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open access

Vol 55, No 6 (2021)
Research Paper
Submitted: 2021-05-26
Accepted: 2021-08-08
Published online: 2021-10-13
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Effects of sex and APOE on Parkinson’s Disease-related cognitive decline

Philip W. Tipton1, Nazli Bülbül2, Julia Crook3, Zachary Quicksall3, Owen A. Ross24, Ryan J. Uitti1, Zbigniew K. Wszolek1, Nilüfer Ertekin-Taner12
DOI: 10.5603/PJNNS.a2021.0071
·
Pubmed: 34642926
·
Neurol Neurochir Pol 2021;55(6):559-566.
Affiliations
  1. Department of Neurology, Mayo Clinic, Jacksonville, Florida, United States
  2. Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA
  3. Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida, USA
  4. Department of Clinical Genomics, Mayo Clinic, Jacksonville, Florida, USA

open access

Vol 55, No 6 (2021)
RESEARCH PAPERS — LEADING TOPIC
Submitted: 2021-05-26
Accepted: 2021-08-08
Published online: 2021-10-13

Abstract

Introduction. Cognitive impairment is common in Parkinson’s Disease, but the impact of predictive factors on incidence and rate of cognitive decline is incompletely understood. We aimed to determine the effects of sex and APOE allele status on cognitive performance in patients with Parkinson’s Disease (PD).

Material and methods. We conducted a retrospective analysis of 325 clinically diagnosed PD patients who underwent one or more cognitive screenings with a Mini-Mental Status Examination (MMSE) or Mattis Dementia Rating Scale (DRS-2). We used proportional odds regression models to estimate odds ratios for higher versus lower cognitive scores in association with age, sex, education, disease duration, and APOE allele status.

Results. Higher cognitive scores were independently associated with female sex on the MMSE (OR 2.43; 95% CI 1.14, 5.14) and DRS-2 total (OR 4.14; 95% CI 2.01, 8.53). APOE ε4 dose was associated with lower DRS-2 totals (OR 0.42; 95% CI 0.22, 0.81), but there was no evidence of association with MMSE. Higher education level was also associated with higher scores on the MMSE (OR 1.22; 95% CI 1.07, 1.38) and DRS-2 total (OR 1.31; 95% CI 1.15, 1.50). Disease duration was not associated with cognitive performance on any measure when adjusting for age.

Conclusion. Male sex and APOE ε4, along with age and lower education level, were associated with poorer cognitive performance among a population of predominantly non-demented PD patients.

Abstract

Introduction. Cognitive impairment is common in Parkinson’s Disease, but the impact of predictive factors on incidence and rate of cognitive decline is incompletely understood. We aimed to determine the effects of sex and APOE allele status on cognitive performance in patients with Parkinson’s Disease (PD).

Material and methods. We conducted a retrospective analysis of 325 clinically diagnosed PD patients who underwent one or more cognitive screenings with a Mini-Mental Status Examination (MMSE) or Mattis Dementia Rating Scale (DRS-2). We used proportional odds regression models to estimate odds ratios for higher versus lower cognitive scores in association with age, sex, education, disease duration, and APOE allele status.

Results. Higher cognitive scores were independently associated with female sex on the MMSE (OR 2.43; 95% CI 1.14, 5.14) and DRS-2 total (OR 4.14; 95% CI 2.01, 8.53). APOE ε4 dose was associated with lower DRS-2 totals (OR 0.42; 95% CI 0.22, 0.81), but there was no evidence of association with MMSE. Higher education level was also associated with higher scores on the MMSE (OR 1.22; 95% CI 1.07, 1.38) and DRS-2 total (OR 1.31; 95% CI 1.15, 1.50). Disease duration was not associated with cognitive performance on any measure when adjusting for age.

Conclusion. Male sex and APOE ε4, along with age and lower education level, were associated with poorer cognitive performance among a population of predominantly non-demented PD patients.

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Keywords

Parkinson’s Disease, cognition, sex, genetics, APOE

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About this article
Title

Effects of sex and APOE on Parkinson’s Disease-related cognitive decline

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 55, No 6 (2021)

Article type

Research Paper

Pages

559-566

Published online

2021-10-13

Page views

6942

Article views/downloads

729

DOI

10.5603/PJNNS.a2021.0071

Pubmed

34642926

Bibliographic record

Neurol Neurochir Pol 2021;55(6):559-566.

