Dementia is thought to be an uncommon complication of motor neuron disease (MND). In addition to the characteristic motor system degeneration, pathological studies of MND patients with dementia have demonstrated changes in extramotor cortex; ubiquitin-immunoreactive inclusions are present in neocortical layer II neurons and hippocampal dentate granule cells. To examine how specifically this pathology is associated with dementia in MND, we performed ubiquitin immunohistochemistry on sections of hippocampus, prefrontal and temporal neocortex from 29 cases of MND, 10 with dementia and 19 with no clinical history of cognitive impairment. All cases with dementia had numerous ubiquitin-positive inclusions in dentate granule cells, whereas involvement of the neocortex was more variable. Six (32%) of the nondemented cases had ubiquitin pathology, which was similar to the demented cases in its morphology and distribution but of slightly less severe degree. These findings demonstrate that, although ubiquitinated inclusions in extramotor cortex are a consistent finding in MND with dementia, they are also common in MND in the absence of documented cognitive abnormalities. Such cases may either represent a subclinical stage of pathology or indicate that cognitive dysfunction is an underrecognized complication of MND.