de Pablo-Fernández, E;
Courtney, R;
Rockliffe, A;
Gentleman, S;
Holton, JL;
Warner, TT;
(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)
pp. 1080-1091.
10.1111/nan.12728.
Preview |
Text
nan.12728.pdf - Accepted Version Download (16MB) | Preview |
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 is 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.
| Type: | Article |
|---|---|
| Title: | Faster disease progression in Parkinson's disease with type 2 diabetes is not associated with increased α-synuclein, tau, amyloid-β or vascular pathology |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/nan.12728 |
| Publisher version: | https://doi.org/10.1111/nan.12728 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Parkinson’s disease, alpha-synuclein, amyloid beta, diabetes mellitus, survival, tau, vascular pathology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Clinical and Movement Neurosciences |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10127765 |
Archive Staff Only
 |
View Item |
