Carla Abdelnour1, Inger van Steenoven2, Elisabet Londos3, Frédéric Blanc4, Bjørn Auestad5,6, Milica G Kramberger7, Henrik Zetterberg8,9, Brit Mollenhauer10, Mercè Boada1, Dag Aarsland5,11. 1. Fundació ACE, Alzheimer Research Center and Memory Clinic, Institut Català de Neurociències Aplicades, Barcelona, Spain. 2. Alzheimer Center, Department of Neurology, VU Medical Center, Amsterdam, The Netherlands. 3. Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden. 4. Neuropsychology Unit and Geriatric Day Hospital (Strasbourg Resource and Research Memory Center, CMRR), University Hospital of Strasbourg and ICube laboratory, FMTS, University of Strasbourg and CNRS, Strasbourg, France. 5. Research Department, Stavanger University Hospital, Stavanger, Norway. 6. Department of Mathematics and Natural Sciences, University of Stavanger, Stavanger, Norway. 7. Department of Neurology, University Medical Center, Ljubljana, Slovenia. 8. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden. 9. Department of Molecular Neuroscience, UCL Institute of Neurology, London, United Kingdom. 10. Paracelsus-Elena-Klinik, Kassel and University Medical Center, Department of Neurosurgery and Institute of Neuropathology, Göttingen, Germany. 11. Karolinska Institutet, Department of Neurobiology, Care sciences and Society (NVS), Center for Alzheimer Research Division for Neurogeriatrics, Stockholm, Sweden.
Abstract
INTRODUCTION: Alzheimer's disease pathologies are common in dementia with Lewy bodies, but their clinical relevance is not clear. CSF biomarkers amyloid beta 1-42, total tau, and tau phosphorylated at threonine 181 reflect Alzheimer's disease neuropathology antemortem. In PD, low CSF amyloid beta 1-42 predict long-term cognitive decline, but little is known about these biomarkers as predictors for cognitive decline in Lewy body dementia. The aim of this study was to assess whether Alzheimer's disease CSF biomarkers predict cognitive decline in Lewy body dementia. METHODS: From a large European dementia with Lewy bodies multicenter study, we analyzed baseline Alzheimer's disease CSF biomarkers and serial MMSE (baseline and 1- and 2-year follow-up) in 100 patients with Lewy body dementia. Linear mixed-effects analyses, adjusted for sex, age, baseline MMSE, and education, were performed to model the association between CSF biomarkers and rate of cognitive decline measured with MMSE. An Alzheimer's disease CSF profile was defined as pathological amyloid beta 1-42 plus pathological total tau or phosphorylated tau. RESULTS: The Alzheimer's disease CSF profile, and pathological levels of amyloid beta 1-42, were associated with a more rapid decline in MMSE (2.2 [P < 0.05] and 2.9 points difference [P < 0.01], respectively). Higher total tau values showed a trend toward association without statistical significance (2.0 points difference; P = 0.064), whereas phosphorylated tau was not associated with decline. CONCLUSIONS: Reduced levels of CSF amyloid beta 1-42 were associated with more rapid cognitive decline in Lewy body dementia patients. Future prospective studies should include larger samples, centralized CSF analyses, longer follow-up, and biomarker-pathology correlation.
INTRODUCTION:Alzheimer's disease pathologies are common in dementia with Lewy bodies, but their clinical relevance is not clear. CSF biomarkers amyloid beta 1-42, total tau, and tau phosphorylated at threonine 181 reflect Alzheimer's disease neuropathology antemortem. In PD, low CSF amyloid beta 1-42 predict long-term cognitive decline, but little is known about these biomarkers as predictors for cognitive decline in Lewy body dementia. The aim of this study was to assess whether Alzheimer's disease CSF biomarkers predict cognitive decline in Lewy body dementia. METHODS: From a large European dementia with Lewy bodies multicenter study, we analyzed baseline Alzheimer's disease CSF biomarkers and serial MMSE (baseline and 1- and 2-year follow-up) in 100 patients with Lewy body dementia. Linear mixed-effects analyses, adjusted for sex, age, baseline MMSE, and education, were performed to model the association between CSF biomarkers and rate of cognitive decline measured with MMSE. An Alzheimer's disease CSF profile was defined as pathological amyloid beta 1-42 plus pathological total tau or phosphorylated tau. RESULTS: The Alzheimer's disease CSF profile, and pathological levels of amyloid beta 1-42, were associated with a more rapid decline in MMSE (2.2 [P < 0.05] and 2.9 points difference [P < 0.01], respectively). Higher total tau values showed a trend toward association without statistical significance (2.0 points difference; P = 0.064), whereas phosphorylated tau was not associated with decline. CONCLUSIONS: Reduced levels of CSF amyloid beta 1-42 were associated with more rapid cognitive decline in Lewy body dementiapatients. Future prospective studies should include larger samples, centralized CSF analyses, longer follow-up, and biomarker-pathology correlation.
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