FTLD) syndrome: behavioral variant frontotemporal
dementia (bvFTD), primary progressive aphasia (PPA), semantic variant primary
progressive aphasia (svPPA), nonfluent variant primary progressive aphasia (nfvPPA),
frontotemporal dementia with amyotrophic lateral sclerosis (FTD/ALS), amyotrophic
lateral sclerosis alone, corticobasal syndrome (CBS), progressive supranuclear palsy
(PSP) or oligosymptomatic PSP (oPSP), or have a strong family history of FTLD
syndromes.
2. Between 18 and 85 (inclusive) years of age.
3. Able to walk (with assistance) at the time of enrollment.
4. Have a reliable study partner who can provide an independent evaluation of
functioning.
5. Speak English or Spanish
6. Have Mini Mental State Exam (MMSE) scores between 15 - 30 (inclusive).
Exclusion Criteria:
1. Known presence of a structural brain lesion (e.g. tumor,cortical infarct) that could
reasonably explain symptoms in a symptomatic participant without a known f-FTLD
causing mutation.
2. Known presence of an Alzheimer's disease causing mutation in PSEN1, PSEN2 or APP; or
neuropathological evidence for Alzheimer's disease as a cause of syndrome (from brain
biopsy).
3. A previous history of Korsakoff encephalopathy, severe alcohol dependence (within 5
years of onset of dementia), frequent alcohol or other substance intoxication, or
other neurological disorder (such as multiple sclerosis)
4. Evidence through history or laboratory testing of B12 deficiency (B12 < 95% of local
laboratory's normal value), hypothyroidism (TSH >150% of normal), HIV positive,renal
failure (creatinine > 2), liver failure (ALT or AST > two times normal), respiratory
failure (requiring oxygen), extra-axial brain tumor (with visible compression of the
brain parenchyma), large cerebral infarct that could account for clinical syndrome,
large confluent white matter lesions (grades 3 or 4, [107] significant systemic
medical illnesses such as deteriorating cardiovascular disease;
5. Current medication likely to affect CNS functions in the opinion of the site PI: long
acting benzodiazepines such as diazepam (short-acting benzodiazepines are OK),
non-SSRI antidepressants (SSRIs or trazodone are OK), no lithium, typical neuroleptics
as listed in the Manual of Procedures, narcotics (codeine is OK, but hold 24 hours
before neuropsychological testing), anticonvulsants (outside of therapeutic ranges),
antihistamines (if taking greater than three times per week; hold 24 hours before
neuropsychological testing).
6. In the site investigator's opinion, the participant cannot complete sufficient key
study procedures, or equivalent assessment of impairment level.
7. For groups where MRI scans are planned procedures, any contraindication for MRI
scanning, such as pacemaker or other implanted metals.