Abstract
Objective: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD). Methods: We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age-and PD duration-matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed. Results: Demographics, UPSIT, and Unified Parkinson's Disease Rating Scale-III performance did not differ between GBA carriers and noncarriers. GBA mutation carriers performed more poorly than noncarriers on the Mini-Mental State Examination (p < 0.035), and on the memory (p < 0.017) and visuospatial (p < 0.028) domains. The most prominent differences were observed in nonverbal memory performance (p = 0.001). Carriers were more likely to receive scores of 0.5 or higher on the CDR (p = 0.001), and a clinical diagnosis of either MCI or dementia (p < 0.004). Conclusion: GBA mutation status may be an independent risk factor for cognitive impairment in patients with PD.
Original language | English (US) |
---|---|
Pages (from-to) | 1434-1440 |
Number of pages | 7 |
Journal | Neurology |
Volume | 78 |
Issue number | 18 |
DOIs | |
State | Published - May 1 2012 |
Externally published | Yes |
ASJC Scopus subject areas
- Clinical Neurology
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Cognitive performance of GBA mutation carriers with early-onset PD The CORE-PD study. / Alcalay, R. N.; Caccappolo, E.; Mejia-Santana, H. et al.
In: Neurology, Vol. 78, No. 18, 01.05.2012, p. 1434-1440.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Cognitive performance of GBA mutation carriers with early-onset PD The CORE-PD study
AU - Alcalay, R. N.
AU - Caccappolo, E.
AU - Mejia-Santana, H.
AU - Tang, M. X.
AU - Rosado, L.
AU - Reilly, M. Orbe
AU - Ruiz, D.
AU - Ross, B.
AU - Verbitsky, M.
AU - Kisselev, S.
AU - Louis, E.
AU - Comella, C.
AU - Colcher, A.
AU - Jennings, D.
AU - Nance, M.
AU - Bressman, S.
AU - Scott, W. K.
AU - Tanner, C.
AU - Mickel, S.
AU - Andrews, H.
AU - Waters, C.
AU - Fahn, S.
AU - Cote, L.
AU - Frucht, S.
AU - Ford, B.
AU - Rezak, M.
AU - Novak, K.
AU - Friedman, J. H.
AU - Pfeiffer, R.
AU - Marsh, L.
AU - Hiner, B.
AU - Siderowf, A.
AU - Payami, H.
AU - Molho, E.
AU - Factor, S.
AU - Ottman, R.
AU - Clark, L. N.
AU - Marder, K.
N1 - Funding Information: Dr. Alcalay receives research support from the NIH (K12 part of UL1 RR024156) and the Brookdale Leadership in Aging Fellowship and received research support from the Michael J. Fox Foundation. Dr. Caccappolo, H. Mejia-Santana, Dr. Tang, Dr. Rosado, Dr. Reilly, D. Ruiz, B. Ross, Dr. Verbitsky, and S. Kisselev report no disclosures. Dr. Louis receives research support from the NIH [NINDS #R01 NS42859 (principal investigator), NINDS #R01 NS39422 (principal investigator), NINDS #R56 NS042859 (principal investigator), NINDS #T32 NS07153-24 (principal investigator), NIA #2P01 AG0027232-16 (principal investigator), and NINDS #R01 NS36630 (coinvestigator)] and the Parkinson's Disease Foundation (principal investigator). Dr. Comella reports no disclosures. Dr. Colcher is on a speaker's bureau for Lundbeck Pharmaceuticals and Teva Pharmaceuticals and has received honoraria from Plan 365, Advanced Health Media, and Healthlogix and Robert Wood Johnson for speaking engagements in 2009. Dr. Jennings reports no disclosures. Dr. Nance has received research funding from Medivation, Santhera, Neurosearch, Juvantia, Schwarcz, Pfizer, Neuraltus, Impax, CHDI, NINDS 5 U10 NS044466-05 (site investigator), NINDS 5 RO1 NS36630 (site investigator), NINDS NS640068-08 (site investigator, Steering Committee), NHGRI/NINDS 501 HG 02449-07 (site investigator), NINDS 1RO1 NS052592-01 (site investigator), NCCAM (site investigator), and 1 RO1 NS060118-01A1 (site investigator) ; support for Centers of Excellence from National Parkinson Foundation and Huntington Disease Society of America; speaking honoraria from American Academy of Neurology, Huntington Disease Society of America, and Augsburg College; and royalties from Oxford University Press (Juvenile Huntington's Disease, published 2009); and her spouse has served on speaker's bureaus for Genentech and Schering-Plough. Dr. Bressman reports no disclosures. Dr. Scott is a coinventor on patent regarding use of genetic data for assessing risk of developing age-related macular degeneration, licensed to ArcticDx. Dr. Tanner serves on the advisory board of the Michael J. Fox Foundation Scientific Advisory Board and the National Spasmodic Dystonia Association Scientific