Aphasia Clinical Trial
Official title:
PiB PET Scanning in Speech and Language Based Dementias
The study is designed to determine whether there are clinical features that can be used as biomarkers to predict whether underlying Alzheimer's pathology is the cause of a speech and language based dementia. The primary hypothesis is that the proportion of patients who test positive for beta-amyloid deposition will vary across different speech and language based dementias.
Speech and language based dementias (SLDs) (often referred to as primary progressive
aphasias or PPA) are neurodegenerative diseases in which speech or language impairments are
the most salient features of the disease and explain deficits in activities of daily living.
Patients with SLDs may have poor grammar, prominent anomia, comprehension deficits, speech
production and articulation problems, difficulty with repetition of words or sentences, word
finding pauses, or a combination of all these features. The SLDs can be further divided into
different subtypes. Up to 50% of patients with SLDs that go on to autopsy have shown
Alzheimer type pathology where beta-amyloid deposition is observed; the rest have pathology
consistent with frontotemporal lobar degeneration where beta-amyloid deposition is absent.
Future disease modifying treatments that target beta-amyloid will most likely differ from
treatments that do not target beta-amyloid. As a consequence, biomarkers are needed to
differentiate patients with SLDs with and without beta-amyloid deposition.
Little research has been done to identify biomarkers that could differentiate patients with
SLDs with and without beta-amyloid, mainly because the gold standard to identify the
presence of beta-amyloid has been pathological examination, which does not always occur, and
may not occur until more than 10 years after onset. The recent development of
[N-methyl-11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole also known as 11C Pittsburgh
Compound B or PiB is a solution to this problem since PiB allows the in vivo detection of
beta-amyloid. Unfortunately, PiB is very expensive.
The long term goal of our research is to develop a cost effective algorithmic approach to
the evaluation and diagnosis of patients presenting with SLDs. The objective of the studies
outlined in this proposal is to identify clinical, neuropsychological, or imaging biomarkers
that are readily available, relatively inexpensive, and non-invasive that will allow the
differentiation of patients with SLDs with and without beta-amyloid deposition. We will use
PiB as an indicator of beta-amyloid pathology. Our proposal is predicated upon our strong
preliminary data showing that clinical, neuropsychological and radiological features differ
between patients with SLDs with and without beta-amyloid deposition. Our central hypothesis
is that temporo-parietal lobe findings such as memory loss, visuospatial/perceptual
impairment, parietal lobe atrophy on magnetic resonance imaging (MRI), and parietal lobe
hypometabolism on [18-F]-fluoro-deoxy-glucose positron emission tomography (FDG-PET), will
be associated with beta-amyloid deposition (PiB positive status). On-the-other hand, frontal
lobe features, such as apraxia of speech and behavioral and executive dysfunction, as well
as extrapyramidal features such as Parkinsonism, will be associated with absence of
beta-amyloid deposition (PiB negative status). The rationale for examining these
clinical-imaging relationships is that successful predictions will provide a solid
scientific foundation for the ultimate development of a cost effective algorithm to guide
the diagnosis of SLDs.
Patients found to be eligible and willing to enroll in this study will be asked to undergo a
Neurologic Examination, a Speech Pathology Consultation, Neuropsychometric testing, an MRI
scan, an FDG PET scan and a PiB PET scan of the brain. This will be done over a period of
two days at the Mayo Clinic in Rochester, MN.
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Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
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