Regional atrophy associated with cognitive and motor function in prodromal Huntington disease.

Elizabeth H Aylward; Deborah L Harrington; James A Mills; Peggy C Nopoulos; Jeffrey D Long; Dawei Liu; Holly K Westervelt; Jane S Paulsen; Stephen Cross; Patricia Ryan; Eric A Epping; Edmund Chiu; Joy Preston; Anita Goh; Stephanie Antonopoulos; Samantha Loi; Lynn Raymond; Joji Decolongon; Mannie Fan; Allison Coleman; William M Mallonee; Greg Suter; Christopher A Ross; Mark Varvaris; Nadine Yoritomo; Elizabeth McCusker; Jane Griffith; Clement Loy; David Gunn; Mark Guttman; Alanna Sheinberg; Albie Law; Kimberly Quaid; Melissa Wesson; Joanne Wojcieszek; Joel Perlmutter; Stacey Barton; Shineeka Smith; Roger A Barker; Sarah Mason; Natalie Valle Guzman; Susan Perlman; Brian Clemente; Randi Jones; Cathy Wood-Siverio; Stewart A Factor; Ali Samii; Alma Macaraeg; Peter Panegyres; Joseph Lee; Maria Tedesco; Brenton Maxwell; Rajeev Kumar; Diane Erickson; Breanna Nickels; Frederick Marshall; Amy Chesire; Mary Wodarski; Charlyne Hickey; Michael D Geschwind; Sharon Sha; Gabriela Satris; Anwar Ahmed; Christine Reece; Alex Bura; Lyla Mourany; Jagan Pallai; Pietro Mazzoni; Karen Marder; Paula Wasserman; David Craufurd; Judith Bek; Elizabeth Howard; Tom Warner; Maggie Burrows; Michael Orth; Sigurd Süssmuth; Katrin Barth; Sonja Trautmann; Daniela Schwenk; Carolin Eschenbach; Vicki Wheelock; Lisa Kjer; Amanda Martin; Sarah Farias; Zosia Miedzybrodzka; Daniela Rae; Mariella D'Alessandro; Oksana Suchowersky; Phyllis Chua; Angela Komiti; Diana Rosas; Anne Rosser; Kathy Price; Sarah Hunt; Joseph Jankovic; William Ondo; Wayne Martin; Pamela King; Marguerite Wieler; Satwinder Sran; Martha Nance; Justo Garcia De Yebenes; Richard Dubinsky

doi:10.3233/JHD-130076

Regional atrophy associated with cognitive and motor function in prodromal Huntington disease.

Elizabeth H Aylward, Deborah L Harrington, James A Mills, Peggy C Nopoulos, Jeffrey D Long, Dawei Liu, Holly K Westervelt, Jane S Paulsen, Stephen Cross (Collaborator), Patricia Ryan (Collaborator), Eric A Epping (Collaborator), Edmund Chiu (Collaborator), Joy Preston (Collaborator), Anita Goh (Collaborator), Stephanie Antonopoulos (Collaborator), Samantha Loi (Collaborator), Lynn Raymond (Collaborator), Joji Decolongon (Collaborator), Mannie Fan (Collaborator), Allison Coleman (Collaborator)William M Mallonee (Collaborator), Greg Suter (Collaborator), Christopher A Ross (Collaborator), Mark Varvaris (Collaborator), Nadine Yoritomo (Collaborator), Elizabeth McCusker (Collaborator), Jane Griffith (Collaborator), Clement Loy (Collaborator), David Gunn (Collaborator), Mark Guttman (Collaborator), Alanna Sheinberg (Collaborator), Albie Law (Collaborator), Kimberly Quaid (Collaborator), Melissa Wesson (Collaborator), Joanne Wojcieszek (Collaborator), Joel Perlmutter (Collaborator), Stacey Barton (Collaborator), Shineeka Smith (Collaborator), Roger A Barker (Collaborator), Sarah Mason (Collaborator), Natalie Valle Guzman (Collaborator), Susan Perlman (Collaborator), Brian Clemente (Collaborator), Randi Jones (Collaborator), Cathy Wood-Siverio (Collaborator), Stewart A Factor (Collaborator), Ali Samii (Collaborator), Alma Macaraeg (Collaborator), Peter Panegyres (Collaborator), Joseph Lee (Collaborator), Maria Tedesco (Collaborator), Brenton Maxwell (Collaborator), Rajeev Kumar (Collaborator), Diane Erickson (Collaborator), Breanna Nickels (Collaborator), Frederick Marshall (Collaborator), Amy Chesire (Collaborator), Mary Wodarski (Collaborator), Charlyne Hickey (Collaborator), Michael D Geschwind (Collaborator), Sharon Sha (Collaborator), Gabriela Satris (Collaborator), Anwar Ahmed (Collaborator), Christine Reece (Collaborator), Alex Bura (Collaborator), Lyla Mourany (Collaborator), Jagan Pallai (Collaborator), Pietro Mazzoni (Collaborator), Karen Marder (Collaborator), Paula Wasserman (Collaborator), David Craufurd (Collaborator), Judith Bek (Collaborator), Elizabeth Howard (Collaborator), Tom Warner (Collaborator), Maggie Burrows (Collaborator), Michael Orth (Collaborator), Sigurd Süssmuth (Collaborator), Katrin Barth (Collaborator), Sonja Trautmann (Collaborator), Daniela Schwenk (Collaborator), Carolin Eschenbach (Collaborator), Vicki Wheelock (Collaborator), Lisa Kjer (Collaborator), Amanda Martin (Collaborator), Sarah Farias (Collaborator), Zosia Miedzybrodzka (Collaborator), Daniela Rae (Collaborator), Mariella D'Alessandro (Collaborator), Oksana Suchowersky (Collaborator), Phyllis Chua (Collaborator), Angela Komiti (Collaborator), Diana Rosas (Collaborator), Anne Rosser (Collaborator), Kathy Price (Collaborator), Sarah Hunt (Collaborator), Joseph Jankovic (Collaborator), William Ondo (Collaborator), Wayne Martin (Collaborator), Pamela King (Collaborator), Marguerite Wieler (Collaborator), Satwinder Sran (Collaborator), Martha Nance (Collaborator), Justo Garcia De Yebenes (Collaborator), Richard Dubinsky (Collaborator)

