Functional Connectivity Changes Indicate Cerebellar Network Compensation in Early Alzheimer’s Disease
Chi-Ying (Roy) Lin1, Shayla Yonce1, Hyuntaek Oh2, Melissa Yu1, Jonathan Sober1, Valory Pavlik1, Ramiro Salas2
1Neurology, 2Psychiatry, Baylor College of Medicine
Objective:
We examined lobule-specific cerebello-cerebral functional connectivity in early Alzheimer's disease (AD), aiming to i) characterize the reorganization of cerebello-cerebral networks and ii) assess whether these connectivity changes reflect compensatory recruitment to sustain cognition in early AD.
Background:
The cerebellum is increasingly recognized as a key contributor to cognitive networks. Prior work suggests compensatory cerebellar involvement in mild cognitive impairment, the prodromal stage of AD. Whether such compensation persists into early clinical AD remains unknown.
Design/Methods:
Twenty early AD (Mini-Mental Status Exam score of 22 to 28) and 19 cognitively normal participants underwent resting-state functional MRI. Seed-based functional connectivity analyses were performed for individual cerebellar lobules, with between-group comparison and correlations with clinical measures, including Clinical Dementia Rating–Sum of Boxes(CDR-SB) and 13- item AD Assessment Scale-Cognitive(ADAS-Cog).
Results:
Early AD participants showed reduced cerebello-thalamic and cerebello-parietal functional connectivity; however, greater functional connectivity was identified between the cerebellum (lobule III, VI, and VIIb) and the i) cerebral sensorimotor (e.g., the postcentral and precentral gyrus), ii) auditory (e.g., the Heschl's gyrus), and iii) paralimbic cortices. This indicates a shift away from canonical associative loops toward recruitment of additional, noncanonical networks. Stronger functional connectivity was significantly correlated with cognitive subdomain of orientation, constructional praxis, and command, rather than global severity. In controls, the association between cerebello-cerebral functional connectivity and cognition primarily involved canonical frontoparietal and temporal networks. By contrast, in early AD, these relationships shifted toward noncanonical networks in limbic and paralimbic regions.
Conclusions:
Early AD is marked by lobule-specific reorganization of cerebello-cerebral networks, displayed as weakening of canonical loops with compensatory recruitment of alternative circuits. These findings highlight the cerebellum’s ongoing role in sustaining cognition despite cerebral cortical networks become disrupted in early AD. Our results suggests that stage- and domain-specific cerebellar connectivity may serve as a novel imaging biomarker of the cerebellum-driven compensatory network in early AD.
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