Speech and language based dementias (SLDs) (often referred to as primary progressive aphasias) are neurodegenerative diseases in which speech and language impairments are the most salient features of the disease and explain deficits in activities of daily living. These dementias may or may not be associated with the deposition of the protein beta-amyloid in the brain, which until recently could only be determined at postmortem. Since new treatments will likely target underlying abnormal proteins, accurate prediction of the pathology underlying the SLDs is critical. The recent development of amyloid imaging compounds now allows the in vivo detection of beta-amyloid in the brain. Unfortunately, amyloid imaging compounds are expensive and are not accessible to most medical centers throughout the United States. The objectives of the studies outlined in this proposal are to identify clinical, neuropsychological or non-amyloid imaging biomarkers that are readily available, relatively inexpensive, and non-invasive, that will allow the prediction of beta-amyloid in the brain in patients with SLDs. To accomplish this goal we will be using the amyloid imaging compound 11C Pittsburgh Compound B (PiB) as the gold standard for the detection of beta-amyloid. The methods will include detailed neurological, speech and language and neuropsychological assessments, magnetic resonance imaging, and [18-F]-fluoro-deoxy-glucose (FDG) and PiB PET scanning. Associations between PiB positive scanning and these techniques will be sought. One of the most salient features of the speech and language assessments will be the determination of the presence and severity of apraxia of speech and its association with beta-amyloid deposition. This study will be carried out at the Mayo Clinic in Rochester, MN, which evaluates a large number of patients with SLDs annually. The study also intends to recruit minorities with SLDs which are currently understudied. The methods will be performed by a team of world renowned scientists including dementia, movement disorders and speech pathology specialists, radiology researchers, a nuclear medicine scientist, neuropsychologists, and biostatisticians. The long term goal of our research is to develop a cost effective algorithmic approach to the evaluation and diagnosis of patients with SLDs.
This study will identify ways to determine whether Alzheimer's disease is the underlying cause of a patient's progressive speech and language problem. In addition, the study aims to identify the most cost effective way to do this so that more patients, including minorities, can be given an accurate diagnosis. Results from this grant will ultimately lead to better targeted future treatments for patients with problems with speech and language.
|Flanagan, Eoin P; Duffy, Joseph R; Whitwell, Jennifer L et al. (2016) Mixed tau and TDP-43 pathology in a patient with unclassifiable primary progressive aphasia. Neurocase 22:55-9|
|Josephs, Keith A; Whitwell, Jennifer L; Tacik, Pawel et al. (2016) [18F]AV-1451 tau-PET uptake does correlate with quantitatively measured 4R-tau burden in autopsy-confirmed corticobasal degeneration. Acta Neuropathol 132:931-933|
|Whitwell, Jennifer L; Weigand, Stephen D; Duffy, Joseph R et al. (2016) Clinical and MRI models predicting amyloid deposition in progressive aphasia and apraxia of speech. Neuroimage Clin 11:90-8|
|Lowe, Val J; Curran, Geoffry; Fang, Ping et al. (2016) An autoradiographic evaluation of AV-1451 Tau PET in dementia. Acta Neuropathol Commun 4:58|
|Whitwell, Jennifer L; Duffy, Joseph R; Machulda, Mary M et al. (2016) Tracking the development of agrammatic aphasia: A tensor-based morphometry study. Cortex :|
|Madhavan, Ajay; Schwarz, Christopher G; Duffy, Joseph R et al. (2016) Characterizing White Matter Tract Degeneration in Syndromic Variants of Alzheimer's Disease: A Diffusion Tensor Imaging Study. J Alzheimers Dis 49:633-43|
|Jung, Y; Whitwell, J L; Duffy, J R et al. (2016) Regional Î²-amyloid burden does not correlate with cognitive or language deficits in Alzheimer's disease presenting as aphasia. Eur J Neurol 23:313-9|
|Tacik, Pawel; DeTure, Michael; Lin, Wen-Lang et al. (2015) A novel tau mutation, p.K317N, causes globular glial tauopathy. Acta Neuropathol 130:199-214|
|Duffy, Joseph R; Strand, Edythe A; Clark, Heather et al. (2015) Primary progressive apraxia of speech: clinical features and acoustic and neurologic correlates. Am J Speech Lang Pathol 24:88-100|
|Botha, Hugo; Duffy, Joseph R; Whitwell, Jennifer L et al. (2015) Classification and clinicoradiologic features of primary progressive aphasia (PPA) and apraxia of speech. Cortex 69:220-36|
Showing the most recent 10 out of 71 publications