Recently, the conceptualisation of Parkinson’s disease (PD) has shifted from a classical motor disorder to a neurodegenerative condition associated with both motor and non-motor symptoms, such as cognitive impairment. At present, the underlying causes of cognitive impairment in PD remain only partially understood, underscoring the need to establish imaging biomarkers (such as brain volumes or cortical thickness) that are capable of aiding the identification of patients at increased risk of developing dementia (PDD).
A recent magnetic resonance imaging (MRI) study from the Department of Psychiatry has provided evidence that PD patients with co-occurring mild cognitive impairment (PD-MCI) exhibited a distinct pattern of cortical thinning compared to those who remained cognitively stable (PD-NC). The findings, published in the journal Brain, also highlighted the growing recognition of longitudinal MRI as a sensitive technique to track disease progression over time, as well as serving as an outcome measure to assess the efficacy of novel therapies.
Led by Elijah Mak, a Gates Scholar from Professor John O’Brien’s Old Age Psychiatry Group, the study followed newly diagnosed PD patients over a period of 18 months with repeated neuropsychological and neuroimaging assessments to quantify cognitive decline and cortical thickness – a brain measure used to quantify the combined thickness of the layers of the cerebral cortex. Previous studies have found robust associations between thicker cortices and better cognitive abilities. Based on their performances in domains including executive function, attention, visuospatial ability, episodic memory and language, PD patients were subsequently categorised as PD-MCI or PD-NC. At baseline, there were no significant differences in cortical thickness between PD-NC and healthy controls. However, the PD-NC group subsequently developed significant cortical thinning in the frontal regions of the brain over 18 months, suggesting that cortical thinning may precede cognitive impairment. Based on this finding, the researchers proposed that compensatory functional mechanisms might be masking or buffering against cognitive decline during the early stage of the disease.
In contrast, PD-MCI patients exhibited a more widespread and rapid pattern of cortical thinning at baseline and over 18 months, involving the frontal regions as well as an extension to the posterior regions such as the temporal and parietal cortices. The widespread pattern of cortical thinning is consistent with prevailing theories of neurochemical deficits underpinning cognitive impairment in PD. Furthermore, the temporal and parietal regions have often been associated with memory and visuospatial function, both of which are common cognitive deficits in PD. Interestingly, the observed spatial pattern of cortical thinning in PD-MCI patients has also been regarded as a marker of Alzheimer’s disease in other studies while thinning in the temporal cortex is implicated in PDD patients.
Regarding the significance of this study, Elijah Mak stated: “Although cross-sectional neuroimaging studies in PD have made important contributions to our early understanding of its pathological effects on the brain, they only capture a single snapshot of a pathological process that often spans a decade. As such, there is still a lot that we do not know about the trajectory of brain changes over time and therefore our longitudinal design allowed us to probe these questions. In future, we intend to investigate the integrity of white matter tracts from diffusion weighted imaging data.”
Elijah will be presenting this study at the International Dementia with Lewy Bodies Conference 2015 in Florida.