Clinical and Structural Markers Associated with Cognitive Impairment in Non-Demented Parkinson’s Disease Patients

Abstract

Parkinson's disease (PD) is associated with motor as well as a variety of non-motor symptoms (NMS). Cognitive disorders are one of the most common NMS in PD and reduce patients’ quality of life. Patients with mild cognitive impairment (PD-MCI) are at higher risk of developing Parkinson's disease (PDD), but not all eventually develop PDD. Currently, no single marker can predict the development of a PDD in a short time. Therefore, identifying risk factors for the progression of cognitive disorders remains an important research priority. The aim of the present thesis was to investigate the relationships between possible risk markers in non-demented patients. Loss of the ability to perform activities of daily living (ADL) related to cognitive, but not motor, functioning is the core criterion for diagnosing PDD. In the first publication we were able to differentiate cognitive from motor influences on ADL function based on newly developed scores from the Functional Activities Questionnaire (FAQ). PD-MCI patients with cognitive-driven ADL impairments exhibited stronger deficits in the attention and language domains than those with motor-driven ADL dysfunction. Based on these study results, the second publication aimed to investigate the relationship between cognitive disorders and other prodromal markers of PDD (depression, anxiety, sleep disorders and hallucinations, DASH). The DASH score was able to differentiate between cognitive groups and was significantly associated with cognitive ADL impairment, as defined by the FAQ. A combination of DASH burden and cognitive ADL impairment shows promise in characterizing a risk group for PDD among PD-MCI. The last publication was primarily concerned with coexisting Alzheimer's pathology in PD, namely the hippocampus as a structural marker and Alzheimer's pathology (amyloid-β and tau) in cerebrospinal fluid as a biomarker. Although both play a role in PDD development, their association with cognitive progression is still unclear. Study results suggest that the hippocampal amygdaloid transition area has the potential to differentiate cognitive status in PD, while hippocampal subfields were associated with memory, language, spatial working memory, and executive functions. No association was found between hippocampal subfields and amyloid-β 1-42; however, tau values correlated with smaller hippocampal volumes. The results of this work emphasize that combinations of dementia risk markers (especially ADL function and DASH symptoms) show associations with cognitive function in the prodromal stage of PDD. Longitudinal studies are now needed to determine whether the groups identified are at a high risk for developing dementia.