Structural brain correlates of fatigue in older adults with and without Parkinson's disease

Abstract

Fatigue is one of the most common and disabling nonmotor symptoms seen in Parkinson's disease (PD) and is also commonly seen in healthy older adults. Our understanding of the etiology of fatigue in older adults with or without PD is limited and it remains unclear whether fatigue in PD is specifically related to PD pathology. The objective of this study was thus to determine whether fatigue in PD was associated with structural changes in gray or white matter and explore whether these changes were similar in older adults without PD. Magnetic resonance imaging (T 1 weighted) and diffusion tensor imaging were performed in 60 patients with PD (17 females; age = 67.58 ± 5.51; disease duration = 5.67 ± 5.83 years) and 41 age- and sex- matched healthy controls. FSL image processing was used to measure gray matter volume, fractional anisotropy, and leukoariosis differences. Voxel-based morphometry confirmed gray matter loss across the dorsal striatum and insula in the PD patient cohort. PD patients with fatigue had reduced gray matter volume in dorsal striatum relative to PD patients without fatigue (P < 0.05 False Discovery Rate corrected). No significant fatigue-related structural atrophy was found in controls. There were no areas of significant fractional anisotropy differences between high and low fatigue subjects in either the PD or non-PD groups. Control participants with high fatigue, but not PD, showed significantly greater total leukoariosis volumes (p = 0.03). Fatigue in PD is associated with unique structural changes in the caudate and putamen suggesting fatigue in PD is primarily related to PD pathology, particularly in the dorsal striatum, and not simply a consequence of aging.

Subjective memory decline in Parkinson's disease patients with and without fatigue

“…Growing neuroimaging evidence in PD (e.g., Refs. [6][7][8][9]) revealed the involvement of nondopaminergic prefrontal-basal ganglia loops in fatigue, consistent with the presumed 'central' origin of fatigue [10].…”

Distinct large-scale networks are associated with motor and nonmotor symptoms in Parkinson’s disease

“…These findings are in line with previous reports of cortical and subcortical atrophy pattern in PD and its relationship to motor severity (Zeighami et al, 2015;Fereshtehnejad et al, 2017). Nonmotor symptoms of PD have been linked to atrophy in the frontostriatal regions and limbic cortical and subcortical structures (Kostic et al, 2010;Reijnders et al, 2010;Carriere et al, 2014;van Mierlo et al, 2015;Vriend et al, 2016;Wee et al, 2016;Hanganu et al, 2017;Ye et al, 2018;Kluger et al, 2019). However, we found no significant correlation between the composite or individual nonmotor symptom scores and structural brain data.…”

“…A possible explanation for this discrepancy is that, unlike in most previous studies, our PD cohort as a whole did not have significant fatigue, apathy, depression, or anxiety. Moreover, we used a whole-brain approach, but not all previous reports were based on whole-brain structural data and focused on a limited number of regions selected a priori (Carriere et al, 2014;van Mierlo et al, 2015;Vriend et al, 2016;Wee et al, 2016;Kluger et al, 2019).…”

“…In the nonmotor domain, fatigue in PD has been found to be associated with atrophy in the dorsal striatum (Kluger et al, 2019), increased functional connectivity between cortical limbic and frontotemporal regions (Zhang et al, 2017) and within the default mode network (Tessitore et al, 2016); and decreased functional connectivity in the sensorimotor network (Tessitore et al, 2016). Apathy in PD has been shown to be associated with atrophy in the nucleus accumbens (Carriere et al, 2014), putamen (Ye et al, 2018) and frontoparietal and limbic regions (Reijnders et al, 2010;Ye et al, 2018), as well as with reduced functional connectivity between predominantly limbic frontostriatal regions (Baggio et al, 2015).…”

Environmental toxicant exposure and Parkinson’s disease: LRRK2 and inflammatory processes

“…Moreover, human MRI studies reported that PD patients had reduced hippocampal volume and this was asymmetrical (with left hemisphere most affected) [268]. The dorsal striatum was also diminished in PD patients and this effect was exacerbated in patients with excessive fatigue [269]. In contrast, while we did find enlarged ventricular size, we did not find any reduction of volume in the nigrostriatal pathway or hippocampus.…”