Advisory Board; has consulted for Impax Pharmaceuticals, Lundbeck Pharmaceuticals, Pacific Health Research Institute (consultant on NIH & Department of Defense funded research), Stanford University (consultant on Muscular Dystrophy Association funded research), and SunHealth Research Institute (consultant on MJFF founded research); and has received research support from the Michael J. Fox Foundation, Brin Foundation, James and Sharron Clark, National Institutes of Health (NIH), Parkinson's Institute and Clinical Center, Parkinson's Disease Foundation, Department of Defense, and Welding Products Manufacturer's Group. Dr. Mickel and Dr. Andrews report no disclosures. Dr. Waters received speaking honorarium from Boehringer and Teva. Dr. Fahn reports receiving support from consulting and advisory board membership with honoraria from Oxford Biomedica (September 2009), Proctor-Goodwin (November 2009), GE Healthcare (November 2009), RJG Foundation (March 2010), IMPAX Pharmaceuticals (May 2010), and Lundbeck (June 2010); he is receiving research support from the Parkinson's Disease Foundation (no salary support); he received a grant from the Smart Family Foundation (no salary support); and received a grant from the US Department of Defense's Telemedicine and Advanced Technology Research Center (TATRC) for the World Parkinson Congress 2010, and a grant from the National Institutes of Health for the World Parkinson Congress 2010. Dr. Fahn received lecture honoraria from Columbia University (July 2009), Sun Pharmaceuticals India (September 2009), World Association of Sleep Medicine (November 2009), American Academy of Neurology (April 2010), and Columbia University (July 2010). Dr. Fahn reports serving as an editor with author honoraria from “Current Neurology and Neurosurgery Report” (annual); and Elsevier for co-author of book Principles and Practice of Movement Disorders. Dr. Cote reports no disclosures. Dr. Frucht has received consultation fees from Lundbeck, Jazz Pharmaceuticals, and Merz. Dr. Ford serves on the physician advisory board for Medtronic, Inc. Dr. Rezak is on the speaker bureau of Teva, Medtronic, Novartis, Boehringer Ingelheim, and Galxo. Dr. Novak reports no disclosures. Dr. Friedman has received speaking honorarium from Teva, Boehringer-Ingelheim, and GlaxoSmithKline; received research support from Epivax, Teva, Cephalon, EMD Serono, Acadia, the Michael J. Fox Foundation, and the National Institute of Health; has received consultation fee from Teva, EMD Serono, Acadia, United Biosource, and Clintara; and has received book royalties from Demos Press. Dr. Pfeiffer has received royalties for book editing from CRC Press (Taylor & Francis) and Humana Press; has received speaking honorarium from Boehringer-Ingelheim, Novartis, and Teva; has received consultation honoraria from Solvay, Theravance, Genactis, and Schlesinger Associates; has research support from Novartis, Boehringer-Ingelheim, UCB/Schwarz, and Santhera; received legal consulting fees from Spriggs & Hollingsworth, Davis Graham & Stubbs, and Tucker Ellis & West; and is the journal editor of Parkinsonism and Related Disorders (Elsevier). Dr. Marsh served on the advisory board of the National Parkinson Foundation and the American Parkinson's Disease Association; has received consultation fee from Acadia Pharmaceutical, Ovation Pharmaceutical, Merck Serono, and Boehringer Ingelheim; has received research support from the National Institutes of Health, Forest Research Institute, Eli Lilly, Michael J. Fox Foundation for Parkinson's Research, and the National Parkinson Foundation; and has received book royalties from Taylor and Francis/Informa. Dr. Hiner has received speaking honorarium from Teva Neuroscience. Dr. Siderowf is supported by a Morris K. Udall Parkinson's Disease Research Center of Excellence grant from NINDS (NS-053488), and has been supported by SAP4100027296, a health research grant awarded by the Department of Health of the Commonwealth of Pennsylvania from the Tobacco Master Settlement Agreement under Act 2001-77; has received consulting fees from Teva Neuroscience, Supernus Pharmaceuticals, Schering-Plough, and Merck Serono; and has received speaking honorarium from Teva Neuroscience. Dr. Payami has received funding from the NIH (NS36960). Dr. Molho is supported by the Riley Family Chair in Parkinson's Disease. Dr. Factor reports no disclosures. Dr. Ottman serves on the scientific