Neurology: Relationship between the white matter network and the striatal dopamine depletion pattern in patients with Parkinson's disease

Parkinson's disease (PD) is a heterogeneous neurodegenerative disease with individual differences in clinical phenotype and rate of disease
progression.
This clinical heterogeneity suggests that there are different subtypes of Parkinson's disease, and several studies have attempted to define subtypes
of Parkinson's disease based on clinical presentation and biomarkers.
The pattern of dopaminergic innervation in the substantia nigrastriatum, which varies in individuals with Parkinson's disease and persists throughout the course of the disease, has been suggested as a possible marker for characterizing Parkinson's disease subtypes in autopsy and in vivo PET imaging studies
.

Recently, studies have demonstrated that patterns of striatal dopamine depletion (i.
e.
, which striatal subregions are selectively involved or relatively reserved) can provide information about the long-term prognosis of patients with early Parkinson's disease, including motor complications and the development of
dementia.
Individual differences in dopaminergic innervation in the substantia nigra are an important factor
in the clinical heterogeneity of Parkinson's disease (PD).
A study published in Neurology aims to explore whether the pattern of striatal dopamine depletion is related
to the white matter network (WM) in Parkinson's disease patients.

A total of 240 newly diagnosed Parkinson's patients participated in the study, who underwent an 18F-FP-CIT PET scan and brain diffusion tensor imaging
during the initial evaluation.
Measurement of 18F-F-F-CIT tracer uptake as an indirect marker
of striatal dopamine depletion.
Factor Analysis - Each patient was assessed on the striatal dopamine loss pattern based on the availability of the striatal dopamine transporter to calculate the composite score
of the four striatal subregional factors (caudate nucleus, more and less affected sensorimotor striatum, and anterior putamen).
Through network-based statistical analysis, the WM structural network
correlated with the composite score of each striatal subregion factor was identified.

A higher overall score of the caudate nucleus (ie, relatively well-preserved dopaminergic innervation in the caudate nucleus) is associated with
stronger structural connectivity in a single subnetwork consisting of the left caudate gyrus and the left frontal gyrus.
Selective loss of caudate nuclear dopamine is associated
with strong connectivity in a structural subnetwork of connected anterior cingulate nuclei centered on the bilateral thalamus and left insulus.

However, no subnetwork correlated with
composite scores for other subregional factors of the striatum.
Networks positively correlated with the caudate nucleus connectivity dominance composite score directly or indirectly affect frontal/executive function, possibly through mediating dopamine depletion in the caudate nucleus
.

The findings suggest that different patterns of striatal dopamine consumption are strongly associated with structural alterations in WM, which may lead to heterogeneity
in cognitive characteristics in PD patients.

Sources:

Öhrfelt A, Benedet AL, Ashton NJ, et al.
Association of CSF GAP-43 With the Rate of Cognitive Decline and Progression to Dementia in Amyloid-Positive Individuals [published online ahead of print, 2022 Oct 3].
Neurology.
2022; 10.
1212/WNL.
0000000000201417.
doi:10.
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