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Faster disease progression in Parkinson's disease with type 2 diabetes is not associated with increased α-synuclein, tau, amyloid-β or vascular pathology.
Neuropathol Appl Neurobiol. 2021 Dec; 47(7):1080-1091.NA

Abstract

AIMS

Growing evidence suggests a shared pathogenesis between Parkinson's disease and diabetes although the underlying mechanisms remain unknown. The aim of this study was to evaluate the effect of type 2 diabetes on Parkinson's disease progression and to correlate neuropathological findings to elucidate pathogenic mechanisms.

METHODS

In this cohort study, medical records were retrospectively reviewed of cases with pathologically confirmed Parkinson's disease with and without pre-existing type 2 diabetes. Time to disability milestones (recurrent falls, wheelchair dependence, dementia and care home placement) and survival were compared to assess disease progression and their risk estimated using Cox hazard regression models. Correlation with pathological data was performed, including quantification of α-synuclein in key brain regions and staging of vascular, Lewy and Alzheimer's pathologies.

RESULTS

Patients with PD and diabetes (male 76%; age at death 78.6 ± 6.2 years) developed earlier falls (p < 0.001), wheelchair dependence (p = 0.004), dementia (p < 0.001), care home admission (p < 0.001) and had reduced survival (p < 0.001). Predating diabetes was independently associated with a two to three-fold increase in the risk of disability and death. Neuropathological assessment did not show any differences in global or regional vascular pathology, α-synuclein load in key brain areas, staging of Lewy pathology or Alzheimer's disease pathology.

CONCLUSIONS

Pre-existing type 2 diabetes contributes to faster disease progression and reduced survival in Parkinson's disease which is not driven by increased vascular, Lewy or Alzheimer's pathologies. Additional non-specific neurodegeneration related to chronic brain insulin resistance may be involved.

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Publisher Full Text (DOI)

Authors+Show Affiliations

de Pablo-Fernández E
Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK. Department of Clinical and Movement Neurosciences, Reta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology, London, UK.
Courtney R
Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Rockliffe A
Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Gentleman S
Neuropathology Unit, Department of Brain Sciences, Imperial College London, London, UK.
Holton JL
Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK.
Warner TT
Queen Square Brain Bank for Neurological Disorders, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK. Department of Clinical and Movement Neurosciences, Reta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology, London, UK.

MeSH

AgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesBrainDiabetes Mellitus, Type 2HumansLewy Body DiseaseMaleParkinson Diseasealpha-Synucleintau Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33969516

Citation

de Pablo-Fernández, Eduardo, et al. "Faster Disease Progression in Parkinson's Disease With Type 2 Diabetes Is Not Associated With Increased Α-synuclein, Tau, Amyloid-β or Vascular Pathology." Neuropathology and Applied Neurobiology, vol. 47, no. 7, 2021, pp. 1080-1091.
de Pablo-Fernández E, Courtney R, Rockliffe A, et al. Faster disease progression in Parkinson's disease with type 2 diabetes is not associated with increased α-synuclein, tau, amyloid-β or vascular pathology. Neuropathol Appl Neurobiol. 2021;47(7):1080-1091.
de Pablo-Fernández, E., Courtney, R., Rockliffe, A., Gentleman, S., Holton, J. L., & Warner, T. T. (2021). Faster disease progression in Parkinson's disease with type 2 diabetes is not associated with increased α-synuclein, tau, amyloid-β or vascular pathology. Neuropathology and Applied Neurobiology, 47(7), 1080-1091. https://doi.org/10.1111/nan.12728
de Pablo-Fernández E, et al. Faster Disease Progression in Parkinson's Disease With Type 2 Diabetes Is Not Associated With Increased Α-synuclein, Tau, Amyloid-β or Vascular Pathology. Neuropathol Appl Neurobiol. 2021;47(7):1080-1091. PubMed PMID: 33969516.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Faster disease progression in Parkinson's disease with type 2 diabetes is not associated with increased α-synuclein, tau, amyloid-β or vascular pathology. AU - de Pablo-Fernández,Eduardo, AU - Courtney,Robert, AU - Rockliffe,Alice, AU - Gentleman,Steve, AU - Holton,Janice L, AU - Warner,Thomas T, Y1 - 2021/05/19/ PY - 2021/4/23/revised PY - 2020/12/22/received PY - 2021/5/2/accepted PY - 2021/5/11/pubmed PY - 2022/3/5/medline PY - 2021/5/10/entrez KW - Parkinson's disease KW - alpha-synuclein KW - amyloid beta KW - diabetes mellitus KW - survival KW - tau KW - vascular pathology SP - 1080 EP - 1091 JF - Neuropathology and applied neurobiology JO - Neuropathol Appl Neurobiol VL - 47 IS - 7 N2 - AIMS: Growing evidence suggests a shared pathogenesis between Parkinson's disease and diabetes although the underlying mechanisms remain unknown. The aim of this study was to evaluate the effect of type 2 diabetes on Parkinson's disease progression and to correlate neuropathological findings to elucidate pathogenic mechanisms. METHODS: In this cohort study, medical records were retrospectively reviewed of cases with pathologically confirmed Parkinson's disease with and without pre-existing type 2 diabetes. Time to disability milestones (recurrent falls, wheelchair dependence, dementia and care home placement) and survival were compared to assess disease progression and their risk estimated using Cox hazard regression models. Correlation with pathological data was performed, including quantification of α-synuclein in key brain regions and staging of vascular, Lewy and Alzheimer's pathologies. RESULTS: Patients with PD and diabetes (male 76%; age at death 78.6 ± 6.2 years) developed earlier falls (p < 0.001), wheelchair dependence (p = 0.004), dementia (p < 0.001), care home admission (p < 0.001) and had reduced survival (p < 0.001). Predating diabetes was independently associated with a two to three-fold increase in the risk of disability and death. Neuropathological assessment did not show any differences in global or regional vascular pathology, α-synuclein load in key brain areas, staging of Lewy pathology or Alzheimer's disease pathology. CONCLUSIONS: Pre-existing type 2 diabetes contributes to faster disease progression and reduced survival in Parkinson's disease which is not driven by increased vascular, Lewy or Alzheimer's pathologies. Additional non-specific neurodegeneration related to chronic brain insulin resistance may be involved. SN - 1365-2990 UR - https://www.unboundmedicine.com/medline/citation/33969516/Faster_disease_progression_in_Parkinson's_disease_with_type_2_diabetes_is_not_associated_with_increased_α_synuclein_tau_amyloid_β_or_vascular_pathology_ DB - PRIME DP - Unbound Medicine ER -