Abstract
Degeneration of the substantia innominata (SI) is significantly correlated with cognitive performance in Parkinson’s disease (PD). We examined functional and structural patterns of SI degeneration in drug-naïve PD patients according to the duration of parkinsonism before mild cognitive impairment (MCI) diagnosis. Twenty PD patients with a shorter duration (PD-MCI-SD, <1 year), 18 patients with a longer duration (PD-MCI-LD, ≥1 year), and 29 patients with intact cognition (PD-IC) were included. Seed-based resting-state functional connectivity (rsFC) analysis using bilateral SI seed and region-of-interest-based volumetric analysis were performed. Compared to PD-IC, the collapsed PD-MCI group showed altered rsFC in the right frontal and bilateral parietal areas. PD-MCI-SD showed rsFC alteration in broader frontal and parietal areas compared to the other groups. Decreased rsFC in the right frontal area was also significantly correlated with shorter disease duration. No significant SI volume change was found between the groups. Altered rsFC between the SI and the frontal and parietal areas might be relevant to cognitive dysfunction in PD. Decreased rsFC between the SI and frontal area might be associated with early-onset MCI, suggesting that cholinergic deficits in the frontal brain areas might play an important role in the acceleration of cognitive decline in PD.
Highlights
There was no significant structural change in substantia innominata (SI) between the groups; we found altered resting-state functional connectivity (rsFC) in the corticopetal cholinergic network according to the cognitive status and duration of parkinsonism before mild cognitive impairment (MCI) diagnosis in Parkinson’s disease (PD) patients
Decreased rsFC in the frontal areas and increased rsFC in the parietal areas with SI seed were associated with cognitive decline in drug-naïve PD patients
Decreased rsFC in the frontal area was associated with shorter disease duration before MCI diagnosis, suggesting that this area possibly plays a role in increasing the rate of cognitive decline
Summary
Degeneration of the substantia innominata (SI) is significantly correlated with cognitive performance in Parkinson’s disease (PD). Compared to PD-IC, the collapsed PD-MCI group showed altered rsFC in the right frontal and bilateral parietal areas. Decreased rsFC between the SI and frontal area might be associated with early-onset MCI, suggesting that cholinergic deficits in the frontal brain areas might play an important role in the acceleration of cognitive decline in PD. This different underlying neuropathology may influence both the functional and structural patterns of SI degeneration. Given that cholinergic projections from the SI innervate the entire cerebral cortex, we need to identify the specific brain cortical regions relevant to early-onset MCI, in other words, rapid cognitive decline, to understand the underlying pathophysiology of SI degeneration and to define new treatment targets. Year Age at onset, year Male, n (%) Education duration, year Parkinsonism duration prior to MCI, month, median (range) UPDRS III K-MMSE BDI Interval between MR scan and NP test, d, median (range)
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