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. •Alzheimer's disease co-pathology is commonly seen in Lewy body dementia.•This is associated with a poorer prognosis in longitudinal studies of LBD.•This is seen in most autopsy, PET imaging, and plasma biomarker studies.•CSF studies show discrepant findings in LBD.•This has important implications for clinical trial design and prognostication.