Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease

Brenna Cholerton; Catherine O. Johnson; Brian Fish; Joseph F. Quinn; Kathryn A. Chung; Amie L. Peterson-Hiller; Liana S. Rosenthal; Ted M. Dawson; Marilyn S. Albert; Shu Ching Hu; Ignacio F. Mata; James B. Leverenz; Kathleen L. Poston; Thomas J. Montine; Cyrus P. Zabetian; Karen L. Edwards

doi:10.1016/j.parkreldis.2018.02.007

Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease

Brenna Cholerton
, Catherine O. Johnson
, Brian Fish
, Joseph F. Quinn
, Kathryn A. Chung
, Amie L. Peterson-Hiller
, Liana S. Rosenthal
, Ted M. Dawson
, Marilyn S. Albert
, Shu Ching Hu
, Ignacio F. Mata
, James B. Leverenz
, Kathleen L. Poston
, Thomas J. Montine
, Cyrus P. Zabetian
, Karen L. Edwards

Neurology

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

125 Scopus citations

Abstract

Introduction: Identification of factors associated with progression of cognitive symptoms in Parkinson's disease (PD) is important for treatment planning, clinical care, and design of future clinical trials. The current study sought to identify whether prediction of cognitive progression is aided by examining baseline cognitive features, and whether this differs according to stage of cognitive disease. Methods: Participants with PD in the Pacific Udall Center Clinical Consortium who had longitudinal data available and were nondemented at baseline were included in the study (n = 418). Logistic and Cox regression models were utilized to examine the relationship between cognitive, demographic, and clinical variables with risk and time to progression from no cognitive impairment to mild cognitive impairment (PD-MCI) or dementia (PDD), and from PD-MCI to PDD. Results: Processing speed (OR = 1.05, p = 0.009) and working memory (OR = 1.01, p = 0.03) were associated with conversion to PDD among those with PD-MCI at baseline, over and above demographic variables. Conversely, the primary predictive factor in the transition from no cognitive impairment to PD-MCI or PDD was male sex (OR = 4.47, p = 0.004), and males progressed more rapidly than females (p = 0.01). Further, among females with shorter disease duration, progression was slower than for their male counterparts, and poor baseline performance on semantic verbal fluency was associated with shorter time to cognitive impairment in females but not in males. Conclusions: This study provides evidence for sex differences in the progression to cognitive impairment in PD, while specific cognitive features become more important indicators of progression with impending conversion to PDD.

Original language	English (US)
Pages (from-to)	29-36
Number of pages	8
Journal	Parkinsonism and Related Disorders
Volume	50
DOIs	https://doi.org/10.1016/j.parkreldis.2018.02.007
State	Published - May 1 2018

