The effect of Amyloid and Tau Co-pathology on disease progression in Lewy body dementia: A systematic review

Co-morbid Alzheimer's disease (AD) pathology (amyloid-beta and tau) is commonly observed in Lewy body dementia (LBD), and this may affect clinical outcomes. A systematic review of the effect of AD co-pathology on longitudinal clinical outcomes in LBD was conducted. A search of MEDLINE and EMBASE (October 2024) yielded n = 3558 records that were screened by two independent reviewers. Included studies (n = 31) assessed AD co-pathology in LBD by neuropathologic examination (n = 10), positron emission tomography (PET) imaging (n = 7), cerebrospinal fluid (CSF) (n = 8) or plasma biomarkers (n = 6); and reported longitudinal clinical outcomes including cognitive and functional decline, mortality, or treatment response. Most neuropathology, PET and plasma studies reviewed demonstrated poorer prognosis in LBD + compared to LBD-, but discrepant findings were seen among CSF studies. No included study reported better outcomes in LBD+. The risk of bias was assessed with the Quality in Prognosis Studies tool. All studies rated as low risk of bias (n = 12) reported that the presence of AD co-pathology in LBD (LBD+) was associated with accelerated cognitive decline (n = 7/7), accelerated functional decline (n = 3/3), greater mortality (n = 2/2) and poorer response to treatment (n = 1/1). Among these studies, LBD+ was associated with an additional decline of -0.53 to -2.9 MMSE points/year compared to LBD-, while one study reported an adjusted hazard ratio for mortality in LBD + as 3.70. We conclude that AD co-pathology is associated with worse clinical outcomes in LBD whether assessed by greater cognitive decline, increased mortality or greater decline on functional assessment scales.