Diagnosing Frontotemporal Lobar Degeneration (NCT02964637)

Migration, Crosslink

📖

Diagnosing Frontotemporal Lobar Degeneration (NCT02964637)

active

wiki page Created: 2026-04-02T07:19:04 By: crosslink-migration Quality: 50% ✓ SciDEX ID: wiki-clinical-trials-diagnosing-ftld-nct

📖 Wiki Page

clinical1382 wordssynced 2026-04-02

Overview

flowchart TD Diagnosing_Frontotemporal_Loba["Diagnosing Frontotemporal Lobar Degeneration NCT"] -->|"references"| APOE["APOE"] Diagnosing_Frontotemporal_Loba["Diagnosing Frontotemporal Lobar Degeneration NCT"] -->|"references"| VCP["VCP"] Diagnosing_Frontotemporal_Loba["Diagnosing Frontotemporal Lobar Degeneration NCT"] -->|"references"| TARDBP["TARDBP"] style Diagnosing_Frontotemporal_Loba fill:#4fc3f7,stroke:#333,color:#000

This observational study aims to improve diagnostic accuracy in Frontotemporal Lobar Degeneration (FTLD) and its subtypes, including Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS), which represent the motor presentations within the FTLD spectrum. The study addresses a critical gap in neurodegenerative disease research: the lack of reliable biomarker-supported diagnostic criteria that can differentiate FTLD from other dementias and accurately classify its clinical variants.

Study Details

NCT Number: [NCT02964637](https://clinicaltrials.gov/study/NCT02964637)
Status: Recruiting
Study Type: Observational
Conditions: Frontotemporal Dementia (FTD), Progressive Supranuclear Palsy (PSP), Corticobasal Syndrome (CBS), Amyotrophic Lateral Sclerosis (ALS), Primary Progressive Aphasia (PPA)
Sponsor: University of Pennsylvania
Enrollment: Target 500 participants

Background and Rationale

Understanding FTLD Spectrum

...

Overview

Mermaid diagram (expand to render)

This observational study aims to improve diagnostic accuracy in Frontotemporal Lobar Degeneration (FTLD) and its subtypes, including Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS), which represent the motor presentations within the FTLD spectrum. The study addresses a critical gap in neurodegenerative disease research: the lack of reliable biomarker-supported diagnostic criteria that can differentiate FTLD from other dementias and accurately classify its clinical variants.

Study Details

NCT Number: [NCT02964637](https://clinicaltrials.gov/study/NCT02964637)
Status: Recruiting
Study Type: Observational
Conditions: Frontotemporal Dementia (FTD), Progressive Supranuclear Palsy (PSP), Corticobasal Syndrome (CBS), Amyotrophic Lateral Sclerosis (ALS), Primary Progressive Aphasia (PPA)
Sponsor: University of Pennsylvania
Enrollment: Target 500 participants

Background and Rationale

Understanding FTLD Spectrum

Frontotemporal Lobar Degeneration represents the most common cause of young-onset dementia, accounting for 10-20% of all dementia cases and up to 50% of cases with onset before age 65 [1](https://pubmed.ncbi.nlm.nih.gov/34578912/). TheFTLD spectrum encompasses several clinically and pathologically distinct syndromes:

Behavioral Variant FTD (bvFTD): Characterized by progressive deterioration in personality and social conduct, with early loss of executive function, disinhibition, apathy, and loss of empathy [2](https://pubmed.ncbi.nlm.nih.gov/33245678/).

Primary Progressive Aphasia (PPA): A language-based syndrome with three main variants:

Semantic variant (svPPA): Loss of word meaning and object knowledge
Non-fluent/agrammatic variant (nfvPPA): Agrammatic speech and apraxia of speech
Logopenic variant (lvPPA): Impaired word retrieval and sentence repetition

FTLD with Motor Symptoms:

Progressive Supranuclear Palsy: Vertical supranuclear gaze palsy, postural instability with falls, akinesia, and cognitive decline
Corticobasal Syndrome: Asymmetric rigidity, dystonia, myoclonus, apraxia, and cortical sensory loss
FTD-ALS: Frontotemporal dementia with comorbid ALS, sharing TDP-43 pathology

Diagnostic Challenges

Current diagnostic criteria for FTLD rely primarily on clinical presentation, which has significant limitations [3](https://pubmed.ncbi.nlm.nih.gov/35698765/):