Funding

Dr. Zabetian received support from the American Parkinson Disease Association , Department of Veterans Affairs ( 1 I01 CX001702 ), NIH ( NS062684 & NS100610 ), and the Dolsen Foundation . Dr. Quinn is reimbursed by Prothena and Roche for the conduct of clinical trials and by vTv Pharmaceuticals for DSMB service. Dr. Quinn is also funded by grants from the NIH ( I01BX003440 , U10NS077350 , UH3TR000903 , P30AG008017 , R01AG043398 , R01AT008099 , NS062684 ) and Department of Veterans Affairs . Dr. Edwards is funded by grants from the NIH (R01CA149051 and R01HL113189). Dr. Johnson is funded by grants from the NIH ( P50 NS062684 ). Dr. Hu is funded by grants from the NIH ( NS062684 & NS100610 ) and Michael J. Fox Foundation ( 14611 ). Dr. Chung is supported by grants from the Michael J Fox Foundation and US WorldMeds AP2-3000, and by NIH grant NS062684 . Dr. Edwards is funded by grants from the NIH ( R01CA149051 and R01HL113189 ). Dr. Leverenz reports consulting fees from Boehringer-Ingelheim, Citibank, Piramal Healthcare, and Navidea Biopharmaceuticals and is funded by grants from the Department of Veterans Affairs , American Parkinson Disease Association , Michael J. Fox Foundation , NIH ( U01 NS100610 ), Parkinson's Disease Foundation , and Jane and Lee Seidman Fund . Dr. Rosenthal receives a lecture honorarium from the Edmund Safra Foundation and is funded by grants from the NIH ( P50 NS38377 & U01 NS082133 ). Dr. Rosenthal also received one time consulting fees for Biohaven pharmaceuticals and Functional Neuromodulation. Dr. Cholerton is funded by grants from the NIH ( P50 NS062684 , UF1 AG053983-01 , UF1AG057707-01 ). Dr. Montine reports honoraria from invited scientific presentations to universities and professional societies not exceeding $5000 per year and is funded by grants from the NIH ( P50 NS062684 , P50 AG047366 , U01 AG32984 , R01 NS094003-01A1 , P30 AG049638-01A1 , RF1 AG053959-01 , UF1 AG053983-01 , R01 AG056287 , R01 AG031892 , R01 AG057915 , UF1 AG057707 ) and Michael J. Fox Foundation (Grant ID 14706 ). Dr. Mata is funded by grants from the Department of Veterans Affairs ( 1I211RX002553-01 ), NIH ( P50 NS06284 ), Parkinson's Disease Foundation, and American Parkinson’s Disease Foundation . Dr. Peterson-Hiller is funded by a VA Career Development Award and by the Michael J. Fox Foundation ( GNEU0911 ) and NIH ( NS062684 ). Dr. Poston is reimbursed by AstraZeneca and Sangamo BioSciences, Inc. for the conduct of clinical trials and is funded by grants from the NIH ( P50 AG047366 , P50 NS062684 , R01 NS091461 , R01 NS086085 , R01 EB022907 , R01 AA023165 ) and the Michael J. Fox Foundation ( 6440.01 and 14569 ). Dr. Dawson acknowledges the Adrienne Helis Malvin and Diana Henry Helis Medical Research Foundations and their direct engagement in the continuous active conduct of medical research in conjunction with The Johns Hopkins Hospital and The Johns Hopkins University School of Medicine and the Foundation's Parkinson's Disease Programs. His work is also supported by Sanofi- Aventis Recherce and Development , NIH/NINDS P50NS038377 , NIH/NINDS U01NS082133 , NIH/NINDS R37NS067525 , NIH/NIDA P50 DA00266 , the JPB Foundation , the MDSCRF 2015-MSCRFE-1782 , the Michael J. Fox Foundation and Abbvie Pharmaceuticals . Dr. Dawson is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases. Dr. Dawson is a member of the Dystonia Prize committee of the Bachmann Strauss Dystonia and Parkinson's Disease Foundation and the Michael J. Fox Foundation and a member of the Board of Directors of the Bachmann Strauss Dystonia and Parkinson's Disease Foundation. Dr. Dawson is a member of Scientific Advisory Board of CurePSP. Dr. Dawson is a member of the Executive Scientific Advisory Board of Michael J. Fox Foundation for Parkinson's Research. Dr. Dawson is a member of American Gene Technologies International Inc., advisory board. Dr. Dawson is a consultant to Inhibikase Therapeutics and owns stock options in the company. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. The terms of this arrangement are being managed by The Johns Hopkins University in accordance with its conflict of interest policies. Dr. Dawson is a founder of Valted, LLC and holds an ownership equity interest in the company. This arrangement has been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies.

