In our own recent studies we found indications of the existence of particular executive functioning deficits as well as memory impairments following different regimens of cytotoxic agents. Together with the indication from our animal study of a…
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Brief title
Condition
- Cognitive and attention disorders and disturbances
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
MR scanning will be performed using a Philips Intera 3.0 Tesla scanner with an
eight channel Sense head coil.
MRI imaging parameters:
1. 3-dimensional T1-weighted sequences followed by (automated) volumetric
measurement, as a gross marker for tissue loss.
2. FLAIR sequence to determine presence and extent of demyelation.
3. MR Spectroscopy allows the safe in vivo measurement of brain neurochemistry.
Compounds that can be identified are N-acetylaspartate (NAA), choline (Cho) and
myo-inositol (MI). NAA is contained almost exclusively within neurons and is
considered a neuronal marker for neuronal density and viability. MI reflects
glial content.
4. Diffusion Tensor Imaging (DTI) will be used to study the (density of) fibers
subserving well-defined functional networks and as such provide an index of
damage in the normal appearing white matter. The outcome measures will be used
to study correlations with specific functional deficits.
5. Functional MRI: EPI sequence, 35 slices/3.0 mm, TR * 2.0 s, axial sequential
acquisition: We will use the following well-studied paradigms measuring
executive functioning and memory to investigate changes in the blood oxygen
level dependent (BOLD) response, reflecting neural activity. Tower of London
Task: A task widely used to investigate executive/planning processes and known
to robustly activate dorsolateral prefrontal cortex. The Flanker task (20):
Previous studies from our group consistently show impaired performance on this
task by patients treated with chemotherapy. It provides a means for examining
interference control processes. Activation of the anterior cingulate cortex
(viewed as a central component of the neural circuit for action monitoring) is
reliably observed during this task. Paired associates task, measured both at
encoding and retrieval. This memory paradigm has demonstrated to reliably
activate medial temporal lobe (e.g., hippocampus).
Secondary outcome
In addition to the tests that are administrated while MRI scans are being
acquired, the patients will also be tested with a neuropsychological
examination after the scanning procedure. This examination will consist of the
following classical neuropsychological tests, that were also included in the
previous neuropsychological examinations conducted at the NKI-AvL: California
Verbal Learning test, Stroop color-word naming, Trail making, Verbal Fluency,
Digit symbol (WAIS), Wechsler memory scale (visual memory). These tests are
included to obtain information on the current cognitive status of the
participants.
The following data will be collected for all participants: Age, educational
status, smoking habits, alcohol intake, body mass index, age at menopause (if
appropriate) and type of menopause (natural or artificial), use of hormone
replacement therapy, psychological distress, self-reported cognitive problems,
self-reported medical history and medication use.
For the breast cancer patients previously treated with chemotherapy the
following additional information will be obtained through the medical records:
kind of cytotoxic treatment, radiotherapy yes/no, endocrine therapy yes/no.
Background summary
There is increasing interest in cognitive deficits after chemotherapy. In
several neuropsychological studies in breast cancer patients treated with
chemotherapy we and others found impairment in cognitive functioning. In a
series of neurophysiological studies we also found abnormalities in brain
functioning in this patient population. A recent study by our group showed,
furthermore, converging evidence for neurocognitive problems from
neuropsychological, neurophysiological as well as self-report measures up to
five years after cessation of treatment with chemotherapeutics. In addition,
our animal studies demonstrate long lasting dose-dependent decreases in cell
proliferation in the hippocampal formation in rats following single intravenous
administration of methotrexate, one of the frequently used cytotoxic agents.
Despite these indications of long-lasting effects on the central nervous system
resulting in persistent cognitive dysfunction, our understanding of the nature
of cognitive impairment and the mechanism(s) driving this compromise is
fragmentary at best.
Study objective
In our own recent studies we found indications of the existence of particular
executive functioning deficits as well as memory impairments following
different regimens of cytotoxic agents. Together with the indication from our
animal study of a potential contributory role of reduced neurogenesis in the
pathogenesis of the observed cognitive impairment and the availability of new
and advanced MR techniques, compelling arguments are provided to initiate a
study aiming:
1.To delineate a more specific neurotoxicity profile by studying brain activity
with functional MRI during performance on tasks that are specifically sensitive
to executive functioning and memory
2.To investigate anatomical changes in order to clarify underlying mechanism(s)
by performing structural and chemical MR imaging
We will, in addition, examine whether there are indications that the pattern of
abnormalities is modulated by type of cytotoxic regimen.
With the help of brain structural and functional morphology indices our
understanding will be enhanced of the specific influence of cytotoxic agents on
brain functioning, its consequences and its underlying mechanism.
Study design
This one-year project is a joint venture of the department of Psychosocial
Research and Epidemiology of the NKI-AVL and the departments of Radiology and
Psychiatrics of the Academic Medical Center.
The study consists of two parts:
1) cross-sectional design
2) prospective design
Study burden and risks
Patients will be tested once (cross-sectional part) or twice (prospective
part). Each test assessment will last two hours and consists of a
semi-structured interview, several questionnaires, a practice session, and an
MRI scanning session of one hour and 15 minutes. Half of the scanning time, the
patient is actively engaged in task performance. The other half of the time, MR
sequences are acquired for which no active involvement of the patient is
required.
The patient has to lie still in the scanner which is sometimes considered
inconvenient. Moreover, the scanner produces noise, which is effectively
reduced by the use of earplugs and headphones. When standard safety rules are
applied (no ferromagnetic objects inside the scanner room) no risks exist for
the patient. Ample experience with patient populations have indicated that this
procedure is feasible and is not considered too burdensome.
Plesmanlaan 121
1066 CX Amsterdam
Nederland
Plesmanlaan 121
1066 CX Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
all groups:
-female
-sufficient proficiency in the Dutch language;cross-sectional part:
-participation in previous neuropsychological study
-having been treated with high-dose chemotherapy (CTC);prospective part, experimental group
-newly diagnosed breast cancer patients without distant metastases that will receive chemotherapy (ACdd + T);prospective part, control group
-newly diagnosed breast cancer patients without distant metastases that will not receive chemotherapy
Exclusion criteria
-relapse and/or metastases
-excessive use of alcohol or drugs
-use of psychotropic medication
-neurologic or psychiatric disorders that may influence cognitive functioning
-conditions that preclude MRI examination
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 | NL17835.031.07 |