Rate of Frontotemporal Dementia in Patients With ALS Higher Than Previous Estimates

More than a third of patients with amyotrophic lateral sclerosis (ALS) had neuropathological signs of frontotemporal dementia, according to study results published in Brain.

The findings stem from an analysis of data from brain samples of 124 patients meeting neuropathological criteria for ALS, or motor neuron disease, from the Neurological Tissue Bank of the FRCB-IDIBAPS-Clinic Hospital of Barcelona, Spain. Researchers performed a clinicopathologic series to investigate the frequency of concurrent frontotemporal lobar degeneration in the sample.

“Neuropathological studies and correlation with clinical characteristics help us expand our knowledge of the basis of diseases such as ALS and frontotemporal dementia,” said study lead author Alvaro Carbayo, MD, of the Sant Pau Research Institute in Barcelona, “opening doors to future studies on biomarkers and specific therapies.”

>>NEWS: FDA Declines Accelerated Approval for Novel ALS Drug

Although previous research has suggested between 10% and 15% of patients with ALS meet diagnostic criteria for frontotemporal dementia, this observational case study revealed a 35.5% rate of pathological features of frontotemporal dementia in the ALS sample.

Additionally, the study found pathological aggregation of the TDP-43 protein in 93.6% of patients with ALS. Aggregated TDP-43 was more extensive in brain samples of patients with concurrent frontotemporal lobar degeneration, according to the study.

At the outset of the investigation, researchers aimed to define specific subgroups but wrote in their paper that the task was “particularly difficult.” They reported high heterogeneity in the spectrum of frontotemporal lobar degeneration and motor neuron disease, particularly in patients with pathological signs of frontotemporal dementia.

“We have observed astonishing heterogeneity in the clinical presentation and pathological and genetic characteristics of patients, with a higher frequency of frontotemporal dementia than described in other series," Dr Carbayo said.

He believes the findings support the need for collaboration between ALS and frontotemporal dementia specialists.

“It is crucial that we work together to better understand this spectrum of neurodegenerative diseases and to better care for our patients,” he said. “In fact, at Sant Pau, we have been working with this structure for 6 or 7 years.”

References

Carbayo Á, Borrego-Écija S, Turon-Sans J, et al. Clinicopathological correlates in frontotemporal lobar degeneration: motor neuron disease spectrum. Brain. Published online January 16, 2024. doi:10.1093/brain/awae011

Deciphering brain connections between amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. News release. Sant Pau Research Institute; January 30, 2024. Accessed March 1, 2024.