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June 26, 2013
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Syndromes dominated by apraxia of speech show distinct characteristics from agrammatic PPA

Keith A. Josephs, MD, MST, MSc, Joseph R. Duffy, PhD, Edythe A. Strand, PhD, Mary M. Machulda, PhD, Matthew L. Senjem, MS, Val J. Lowe, MD, Clifford R. Jack, Jr, MD, and Jennifer L. Whitwell, PhDAuthors Info & Affiliations
July 23, 2013 issue
81 (4) 337-345
https://doi.org/10.1212/WNL.0b013e31829c5ed5
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Abstract

Objective:

We assessed whether clinical and imaging features of subjects with apraxia of speech (AOS) more severe than aphasia (dominant AOS) are more similar to agrammatic primary progressive aphasia (agPPA) or to primary progressive AOS (PPAOS).

Methods:

Sixty-seven subjects (PPAOS = 18, dominant AOS = 10, agPPA = 9, age-matched controls = 30) who all had volumetric MRI, diffusion tensor imaging, F18-fluorodeoxyglucose and C11-labeled Pittsburgh compound B (PiB)-PET scanning, as well as neurologic and speech and language assessments, were included in this case-control study. AOS was classified as either type 1, predominated by sound distortions and distorted sound substitutions, or type 2, predominated by syllabically segmented prosodic speech patterns.

Results:

The dominant AOS subjects most often had AOS type 2, similar to PPAOS. In contrast, agPPA subjects most often had type 1 (p = 0.01). Both dominant AOS and PPAOS showed focal imaging abnormalities in premotor cortex, whereas agPPA showed widespread involvement affecting premotor, prefrontal, temporal and parietal lobes, caudate, and insula. Only the dominant AOS and PPAOS groups showed midbrain atrophy compared with controls. No differences were observed in PiB binding across all 3 groups, with the majority being PiB negative.

Conclusion:

These results suggest that dominant AOS is more similar to PPAOS than agPPA, with dominant AOS and PPAOS exhibiting a clinically distinguishable subtype of progressive AOS compared with agPPA.

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Supplementary Material

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Information & Authors

Information

Published In

Neurology®
Volume 81 • Number 4 • July 23, 2013
Pages: 337-345
PubMed: 23803320

Copyright

© 2013 American Academy of Neurology.

Publication History

Received: February 3, 2013
Accepted: April 5, 2013
Published online: June 26, 2013
Published in print: July 23, 2013

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Disclosure

K. Josephs receives research support from the NIH (NIDCD and NIA) and the Dana Foundation. J. Duffy, E. Strand, and M. Machulda receive research support from the NIH (NIDCD). M. Senjem has no disclosures. V. Lowe serves as a consultant for Bayer Schering Pharma and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, the NIH (NIA, NCI), the MN Partnership for Biotechnology and Medical Genomics, and the Leukemia & Lymphoma Society. C. Jack serves as a consultant for Janssen, Bristol-Myers Squibb, General Electric, Siemens, and Johnson & Johnson and is involved in clinical trials sponsored by Allon and Baxter, Inc. He receives research funding from the NIH and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Foundation. J. Whitwell receives research support from the NIH (NIDCD and NIA) and the Dana Foundation, and has served as a consultant for Bristol-Myers Squibb. Go to Neurology.org for full disclosures.

Study Funding

Supported by NIH grant R01-DC010367.