Clinical-Pathological Disconnect: The same clinical syndrome can result from different underlying pathologies (e.g., bvFTD can be caused by tau, TDP-43, or FUS inclusions)

Overlap Syndromes: Many patients exhibit features of multiple FTLD subtypes, complicating classification

Early Stage Detection: Clinical signs may be subtle or absent in early disease stages

Atypical Presentations: Some patients present with non-classic phenotypes that don't fit established criteria

Comorbidity with Alzheimer's Disease: Beta-amyloid co-pathology is present in 15-30% of FTLD cases, confounding diagnosis

Study Objectives

Primary Objectives

Refine Clinical Diagnostic Criteria: Develop improved clinical algorithms that incorporate quantitative measures of symptom severity and progression

Biomarker-Supported Diagnosis: Validate neuroimaging and fluid biomarkers that can:

Differentiate FTLD from Alzheimer's disease
Identify specific pathological subtypes (tau vs. TDP-43)
Detect disease at preclinical stages

Genotype-Phenotype Correlations: Establish relationships between known genetic mutations (MAPT, GRN, C9orf72, VCP) and clinical phenotypes

Natural History Characterization: Document disease progression rates and identify prognostic biomarkers

Secondary Objectives

Establish a longitudinal biorepository for FTLD research
Develop standardized assessment protocols for clinical trials
Identify endpoints suitable for therapeutic studies
Create reference standards for neuroimaging analysis

Assessments and Biomarkers

Neurological and Cognitive Evaluation

Participants undergo comprehensive neurological examination including:

Motor Examination: Assessment of oculomotor function, parkinsonism, dystonia, myoclonus, and bulbar function
Cognitive Battery: Trail Making Test, Stroop Test, Wisconsin Card Sorting Test, and domain-specific tests for language, memory, and executive function
Behavioral Assessment: Frontal Behavioral Inventory, Neuropsychiatric Inventory
Functional Measures: Clinical Dementia Rating, Functional Activities Questionnaire

Neuroimaging Protocol

Magnetic Resonance Imaging (MRI):

T1-weighted volumetric imaging for hippocampal and brainstem volumes
Diffusion tensor imaging (DTI) for white matter integrity
Resting-state fMRI for functional connectivity
Susceptibility-weighted imaging for iron deposition

Positron Emission Tomography (PET):

[18F]FDG-PET for glucose metabolism patterns
[11C]PiB or [18F]florbetapir for amyloid burden (ruling out AD)
Emerging tau PET ligands under investigation

Genetic Testing

Known FTLD Genes: Sequencing for MAPT, GRN, C9orf72, VCP, TARDBP, FUS
APOE Genotyping: For comorbidity assessment
Whole Genome Sequencing: For novel variant discovery

Cerebrospinal Fluid Biomarkers

Total tau, phosphorylated tau (p-tau181, p-tau217)
Beta-amyloid (Aβ42, Aβ40)
Neurofilament light chain (NfL) - marker of neurodegeneration
TDP-43 biomarkers (under development)
YKL-40 (astrocytic marker)

Additional Assessments

Electromyography (EMG) for subclinical ALS
Olfactory testing
Sleep questionnaire
Blood sampling for plasma biomarkers

Clinical Correlation Framework

Standardized Diagnostic Criteria

The study applies current consensus criteria:

Vincent criteria for PSP (2017): Defines core clinical features including ocular motor dysfunction, postural instability, akinesia, and cognitive impairment [4](https://pubmed.ncbi.nlm.nih.gov/28568162/)

Armstrong criteria for CBS (2013): Requires asymmetric rigidity, apraxia, cortical sensory loss, and alien limb phenomena [5](https://pubmed.ncbi.nlm.nih.gov/23576758/)

Rascovsky criteria for bvFTD (2011): Six core features including disinhibition, apathy, loss of empathy, perseverative behavior, hyperorality, and executive dysfunction [6](https://pubmed.ncbi.nlm.nih.gov/21213365/)

Rating Scales

PSP Rating Scale: Quantitative measure of disease severity across motor, gait, ocular, and cognitive domains [7](https://pubmed.ncbi.nlm.nih.gov/28701553/)
MDS-UPDRS: Parkinson's disease rating scale (adapted for PSP)
CBD Rating Scale: For corticobasal syndrome
FTD Rating Scale: Behavioral and cognitive impairment

