Cognitive impairment in lewy body diseases: treatments and assessments

Thesis

This thesis explores the efficacy, and cognitive implications of pharmacological treatments for Lewy body diseases (LBD), alongside cognitive profiling and remote assessment methodologies. A network meta-analysis of 22 randomised controlled trials, involving over 3300 patients with Parkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB), revealed that rivastigmine is likely to be the most effective treatment for cognitive and neuropsychiatric symptoms even though it is associated with significant adverse events. Experimental studies examining the effects of rivastigmine on eye movements and reward sensitivity demonstrated significant improvements in saccadic measures but no enhancement in reward sensitivity, suggesting a limited role for cholinergic modulation in reward processing. Cognitive profiling using remote online tools detected distinct deficits in attention, executive function, memory and language among Parkinson’s disease (PD) and REM sleep behavioural disorder (RBD) patients, supporting the dual syndrome hypothesis of early dopaminergic and later cholinergic dysfunctions. The feasibility of remote cognitive testing in clinical trials was confirmed, with high completion rates indicating its potential for broader application despite challenges related to technical variability. A study examining the relationship between dopaminergic function and cognitive/motor performance found a double dissociation, with cognitive measures correlating with frontal dopamine transporter (DAT) uptake and motor measures correlating with striatal DAT uptake, reinforcing the role of these networks in cognitive and motor functions. This thesis highlights the importance of individualised treatment, the development of specialised cognitive tools and the integration of remote assessments into clinical practice. Future research should focus on extended longitudinal studies and advanced imaging techniques to further elucidate the progression of cognitive decline and optimise therapeutic strategies for LBD.

Authors: Alhajraf, FH

• DOI: 10.5287/ora-dqzz1bap5
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: drug treatment; neuroimaging; cholinergic and dopaminergic dysfunctions; dopamine; remote cognitive assessments; neuropsychology; vision; rivastigmine; dementia with lewy bodies; Parkinson's disease dementia; Lewy body diseases; acetylcholine; drug trials; network meta-analysis; Parkinson's disease; cognitive impairment
• Subjects: Neurology; Neuropsychopharmacology; Lewy body dementia; Clinical trials; Clinical pharmacology; Dementia