Dopaminergic- and Cholinergic-Related Structural MRI Patterns Across Cognitive Subtypes of Parkinson's Disease With Mild Cognitive Impairment.

BACKGROUND

The dual syndrome hypothesis distinguishes frontostriatal and posterior cortical cognitive subtypes in Parkinson's disease with mild cognitive impairment (PD-MCI), which are associated with distinct cognitive profiles and different risks of dementia.

OBJECTIVE

To characterize dopaminergic- and cholinergic-related structural MRI patterns across cognitive subtypes of PD-MCI.

METHODS

A total of 182 non-demented patients with Parkinson's disease (PD) and 38 healthy controls (HC) were included. Based on comprehensive neuropsychological assessments, PD patients were classified as having normal cognition (PD-NC, n = 112), PD-MCI with frontostriatal deficits (n = 20), posterior cortical deficits (n = 28), or mixed deficits (n = 22). All participants underwent T1-weighted MRI. Normalized volumetric measures of subcortical nuclei (caudate, putamen, globus pallidus, and thalamus) and the basal forebrain were obtained.

RESULTS

Distinct subtype-specific patterns of subcortical and basal forebrain atrophy were observed. PD-MCI patients with posterior cortical deficits showed significant atrophy of cholinergic nucleus 4 (Ch4) compared with HC and PD-MCI patients with frontostriatal deficits. In contrast, PD-MCI patients with frontostriatal deficits exhibited atrophy of the caudate nucleus and putamen relative to HC. The mixed deficits subtype showed putamen and thalamic atrophy compared with HC. In addition, basal forebrain Ch4 volume was significantly associated with visuospatial performance in PD-MCI patients.

CONCLUSIONS

Different PD-MCI subtypes exhibit distinct patterns of dopaminergic- and cholinergic-related structural alterations on MRI. Posterior cortical deficits are predominantly associated with cholinergic basal forebrain degeneration, whereas frontostriatal deficits are linked to dopaminergic involvement. These findings support the neural heterogeneity underlying cognitive impairment in PD.