In this project, we will combine cohorts from several countries into a comprehensive retrospective discovery cohort to examine theabove-mentioned markers focusing on sporadic cases and PPD, in addition to a large number ofpathologically confirmed…
ID
Source
Brief title
Condition
- Congenital and hereditary disorders NEC
- Neurological disorders NEC
- Psychiatric and behavioural symptoms NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Our goal is to provide an early, accurate diagnosis and a prognosis to patients
presenting with
adult onset behavioral changes between 45 and 75 years by:
1. Creating a diagnostic algorithm to differentiate between bvFTD and
late-onset PPD, using
clinical features including social cognition, neuroimaging patterns, genetic
and peripheral neuronal
markers.
2. Creating a prognostic algorithm for bvFTD and late-onset PPD using clinical
features including
social cognition, neuroimaging patterns, genetic and peripheral neuronal
markers.
3. Differentiating between the main FTD pathological subgroups (FTLD-tau and
FTLD-TDP) based
on biologically derived materials including neuron-derived exosomes and
cell-free DNA
Secondary outcome
- enable future patient stratification, trial design and personalized
treatments.
- Creation of animation movie and online precision medicine tool
- Usage of the animation movie and the online tool as communicaton tool to
stakeholders
Background summary
The behavioural variant of frontotemporal dementia (bvFTD) is a common cause of
early-onset
dementia with heterogeneity in underlying pathology, genetics, and natural
course, demanding a
customized approach to predict individual prognosis and develop personalized
treatments.
BvFTD is often mistaken for a primary psychiatric disorder (PPD), causing
substantial diagnostic
delay of up to 6 years on average. Unlike with Alzheimer*s disease, reliable in
vivo biomarkers
for FTD are not available yet. Recent research attention has been on genetic
FTD (now known
to differ pathologically and often clinically); however, the critical challenge
is how to diagnose
non-familial forms of bvFTD (which accounts for 80% of all cases) early in the
disease course
and therefore distinguish it from late-onset psychiatric disorders that may
mimic bvFTD, in order
to deliver relevant interventions and treatments. The creation of a diagnostic
and prognostic
model of sporadic bvFTD is highly needed and crucial to enable performing
precision medicine..
We selected the most promising results of our ongoing research, including
neuropsychological
and social cognitive markers; neuroimaging- based classifiers; serum
neurofilaments, plasma
neuronal derived exosome signatures, and cell free DNA. Our project will
contribute towards an early and accurate
bvFTD identification, that is crucial for trial enrolment, whereas early PPD
identification will lead
to the appropriate psychiatric treatments.
Study objective
In this project, we will combine cohorts from several countries into a
comprehensive retrospective discovery cohort to examine the
above-mentioned markers focusing on sporadic cases and PPD, in addition to a
large number of
pathologically confirmed bvFTD and PPD cases. We will further collect a deeply
phenotyped
prospective multi-national cohort to validate these markers, in addition to
collecting postmortem
cases of clinically less well-defined bvFTD / PPD cases. We will use
statistical modeling to
create the best diagnostic and prognostic model for non-familial forms of bvFTD
and PPD. As a
subgoal we aim to determine underlying FTD pathology within the sporadic bvFTD
group, to
enable eventual patient stratification.
Study design
Retrospective and prospective cohort study
Study burden and risks
The extra MRI and blood withdrawl are normally part of standard care.
Therefore, there is enough experience to follow standard protocol to decrease
the risk and burden to a minimum. The tests and questionnaires from the
DIPPA-FTD Test battery are already part of neurological and psychiatric
diagnostic care and science. The combination of these tests is new however.
With this combination, we will create a specific questionnaire to distinguish
late onset psychiatry from FTD. It is possible the primary caregiver will be
asked to complete a few of the DIPPA-FTD Test Battery questionnaires about the
patient. The patient will give informed consent approval. The primary caregiver
will be asked informed consent on a separate form.
De Boelelaan 1117
Amsterdam 1081HV
NL
De Boelelaan 1117
Amsterdam 1081HV
NL
Listed location countries
Age
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
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL72988.029.20 |