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Advancing Research and Treatment for Frontotemporal Lobar Degeneration (ARTFL)

Overview

About this study

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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  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.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Jacksonville, Fla.

Mayo Clinic principal investigator

Neill Graff Radford, M.D.

Closed for enrollment

Rochester, Minn.

Mayo Clinic principal investigator

David Knopman, M.D.

Closed for enrollment

More information

Publications

  • In preclinical studies, davunetide promoted microtubule stability and reduced tau phosphorylation. Because progressive supranuclear palsy (PSP) is linked to tau pathology, davunetide could be a treatment for PSP. We assessed the safety and efficacy of davunetide in patients with PSP. Read More on PubMed
  • Impaired self-awareness is characteristic of nearly all dementias, including Alzheimer's disease (AD), but the deficit is most severe in the behavioral variant of frontotemporal dementia (bvFTD). The prominence of frontal pathology in bvFTD suggests that failure of online monitoring, the process by which individuals monitor their own cognitive processing in real time, is an important contributor. Metacognitive research offers several approaches to measure self-assessment, some more and others less sensitive to online monitoring. The goal of this study was to assess metacognition in bvFTD using several approaches, and to compare the results with those in AD. Read More on PubMed
  • The term frontotemporal dementia (FTD) refers to a group of neurodegenerative disorders that are associated with atrophy of the frontal and temporal lobes, and present clinically with impairments of behaviour or language. Three main subtypes are described, behavioural variant FTD (bvFTD) and two subtypes of the language presentation (known as primary progressive aphasia or PPA) called semantic variant of PPA and non-fluent variant of PPA. Most imaging studies of FTD have used volumetric T1 magnetic resonance imaging (MRI) or positron emissions tomography imaging to identify patterns of grey matter atrophy or hypometabolism in these different subtypes, but more recently newer imaging techniques have been used to help define abnormalities in structural connectivity (white matter tract integrity using diffusion tensor imaging), functional connectivity (resting state networks using resting state functional MRI) and perfusion (using arterial spin labelling perfusion MRI) in FTD. These techniques have the potential to improve the differential diagnosis of FTD from other disorders and to provide more informative imaging signatures of FTD syndromes. Read More on PubMed
  • Memantine has been used off-label to treat frontotemporal lobar degeneration (FTD). A previous 26-week open-label study suggested a transient, modest benefit on neuropsychiatric symptoms as measured by the neuropsychiatric inventory (NPI). We aimed to determine whether memantine is an effective treatment for FTD. Read More on PubMed
  • Deficits in the generation and control of saccades have been described in clinically defined frontotemporal dementia (FTD) and Alzheimer disease (AD). Read More on PubMed
  • Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy which can manifest clinically in a variety of syndromes. In this review, the classic and most common variant syndrome -PSP-Richardson's syndrome (PSP-RS) -is the focus, with the core clinical features, varying cognitive/motor/neuropsychiatric/sleep manifestations, neuropsychological findings, and typical neuroimaging findings all reviewed. Management strategies are also discussed. Of particular interest are the recently commenced clinical trials involving agents which affect key steps in the presumed pathogenesis of the tauopathies. The distinctive and recognizable characteristics of PSP-RS and advent of clinical trials involving potential disease modifying agents underscore the importance of identifying patients with this disorder and encouraging their involvement in trials. Read More on PubMed
  • Corticobasal degeneration (CBD) is a complex neurodegenerative disorder which nomenclature of which its nomenclature and characterization continues to evolve. The core clinical features that have been considered characteristic of the disorder include progressive asymmetric rigidity and apraxia, with other findings suggesting additional cortical (e.g., alien limb phenomena, cortical sensory loss, myoclonus, and mirror movements) and basal ganglionic (e.g., bradykinesia, dystonia, and tremor) dysfunctions. The characteristic findings at autopsy are asymmetric cortical atrophy that is typically maximal in the frontoparietal regions, as well as basal ganglia and nigral degeneration. Microscopically, abnormal accumulations of the microtubule-associated tau protein are found in both neurons and glia, and this disorder is now considered one of the "tauopathies." CBD was initially thought to represent a distinct clinicopathologic entity. Recent studies have shown considerable clinicopathologic heterogeneity, leading some to use the term "corticobasal syndrome" (CBS) for the constellation of findings initially considered characteristic of the disorder, and the term "corticobasal degeneration" for the histopathologic disorder. In this review, the multiple phenotypes/syndromes associated with CBD pathology, and multiple diseases associated with the CBS, are presented. The clinicopathologic heterogeneity in CBS/CBD and the implications of this heterogeneity on clinical practice, on understanding the focal/asymmetric cerebral degeneration syndromes, and on future research are all reviewed. Read More on PubMed
  • Self-appraisal is a critical cognitive function, which helps us to choose tasks based on an accurate assessment of our abilities. The neural mechanisms of self-appraisal are incompletely understood, although a growing body of literature suggests that several frontal and subcortical regions are important for self-related processing. Anosognosia, or lack of awareness of one's deficits, is common in neurodegenerative dementias, offering an important window onto the brain systems involved in self-appraisal. We examined the neuroanatomical basis of self-appraisal in a mixed group of 39 individuals, including 35 with cognitive impairment due to one of several probable neurodegenerative diseases, using voxel-based morphometry and an objective, neuropsychologically-based measure of self-appraisal accuracy. Self-appraisal accuracy was correlated with tissue content in the right ventromedial prefrontal cortex (vmPFC). We hypothesize that emotional/physiological processing carried out by vmPFC is an important factor mediating self-appraisal accuracy in dementia. Read More on PubMed

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