DIagnostic and prognostic precision (Algorithm) medicine for behavioral variant frontotemporal dementia

Recruiting

• Conditions: Behavioural variant of Frontotemporal dementia; bvFTD and Primary Psychiatric disorders; 10027664; 10029305; 10037173

• Registration Number: NL-OMON55267
• Lead Sponsor: Vrije Universiteit Medisch Centrum

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 150

Inclusion Criteria

In order to be eligible to participate in this study, a subject must meet all
of the following criteria:

1. Retrospective cases
- possible and probable behavioural variant of Frontotemporal dementia (bvFTD)
patients (meeting criteria of Rascovsky et al, 2011) or definite non
familial/sporadic bvFTD cases .
- late-onset Primary Psychiatric cases (onset after 45 years);including Major
depressive disorder, single/ recurrent/ persistent (ICD 10 F32, 33, 34),
Bipolar disorder (ICD 10 F 31), Manic episode (ICD 10 F30), Schizophrenia,
schizotypical disorder (ICD 10: F20, F21), Delusional disorder (ICD 10: F22),
Schizoaffective disorder (ICD 10: F25) and Obsessive-compulsive disorder (ICD
10: 42) according to the DSM5 criteria. .

All above mentioned patients have undergone thorough clinical work-up,
according to the respective national protocols, including neuropsychiatric
examination, neuropsychological exam, MRI of the brain, DNA, and blood
sampling. Follow-up duration was at least one year, and a substantial
proportion had a follow-up duration of two years or more.

2. Prospective clinical cohort.
We will enroll new cases with:
- possible and probable bvFTD (meeting criteria of Rascovsky et al, 2011)
- ambiguous cases (suspect of bvFTD, but not completely fulfilling criteria).
- late-onset PPD diagnosis; including Major depressive disorder, single/
recurrent/ persistent (ICD 10 F32, 33, 34), Bipolar disorder (ICD 10 F 31),
Manic episode (ICD 10 F30), Schizophrenia, schizotypical disorder (ICD 10: F20,
F21), Delusional disorder (ICD 10: F22), Schizoaffective disorder (ICD 10: F25)
and Obsessive-compulsive disorder (ICD 10: 42) according to the DSM5 criteria.

All cases will be kept in follow-up and will have repeated clinical
examinations, plasma sampling and MRI of the brain at baseline and after 1
year.

3. Pathologically verified cohort.
Dutch and Australian subjects are invited into brain donation programs.
In addition, we include pathologically verified patient cohort of
FTD and PPD cases from the Netherlands and Australian Brain Banks (The
Netherlands: FTLDtau, n=40; FTLD-TDP, n=54; schizophrenia n=13; bipolar
disorder n=34; depression, n=40; Australia: FTLD-tau, n=112; FTLD-TDP, n=42;
schizophrenia plus matched controls, n=37; depression plus matched controls,
n=10). During the course of our project, we will keep collecting donated
brains from subjects with FTD, PPD, and ambiguous cases.

Exclusion Criteria

- Mini-mental State Exam score (MMSE) no more than 18
- Traumatic brain injury
- Drugs or alcohol abuse
- Lack of reliable informant
- Familial form of bvFTD, defined as genetic or familial bvFTD
- Patient declined genetic testing offered as part of standard clinical
practise

Study & Design

• Study Type: Observational invasive
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Our goal is to provide an early, accurate diagnosis and a prognosis to patients<br /><br>presenting with<br /><br>adult onset behavioral changes between 45 and 75 years by:<br /><br><br /><br>1. Creating a diagnostic algorithm to differentiate between bvFTD and<br /><br>late-onset PPD, using<br /><br>clinical features including social cognition, neuroimaging patterns, genetic<br /><br>and peripheral neuronal<br /><br>markers.<br /><br>2. Creating a prognostic algorithm for bvFTD and late-onset PPD using clinical<br /><br>features including<br /><br>social cognition, neuroimaging patterns, genetic and peripheral neuronal<br /><br>markers.<br /><br>3. Differentiating between the main FTD pathological subgroups (FTLD-tau and<br /><br>FTLD-TDP) based<br /><br>on biologically derived materials including neuron-derived exosomes and<br /><br>cell-free DNA</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- enable future patient stratification, trial design and personalized<br /><br>treatments.<br /><br>- Creation of animation movie and online precision medicine tool<br /><br>- Usage of the animation movie and the online tool as communicaton tool to<br /><br>stakeholders</p><br>