APOE, thought disorder, and SPARE-AD predict cognitive decline in established Parkinson's disease

Thomas F. Tropea, Sharon X. Xie, Jacqueline Rick, Lana M. Chahine, Nabila Dahodwala, Jimit Doshi, Christos Davatzikos, Leslie M. Shaw, Vivianna Van Deerlin, John Q. Trojanowski, Daniel Weintraub, Alice S. Chen-Plotkin

Research output: Contribution to journalArticle

Abstract

Background: People with PD are at high risk of developing cognitive impairment and dementia. Cross-sectional studies have identified candidate biomarkers associated with cognitive decline. However, longitudinal studies on this topic are rarer, and few have investigated the use of biomarker panels encompassing multiple modalities. The objective of this study was to find baseline predictors of cognitive decline in longitudinally followed, nondemented Parkinson's disease patients. Methods: We performed a prospective cohort study of 100 PD patients with a median disease duration of 6.4 years. All participants were nondemented at baseline. We examined 16 baseline biomarkers from clinical, genetic, biochemical, and MRI-based imaging modalities for their association with longitudinal cognitive decline for up to 8 years. We investigated biomarkers individually, as well as in a multivariate linear mixed-effects model encompassing multimodal biomarkers, with change in the Mattis Dementia Rating Scale-2 over time as the primary outcome. Annual consensus process-derived cognitive diagnosis was used for Cox proportional hazards modeling of risk for cognitive decline. Results: In multivariate analysis, the presence of the APOE E4 allele, thought disorder, and an Alzheimer's disease pattern of brain atrophy (spatial pattern of abnormality for recognition of early Alzheimer's disease index) best predicted cognitive decline, with APOE E4 genotype exerting the greatest effect. The presence of the APOE E4 allele was associated with a 3.5 times higher risk of worsening cognitive diagnosis over time (HR, 3.53; 95% CI, 1.52-8.24; P<0.05). The APOE genotype effect was not specific to any Mattis Dementia Rating Scale-2 domain. Conclusions: Our results confirm the importance of Alzheimer's disease biomarkers as risk factors for cognitive decline in established Parkinson's disease.

Original languageEnglish (US)
JournalMovement Disorders
DOIs
StateAccepted/In press - Jan 1 2017
Externally publishedYes

Fingerprint

Parkinson Disease
Biomarkers
Dementia
Alzheimer Disease
Alleles
Genotype
Cognitive Dysfunction
Atrophy
Longitudinal Studies
Molecular Biology
Consensus
Cohort Studies
Multivariate Analysis
Cross-Sectional Studies
Prospective Studies
Brain

Keywords

  • APOE
  • Dementia
  • Hallucination
  • Parkinson's
  • SPARE-AD

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Tropea, T. F., Xie, S. X., Rick, J., Chahine, L. M., Dahodwala, N., Doshi, J., ... Chen-Plotkin, A. S. (Accepted/In press). APOE, thought disorder, and SPARE-AD predict cognitive decline in established Parkinson's disease. Movement Disorders. https://doi.org/10.1002/mds.27204

APOE, thought disorder, and SPARE-AD predict cognitive decline in established Parkinson's disease. / Tropea, Thomas F.; Xie, Sharon X.; Rick, Jacqueline; Chahine, Lana M.; Dahodwala, Nabila; Doshi, Jimit; Davatzikos, Christos; Shaw, Leslie M.; Van Deerlin, Vivianna; Trojanowski, John Q.; Weintraub, Daniel; Chen-Plotkin, Alice S.

In: Movement Disorders, 01.01.2017.

Research output: Contribution to journalArticle

Tropea, TF, Xie, SX, Rick, J, Chahine, LM, Dahodwala, N, Doshi, J, Davatzikos, C, Shaw, LM, Van Deerlin, V, Trojanowski, JQ, Weintraub, D & Chen-Plotkin, AS 2017, 'APOE, thought disorder, and SPARE-AD predict cognitive decline in established Parkinson's disease', Movement Disorders. https://doi.org/10.1002/mds.27204
Tropea, Thomas F. ; Xie, Sharon X. ; Rick, Jacqueline ; Chahine, Lana M. ; Dahodwala, Nabila ; Doshi, Jimit ; Davatzikos, Christos ; Shaw, Leslie M. ; Van Deerlin, Vivianna ; Trojanowski, John Q. ; Weintraub, Daniel ; Chen-Plotkin, Alice S. / APOE, thought disorder, and SPARE-AD predict cognitive decline in established Parkinson's disease. In: Movement Disorders. 2017.
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AU - Tropea, Thomas F.

