The cerebellum could serve as a potential imaging biomarker of dementia conversion in patients with amyloid-negative amnestic mild cognitive impairment

Abstract

Background and purpose: As part of network-specific neurodegeneration, changes in cerebellar gray matter (GM) volume and impaired cerebello-cerebral functional networks have been reported in Alzheimer disease (AD). Compared with healthy controls, a volume loss in the cerebellum has been observed in patients with continuum of AD. However, little is known about the anatomical or functional changes in patients with clinical AD but no brain amyloidosis. We aimed to identify the relationship between cerebellar volume and dementia conversion of amyloid-negative mild cognitive impairment (MCI).

Methods: This study was a retrospective cohort study of patients over the age 50 years with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center with no less than a 36-month follow-up period. All subjects underwent detailed neuropsychological tests, 3 T brain magnetic resonance imaging scans including three-dimensional T1 imaging, and fluorine-18[F¹⁸ ]-florbetaben amyloid positron emission tomography scans. A spatially unbiased atlas template of the cerebellum and brainstem was used for analyzing cerebellar GM volume.

Results: During the 36 months of follow-up, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairments in all visual memory tasks. In terms of volumetric analysis, reduced crus I/II volume adjusted with total intracranial volume, and age was observed in the converter group.

Conclusions: Significant cerebellar GM atrophy involving the bilateral crus I/II may be a novel imaging biomarker for predicting dementia progression in amyloid-negative amnestic MCI patients.

Keywords: Alzheimer disease; amyloid; cerebellum; florbetaben; mild cognitive impairment.