advisory board for and holds stock options in Trigeminal Solutions, Inc; has received funding for travel from the International League Against Epilepsy, the National Institute for Mental Health, and Coriell Institute for Medical Research; has received speaker honoraria for non-industry sponsored lectures; serves as a consultant to Ortho-McNeil Janssen Scientific Affairs, LLC.; and received research support from the NIH through #R01 NS043472 [PI], #R01 NS036319 [PI], #R01 NS036630 [Co-I], #R03 NS065346 [PI], #RC2 NS070344 [MPI], #R01 NS039422 [Co-I], and #R01 NS053998 [Co-I] . Dr. Clark reports no disclosures. Dr. Marder served on the editorial board of Neurology® ; received research support from Amarin Corporation, and NeuroSearch Sweden AB; and receives research support from the NIH [#NS36630 (PI), 1UL1 RR024156-01 (Director PCIR), PO412196-G (Co-I), and PO412196-G (Co-I)] , and from the Parkinson Disease Foundation, Huntington's Disease Society of America, and the Parkinson Study Group, and the Michael J. Fox Foundation. Go to Neurology.org for full disclosures . Funding Information: This study was funded by NIH NS036630, UL1 RR024156 (K.S.M.), NS050487, NS060113 (L.N.C.), the Parkinson's Disease Foundation (K.S.M., S.F., and L.N.C.), P50 NS039764 (W.K.S.), and NS36960 (H.P.). R.N.A. is a Brookdale Foundation Leadership in Aging Fellow.
PY - 2012/5/1
Y1 - 2012/5/1
N2 - Objective: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD). Methods: We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age-and PD duration-matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed. Results: Demographics, UPSIT, and Unified Parkinson's Disease Rating Scale-III performance did not differ between GBA carriers and noncarriers. GBA mutation carriers performed more poorly than noncarriers on the Mini-Mental State Examination (p < 0.035), and on the memory (p < 0.017) and visuospatial (p < 0.028) domains. The most prominent differences were observed in nonverbal memory performance (p = 0.001). Carriers were more likely to receive scores of 0.5 or higher on the CDR (p = 0.001), and a clinical diagnosis of either MCI or dementia (p < 0.004). Conclusion: GBA mutation status may be an independent risk factor for cognitive impairment in patients with PD.
AB - Objective: To assess the cognitive phenotype of glucocerebrosidase (GBA) mutation carriers with early-onset Parkinson disease (PD). Methods: We administered a neuropsychological battery and the University of Pennsylvania Smell Identification Test (UPSIT) to participants in the CORE-PD study who were tested for mutations in PARKIN, LRRK2, and GBA. Participants included 33 GBA mutation carriers and 60 noncarriers of any genetic mutation. Primary analyses were performed on 26 GBA heterozygous mutation carriers without additional mutations and 39 age-and PD duration-matched noncarriers. Five cognitive domains, psychomotor speed, attention, memory, visuospatial function, and executive function, were created from transformed z scores of individual neuropsychological tests. Clinical diagnoses (normal, mild cognitive impairment [MCI], dementia) were assigned blind to genotype based on neuropsychological performance and functional impairment as assessed by the Clinical Dementia Rating (CDR) score. The association between GBA mutation status and neuropsychological performance, CDR, and clinical diagnoses was assessed. Results: Demographics, UPSIT, and Unified Parkinson's Disease Rating Scale-III performance did not differ between GBA carriers and noncarriers. GBA mutation carriers performed more poorly than noncarriers on the Mini-Mental State Examination (p < 0.035), and on the memory (p < 0.017) and visuospatial (p < 0.028) domains. The most prominent differences were observed in nonverbal memory performance (p = 0.001). Carriers were more likely to receive scores of 0.5 or higher on the CDR (p = 0.001), and a clinical diagnosis of either MCI or dementia (p < 0.004). Conclusion: GBA mutation status may be an independent risk factor for cognitive impairment in patients with PD.
UR - http://www.scopus.com/inward/record.url?scp=84860708754&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84860708754&partnerID=8YFLogxK
U2 - 10.1212/WNL.0b013e318253d54b
DO - 10.1212/WNL.0b013e318253d54b
M3 - Article
C2 - 22442429
AN - SCOPUS:84860708754
VL - 78
SP - 1434
EP - 1440
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 18
ER -