Alzheimer’s Disease and the Cerebellum: A Morphologic Study on Neuronal and Glial Changes

Abstract

Structural manifestations of Alzheimer’s disease (AD) including neuronal loss were investigated in 12 cases of AD and in 10 healthy age-matched controls, with focus on the cerebellum. Linear Purkinje cell (PC) density was measured in the vermis and cerebellar hemispheres. Neurons were also counted in the inferior olivary nucleus. In vermis of the AD cases, the mean PC number was significantly lower (p = 0.019) than in the controls. The neurons in the inferior olive were similarly fewer, though not significantly (p = 0.13). Molecular layer gliosis and atrophy in the vermis was clearly severer in AD than in the controls. Features typical of cerebral Alzheimer encephalopathy (plaques, tangles and microvacuolization) were inconspicious. The structural cerebellar changes in the AD cases were thus neuronal loss, atrophy and gliosis, judged to represent the disease process, and with a main involvement in the vermis. This may be reflected in some of the symptoms and signs seen in AD, signs that are generally overlooked or judged to be of noncerebellar origin.

Cerebellar volume in patients with dementia

“…33 Diaschisis is the cerebellar reduction related to the atrophy of superior structures and is commonly observed at late stages of dementia. 13 The main hypothesis suggesting the implication of the cerebellum in dementia invokes a possible role for diaschisis, 13,23,30 but our results show that cerebellar volume reductions can be observed even at early stages of the disease. Moreover, there are reports that secondarily affected regions could present mild atrophy and no histopathological changes, 33 and this is what we investigated here.…”

“…29 Previous studies have reported cerebellar abnormalities in dementia. 13,30,31 In neuropathological studies, neuronal shrinkage and loss are well known changes that accompany AD and are most notable in the temporoparietal neocortex, limbic system, and some neuronal groups such as the locus coeruleus of the brain stem and the basal nucleus of Meynert in the basal forebrain. 30 Morphological studies, conversely, have focused on the traditional neuropathological hallmarks of AD, such as amyloid plaques, neurofibrillary tangles, and amyloid angiopathy, 30 and little has been reported on neuronal loss and other structural changes in AD.…”

“…13,30,31 In neuropathological studies, neuronal shrinkage and loss are well known changes that accompany AD and are most notable in the temporoparietal neocortex, limbic system, and some neuronal groups such as the locus coeruleus of the brain stem and the basal nucleus of Meynert in the basal forebrain. 30 Morphological studies, conversely, have focused on the traditional neuropathological hallmarks of AD, such as amyloid plaques, neurofibrillary tangles, and amyloid angiopathy, 30 and little has been reported on neuronal loss and other structural changes in AD. 13 There is only one structural MRI study that has previously demonstrated that the posterior cerebellar lobes are smaller in AD patients when compared to healthy controls, and that this atrophy is associated with poorer cognitive performance in AD subjects, but not in MCI patients.…”

“…Possible reasons for cerebellar volume reductions in dementia include vascular factors, toxins (e.g. alcoholic dementia), 13,23,30 and normal aging. 30 In this study, we observed correlations between cerebellar volume reduction and cognitive decline in AD patients.…”

“…alcoholic dementia), 13,23,30 and normal aging. 30 In this study, we observed correlations between cerebellar volume reduction and cognitive decline in AD patients. Although the cerebellum is virtually free of neurofibrillary pathology, the magnitude of cerebellar atrophy strongly correlates with the duration and stage of illness.…”