Cognitive profile of LRRK2-related Parkinson's disease

Sindhu Srivatsal, Brenna Cholerton, James B. Leverenz, Zbigniew K. Wszolek, Ryan J. Uitti, Dennis W. Dickson, Daniel Weintraub, John Q. Trojanowski, Vivianna M. Van Deerlin, Joseph F. Quinn, Kathryn A. Chung, Amie L. Peterson, Stewart A. Factor, Cathy Wood-Siverio, Jennifer G. Goldman, Glenn T. Stebbins, Bryan Bernard, Beate Ritz, Rebecca Rausch, Alberto J. EspayFredy J. Revilla, Johnna Devoto, Liana Isa Shapiro Rosenthal, Ted M Dawson, Marilyn Albert, Ignacio F. Mata, Shu Ching Hu, Kathleen S. Montine, Catherine Johnson, Thomas J. Montine, Karen L. Edwards, Jing Zhang, Cyrus P. Zabetian

Research output: Contribution to journalArticle

Abstract

Background: Increasing evidence suggests that genetic factors play a role in the variability associated with cognitive performance in Parkinson's disease (PD). Mutations in the LRRK2 gene are the most common cause of monogenic PD; however, the cognitive profile of LRRK2-related PD is not well-characterized. Methods: A cohort of 1,447 PD patients enrolled in the PD Cognitive Genetics Consortium was screened for LRRK2 mutations and completed detailed cognitive testing. Associations between mutation carrier status and cognitive test scores were assessed using linear regression models. Results: LRRK2 mutation carriers (n=29) demonstrated better performance on the Mini Mental State Examination (P=0.03) and the Letter-Number Sequencing Test (P=0.005). A smaller proportion of LRRK2 carriers were demented (P=0.03). Conclusions: Our cross-sectional study demonstrates better performance on certain cognitive tests, as well as lower rates of dementia in LRRK2-related PD. Future longitudinal studies are needed to determine whether LRRK2 mutation carriers exhibit slower cognitive decline.

Original languageEnglish (US)
Pages (from-to)728-733
Number of pages6
JournalMovement disorders : official journal of the Movement Disorder Society
Volume30
Issue number5
DOIs
StatePublished - Apr 15 2015

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Parkinson Disease
Mutation
Linear Models
Longitudinal Studies
Dementia
Cross-Sectional Studies
Genes

Keywords

  • Cognition
  • LRRK2
  • Neuropsychological tests
  • Parkinson's disease
  • Working memory

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Srivatsal, S., Cholerton, B., Leverenz, J. B., Wszolek, Z. K., Uitti, R. J., Dickson, D. W., ... Zabetian, C. P. (2015). Cognitive profile of LRRK2-related Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society, 30(5), 728-733. https://doi.org/10.1002/mds.26161

Cognitive profile of LRRK2-related Parkinson's disease. / Srivatsal, Sindhu; Cholerton, Brenna; Leverenz, James B.; Wszolek, Zbigniew K.; Uitti, Ryan J.; Dickson, Dennis W.; Weintraub, Daniel; Trojanowski, John Q.; Van Deerlin, Vivianna M.; Quinn, Joseph F.; Chung, Kathryn A.; Peterson, Amie L.; Factor, Stewart A.; Wood-Siverio, Cathy; Goldman, Jennifer G.; Stebbins, Glenn T.; Bernard, Bryan; Ritz, Beate; Rausch, Rebecca; Espay, Alberto J.; Revilla, Fredy J.; Devoto, Johnna; Rosenthal, Liana Isa Shapiro; Dawson, Ted M; Albert, Marilyn; Mata, Ignacio F.; Hu, Shu Ching; Montine, Kathleen S.; Johnson, Catherine; Montine, Thomas J.; Edwards, Karen L.; Zhang, Jing; Zabetian, Cyrus P.

In: Movement disorders : official journal of the Movement Disorder Society, Vol. 30, No. 5, 15.04.2015, p. 728-733.