Authors

Affiliations & Disclosures

Keith A. Josephs, MD, MST, MSc
From the Departments of Neurology (Behavioral Neurology [K.A.J.], Movement Disorders [K.A.J.], and Speech Pathology [J.R.D., E.A.S.]), Psychiatry and Psychology (Neuropsychology [M.M.M.]), Information Technology (M.L.S.), and Radiology (Neuroradiology [C.R.J., J.L.W.] and Nuclear Medicine [V.J.L.]), Mayo Clinic, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH/NIDCD (R01-DC010367), PI NIH/NIA (R01-AG037491), PI NIH/NIA (R21-AG38736), Co-I
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
The DANA Foundation - PI The Alzheimer's Association
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Joseph R. Duffy, PhD
From the Departments of Neurology (Behavioral Neurology [K.A.J.], Movement Disorders [K.A.J.], and Speech Pathology [J.R.D., E.A.S.]), Psychiatry and Psychology (Neuropsychology [M.M.M.]), Information Technology (M.L.S.), and Radiology (Neuroradiology [C.R.J., J.L.W.] and Nuclear Medicine [V.J.L.]), Mayo Clinic, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
South Dakota Speech-Language-Hearing Association, non- profit, cash honorarium, Full day presentation, Sioux Falls, SD, September 23, 2011. Canadian Speech-language-hearing Association. Non profit. Cash honorarium. Two day workshopwo-day workshop presented, Deer Lodge Centre, Winnipeg, Canada, October 21-22, 2011. Clear Speech (commercial entity). Cash honorarium, Three two-day workshops, Albury, Sydney, and Brisbane Australia, September, 2012. Vancouver General Hospital. Non profit. Cash honorarium. Two-day workshop, Vancouver, Canada, November 2-3, 2012. Alabama Speech-Language-Hearing Association. Non porfit. Cash honorarium. One-day workshop, Birmingham, AL, March 8, 2013.
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
1. Duffy, J.R. Motor Speech Disorders: Substrates, Differential Diagnosis, and Management (2nd and 3rd Edition St. Louis: Elsevier (2013). Royalties
Employment, Commercial Entity:
1.
Mayo Clinic, Consultant and Professor, Speech Pathology, Dept. of Neurology
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH (NIDCD), RO1 DC010367, co-investigator (5%), 2008- present.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Edythe A. Strand, PhD
From the Departments of Neurology (Behavioral Neurology [K.A.J.], Movement Disorders [K.A.J.], and Speech Pathology [J.R.D., E.A.S.]), Psychiatry and Psychology (Neuropsychology [M.M.M.]), Information Technology (M.L.S.), and Radiology (Neuroradiology [C.R.J., J.L.W.] and Nuclear Medicine [V.J.L.]), Mayo Clinic, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
1. Yorkston KM, Miller R, Strand E. Management of Speech and Swallowing in Degenerative Neurologic Disease. Tucson: Communication Skill Builders; 1995; 3rd Edition, 2013; (Book) 2. Caruso A, Strand EA. Clinical Management of Motor Speech Disorders of Children. New York: Thieme Publishing Co.; 1999. (Book) 3. Yorkston KM, Beukelman D, Strand E, Bell K. Clinical Management of Motor Speech Disorders. Boston: Little, Brown & Co.; 2cd. Edition, 1999; 3rd edition, 2010; (Book)
Employment, Commercial Entity:
1.
Consultant in Speech Pathology, Department of Neurology, Mayo Clinic Associate Professor, Mayo College of Medicine (1999- present)
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) NIH/NIDCD R01 DC000496-24; Role: Co-Investigator 5/1/08–4/30/13 Developmental Phonological Disorders (2) NIH/NIDCD R01 DC 10367 Role: Co-Investigator 02/2010 - 01/2015 PIB PET Scanning in Speech and Language Based Dementias.
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Mary M. Machulda, PhD
From the Departments of Neurology (Behavioral Neurology [K.A.J.], Movement Disorders [K.A.J.], and Speech Pathology [J.R.D., E.A.S.]), Psychiatry and Psychology (Neuropsychology [M.M.M.]), Information Technology (M.L.S.), and Radiology (Neuroradiology [C.R.J., J.L.W.] and Nuclear Medicine [V.J.L.]), Mayo Clinic, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) National Institutes of Health; R01 DC 010367; Co- investigator
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Matthew L. Senjem, MS
