To elucidate the role of the cerebellum in mild cognitive impairment (MCI) and Alzheimer’s disease (AD).

Previous studies found the cerebellar volume changes over the disease course of AD. However, the role of the cerebellum and its association with cognitive function in MCI and AD remains unclear.

We analyzed data from Alzheimer’s Disease Neuroimaging Initiative (ADNI; n = 230 in controls, 399 in MCI, and 193 in AD) and assessed cognitive function with the Alzheimer’s Disease Assessment Scale-Cognitive Behavior section (ADAS-Cog). We used linear regression and linear mixed effects models to examine whether cerebellar volume is associated with either baseline cognition or with cognitive changes over time in MCI or in AD. We used logistic regression to assess the relationship between cerebellar volume and disease progression to MCI and AD.

Mean cerebellar volume exhibited a step-wise decrease across the disease stage (NC vs. MCI vs. AD = 8.02% ± 0.82% vs. 7.87% ± 0.83% vs. 7.77% ± 0.93%, p = 0.007, % = the percentage of intracranial volume). Interestingly, within MCI, larger cerebellar volume was associated with lower baseline cognitive function (ADAS-Cog13, β = 0.13, p = 0.003) after adjusting for age, gender, education, hippocampal volume, and APOE4 status. Similarly, cerebellar volume was associated with increased odds of being diagnosed with MCI (compared to controls; odds ratio = 1.36, p = 0.01), but was not associated with increased odds of AD diagnosis compared to MCI. However, cerebellar volume was not associated with cognitive changes over time in either MCI or AD.

Increased cerebellar volume may be a result of maladaptive compensation for decreased cognitive function in MCI, but not in AD, indicating the role of the cerebellum and cerebellar network modulation in this early stage of the disease. The cerebellum may be a potential target for neuromodulation in treating MCI.