Kai Sin Chin1, Nawaf Yassi2, Leonid Churilov3, Colin Louis Masters4, Rosie Watson5. 1. Department of Medicine - The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, 3050, Australia; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia. Electronic address: kai.chin@mh.org.au. 2. Department of Medicine - The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, 3050, Australia; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia; Department of Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, 3050, Australia. 3. Department of Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, 3050, Australia; Department of Medicine (Austin Health), Melbourne Medical School, University of Melbourne, Heidelberg, VIC, 3084, Australia. 4. The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, 3052, Australia. 5. Department of Medicine - The Royal Melbourne Hospital, University of Melbourne, Parkville, VIC, 3050, Australia; Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, 3052, Australia.
Abstract
INTRODUCTION: Alzheimer's disease neuropathologies (amyloid-β and tau) frequently co-exist to varying degrees in Lewy body dementias (LBD), which include dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). OBJECTIVES: To investigate the prevalence of tau in DLB and PDD, and its associations with clinical outcomes. METHODS: We searched the major electronic databases using the search term: ("dementia with Lewy bodies" OR "diffuse Lewy body disease" OR "Lewy body variant of Alzheimer's disease") AND ("tau protein" OR "tauopathy" OR "neurofibrillary tangle"), for relevant studies which evaluated tau in LBD. Forty-nine articles met the inclusion criteria for data extraction. Where appropriate, a random-effect meta-analysis was performed to obtain pooled estimates for prevalence and risk ratios (RR) or standardized mean differences (SMD) for clinical features, diagnostic accuracy and cognition. RESULTS: Braak neurofibrillary tangle stage ≥ III was observed in 66% (n = 1511, 95%CI 60%-73%) of DLB and 52% (n = 433, 95%CI 27%-76%) of PDD at autopsy. Abnormal CSF phosphorylated-tau levels were present in 28% (n = 925, 95%CI 25%-31%) of DLB and 15% (n = 172, 95%CI 5%-24%) of PDD cases. Higher tau burden in DLB was associated with reduced likelihood of manifesting visual hallucinations (RR 0.56; 95%CI 0.40-0.77) and motor parkinsonism (RR 0.62; 95%CI 0.40-0.98), lower diagnostic accuracy of DLB during life (RR 0.49; 95%CI 0.38-0.64) and worse cognition prior to death (SMD 0.63; 95%CI 0.46-0.81). CONCLUSIONS: Tau is common in LBD and may reduce clinical diagnostic accuracy in people with DLB. Prospective longitudinal studies are needed to understand the roles of co-morbid neuropathologies in Lewy body dementias.
INTRODUCTION:Alzheimer's disease neuropathologies (amyloid-β and tau) frequently co-exist to varying degrees in Lewy body dementias (LBD), which include dementia with Lewy bodies (DLB) and Parkinson's diseasedementia (PDD). OBJECTIVES: To investigate the prevalence of tau in DLB and PDD, and its associations with clinical outcomes. METHODS: We searched the major electronic databases using the search term: ("dementia with Lewy bodies" OR "diffuse Lewy body disease" OR "Lewy body variant of Alzheimer's disease") AND ("tau protein" OR "tauopathy" OR "neurofibrillary tangle"), for relevant studies which evaluated tau in LBD. Forty-nine articles met the inclusion criteria for data extraction. Where appropriate, a random-effect meta-analysis was performed to obtain pooled estimates for prevalence and risk ratios (RR) or standardized mean differences (SMD) for clinical features, diagnostic accuracy and cognition. RESULTS: Braak neurofibrillary tangle stage ≥ III was observed in 66% (n = 1511, 95%CI 60%-73%) of DLB and 52% (n = 433, 95%CI 27%-76%) of PDD at autopsy. Abnormal CSF phosphorylated-tau levels were present in 28% (n = 925, 95%CI 25%-31%) of DLB and 15% (n = 172, 95%CI 5%-24%) of PDD cases. Higher tau burden in DLB was associated with reduced likelihood of manifesting visual hallucinations (RR 0.56; 95%CI 0.40-0.77) and motor parkinsonism (RR 0.62; 95%CI 0.40-0.98), lower diagnostic accuracy of DLB during life (RR 0.49; 95%CI 0.38-0.64) and worse cognition prior to death (SMD 0.63; 95%CI 0.46-0.81). CONCLUSIONS:Tau is common in LBD and may reduce clinical diagnostic accuracy in people with DLB. Prospective longitudinal studies are needed to understand the roles of co-morbid neuropathologies in Lewy body dementias.
Authors: Sean A P Clouston; Charles B Hall; Minos Kritikos; David A Bennett; Steven DeKosky; Jerri Edwards; Caleb Finch; William C Kreisl; Michelle Mielke; Elaine R Peskind; Murray Raskind; Marcus Richards; Richard P Sloan; Avron Spiro; Neil Vasdev; Robert Brackbill; Mark Farfel; Megan Horton; Sandra Lowe; Roberto G Lucchini; David Prezant; Joan Reibman; Rebecca Rosen; Kacie Seil; Rachel Zeig-Owens; Yael Deri; Erica D Diminich; Bernadette A Fausto; Sam Gandy; Mary Sano; Evelyn J Bromet; Benjamin J Luft Journal: Nat Rev Neurol Date: 2021-11-18 Impact factor: 42.937
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Authors: Laura Torres-Garcia; Joana M P Domingues; Edoardo Brandi; Caroline Haikal; Janitha M Mudannayake; Inês C Brás; Ellen Gerhardt; Wen Li; Alexander Svanbergsson; Tiago F Outeiro; Gunnar K Gouras; Jia-Yi Li Journal: Sci Rep Date: 2022-02-22 Impact factor: 4.379