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: Neuroimaging studies suggest that volumetric MRI measures of specific brain structures may serve as excellent biomarkers in future clinical trials of Huntington disease (HD). OBJECTIVE: Demonstration of the clinical significance of these measures is an important step in determining their appropriateness as potential outcome measures. METHODS: Measures of gray- and white-matter lobular volumes and subcortical volumes (caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus) were obtained from MRI scans of 516 individuals who tested positive for the HD gene expansion, but were not yet exhibiting signs or symptoms severe enough to warrant diagnosis ("pre-HD"). MRI volumes (corrected for intracranial volume) were correlated with cognitive, motor, psychiatric, and functional measures known to be sensitive to subtle changes in pre-HD. RESULTS: Caudate, putamen, and globus pallidus volumes consistently correlated with cognitive and motor, but not psychiatric or functional measures in pre-HD. Volumes of white matter, nucleus accumbens, and thalamus, but not cortical gray matter, also correlated with some of the motor and cognitive measures. CONCLUSIONS: Results of regression analyses suggest that volumes of basal ganglia structures contributed more highly to the prediction of most motor and cognitive variables than volumes of other brain regions. These results support the use of volumetric measures, especially of the basal ganglia, as outcome measures in future clinical trials in pre-HD. Results may also assist investigators in selecting the most appropriate measures for treatment trials that target specific clinical features or regions of neuropathology.

Original language	English
Journal	Journal of Huntington's disease
Volume	2
Issue number	4
DOIs	https://doi.org/10.3233/JHD-130076
Publication status	Published - 2013

Keywords

Huntington disease
cognitive
magnetic resonance imaging
motor
psychiatric

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10.3233/JHD-130076

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Aylward, E. H., Harrington, D. L., Mills, J. A., Nopoulos, P. C., Long, J. D., Liu, D., Westervelt, H. K., Paulsen, J. S., Cross, S., Ryan, P., Epping, E. A., Chiu, E., Preston, J., Goh, A., Antonopoulos, S., Loi, S., Raymond, L., Decolongon, J., Fan, M., ... Dubinsky, R. (2013). Regional atrophy associated with cognitive and motor function in prodromal Huntington disease. Journal of Huntington's disease, 2(4). https://doi.org/10.3233/JHD-130076