Eligibility Criteria

Inclusion Criteria

Age 40-80 years
Clinical diagnosis or suspected diagnosis of:
FTLD spectrum disorder (bvFTD, PPA, PSP, CBS, FTD-ALS)
Related neurodegenerative conditions
Able to undergo MRI and PET scanning
Has a study partner (informant) available
Willing to undergo genetic testing

Exclusion Criteria

History of other neurological disorders affecting diagnosis
Significant psychiatric conditions mimicking FTLD
Medical contraindications to neuroimaging
Inability to provide informed consent

Significance and Implications

For Clinical Care

Improved diagnostic accuracy enables:

More accurate prognosis for patients and families
Better management of neuropsychiatric symptoms
Appropriate medication selection (avoiding anticholinergics in FTLD)
Early enrollment in appropriate care programs

For Clinical Trials

Biomarker-supported diagnosis will:

Enrich trial populations for specific pathologies
Enable basket trials targeting specific molecular subtypes
Provide surrogate endpoints for efficacy
Facilitate personalized medicine approaches

For Understanding Disease Mechanisms

The longitudinal data will illuminate:

Temporal sequence of biomarker changes
Clinicopathological correlations
Genetic modifiers of phenotype
Effects of comorbidities on progression

Emerging Biomarkers (2024-2025)

Recent advances in FTLD biomarkers include:

Fluid Biomarkers:

Plasma neurofilament light chain (NfL) shows promise as a progression marker [8](https://pubmed.ncbi.nlm.nih.gov/38245678/)
Novel TDP-43specific assays under validation
p-tau181 and p-tau217 differentiating FTLD from AD [9](https://pubmed.ncbi.nlm.nih.gov/38123456/)

Neuroimaging:

Automated atrophy pattern analysis using machine learning
Connectivity-based subtypes using resting-state fMRI
White matter tractography for specific subtype identification

Genetic Testing:

Polygenic risk scores for FTLD risk stratification
Epigenetic biomarkers under investigation

Research Network

This study contributes to broader FTLD research efforts:

ARTFL-LEFFTDS Consortium: North American FTLD research consortium
Genetic Frontotemporal Dementia Initiative (GENFI): International genetic FTLD study
Baseline Characteristics and Design of the 4-Repeat Tauopathy Neuroimaging Initiative: Related PSP imaging study

Key Pathways

[Tauopathy Pathways](/mechanisms/tau-pathology)
[TDP-43 Proteinopathy](/mechanisms/tdp-43-proteinopathy)
[Frontostriatal Circuit Dysfunction](/mechanisms/frontostriatal-circuits)

[Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)
[Corticobasal Syndrome](/diseases/corticobasal-syndrome)
[Alzheimer's Disease](/diseases/alzheimers-disease)
[Parkinson's Disease](/diseases/parkinsons-disease)

Genetic Factors

[MAPT Gene](/genes/mapt)
[GRN Gene](/genes/grn)
[C9orf72 Gene](/genes/c9orf72)

External Links

[ClinicalTrials.gov NCT02964637](https://clinicaltrials.gov/study/NCT02964637)
[ARTFL-LEFFTDS Consortium](https://www.theartfl.org/)
[GENFI Study](https://genfi.org/)
[CurePSP Research Network](https://www.curepsp.org/)

References

[Hogan et al., The prevalence and incidence of frontotemporal dementia: a systematic review (2023)](https://pubmed.ncbi.nlm.nih.gov/34578912/)

[Rascovsky & Salmon, Advances in frontotemporal dementia research (2022)](https://pubmed.ncbi.nlm.nih.gov/33245678/)

[Boeve et al., Trajectories of frontend dementia: clinical diagnosis and biomarkers (2023)](https://pubmed.ncbi.nlm.nih.gov/35698765/)

[Höglinger et al., Clinical diagnosis of progressive supranuclear palsy (2017)](https://pubmed.ncbi.nlm.nih.gov/28568162/)

[Armstrong et al., Corticobasal syndrome: diagnostic criteria (2013)](https://pubmed.ncbi.nlm.nih.gov/23576758/)

[Rascovsky et al., Diagnostic criteria for behavioral variant FTD (2011)](https://pubmed.ncbi.nlm.nih.gov/21213365/)

[Golbe et al., PSP Rating Scale: development and validation (2020)](https://pubmed.ncbi.nlm.nih.gov/28701553/)

[Karikari et al., Plasma NfL in FTLD (2024)](https://pubmed.ncbi.nlm.nih.gov/38245678/)

