Cognitive impairment in Parkinson’s disease: Impact and identification of comorbid disease mechanisms

Smith, Callum R. (2020) Cognitive impairment in Parkinson’s disease: Impact and identification of comorbid disease mechanisms. PhD thesis, University of Glasgow.

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Abstract

Cognitive impairment is a common and debilitating feature of Parkinson's disease (PD). While it is primarily caused by cerebral propagation of α-synuclein protein, evidence of comorbid diseases is frequently found in autopsy samples. This includes tau and amyloid-β pathologies – the hallmarks of Alzheimer's disease (AD) – and cerebrovascular damage. Comorbid diseases may influence cognition in PD over and above the effects of α-synuclein alone, and this influence may interfere with the results of clinical trials of next-generation medical treatments that target α-synuclein.

The primary aims of this thesis were to define the extent and the effects of comorbid disease mechanisms in PD, and to identify viable clinical strategies for detecting coexistent disorders in vivo. Methods included a systematic review of autopsy studies; a factor analysis of the Montreal Cognitive Assessment (MoCA); a regression analysis of two genes; and a cross-sectional neuropsychological study of 45 patients.

The systematic review found significant tau pathology in around one-third of PD patients at death. Significant amyloid-β pathology affected over half, and conferred a worse prognosis. Other pathologies (e.g. cerebrovascular disease) were less common, and did not contribute to dementia in PD. The factor analysis showed that the MoCA has limited value for distinguishing cognitive profiles in PD, suggesting that it should be used only for screening. The genetic project found that variation in the APOE gene influenced cognitive decline in early PD; the effect varied between men and women. Variation in MAPT did not affect cognitive decline. Finally, the neuropsychological study found that over half of cognitively impaired PD patients could be clinically diagnosed with a coexistent cognitive disorder, with AD being the most common.

Collectively, the results of this thesis show that comorbid diseases, particularly AD, are common in PD, and these contribute to the cognitive phenotype. Consequently, a clinical assessment incorporating selected neuropsychological tests can be used to identify comorbid diseases in PD patients. It is important to consider the potentially confounding impact of multimorbidity in the design and analysis of clinical trials that aim to modulate neurodegeneration in PD by targeting α-synuclein.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Parkinson's disease, cognitive impairment, dementia.
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Supervisor's Name: Grosset, Dr. Donald and Cullen, Dr. Breda and Jonathan, Professor Cavanagh and Matthew, Dr. Sheridan
Date of Award: 2020
Depositing User: Mr Callum Smith
Unique ID: glathesis:2020-77862
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 22 Jan 2020 11:42
Last Modified: 11 Mar 2020 16:07
URI: http://theses.gla.ac.uk/id/eprint/77862
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