npj Parkinsons Dis: How does white matter structure change in early tremor-dominant Parkinson's?

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by predominant motor symptoms, including stiffness, resting tremor, and bradykinesia, manifested by selective loss of dopaminergic neurons in the substantia nigra and alpha- Synapsin is widely aggregated in the form of Lewy neurons and Lewy bodies
.
Two main subtypes of Parkinson's disease (PD) have been described according to the predominance of specific motor signs at diagnosis : tremor-dominant (TD) and postural instability and gait disturbance (PIGD)
.

It has been argued that TD-PD and PIGD-PD have inconsistent patterns of clinical progression
.
PIGD-PD is associated with a faster rate of motor decline and a weaker response to levodopa therapy, whereas TD-PD is known to have a better prognosis and slower disease progression
.
The different clinical manifestations and progression of these two PD motor subtypes suggest different underlying neural mechanisms
.
Previous autopsy studies have shown that PIGD-PD patients have greater cellular loss of dopaminergic and non-dopaminergic neural circuits than TD-PD patients
.
However, while a detailed understanding of white matter (WM) changes in TD-PD and PIGD-PD, especially at early stages, is critical for successfully guiding future disease modification strategies, to date, TD-PD and PIGD-PD have The WM structural changes have not been fully elucidated
.

Diffusion tensor imaging (DTI) is currently the most widely used method to estimate changes in WM microstructural integrity in PD
.
PD is usually associated with a reduction in fractional anisotropy (FA)
.

Fractional anisotropy corresponds to the degree of orientation of water diffusion, reflecting the integrity of white matter
.
However, a recent study in patients with early TD-PD reported greater FA values ​​in the WM motor pathway compared to healthy controls (HC) and PIGD-PD patients, which was interpreted as more WM tissue to compensate Results of PD pathology
.
However, given the limitations of tensor models, this interpretation may not be strictly accurate
.

The inability to resolve the multiple fiber orientations of intersecting or kissing fiber regions, which include up to 90% of WM voxels in the brain, can lead to unreliable estimates of DTI measurements in these regions
.
Selective deletion of specific fiber orientations in the intersecting fiber region may also lead to an increase in FA
.
Furthermore, FA is influenced by many tissue characteristics, including axon diameter, fiber density, tissue geometry, and degree of myelination; therefore, interpretation of changes in this indicator must be done with caution
.

Advances in diffusion modeling techniques allow the quantification of WM fiber properties in the presence of complex fiber geometries
.
Fixed-point based analysis (FBA) is a framework that facilitates the measurement of specific groups of fiber tracts within voxels or so-called "fixed points"
.

Briefly, FBA utilizes fiber orientation distributions (FODs) estimated by constrained spherical deconvolution (CSD), enabling measurement of microstructural differences in fiber density (FD), macroscopic fiber bundle cross-sections (FC) Structural differences or differences resulting from the combination of FD and FC (fiber density and cross-section [FDC])
.

In the developing brain, the increase in fixel may be due to an increase in axonal diameter or axonal number, while the decrease in these indicators may be due to axonal loss or atrophy, as in PD
.

Whether the WM microstructural changes detected in early PD, especially TD-PD (as measured by increased FA) detected on DTI, reflect selective neurodegenerative or compensatory mechanisms, remains unknown
.
Furthermore, understanding the pathogenesis of PD at the initial stage is critical for more effective treatment of these patients
.

In the current cross-sectional study, Christina Andica et al.
of Juntendo University Graduate School of Medicine, Japan, applied FBA to assess fiber-specific WM changes in drug-naïve patients with early TD-PD and PIGD-PD
.

Using FBA-based, they assessed fiber-specific white matter (WM) changes in drug-naive patients with early Parkinson's disease (PD), who were predominantly tremor (TD; n = 53; mean age, 61.
7 ± 8.
7 years).
) and postural instability and gait disturbance (PIGD; n = 27; mean age, 57.
8 ± 8.
1 years), motor subtypes, and age- and sex-matched healthy controls (HC; n = 43; mean age, 61.
6 ± 9.
2 years) )
.

FBA revealed a significant increase in the cross-section of large structural fibers within the corticospinal tract and the combination of fiber density and cross-sectional metrics in TD-PD patients compared with HC .

However, no significant changes were found in FBA-derived measures in PIGD-PD patients compared with HC or TD-PD patients
.

These results provide: Evidence for WM neurocompensatory mechanisms in TD-PD patients marked by increased fiber tract size and the ability to transmit information between brain regions
.

Source:
Andica C, Kamagata K, Saito Y, et al.
Fiber-specific white matter alterations in early-stage tremor-dominant Parkinson's disease.
npj Parkinsons Dis .
2021;7(1):51.
doi:10.
1038/s41531- 021-00197-4