Keywords

Parkinson’s Disease
cognition
sex
genetics
APOE

Authors

Philip W. Tipton
Nazli Bülbül
Julia Crook
Zachary Quicksall
Owen A. Ross
Ryan J. Uitti
Zbigniew K. Wszolek
Nilüfer Ertekin-Taner

References (41)
  1. Corallo F, De Cola MC, Lo Buono V, et al. Observational study of quality of life of Parkinson's patients and their caregivers. Psychogeriatrics. 2017; 17(2): 97–102.
    CrossRefPubMed
  2. Litvan I, Aarsland D, Adler CH, et al. MDS Task Force on mild cognitive impairment in Parkinson's disease: critical review of PD-MCI. Mov Disord. 2011; 26(10): 1814–1824.
    CrossRefPubMed
  3. Aarsland D, Brønnick K, Larsen JP, et al. Norwegian ParkWest Study Group. Cognitive impairment in incident, untreated Parkinson disease: the Norwegian ParkWest study. Neurology. 2009; 72(13): 1121–1126.
    CrossRefPubMed
  4. Weintraub D, Simuni T, Caspell-Garcia C, et al. Parkinson's Progression Markers Initiative. Cognitive performance and neuropsychiatric symptoms in early, untreated Parkinson's disease. Mov Disord. 2015; 30(7): 919–927.
    CrossRefPubMed
  5. Yarnall AJ, Breen DP, Duncan GW, et al. ICICLE-PD Study Group. Characterizing mild cognitive impairment in incident Parkinson disease: the ICICLE-PD study. Neurology. 2014; 82(4): 308–316.
    CrossRefPubMed
  6. Broeders M, de Bie RMA, Velseboer DC, et al. Evolution of mild cognitive impairment in Parkinson disease. Neurology. 2013; 81(4): 346–352.
    CrossRefPubMed
  7. Pedersen KF, Larsen JP, Tysnes OB, et al. Natural course of mild cognitive impairment in Parkinson disease: A 5-year population-based study. Neurology. 2017; 88(8): 767–774.
    CrossRefPubMed
  8. Kehagia A, Barker R, Robbins T. Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson's disease. The Lancet Neurology. 2010; 9(12): 1200–1213.
    CrossRef
  9. Litvan I, Goldman JG, Tröster AI, et al. Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines. Mov Disord. 2012; 27(3): 349–356.
    CrossRefPubMed
  10. Emre M, Aarsland D, Brown R, et al. Clinical diagnostic criteria for dementia associated with Parkinson's disease. Mov Disord. 2007; 22(12): 1689–707; quiz 1837.
    CrossRefPubMed
  11. Hoogland J, Boel JA, de Bie RMA, et al. MDS Study Group “Validation of Mild Cognitive Impairment in Parkinson Disease”. Risk of Parkinson's disease dementia related to level I MDS PD-MCI. Mov Disord. 2019; 34(3): 430–435.
    CrossRefPubMed
  12. Fagan ES, Pihlstrøm L. Genetic risk factors for cognitive decline in Parkinson's disease: a review of the literature. Eur J Neurol. 2017; 24(4): 561–e20.
    CrossRefPubMed
  13. Iwaki H, Blauwendraat C, Leonard HL, et al. International Parkinson's Disease Genomics Consortium. Genomewide association study of Parkinson's disease clinical biomarkers in 12 longitudinal patients' cohorts. Mov Disord. 2019; 34(12): 1839–1850.
    CrossRefPubMed
  14. Kim R, Park S, Yoo D, et al. Impact of the apolipoprotein E ε4 allele on early Parkinson's disease progression. Parkinsonism Relat Disord. 2021; 83: 66–70.
    CrossRefPubMed
  15. Pierzchlińska A, Białecka M, Kurzawski M, et al. The impact of Apolipoprotein E alleles on cognitive performance in patients with Parkinson's disease. Neurol Neurochir Pol. 2018; 52(4): 477–482.
    CrossRefPubMed
  16. Konno T, Deutschländer A, Heckman MG, et al. Comparison of clinical features among Parkinson's disease subtypes: A large retrospective study in a single center. J Neurol Sci. 2018; 386: 39–45.
    CrossRefPubMed
  17. Haaxma CA, Bloem BR, Borm GF, et al. Gender differences in Parkinson's disease. J Neurol Neurosurg Psychiatry. 2007; 78(8): 819–824.
    CrossRefPubMed
  18. Tombaugh TN, McIntyre NJ. The mini-mental state examination: a comprehensive review. J Am Geriatr Soc. 1992; 40(9): 922–935.
    CrossRefPubMed
  19. Llebaria G, Pagonabarraga J, Kulisevsky J, et al. Cut-off score of the Mattis Dementia Rating Scale for screening dementia in Parkinson's disease. Mov Disord. 2008; 23(11): 1546–1550.
    CrossRefPubMed