AU - Xie, Sharon X.

AU - Rick, Jacqueline

AU - Chahine, Lana M.

AU - Dahodwala, Nabila

AU - Doshi, Jimit

AU - Davatzikos, Christos

AU - Shaw, Leslie M.

AU - Van Deerlin, Vivianna

AU - Trojanowski, John Q.

AU - Weintraub, Daniel

AU - Chen-Plotkin, Alice S.

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N2 - Background: People with PD are at high risk of developing cognitive impairment and dementia. Cross-sectional studies have identified candidate biomarkers associated with cognitive decline. However, longitudinal studies on this topic are rarer, and few have investigated the use of biomarker panels encompassing multiple modalities. The objective of this study was to find baseline predictors of cognitive decline in longitudinally followed, nondemented Parkinson's disease patients. Methods: We performed a prospective cohort study of 100 PD patients with a median disease duration of 6.4 years. All participants were nondemented at baseline. We examined 16 baseline biomarkers from clinical, genetic, biochemical, and MRI-based imaging modalities for their association with longitudinal cognitive decline for up to 8 years. We investigated biomarkers individually, as well as in a multivariate linear mixed-effects model encompassing multimodal biomarkers, with change in the Mattis Dementia Rating Scale-2 over time as the primary outcome. Annual consensus process-derived cognitive diagnosis was used for Cox proportional hazards modeling of risk for cognitive decline. Results: In multivariate analysis, the presence of the APOE E4 allele, thought disorder, and an Alzheimer's disease pattern of brain atrophy (spatial pattern of abnormality for recognition of early Alzheimer's disease index) best predicted cognitive decline, with APOE E4 genotype exerting the greatest effect. The presence of the APOE E4 allele was associated with a 3.5 times higher risk of worsening cognitive diagnosis over time (HR, 3.53; 95% CI, 1.52-8.24; P<0.05). The APOE genotype effect was not specific to any Mattis Dementia Rating Scale-2 domain. Conclusions: Our results confirm the importance of Alzheimer's disease biomarkers as risk factors for cognitive decline in established Parkinson's disease.

AB - Background: People with PD are at high risk of developing cognitive impairment and dementia. Cross-sectional studies have identified candidate biomarkers associated with cognitive decline. However, longitudinal studies on this topic are rarer, and few have investigated the use of biomarker panels encompassing multiple modalities. The objective of this study was to find baseline predictors of cognitive decline in longitudinally followed, nondemented Parkinson's disease patients. Methods: We performed a prospective cohort study of 100 PD patients with a median disease duration of 6.4 years. All participants were nondemented at baseline. We examined 16 baseline biomarkers from clinical, genetic, biochemical, and MRI-based imaging modalities for their association with longitudinal cognitive decline for up to 8 years. We investigated biomarkers individually, as well as in a multivariate linear mixed-effects model encompassing multimodal biomarkers, with change in the Mattis Dementia Rating Scale-2 over time as the primary outcome. Annual consensus process-derived cognitive diagnosis was used for Cox proportional hazards modeling of risk for cognitive decline. Results: In multivariate analysis, the presence of the APOE E4 allele, thought disorder, and an Alzheimer's disease pattern of brain atrophy (spatial pattern of abnormality for recognition of early Alzheimer's disease index) best predicted cognitive decline, with APOE E4 genotype exerting the greatest effect. The presence of the APOE E4 allele was associated with a 3.5 times higher risk of worsening cognitive diagnosis over time (HR, 3.53; 95% CI, 1.52-8.24; P<0.05). The APOE genotype effect was not specific to any Mattis Dementia Rating Scale-2 domain. Conclusions: Our results confirm the importance of Alzheimer's disease biomarkers as risk factors for cognitive decline in established Parkinson's disease.

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