From the Departments of Neurology (Behavioral Neurology [K.A.J.], Movement Disorders [K.A.J.], and Speech Pathology [J.R.D., E.A.S.]), Psychiatry and Psychology (Neuropsychology [M.M.M.]), Information Technology (M.L.S.), and Radiology (Neuroradiology [C.R.J., J.L.W.] and Nuclear Medicine [V.J.L.]), Mayo Clinic, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Val J. Lowe, MD
From the Departments of Neurology (Behavioral Neurology [K.A.J.], Movement Disorders [K.A.J.], and Speech Pathology [J.R.D., E.A.S.]), Psychiatry and Psychology (Neuropsychology [M.M.M.]), Information Technology (M.L.S.), and Radiology (Neuroradiology [C.R.J., J.L.W.] and Nuclear Medicine [V.J.L.]), Mayo Clinic, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
(1) Bayer Pharmaceuticals
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
(1) GE Health Care (2) Siemens Molecular Imaging (3) AVID Radiopharmaceuticals
Research Support, Government Entities:
1.
(1) NIA R01 DC010367-01, CoI, 12/01/09-11/30/14 (2) NIA P50 AG016574-12, Co-PI Project #1, 05/01/09- 04/30/14 (3) NIA R01 AG011378-16, CoI, 06/01/08-05/31/13 (4) NCI R01 CA136526-02, CoI, 01/01/09-11/30/14 (5) P30 CA015083-35, Program Director, 07/01/09- 06/30/12 (6) P50 CA102701-07, CoI, 09/01/08-08/31/13 (7) R01 CA125614-04, CoI,09/26/06-07/31/11 (8)R21 CA123909-02, CoI, 07/01/07-08/01/12
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1)MN Partnership for Biotechnology and Medical Genomics, PI, 01/01/09- 12/31/13
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Clifford R. Jack, Jr, MD
From the Departments of Neurology (Behavioral Neurology [K.A.J.], Movement Disorders [K.A.J.], and Speech Pathology [J.R.D., E.A.S.]), Psychiatry and Psychology (Neuropsychology [M.M.M.]), Information Technology (M.L.S.), and Radiology (Neuroradiology [C.R.J., J.L.W.] and Nuclear Medicine [V.J.L.]), Mayo Clinic, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
scientific advisory panels: Siemens
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
Investigator in clinical trials sponsored by Baxter and Allon
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
Allon and Baxter, perform MRI related services for clinical trial
Research Support, Government Entities:
1.
RO1 AG011378 PI; U01 AG024904-01 co-I; RO1 AG37551 co-I; 1U01HL096917 co-I; U01 AG032438 co-I; RO1 AG041851-01 co- PI Stock/Stock Options, Medical Equipment & Materials: Johnson and Johnson, 2010
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
View all articles by this author
Jennifer L. Whitwell, PhD
From the Departments of Neurology (Behavioral Neurology [K.A.J.], Movement Disorders [K.A.J.], and Speech Pathology [J.R.D., E.A.S.]), Psychiatry and Psychology (Neuropsychology [M.M.M.]), Information Technology (M.L.S.), and Radiology (Neuroradiology [C.R.J., J.L.W.] and Nuclear Medicine [V.J.L.]), Mayo Clinic, Rochester, MN.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
Bristol Myers Squibb
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
Research support from NIH R21-AG38736 (PI), NIH R01- DC010367 (Co-I) and NIH R01-AG037491 (Co-I)
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
Research support from Dana Foundation (Co-I) 2009-2012 and the Alzheimer's Association (PI)
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
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Notes

Correspondence to Dr. Josephs: [email protected]
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

Author Contributions

Dr. Josephs: drafting/revising the manuscript for content, study concept or design, analysis or interpretation of the data, acquisition of data, statistical analysis, study supervision, obtaining funding. Dr. Duffy and Dr. Strand: drafting/revising the manuscript for content, study concept or design, analysis or interpretation of the data, acquisition of data. Dr. Machulda: drafting/revising the manuscript for content, analysis or interpretation of the data, acquisition of data. Dr. Senjem, Dr. Lowe, and Dr. Jack: drafting/revising the manuscript for content, acquisition of data. Dr. Whitwell: drafting/revising the manuscript for content, study concept or design, analysis or interpretation of the data, acquisition of data.

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