@article{ab0da160538848a3aa73309031cc2193,

title = "Regional atrophy associated with cognitive and motor function in prodromal Huntington disease.",

abstract = "BACKGROUND: Neuroimaging studies suggest that volumetric MRI measures of specific brain structures may serve as excellent biomarkers in future clinical trials of Huntington disease (HD). OBJECTIVE: Demonstration of the clinical significance of these measures is an important step in determining their appropriateness as potential outcome measures. METHODS: Measures of gray- and white-matter lobular volumes and subcortical volumes (caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus) were obtained from MRI scans of 516 individuals who tested positive for the HD gene expansion, but were not yet exhibiting signs or symptoms severe enough to warrant diagnosis ({"}pre-HD{"}). MRI volumes (corrected for intracranial volume) were correlated with cognitive, motor, psychiatric, and functional measures known to be sensitive to subtle changes in pre-HD. RESULTS: Caudate, putamen, and globus pallidus volumes consistently correlated with cognitive and motor, but not psychiatric or functional measures in pre-HD. Volumes of white matter, nucleus accumbens, and thalamus, but not cortical gray matter, also correlated with some of the motor and cognitive measures. CONCLUSIONS: Results of regression analyses suggest that volumes of basal ganglia structures contributed more highly to the prediction of most motor and cognitive variables than volumes of other brain regions. These results support the use of volumetric measures, especially of the basal ganglia, as outcome measures in future clinical trials in pre-HD. Results may also assist investigators in selecting the most appropriate measures for treatment trials that target specific clinical features or regions of neuropathology.",

keywords = "Huntington disease, cognitive, magnetic resonance imaging, motor, psychiatric",

author = "Aylward, {Elizabeth H} and Harrington, {Deborah L} and Mills, {James A} and Nopoulos, {Peggy C} and Long, {Jeffrey D} and Dawei Liu and Westervelt, {Holly K} and Paulsen, {Jane S} and Stephen Cross and Patricia Ryan and Epping, {Eric A} and Edmund Chiu and Joy Preston and Anita Goh and Stephanie Antonopoulos and Samantha Loi and Lynn Raymond and Joji Decolongon and Mannie Fan and Allison Coleman and Mallonee, {William M} and Greg Suter and Ross, {Christopher A} and Mark Varvaris and Nadine Yoritomo and Elizabeth McCusker and Jane Griffith and Clement Loy and David Gunn and Mark Guttman and Alanna Sheinberg and Albie Law and Kimberly Quaid and Melissa Wesson and Joanne Wojcieszek and Joel Perlmutter and Stacey Barton and Shineeka Smith and Barker, {Roger A} and Sarah Mason and Guzman, {Natalie Valle} and Susan Perlman and Brian Clemente and Randi Jones and Cathy Wood-Siverio and Factor, {Stewart A} and Ali Samii and Alma Macaraeg and Peter Panegyres and Joseph Lee and Maria Tedesco and Brenton Maxwell and Rajeev Kumar and Diane Erickson and Breanna Nickels and Frederick Marshall and Amy Chesire and Mary Wodarski and Charlyne Hickey and Geschwind, {Michael D} and Sharon Sha and Gabriela Satris and Anwar Ahmed and Christine Reece and Alex Bura and Lyla Mourany and Jagan Pallai and Pietro Mazzoni and Karen Marder and Paula Wasserman and David Craufurd and Judith Bek and Elizabeth Howard and Tom Warner and Maggie Burrows and Michael Orth and Sigurd S{\"u}ssmuth and Katrin Barth and Sonja Trautmann and Daniela Schwenk and Carolin Eschenbach and Vicki Wheelock and Lisa Kjer and Amanda Martin and Sarah Farias and Zosia Miedzybrodzka and Daniela Rae and Mariella D'Alessandro and Oksana Suchowersky and Phyllis Chua and Angela Komiti and Diana Rosas and Anne Rosser and Kathy Price and Sarah Hunt and Joseph Jankovic and William Ondo and Wayne Martin and Pamela King and Marguerite Wieler and Satwinder Sran and Martha Nance and {De Yebenes}, {Justo Garcia} and Richard Dubinsky",

note = "1U01NS082083, NINDS NIH HHS, United States1U01NS082085, NINDS NIH HHS, United States1U01NS082086, NINDS NIH HHS, United States2 UL1 TR000442-06, NCATS NIH HHS, United States5R01NS040068, NINDS NIH HHS, United States5R01NS054893, NINDS NIH HHS, United StatesPD30 HD02274, NICHD NIH HHS, United StatesR01 NS040068, NINDS NIH HHS, United States",

