Diagnosis of coexistent neurodegenerative dementias in multiple sclerosis

Diana P Londoño; Kogulavadanan Arumaithurai; Eleni Constantopoulos; Michael R Basso; R Ross Reichard; Eoin P Flanagan; B Mark Keegan

doi:10.1093/braincomms/fcac167

Diagnosis of coexistent neurodegenerative dementias in multiple sclerosis

Brain Commun. 2022 Jun 22;4(4):fcac167. doi: 10.1093/braincomms/fcac167. eCollection 2022.

Authors

Diana P Londoño¹, Kogulavadanan Arumaithurai¹, Eleni Constantopoulos², Michael R Basso³, R Ross Reichard², Eoin P Flanagan¹, B Mark Keegan¹

Affiliations

¹ Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
² Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.
³ Division of Neurocognitive Disorders, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55905, USA.

Abstract

Among people with multiple sclerosis, cognitive impairment occurs commonly and is a potent predictor of disability. Some multiple sclerosis patients present with severe cognitive impairment, and distinguishing multiple sclerosis-related cognitive impairment from co-existent progressive neurodegenerative diseases such as Alzheimer disease poses a diagnostic challenge. The use of biomarkers such as PET and CSF proteins may facilitate this distinction. The study was a retrospective, descriptive study on convenience samples of separate cohorts, one of cognitively impaired multiple sclerosis patients evaluated on autopsy to demonstrate coincidence of both multiple sclerosis and neurodegenerative cognitive diseases. The second cohort were cognitively impaired multiple sclerosis patients evaluated by biomarker to investigate possible additional neurodegenerative cognitive disorders contributing to the cognitive impairment. We investigated selected biomarkers among 31 severely impaired patients (biomarker cohort) and 12 severely impaired patients assessed at autopsy and selected 24 (23 biomarker cohort, 1 autopsy cohort) had comprehensive neurocognitive testing. Biomarker cohort investigations included 18F-Fluorodeoxyglucose PET and/or CSF amyloid Aβ1-42, phospho-tau and total tau levels. The autopsy cohort was evaluated with comprehensive neuropathological assessment for aetiology of cognitive impairment. The cohorts shared similar sex, age at multiple sclerosis onset and multiple sclerosis clinical course. The autopsy-cohort patients were older at diagnosis (69.5 versus 57 years, P = 0.006), had longer disease duration [median (range) 20 years (3-59) versus 9 (1-32), P = 0.001] and had more impaired bedside mental status scores at last follow-up [Kokmen median (range) 23 (1-38) versus 31 (9-34) P = 0.01]. Autopsy-cohort patients confirmed, or excluded, coexistent neurogenerative disease by neuropathology gold standard. Most biomarker-cohort patients had informative results evaluating coexistent neurogenerative disease. Biomarkers may be useful in indicating a coexistent neurodegenerative disease earlier, and in life, in patients with multiple sclerosis and significant cognitive impairment.

Keywords: biomarkers; dementia; diagnosis; multiple sclerosis; neurodegenerative disease.