Cerebello-parietal Functional Connectivity in Amnestic Mild Cognitive Impairment Due to Alzheimer’s Disease
Chi-Ying Lin1, Shayla Yonce1, Nat Pacini1, Melissa Yu1, Jeffrey Bishop1, Valory Pavlik1, Ramiro Salas2
1Neurology, 2Neuroscience, Baylor College of Medicine
Objective:
To characterize the cerebello-cerebral functional connectivity (FC) in amnestic mild cognitive impairment (aMCI).
Background:
The cerebellum has disease-specific volume change in Alzheimer’s disease (AD). However, as the brain region typically spared in early stage of AD, the characteristic of cerebello-cerebral functional circuits and its clinical correlates remains to be determined.
Design/Methods:
We recruited 15 controls and 16 aMCI participants. All participants received the Montreal Cognitive Assessment (MoCA), AD Assessment Scale-Cognitive subscale (ADAS-Cog), and resting state functional MRI, analyzed by the Conn Functional Connectivity Toolbox. Lobule-specific cerebello-cerebral connectivity was conducted using seed-to-voxel analysis with the cerebellar seeds/region of interests placed in the cognitive cerebellar lobules, specifically, lobule VI, VII, Crus I and II. We then compared the cerebello-cerebral FC between aMCI vs. controls (i.e., by diagnosis) and between people with higher (MoCA ≥ 25) vs. lower cognitive function (MoCA = 21-24). Clinico-imaging correlates between the ADAS-Cog and cerebellar FC was also studied.
Results:
Using the complete set of significance with peak voxel p < 0.001 and cluster threshold p-FDR < 0.05, we identified when compared to controls, aMCI demonstrated significantly weaker FC between left VIIb of the cerebellum and right supramarginal gyrus of the parietal lobe. Participants with lower cognitive function demonstrated significantly weaker FC between the cerebellar left Crus II and the right superior parietal lobe as well as right supramarginal gyrus of the parietal lobe. Interestingly, higher ADAS-Cog score (i.e., worse cognitive function) was correlated with stronger, instead of weaker FC between the cerebellar right VIIb and thalamus, suggesting the cerebellum might provide a compensatory effect on cognitive function in aMCI via the cerebello-thalamo-cortical pathway.
Conclusions:
The alteration of cerebello-parietal functional network commences from aMCI, the early stages of AD. It is essential to explore whether augmenting cerebello-thalamo or cerebello-parietal FC through neuromodulation could provide insights into future symptomatic and disease-modifying therapeutic implication.