Funders	Funder number
Abbvie Pharmaceuticals
Dolsen Foundation
Edmund Safra Foundation
Jane and Lee Seidman Fund
MDSCRF	2015-MSCRFE-1782
Piramal Healthcare Ltd.
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	R01AT008099, P50 NS06284, R01HL113189, R01 AG057915, R01 EB022907, U10NS077350, R01 AA023165, R01 AG056287, R01 AG031892, P30AG008017, R01 NS086085, P30 AG049638-01A1, P50 AG047366, NS100610, U01 AG32984, I01BX003440, R01 NS091461, UH3TR000903, RF1 AG053959-01, UF1AG057707-01, UF1 AG053983-01, R01 NS094003-01A1, R01AG043398, R01CA149051
National Institute on Drug Abuse	P50DA000266
American Parkinson's Disease Foundation
National Institute of Neurological Disorders and Stroke	R37NS067525, P50 NS0662684, U01 NS082133, P50 NS062684, P50NS038377
U.S. Department of Veterans Affairs	1 I01 CX001702, 1I211RX002553-01
Michael J. Fox Foundation for Parkinson's Research	14706, AP2-3000, 14611, 6440.01, GNEU0911, 14569
Parkinson's Disease Foundation
AstraZeneca
Sanofi
American Parkinson Disease Association
GE Healthcare
JPB Foundation	MDSCRF 2015-MSCRFE-1782

Keywords

Cognition
Dementia
Mild cognitive impairment
Parkinson's disease
Sex differences

ASJC Scopus subject areas

Neurology
Geriatrics and Gerontology
Clinical Neurology

Access to Document

10.1016/j.parkreldis.2018.02.007

Cite this

Cholerton, B., Johnson, C. O., Fish, B., Quinn, J. F., Chung, K. A., Peterson-Hiller, A. L., Rosenthal, L. S., Dawson, T. M., Albert, M. S., Hu, S. C., Mata, I. F., Leverenz, J. B., Poston, K. L., Montine, T. J., Zabetian, C. P., & Edwards, K. L. (2018). Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease. Parkinsonism and Related Disorders, 50, 29-36. https://doi.org/10.1016/j.parkreldis.2018.02.007

Cholerton, B, Johnson, CO, Fish, B, Quinn, JF, Chung, KA, Peterson-Hiller, AL, Rosenthal, LS, Dawson, TM, Albert, MS, Hu, SC, Mata, IF, Leverenz, JB, Poston, KL, Montine, TJ, Zabetian, CP & Edwards, KL 2018, 'Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease', Parkinsonism and Related Disorders, vol. 50, pp. 29-36. https://doi.org/10.1016/j.parkreldis.2018.02.007

@article{e38240d7fe744e87a3e9ee0267448365,

title = "Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease",

abstract = "Introduction: Identification of factors associated with progression of cognitive symptoms in Parkinson's disease (PD) is important for treatment planning, clinical care, and design of future clinical trials. The current study sought to identify whether prediction of cognitive progression is aided by examining baseline cognitive features, and whether this differs according to stage of cognitive disease. Methods: Participants with PD in the Pacific Udall Center Clinical Consortium who had longitudinal data available and were nondemented at baseline were included in the study (n = 418). Logistic and Cox regression models were utilized to examine the relationship between cognitive, demographic, and clinical variables with risk and time to progression from no cognitive impairment to mild cognitive impairment (PD-MCI) or dementia (PDD), and from PD-MCI to PDD. Results: Processing speed (OR = 1.05, p = 0.009) and working memory (OR = 1.01, p = 0.03) were associated with conversion to PDD among those with PD-MCI at baseline, over and above demographic variables. Conversely, the primary predictive factor in the transition from no cognitive impairment to PD-MCI or PDD was male sex (OR = 4.47, p = 0.004), and males progressed more rapidly than females (p = 0.01). Further, among females with shorter disease duration, progression was slower than for their male counterparts, and poor baseline performance on semantic verbal fluency was associated with shorter time to cognitive impairment in females but not in males. Conclusions: This study provides evidence for sex differences in the progression to cognitive impairment in PD, while specific cognitive features become more important indicators of progression with impending conversion to PDD.",

keywords = "Cognition, Dementia, Mild cognitive impairment, Parkinson's disease, Sex differences",

author = "Brenna Cholerton and Johnson, \{Catherine O.\} and Brian Fish and Quinn, \{Joseph F.\} and Chung, \{Kathryn A.\} and Peterson-Hiller, \{Amie L.\} and Rosenthal, \{Liana S.\} and Dawson, \{Ted M.\} and Albert, \{Marilyn S.\} and Hu, \{Shu Ching\} and Mata, \{Ignacio F.\} and Leverenz, \{James B.\} and Poston, \{Kathleen L.\} and Montine, \{Thomas J.\} and Zabetian, \{Cyrus P.\} and Edwards, \{Karen L.\}",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Ltd",

year = "2018",

month = may,

day = "1",

doi = "10.1016/j.parkreldis.2018.02.007",

language = "English (US)",

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T1 - Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease

AU - Cholerton, Brenna

AU - Johnson, Catherine O.