year = "2013",

doi = "10.3233/JHD-130076",

language = "English",

volume = "2",

journal = "Journal of Huntington's disease",

issn = "1879-6397",

publisher = "IOS Press",

number = "4",

}

Aylward, EH, Harrington, DL, Mills, JA, Nopoulos, PC, Long, JD, Liu, D, Westervelt, HK, Paulsen, JS, Cross, S, Ryan, P, Epping, EA, Chiu, E, Preston, J, Goh, A, Antonopoulos, S, Loi, S, Raymond, L, Decolongon, J, Fan, M, Coleman, A, Mallonee, WM, Suter, G, Ross, CA, Varvaris, M, Yoritomo, N, McCusker, E, Griffith, J, Loy, C, Gunn, D, Guttman, M, Sheinberg, A, Law, A, Quaid, K, Wesson, M, Wojcieszek, J, Perlmutter, J, Barton, S, Smith, S, Barker, RA, Mason, S, Guzman, NV, Perlman, S, Clemente, B, Jones, R, Wood-Siverio, C, Factor, SA, Samii, A, Macaraeg, A, Panegyres, P, Lee, J, Tedesco, M, Maxwell, B, Kumar, R, Erickson, D, Nickels, B, Marshall, F, Chesire, A, Wodarski, M, Hickey, C, Geschwind, MD, Sha, S, Satris, G, Ahmed, A, Reece, C, Bura, A, Mourany, L, Pallai, J, Mazzoni, P, Marder, K, Wasserman, P, Craufurd, D, Bek, J, Howard, E, Warner, T, Burrows, M, Orth, M, Süssmuth, S, Barth, K, Trautmann, S, Schwenk, D, Eschenbach, C, Wheelock, V, Kjer, L, Martin, A, Farias, S, Miedzybrodzka, Z, Rae, D, D'Alessandro, M, Suchowersky, O, Chua, P, Komiti, A, Rosas, D, Rosser, A, Price, K, Hunt, S, Jankovic, J, Ondo, W, Martin, W, King, P, Wieler, M, Sran, S, Nance, M, De Yebenes, JG & Dubinsky, R 2013, 'Regional atrophy associated with cognitive and motor function in prodromal Huntington disease.', Journal of Huntington's disease, vol. 2, no. 4. https://doi.org/10.3233/JHD-130076

TY - JOUR

T1 - Regional atrophy associated with cognitive and motor function in prodromal Huntington disease.

