The Role of APOE in Cognitive Trajectories and Motor Decline in Parkinson's Disease

Overview

Journal Sci Rep

Specialty Science

Date 2021 Apr 10

PMID 33837234

Citations 16

Authors

Sungyang Jo

Seon-Ok Kim

Kye Won Park

Seung Hyun Lee

Yun Su Hwang

Sun Ju Chung

Affiliations

Soon will be listed here.

Abstract

We aimed to investigate the role of the APOE genotype in cognitive and motor trajectories in Parkinson's disease (PD). Using PD registry data, we retrospectively investigated a total of 253 patients with PD who underwent the Mini-Mental State Exam (MMSE) two or more times at least 5 years apart, were aged over 40 years, and free of dementia at the time of enrollment. We performed group-based trajectory modeling to identify patterns of cognitive change using the MMSE. Kaplan-Meier survival analysis was used to investigate the role of the APOE genotype in cognitive and motor progression. Trajectory analysis divided patients into four groups: early fast decline, fast decline, gradual decline, and stable groups with annual MMSE scores decline of - 2.8, - 1.8, - 0.6, and - 0.1 points per year, respectively. The frequency of APOE ε4 was higher in patients in the early fast decline and fast decline groups (50.0%) than those in the stable group (20.1%) (p = 0.007). APOE ε4, in addition to older age at onset, depressive mood, and higher H&Y stage, was associated with the cognitive decline rate, but no APOE genotype was associated with motor progression. APOE genotype could be used to predict the cognitive trajectory in PD.

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References

McKeith I, Boeve B, Dickson D, Halliday G, Taylor J, Weintraub D . Diagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium. Neurology. 2017; 89(1):88-100. PMC: 5496518. DOI: 10.1212/WNL.0000000000004058. View

Ryu H, Park K, Choi N, Kim J, Park Y, Jo S . Genomic Analysis Identifies New Loci Associated With Motor Complications in Parkinson's Disease. Front Neurol. 2020; 11:570. PMC: 7358548. DOI: 10.3389/fneur.2020.00570. View

Iwaki H, Blauwendraat C, Leonard H, Kim J, Liu G, Maple-Grodem J . Genomewide association study of Parkinson's disease clinical biomarkers in 12 longitudinal patients' cohorts. Mov Disord. 2019; 34(12):1839-1850. PMC: 7017876. DOI: 10.1002/mds.27845. View

Kim J, Sunwoo M, Sohn Y, Lee P, Hong J . The MMSE and MoCA for Screening Cognitive Impairment in Less Educated Patients with Parkinson's Disease. J Mov Disord. 2016; 9(3):152-9. PMC: 5035941. DOI: 10.14802/jmd.16020. View

Winder-Rhodes S, Evans J, Ban M, Mason S, Williams-Gray C, Foltynie T . Glucocerebrosidase mutations influence the natural history of Parkinson's disease in a community-based incident cohort. Brain. 2013; 136(Pt 2):392-9. DOI: 10.1093/brain/aws318. View

Gomperts S, Locascio J, Rentz D, Santarlasci A, Marquie M, Johnson K . Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia. Neurology. 2012; 80(1):85-91. PMC: 3589197. DOI: 10.1212/WNL.0b013e31827b1a07. View

Ezquerra M, Campdelacreu J, Gaig C, Compta Y, Munoz E, Marti M . Lack of association of APOE and tau polymorphisms with dementia in Parkinson's disease. Neurosci Lett. 2008; 448(1):20-3. DOI: 10.1016/j.neulet.2008.10.018. View

Egensperger R, Bancher C, Kosel S, Jellinger K, Mehraein P, Graeber M . The apolipoprotein E epsilon 4 allele in Parkinson's disease with Alzheimer lesions. Biochem Biophys Res Commun. 1996; 224(2):484-6. DOI: 10.1006/bbrc.1996.1053. View

Inzelberg R, Schecthman E, Paleacu D, Zach L, Bonwitt R, Carasso R . Onset and progression of disease in familial and sporadic Parkinson's disease. Am J Med Genet A. 2004; 124A(3):255-8. DOI: 10.1002/ajmg.a.20405. View

10.

Lee M, Stirling W, Xu Y, Xu X, Qui D, Mandir A . Human alpha-synuclein-harboring familial Parkinson's disease-linked Ala-53 --> Thr mutation causes neurodegenerative disease with alpha-synuclein aggregation in transgenic mice. Proc Natl Acad Sci U S A. 2002; 99(13):8968-73. PMC: 124407. DOI: 10.1073/pnas.132197599. View

11.

Zhu K, van Hilten J, Marinus J . Predictors of dementia in Parkinson's disease; findings from a 5-year prospective study using the SCOPA-COG. Parkinsonism Relat Disord. 2014; 20(9):980-5. DOI: 10.1016/j.parkreldis.2014.06.006. View

12.

Guo Y, Xu W, Liu F, Li J, Cao X, Tan L . Modifiable risk factors for cognitive impairment in Parkinson's disease: A systematic review and meta-analysis of prospective cohort studies. Mov Disord. 2019; 34(6):876-883. DOI: 10.1002/mds.27665. View

13.

Palmqvist S, Insel P, Zetterberg H, Blennow K, Brix B, Stomrud E . Accurate risk estimation of β-amyloid positivity to identify prodromal Alzheimer's disease: Cross-validation study of practical algorithms. Alzheimers Dement. 2018; 15(2):194-204. PMC: 6374284. DOI: 10.1016/j.jalz.2018.08.014. View

14.

Mengel D, Dams J, Ziemek J, Becker J, Balzer-Geldsetzer M, Hilker R . Apolipoprotein E ε4 does not affect cognitive performance in patients with Parkinson's disease. Parkinsonism Relat Disord. 2016; 29:112-6. DOI: 10.1016/j.parkreldis.2016.04.013. View

15.

Dubois B, Burn D, Goetz C, Aarsland D, Brown R, Broe G . Diagnostic procedures for Parkinson's disease dementia: recommendations from the movement disorder society task force. Mov Disord. 2007; 22(16):2314-24. DOI: 10.1002/mds.21844. View

16.

Aarsland D, Andersen K, Larsen J, Perry R, Wentzel-Larsen T, Lolk A . The rate of cognitive decline in Parkinson disease. Arch Neurol. 2004; 61(12):1906-11. DOI: 10.1001/archneur.61.12.1906. View

17.

Zhao N, Attrebi O, Ren Y, Qiao W, Sonustun B, Martens Y . APOE4 exacerbates α-synuclein pathology and related toxicity independent of amyloid. Sci Transl Med. 2020; 12(529). PMC: 8309690. DOI: 10.1126/scitranslmed.aay1809. View

18.

Kempster P, OSullivan S, Holton J, Revesz T, Lees A . Relationships between age and late progression of Parkinson's disease: a clinico-pathological study. Brain. 2010; 133(Pt 6):1755-62. DOI: 10.1093/brain/awq059. View

19.

Riggeal B, Crucian G, Seignourel P, Jacobson C, Okun M, Rodriguez R . Cognitive decline tracks motor progression and not disease duration in Parkinson patients. Neuropsychiatr Dis Treat. 2009; 3(6):955-8. PMC: 2656340. DOI: 10.2147/ndt.s2237. View

20.

Lichter D, Benedict R, Hershey L . Importance of Balance-Gait Disorder as a Risk Factor for Cognitive Impairment, Dementia and Related Non-Motor Symptoms in Parkinson's Disease. J Parkinsons Dis. 2018; 8(4):539-552. DOI: 10.3233/JPD-181375. View