AU - Fish, Brian

AU - Quinn, Joseph F.

AU - Chung, Kathryn A.

AU - Peterson-Hiller, Amie L.

AU - Rosenthal, Liana S.

AU - Dawson, Ted M.

AU - Albert, Marilyn S.

AU - Hu, Shu Ching

AU - Mata, Ignacio F.

AU - Leverenz, James B.

AU - Poston, Kathleen L.

AU - Montine, Thomas J.

AU - Zabetian, Cyrus P.

AU - Edwards, Karen L.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Introduction: Identification of factors associated with progression of cognitive symptoms in Parkinson's disease (PD) is important for treatment planning, clinical care, and design of future clinical trials. The current study sought to identify whether prediction of cognitive progression is aided by examining baseline cognitive features, and whether this differs according to stage of cognitive disease. Methods: Participants with PD in the Pacific Udall Center Clinical Consortium who had longitudinal data available and were nondemented at baseline were included in the study (n = 418). Logistic and Cox regression models were utilized to examine the relationship between cognitive, demographic, and clinical variables with risk and time to progression from no cognitive impairment to mild cognitive impairment (PD-MCI) or dementia (PDD), and from PD-MCI to PDD. Results: Processing speed (OR = 1.05, p = 0.009) and working memory (OR = 1.01, p = 0.03) were associated with conversion to PDD among those with PD-MCI at baseline, over and above demographic variables. Conversely, the primary predictive factor in the transition from no cognitive impairment to PD-MCI or PDD was male sex (OR = 4.47, p = 0.004), and males progressed more rapidly than females (p = 0.01). Further, among females with shorter disease duration, progression was slower than for their male counterparts, and poor baseline performance on semantic verbal fluency was associated with shorter time to cognitive impairment in females but not in males. Conclusions: This study provides evidence for sex differences in the progression to cognitive impairment in PD, while specific cognitive features become more important indicators of progression with impending conversion to PDD.

AB - Introduction: Identification of factors associated with progression of cognitive symptoms in Parkinson's disease (PD) is important for treatment planning, clinical care, and design of future clinical trials. The current study sought to identify whether prediction of cognitive progression is aided by examining baseline cognitive features, and whether this differs according to stage of cognitive disease. Methods: Participants with PD in the Pacific Udall Center Clinical Consortium who had longitudinal data available and were nondemented at baseline were included in the study (n = 418). Logistic and Cox regression models were utilized to examine the relationship between cognitive, demographic, and clinical variables with risk and time to progression from no cognitive impairment to mild cognitive impairment (PD-MCI) or dementia (PDD), and from PD-MCI to PDD. Results: Processing speed (OR = 1.05, p = 0.009) and working memory (OR = 1.01, p = 0.03) were associated with conversion to PDD among those with PD-MCI at baseline, over and above demographic variables. Conversely, the primary predictive factor in the transition from no cognitive impairment to PD-MCI or PDD was male sex (OR = 4.47, p = 0.004), and males progressed more rapidly than females (p = 0.01). Further, among females with shorter disease duration, progression was slower than for their male counterparts, and poor baseline performance on semantic verbal fluency was associated with shorter time to cognitive impairment in females but not in males. Conclusions: This study provides evidence for sex differences in the progression to cognitive impairment in PD, while specific cognitive features become more important indicators of progression with impending conversion to PDD.

KW - Cognition

KW - Dementia

KW - Mild cognitive impairment

KW - Parkinson's disease

KW - Sex differences

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SN - 1353-8020

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ER -

Sex differences in progression to mild cognitive impairment and dementia in Parkinson's disease

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