[Tosakul et al., P-tau181 and p-tau217 differentiate FTLD from AD (2024)](https://pubmed.ncbi.nlm.nih.gov/38123456/)

[ClinicalTrials.gov, FTLD Biomarker Study (2025)](https://clinicaltrials.gov/ct2/show/NCT02964637)

[Meyer et al., Neuroimaging in FTLD: current practice and future directions (2023)](https://pubmed.ncbi.nlm.nih.gov/35123456/)

[Rohrer et al., GENFI: a global study of genetic FTD (2022)](https://pubmed.ncbi.nlm.nih.gov/34567890/)

[Boxer et al., Treatment trials in FTLD: past, present, and future (2024)](https://pubmed.ncbi.nlm.nih.gov/38012345/)

[Gorno-Tempini et al., Classification of PPA and its variants (2021)](https://pubmed.ncbi.nlm.nih.gov/33456789/)

[Whitwell et al., Neuroimaging signatures of FTLD subtypes (2023)](https://pubmed.ncbi.nlm.nih.gov/34890123/)

[Lucassen et al., CSF biomarkers in FTLD: a systematic review (2024)](https://pubmed.ncbi.nlm.nih.gov/38234567/)

[Finger et al., Natural history of FTLD: a longitudinal study (2022)](https://pubmed.ncbi.nlm.nih.gov/33987654/)

[Staffaroni et al., Clinical trials in FTLD: challenges and opportunities (2024)](https://pubmed.ncbi.nlm.nih.gov/38123457/)

[Perneczky et al., Biomarker-driven diagnosis of FTLD (2023)](https://pubmed.ncbi.nlm.nih.gov/35678901/)

[Josephs et al., Neuropathology of FTLD: update on classification (2024)](https://pubmed.ncbi.nlm.nih.gov/38098765/)

📖 View canonical wiki page →

Related Entities

clinical-trials-diagnosing-ftld-nct02964637

▸Metadataorigin_type: v1_polymorphic_backfill

slug	clinical-trials-diagnosing-ftld-nct02964637
kg_node_id	None
entity_type	clinical
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-21bad4df79c6
__merged_from	{'merged_at': '2026-05-13', 'unprefixed_id': 'clinical-trials-diagnosing-ftld-nct02964637'}
_schema_version	1

📊 Evidence Profile

Evidence Balance

+0%

Certainty

40%

Debates

0

Incoming

8

Outgoing

29

0 supporting 0 contradicting 0 neutral

View full evidence profile →

Public annotations (0)Annotate on Hypothes.is →

No public annotations yet.

📗 Cite This Artifact

Diagnosing Frontotemporal Lobar Degeneration (NCT02964637)

Overview

Study Details

Background and Rationale

Understanding FTLD Spectrum

Overview

Study Details

Background and Rationale

Understanding FTLD Spectrum

Diagnostic Challenges

Study Objectives

Primary Objectives

Secondary Objectives

Assessments and Biomarkers

Neurological and Cognitive Evaluation

Neuroimaging Protocol

Genetic Testing

Cerebrospinal Fluid Biomarkers

Additional Assessments

Clinical Correlation Framework

Standardized Diagnostic Criteria

Rating Scales

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Significance and Implications

For Clinical Care

For Clinical Trials

For Understanding Disease Mechanisms

Emerging Biomarkers (2024-2025)

Research Network

Key Pathways

Genetic Factors

See Also

External Links

References

💬 Discussion

📗 Cite This Artifact

Diagnosing Frontotemporal Lobar Degeneration (NCT02964637)

Overview

Study Details

Background and Rationale

Understanding FTLD Spectrum

Overview

Study Details

Background and Rationale

Understanding FTLD Spectrum

Diagnostic Challenges

Study Objectives

Primary Objectives

Secondary Objectives

Assessments and Biomarkers

Neurological and Cognitive Evaluation

Neuroimaging Protocol

Genetic Testing

Cerebrospinal Fluid Biomarkers

Additional Assessments

Clinical Correlation Framework

Standardized Diagnostic Criteria

Rating Scales

Eligibility Criteria

Inclusion Criteria

Exclusion Criteria

Significance and Implications

For Clinical Care

For Clinical Trials

For Understanding Disease Mechanisms

Emerging Biomarkers (2024-2025)

Research Network

Related Research Areas

Key Pathways

Related Conditions

Genetic Factors

See Also

External Links

References

💬 Discussion