Mixed neurodegenerative dementia: the coexistence of dementia with Lewy bodies and Alzheimer´s diseaseExpanding our knowledge about the interaction of brain proteinopathies

Resum

Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia, and a high percentage of cases show Alzheimer¿s disease (AD) copathology. Patients with DLB and concomitant AD have increased risk of nursing home admission, shorter survival rates, and faster progression to dementia. The aim of this doctoral thesis is to expand our knowledge about the interaction of these two brain proteinopathies by analyzing: demographic, clinical features, global cognition, regional brain atrophy and AD cerebrospinal fluid (CSF) biomarkers of DLB patients from the European dementia with Lewy bodies consortium (E-DLB) cohort. Our findings demonstrate that AD-related pathology is associated with posterior brain atrophy in patients with DLB, while amyloid-ß related pathology is associated with atrophy in the medial temporal lobe. Further, DLB patients with amyloid-ß related pathology present a faster cognitive decline, whereas tau-related pathology does not seem to be linked to cognitive worsening. Finally, we have found that DLB is an heterogeneous disease with endophenotypes that present distinctive demographic and clinical features, as well as different regional brain atrophy and AD CSF profiles. In conclusion, the coexistence of AD pathology influences the neurodegenerative process, longitudinal cognitive decline and heterogeneity in patients with DLB.