Cognitive performance of GBA mutation carriers with early-onset PD The CORE-PD study

R. N. Alcalay, E. Caccappolo, H. Mejia-Santana, M. X. Tang, L. Rosado, M. Orbe Reilly, D. Ruiz, B. Ross, M. Verbitsky, S. Kisselev, E. Louis, C. Comella, A. Colcher, D. Jennings, M. Nance, S. Bressman, William K Scott, C. Tanner, S. Mickel, H. Andrews & 18 others C. Waters, S. Fahn, L. Cote, S. Frucht, B. Ford, M. Rezak, K. Novak, J. H. Friedman, R. Pfeiffer, L. Marsh, B. Hiner, A. Siderowf, H. Payami, E. Molho, S. Factor, R. Ottman, L. N. Clark, K. Marder

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)1434-1440
Number of pages7
JournalNeurology
Volume78
Issue number18
DOIs
StatePublished - May 1 2012
Externally publishedYes

Fingerprint

Glucosylceramidase
Parkinson Disease
Mutation
Dementia
Smell
Cognitive Performance
Carrier
Parkinson's Disease
Onset
Neuropsychological Tests
Executive Function
Genotype
Demography
Phenotype

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Alcalay, R. N., Caccappolo, E., Mejia-Santana, H., Tang, M. X., Rosado, L., Reilly, M. O., ... Marder, K. (2012). Cognitive performance of GBA mutation carriers with early-onset PD The CORE-PD study. Neurology, 78(18), 1434-1440. https://doi.org/10.1212/WNL.0b013e318253d54b

Cognitive performance of GBA mutation carriers with early-onset PD The CORE-PD study. / Alcalay, R. N.; Caccappolo, E.; Mejia-Santana, H.; Tang, M. X.; Rosado, L.; Reilly, M. Orbe; Ruiz, D.; Ross, B.; Verbitsky, M.; Kisselev, S.; Louis, E.; Comella, C.; Colcher, A.; Jennings, D.; Nance, M.; Bressman, S.; Scott, William K; Tanner, C.; Mickel, S.; Andrews, H.; Waters, C.; Fahn, S.; Cote, L.; Frucht, S.; Ford, B.; Rezak, M.; Novak, K.; Friedman, J. H.; Pfeiffer, R.; Marsh, L.; Hiner, B.; Siderowf, A.; Payami, H.; Molho, E.; Factor, S.; Ottman, R.; Clark, L. N.; Marder, K.

In: Neurology, Vol. 78, No. 18, 01.05.2012, p. 1434-1440.

Research output: Contribution to journalArticle

Alcalay, RN, Caccappolo, E, Mejia-Santana, H, Tang, MX, Rosado, L, Reilly, MO, Ruiz, D, Ross, B, Verbitsky, M, Kisselev, S, Louis, E, Comella, C, Colcher, A, Jennings, D, Nance, M, Bressman, S, Scott, WK, Tanner, C, Mickel, S, Andrews, H, Waters, C, Fahn, S, Cote, L, Frucht, S, Ford, B, Rezak, M, Novak, K, Friedman, JH, Pfeiffer, R, Marsh, L, Hiner, B, Siderowf, A, Payami, H, Molho, E, Factor, S, Ottman, R, Clark, LN & Marder, K 2012, 'Cognitive performance of GBA mutation carriers with early-onset PD The CORE-PD study', Neurology, vol. 78, no. 18, pp. 1434-1440. https://doi.org/10.1212/WNL.0b013e318253d54b
Alcalay RN, Caccappolo E, Mejia-Santana H, Tang MX, Rosado L, Reilly MO et al. Cognitive performance of GBA mutation carriers with early-onset PD The CORE-PD study. Neurology. 2012 May 1;78(18):1434-1440. https://doi.org/10.1212/WNL.0b013e318253d54b
Alcalay, R. N. ; Caccappolo, E. ; Mejia-Santana, H. ; Tang, M. X. ; Rosado, L. ; Reilly, M. Orbe ; Ruiz, D. ; Ross, B. ; Verbitsky, M. ; Kisselev, S. ; Louis, E. ; Comella, C. ; Colcher, A. ; Jennings, D. ; Nance, M. ; Bressman, S. ; Scott, William K ; Tanner, C. ; Mickel, S. ; Andrews, H. ; Waters, C. ; Fahn, S. ; Cote, L. ; Frucht, S. ; Ford, B. ; Rezak, M. ; Novak, K. ; Friedman, J. H. ; Pfeiffer, R. ; Marsh, L. ; Hiner, B. ; Siderowf, A. ; Payami, H. ; Molho, E. ; Factor, S. ; Ottman, R. ; Clark, L. N. ; Marder, K. / Cognitive performance of GBA mutation carriers with early-onset PD The CORE-PD study. In: Neurology. 2012 ; Vol. 78, No. 18. pp. 1434-1440.
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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.",
author = "Alcalay, {R. N.} and E. Caccappolo and H. Mejia-Santana and Tang, {M. X.} and L. Rosado and Reilly, {M. Orbe} and D. Ruiz and B. Ross and M. Verbitsky and S. Kisselev and E. Louis and C. Comella and A. Colcher and D. Jennings and M. Nance and S. Bressman and Scott, {William K} and C. Tanner and S. Mickel and H. Andrews and C. Waters and S. Fahn and L. Cote and S. Frucht and B. Ford and M. Rezak and K. Novak and Friedman, {J. H.} and R. Pfeiffer and L. Marsh and B. Hiner and A. Siderowf and H. Payami and E. Molho and S. Factor and R. Ottman and Clark, {L. N.} and K. Marder",
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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, William 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.

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.

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