Diffusion Tensor Imaging of white matter alterations in the aging population: Association with gait, cognition and risk of developing neurodegenerative disease

Abstract

Neurodegenerative diseases progress slowly, often taking years before clinical diagnosis. In the prodromal phase preceding diagnosis, individuals may exhibit subtle signs of neurodegeneration, including gait and cognitive impairments. Identifying these early signs is crucial for effective intervention and disease management, as it provides valuable insights into early disease mechanisms. This dissertation employs DTI to explore the complex interplay among WM alterations, motor and cognitive deficits, and the risk of developing neurodegenerative disease in the aging population.

In the first analysis we focused on individuals with risk factors for PD (Parkinson’s disease risk persons, PD-RP), specifically hyposmia, RBD and history of depression. The analysis revealed no significant differences in DTI-parameters across the whole-brain WM compared to the control group. Also, no correlation was found between DTI-parameters and the severity of the utilized risk factors. However, based on evidence of cognitive impairment in the prodromal phase of PD, particularly EF impairment, we conducted an additional correlation analysis between TMT B-A and DTI-parameters. Despite no significant difference in TMT between groups, a positive correlation between TMT B-A performance and DTI-parameters was observed in frontoparietal pathways within PD-RP group, indicating that deficits in EF in PD-RP might be more related to WM alterations than in healthy older adults.

The second analysis expanded upon the findings of the first and included both the PD-RP and the control group as a whole cohort. This approach was based on the fact that PD-RP, while at risk, have not been clinically diagnosed with a neurodegenerative disease. The cohort thus consisted of community-dwelling older adults with no significant gait or cognitive impairments. Given that gait deficits are common in the age group and can serve as an early indicator of neurodegeneration, albeit often concealed by compensatory strategies, we sought to uncover potential hidden impairments using cognitive-motor dual-tasking. Our investigation aimed to determine whether gait impairments under DT conditions were associated with WM alterations. Considering the frequent occurrence of dual-task gait impairments in individuals with EF deficits and the presumed involvement of common cognitive-motor WM pathways, we also explored the role of EF and the possibility of shared WM pathways. The analysis revealed significant correlations between gait impairment under DT conditions and FA in widespread WM pathways. Moreover, the performance of motor and cognitive tasks under DT conditions correlated significantly with FA in the bilateral ACR. While EF performance was associated with FA in the left ACR, it did not effectively mediate the effects of WM integrity on DTC of gait speed.

In summary, the findings demonstrate an interplay between WM integrity and motor-cognitive deficits in aging. DTI did not differentiate PD-RP from controls based on risk factors alone, but revealed an association between WM alterations and EF deficits in PD-RP. Moreover, gait decline under DT conditions appears to be an early sign of WM deterioration, even in older adults without apparent cognitive or motor impairments. This can be partly attributed to the deterioration of shared WM pathways between the cognitive and motor tasks and pathways involved in EF. These insights highlight the utility of EF and DT gait testing for early neurodegenerative disease detection, with DTI offering crucial insights into early neurodegenerative changes and specific neural pathways involved.