In this clinical article, Dr. Brandy Matthews of Indiana University presents a discussion of dementia associated with amyotrophic lateral sclerosis, including discussion of the consensus criteria for frontotemporal cognitive and behavioral syndromes in amyotrophic lateral sclerosis as well as updated information on the considerable neuropathological overlap between amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Additional updates highlight genetic and protein associations more recently described, including TDP-43, CHMP2B, and FUS, and avenues for clinical investigations and potential therapies to be pursued in light of these advances.
The prevalence of dementia in amyotrophic lateral sclerosis is much higher than historically reported, with some evidence of cognitive or behavioral impairments not meeting criteria for the diagnosis of dementia in the majority of amyotrophic lateral sclerosis patients. The convergence of neuropathological and genetic evidence suggests that amyotrophic lateral sclerosis and frontotemporal dementia may represent a continuum of the same neurodegenerative process in many cases.
A growing understanding of the protein neuropathology of both amyotrophic lateral sclerosis and frontotemporal dementia provides exciting opportunities for the development of disease-modifying therapies for this spectrum of neurodegenerative illnesses.