AU - Aylward, Elizabeth H

AU - Harrington, Deborah L

AU - Mills, James A

AU - Nopoulos, Peggy C

AU - Long, Jeffrey D

AU - Liu, Dawei

AU - Westervelt, Holly K

AU - Paulsen, Jane S

A2 - Cross, Stephen

A2 - Ryan, Patricia

A2 - Epping, Eric A

A2 - Chiu, Edmund

A2 - Preston, Joy

A2 - Goh, Anita

A2 - Antonopoulos, Stephanie

A2 - Loi, Samantha

A2 - Raymond, Lynn

A2 - Decolongon, Joji

A2 - Fan, Mannie

A2 - Coleman, Allison

A2 - Mallonee, William M

A2 - Suter, Greg

A2 - Ross, Christopher A

A2 - Varvaris, Mark

A2 - Yoritomo, Nadine

A2 - McCusker, Elizabeth

A2 - Griffith, Jane

A2 - Loy, Clement

A2 - Gunn, David

A2 - Guttman, Mark

A2 - Sheinberg, Alanna

A2 - Law, Albie

A2 - Quaid, Kimberly

A2 - Wesson, Melissa

A2 - Wojcieszek, Joanne

A2 - Perlmutter, Joel

A2 - Barton, Stacey

A2 - Smith, Shineeka

A2 - Barker, Roger A

A2 - Mason, Sarah

A2 - Guzman, Natalie Valle

A2 - Perlman, Susan

A2 - Clemente, Brian

A2 - Jones, Randi

A2 - Wood-Siverio, Cathy

A2 - Factor, Stewart A

A2 - Samii, Ali

A2 - Macaraeg, Alma

A2 - Panegyres, Peter

A2 - Lee, Joseph

A2 - Tedesco, Maria

A2 - Maxwell, Brenton

A2 - Kumar, Rajeev

A2 - Erickson, Diane

A2 - Nickels, Breanna

A2 - Marshall, Frederick

A2 - Chesire, Amy

A2 - Wodarski, Mary

A2 - Hickey, Charlyne

A2 - Geschwind, Michael D

A2 - Sha, Sharon

A2 - Satris, Gabriela

A2 - Ahmed, Anwar

A2 - Reece, Christine

A2 - Bura, Alex

A2 - Mourany, Lyla

A2 - Pallai, Jagan

A2 - Mazzoni, Pietro

A2 - Marder, Karen

A2 - Wasserman, Paula

A2 - Craufurd, David

A2 - Bek, Judith

A2 - Howard, Elizabeth

A2 - Warner, Tom

A2 - Burrows, Maggie

A2 - Orth, Michael

A2 - Süssmuth, Sigurd

A2 - Barth, Katrin

A2 - Trautmann, Sonja

A2 - Schwenk, Daniela

A2 - Eschenbach, Carolin

A2 - Wheelock, Vicki

A2 - Kjer, Lisa

A2 - Martin, Amanda

A2 - Farias, Sarah

A2 - Miedzybrodzka, Zosia

A2 - Rae, Daniela

A2 - D'Alessandro, Mariella

A2 - Suchowersky, Oksana

A2 - Chua, Phyllis

A2 - Komiti, Angela

A2 - Rosas, Diana

A2 - Rosser, Anne

A2 - Price, Kathy

A2 - Hunt, Sarah

A2 - Jankovic, Joseph

A2 - Ondo, William

A2 - Martin, Wayne

A2 - King, Pamela

A2 - Wieler, Marguerite

A2 - Sran, Satwinder

A2 - Nance, Martha

A2 - De Yebenes, Justo Garcia

A2 - Dubinsky, Richard

N1 - 1U01NS082083, NINDS NIH HHS, United States1U01NS082085, NINDS NIH HHS, United States1U01NS082086, NINDS NIH HHS, United States2 UL1 TR000442-06, NCATS NIH HHS, United States5R01NS040068, NINDS NIH HHS, United States5R01NS054893, NINDS NIH HHS, United StatesPD30 HD02274, NICHD NIH HHS, United StatesR01 NS040068, NINDS NIH HHS, United States

PY - 2013

Y1 - 2013

N2 - BACKGROUND: Neuroimaging studies suggest that volumetric MRI measures of specific brain structures may serve as excellent biomarkers in future clinical trials of Huntington disease (HD). OBJECTIVE: Demonstration of the clinical significance of these measures is an important step in determining their appropriateness as potential outcome measures. METHODS: Measures of gray- and white-matter lobular volumes and subcortical volumes (caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus) were obtained from MRI scans of 516 individuals who tested positive for the HD gene expansion, but were not yet exhibiting signs or symptoms severe enough to warrant diagnosis ("pre-HD"). MRI volumes (corrected for intracranial volume) were correlated with cognitive, motor, psychiatric, and functional measures known to be sensitive to subtle changes in pre-HD. RESULTS: Caudate, putamen, and globus pallidus volumes consistently correlated with cognitive and motor, but not psychiatric or functional measures in pre-HD. Volumes of white matter, nucleus accumbens, and thalamus, but not cortical gray matter, also correlated with some of the motor and cognitive measures. CONCLUSIONS: Results of regression analyses suggest that volumes of basal ganglia structures contributed more highly to the prediction of most motor and cognitive variables than volumes of other brain regions. These results support the use of volumetric measures, especially of the basal ganglia, as outcome measures in future clinical trials in pre-HD. Results may also assist investigators in selecting the most appropriate measures for treatment trials that target specific clinical features or regions of neuropathology.

AB - BACKGROUND: Neuroimaging studies suggest that volumetric MRI measures of specific brain structures may serve as excellent biomarkers in future clinical trials of Huntington disease (HD). OBJECTIVE: Demonstration of the clinical significance of these measures is an important step in determining their appropriateness as potential outcome measures. METHODS: Measures of gray- and white-matter lobular volumes and subcortical volumes (caudate, putamen, globus pallidus, thalamus, nucleus accumbens, hippocampus) were obtained from MRI scans of 516 individuals who tested positive for the HD gene expansion, but were not yet exhibiting signs or symptoms severe enough to warrant diagnosis ("pre-HD"). MRI volumes (corrected for intracranial volume) were correlated with cognitive, motor, psychiatric, and functional measures known to be sensitive to subtle changes in pre-HD. RESULTS: Caudate, putamen, and globus pallidus volumes consistently correlated with cognitive and motor, but not psychiatric or functional measures in pre-HD. Volumes of white matter, nucleus accumbens, and thalamus, but not cortical gray matter, also correlated with some of the motor and cognitive measures. CONCLUSIONS: Results of regression analyses suggest that volumes of basal ganglia structures contributed more highly to the prediction of most motor and cognitive variables than volumes of other brain regions. These results support the use of volumetric measures, especially of the basal ganglia, as outcome measures in future clinical trials in pre-HD. Results may also assist investigators in selecting the most appropriate measures for treatment trials that target specific clinical features or regions of neuropathology.

KW - Huntington disease

KW - cognitive

KW - magnetic resonance imaging

KW - motor

KW - psychiatric

U2 - 10.3233/JHD-130076

DO - 10.3233/JHD-130076

M3 - Article

C2 - 25062732

SN - 1879-6397

VL - 2

JO - Journal of Huntington's disease

JF - Journal of Huntington's disease

IS - 4

ER -

Regional atrophy associated with cognitive and motor function in prodromal Huntington disease.

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