Cerebellar atrophy in biologically confirmed Alzheimer's disease: Associations with amyloidopathy measured by cerebrospinal fluid biomarkers

Background Recently, a role of the cerebellum in cognition has emerged leading to the investigation of its involvement in neurocognitive diseases, such as Alzheimer's disease (AD). A few studies have shown an atrophy of the cerebellar lobes Crus I and II specifically in clinically defined AD patients. So far, no study has been performed to explore the link between biologically defined AD and cerebellar atrophy. Objective To explore in a large cohort, if biological AD profile was associated with cerebellar atrophy and to explore the determinants of this possible association. Methods We used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI2) database, a large prospective and multicentric study. We collected behavioral, structural magnetic resonance imaging and cerebrospinal fluid (CSF) biomarkers data. Groups were clinically and biologically defined using ATN classification. We compared cerebellar volumes based on ATN status. Results 585 participants were analyzed: 295 with biologically defined AD (A + T + or A + T- CSF- profile) and 290 non-AD (A-T- or A-T + CSF profile). Biological AD participants had a significant loss of volume in the Crus II cerebellar lobes compared with non-AD participants (F(1581) = 4.7, p = 0.03), independently from clinical status. In addition, Crus II morphological changes were linked to A + status (F(1564) = 10.6, p = 0.001) and not to T + status, with the existence of a significant correlation between Aβ 1−42 CSF quantification and Crus II volumes (ρ=0.11, p = 0.007). Conclusions Biologically confirmed AD is associated with a selective and early atrophy of the Crus II cerebellar lobes, which seems associated with brain amyloidopathy.