Research output: Contribution to journalArticle

Srivatsal, S, Cholerton, B, Leverenz, JB, Wszolek, ZK, Uitti, RJ, Dickson, DW, Weintraub, D, Trojanowski, JQ, Van Deerlin, VM, Quinn, JF, Chung, KA, Peterson, AL, Factor, SA, Wood-Siverio, C, Goldman, JG, Stebbins, GT, Bernard, B, Ritz, B, Rausch, R, Espay, AJ, Revilla, FJ, Devoto, J, Rosenthal, LIS, Dawson, TM, Albert, M, Mata, IF, Hu, SC, Montine, KS, Johnson, C, Montine, TJ, Edwards, KL, Zhang, J & Zabetian, CP 2015, 'Cognitive profile of LRRK2-related Parkinson's disease', Movement disorders : official journal of the Movement Disorder Society, vol. 30, no. 5, pp. 728-733. https://doi.org/10.1002/mds.26161
Srivatsal S, Cholerton B, Leverenz JB, Wszolek ZK, Uitti RJ, Dickson DW et al. Cognitive profile of LRRK2-related Parkinson's disease. Movement disorders : official journal of the Movement Disorder Society. 2015 Apr 15;30(5):728-733. https://doi.org/10.1002/mds.26161
Srivatsal, Sindhu ; Cholerton, Brenna ; Leverenz, James B. ; Wszolek, Zbigniew K. ; Uitti, Ryan J. ; Dickson, Dennis W. ; Weintraub, Daniel ; Trojanowski, John Q. ; Van Deerlin, Vivianna M. ; Quinn, Joseph F. ; Chung, Kathryn A. ; Peterson, Amie L. ; Factor, Stewart A. ; Wood-Siverio, Cathy ; Goldman, Jennifer G. ; Stebbins, Glenn T. ; Bernard, Bryan ; Ritz, Beate ; Rausch, Rebecca ; Espay, Alberto J. ; Revilla, Fredy J. ; Devoto, Johnna ; Rosenthal, Liana Isa Shapiro ; Dawson, Ted M ; Albert, Marilyn ; Mata, Ignacio F. ; Hu, Shu Ching ; Montine, Kathleen S. ; Johnson, Catherine ; Montine, Thomas J. ; Edwards, Karen L. ; Zhang, Jing ; Zabetian, Cyrus P. / Cognitive profile of LRRK2-related Parkinson's disease. In: Movement disorders : official journal of the Movement Disorder Society. 2015 ; Vol. 30, No. 5. pp. 728-733.
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abstract = "Background: Increasing evidence suggests that genetic factors play a role in the variability associated with cognitive performance in Parkinson's disease (PD). Mutations in the LRRK2 gene are the most common cause of monogenic PD; however, the cognitive profile of LRRK2-related PD is not well-characterized. Methods: A cohort of 1,447 PD patients enrolled in the PD Cognitive Genetics Consortium was screened for LRRK2 mutations and completed detailed cognitive testing. Associations between mutation carrier status and cognitive test scores were assessed using linear regression models. Results: LRRK2 mutation carriers (n=29) demonstrated better performance on the Mini Mental State Examination (P=0.03) and the Letter-Number Sequencing Test (P=0.005). A smaller proportion of LRRK2 carriers were demented (P=0.03). Conclusions: Our cross-sectional study demonstrates better performance on certain cognitive tests, as well as lower rates of dementia in LRRK2-related PD. Future longitudinal studies are needed to determine whether LRRK2 mutation carriers exhibit slower cognitive decline.",
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T1 - Cognitive profile of LRRK2-related Parkinson's disease

AU - Srivatsal, Sindhu

AU - Cholerton, Brenna

AU - Leverenz, James B.

AU - Wszolek, Zbigniew K.

AU - Uitti, Ryan J.

AU - Dickson, Dennis W.

AU - Weintraub, Daniel

AU - Trojanowski, John Q.

AU - Van Deerlin, Vivianna M.

AU - Quinn, Joseph F.

AU - Chung, Kathryn A.

AU - Peterson, Amie L.

AU - Factor, Stewart A.

AU - Wood-Siverio, Cathy

AU - Goldman, Jennifer G.

AU - Stebbins, Glenn T.

AU - Bernard, Bryan

AU - Ritz, Beate

AU - Rausch, Rebecca

AU - Espay, Alberto J.

AU - Revilla, Fredy J.

AU - Devoto, Johnna

AU - Rosenthal, Liana Isa Shapiro

AU - Dawson, Ted M

AU - Albert, Marilyn

AU - Mata, Ignacio F.

AU - Hu, Shu Ching

AU - Montine, Kathleen S.

AU - Johnson, Catherine

AU - Montine, Thomas J.

AU - Edwards, Karen L.

AU - Zhang, Jing

AU - Zabetian, Cyrus P.

PY - 2015/4/15

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N2 - Background: Increasing evidence suggests that genetic factors play a role in the variability associated with cognitive performance in Parkinson's disease (PD). Mutations in the LRRK2 gene are the most common cause of monogenic PD; however, the cognitive profile of LRRK2-related PD is not well-characterized. Methods: A cohort of 1,447 PD patients enrolled in the PD Cognitive Genetics Consortium was screened for LRRK2 mutations and completed detailed cognitive testing. Associations between mutation carrier status and cognitive test scores were assessed using linear regression models. Results: LRRK2 mutation carriers (n=29) demonstrated better performance on the Mini Mental State Examination (P=0.03) and the Letter-Number Sequencing Test (P=0.005). A smaller proportion of LRRK2 carriers were demented (P=0.03). Conclusions: Our cross-sectional study demonstrates better performance on certain cognitive tests, as well as lower rates of dementia in LRRK2-related PD. Future longitudinal studies are needed to determine whether LRRK2 mutation carriers exhibit slower cognitive decline.

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