  20. Song Y, Gu Z, An J, et al. Chinese Parkinson Study Group. Gender differences on motor and non-motor symptoms of de novo patients with early Parkinson's disease. Neurol Sci. 2014; 35(12): 1991–1996.
    CrossRefPubMed
  21. Cereda E, Cilia R, Klersy C, et al. Dementia in Parkinson's disease: Is male gender a risk factor? Parkinsonism Relat Disord. 2016; 26: 67–72.
    CrossRefPubMed
  22. Reekes TH, Higginson CI, Ledbetter CR, et al. Sex specific cognitive differences in Parkinson disease. NPJ Parkinsons Dis. 2020; 6: 7.
    CrossRefPubMed
  23. Blázquez L, Otaegui D, Sáenz A, et al. Apolipoprotein E epsilon4 allele in familial and sporadic Parkinson's disease. Neurosci Lett. 2006; 406(3): 235–239.
    CrossRefPubMed
  24. Jasinska-Myga B, Opala G, Goetz CG, et al. Apolipoprotein E gene polymorphism, total plasma cholesterol level, and Parkinson disease dementia. Arch Neurol. 2007; 64(2): 261–265.
    CrossRefPubMed
  25. Kurz MW, Dekomien G, Nilsen OB, et al. APOE alleles in Parkinson disease and their relationship to cognitive decline: a population-based, longitudinal study. J Geriatr Psychiatry Neurol. 2009; 22(3): 166–170.
    CrossRefPubMed
  26. Williams-Gray CH, Goris An, Saiki M, et al. Apolipoprotein E genotype as a risk factor for susceptibility to and dementia in Parkinson's disease. J Neurol. 2009; 256(3): 493–498.
    CrossRefPubMed
  27. Ryu HG, Kwon OhD. Apolipoprotein E epsilon 4 allele is not associated with age at onset or MMSE of Parkinson's disease in a Korean study. Parkinsonism Relat Disord. 2010; 16(9): 615–617.
    CrossRefPubMed
  28. Federoff M, Jimenez-Rolando B, Nalls MA, et al. A large study reveals no association between APOE and Parkinson's disease. Neurobiol Dis. 2012; 46(2): 389–392.
    CrossRefPubMed
  29. Pankratz N, Byder L, Halter C, et al. Presence of an APOE4 allele results in significantly earlier onset of Parkinson's disease and a higher risk with dementia. Mov Disord. 2006; 21(1): 45–49.
    CrossRefPubMed
  30. Gomperts SN, Locascio JJ, Rentz D, et al. Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia. Neurology. 2013; 80(1): 85–91.
    CrossRefPubMed
  31. Hoops S, Nazem S, Siderowf AD, et al. Validity of the MoCA and MMSE in the detection of MCI and dementia in Parkinson disease. Neurology. 2009; 73(21): 1738–1745.
    CrossRefPubMed
  32. Mata IF, Leverenz JB, Weintraub D, et al. APOE, MAPT, and SNCA genes and cognitive performance in Parkinson disease. JAMA Neurol. 2014; 71(11): 1405–1412.
    CrossRefPubMed
  33. Tsuang D, Leverenz JB, Lopez OL, et al. APOE ε4 increases risk for dementia in pure synucleinopathies. JAMA Neurol. 2013; 70(2): 223–228.
    CrossRefPubMed
  34. Guo Yu, Liu FT, Hou XH, et al. Predictors of cognitive impairment in Parkinson's disease: a systematic review and meta-analysis of prospective cohort studies. J Neurol. 2021; 268(8): 2713–2722.
    CrossRefPubMed
  35. Carrasquillo MM, Crook JE, Pedraza O, et al. Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease. Neurobiol Aging. 2015; 36(1): 60–67.
    CrossRefPubMed
  36. Zhao Na, Attrebi ON, Ren Y, et al. APOE4 exacerbates α-synuclein pathology and related toxicity independent of amyloid. Sci Transl Med. 2020; 12(529).
    CrossRefPubMed
  37. Morley JF, Xie SX, Hurtig HI, et al. Genetic influences on cognitive decline in Parkinson's disease. Mov Disord. 2012; 27(4): 512–518.
    CrossRefPubMed
  38. Hendershott TR, Zhu D, Llanes S, et al. Comparative sensitivity of the MoCA and Mattis Dementia Rating Scale-2 in Parkinson's disease. Mov Disord. 2019; 34(2): 285–291.
    CrossRefPubMed
  39. Domellöf ME, Ekman U, Forsgren L, et al. Cognitive function in the early phase of Parkinson's disease, a five-year follow-up. Acta Neurol Scand. 2015; 132(2): 79–88.
    CrossRefPubMed
  40. Livingston G, Sommerlad A, Orgeta V, et al. Dementia prevention, intervention, and care. The Lancet. 2017; 390(10113): 2673–2734.
    CrossRef
  41. Aarsland D, Muniz G, Matthews F. Nonlinear decline of mini-mental state examination in Parkinson's disease. Mov Disord. 2011; 26(2): 334–337.
    CrossRefPubMed

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