Inger van Steenoven1, Dag Aarsland2,3, Daniel Weintraub4, Elisabet Londos5, Frédéric Blanc6, Wiesje M van der Flier7, Charlotte E Teunissen8, Brit Mollenhauer9, Tormod Fladby10, Milica G Kramberger11, Laura Bonanni12, Afina W Lemstra1. 1. Department of Neurology & Alzheimer Centre, VU University Medical Center, Amsterdam, The Netherlands. 2. Department of Neurobiology, Care Sciences and Society, Division of Neurogeriatrics, Karolinska Institute, Stockholm, Sweden. 3. Center for Age-Related Medicine, Stavanger University Hospital, Stavanger, Norway. 4. Departments of Psychiatry and Neurology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. 5. Clinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden. 6. Neuropsychology Unit and Geriatric Day Hospital (Strasbourg Resource and Research Memory Centre, CMRR) University Hospital of Strasbourg and ICube Laboratory, FMTS, University of Strasbourg and CNRS, Strasbourg, France. 7. Department of Neurology & Alzheimer Centre and Department of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. 8. Neurochemistry Lab and Biobank, Department of Clinical Chemistry, VU University Medical Center Amsterdam, The Netherlands. 9. Paracelsus-Elena-Klinik, Kassel and University Medical Center, Department of Neurosurgery and Institute of Neuropathology, Göttingen, Germany. 10. Department of Neurology, Akershus University Hospital and Faculty of Medicine, University of Oslo, Norway. 11. Department of Neurology, University Medical Centre, Ljubljana, Slovenia. 12. Department of Neuroscience and Imaging and Clinical Science, and Aging Research Centre, G. d'Annunzio University, Chieti, Italy.
Abstract
BACKGROUND: Concomitant Alzheimer's disease (AD) pathology is observed in Lewy body diseases (LBD), but the clinical impact is unknown. Only a few biomarker studies in LBD exist and have included small cohorts from single centers. OBJECTIVE: We aimed to evaluate the prevalence of abnormal cerebrospinal fluid (CSF) AD biomarkers across the spectrum of LBD in a large multicenter cohort and to assess whether an AD biomarker profile was associated with demographic and clinical differences in dementia with Lewy bodies (DLB). METHODS: We included 375 DLB patients, 164 Parkinson's disease (PD) patients without dementia, and 55 PD patients with dementia (PDD) from 10 centers. CSF amyloid-beta42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) values were dichotomized as abnormal or normal according to locally available cut-off values. A CSF AD profile was defined as abnormal Aβ42 combined with abnormal t-tau and/or p-tau. RESULTS: A substantial proportion of DLB patients had abnormal values for CSF Aβ42, t-tau, and p-tau, while abnormal values were uncommon in PD without dementia. Patients with PDD had values in between. A CSF AD profile was observed in 25% of DLB patients, compared with only 9% of PDD and 3% of PD without dementia. Within DLB, patients with a CSF AD profile were older, more often female, performed worse on the Mini-Mental State Examination, and had shorter disease duration compared with patients with normal CSF. CONCLUSION: A CSF AD profile is more common in DLB compared with PDD and PD, and is associated with more severe cognitive impairment in DLB.
BACKGROUND: Concomitant Alzheimer's disease (AD) pathology is observed in Lewy body diseases (LBD), but the clinical impact is unknown. Only a few biomarker studies in LBD exist and have included small cohorts from single centers. OBJECTIVE: We aimed to evaluate the prevalence of abnormal cerebrospinal fluid (CSF) AD biomarkers across the spectrum of LBD in a large multicenter cohort and to assess whether an AD biomarker profile was associated with demographic and clinical differences in dementia with Lewy bodies (DLB). METHODS: We included 375 DLB patients, 164 Parkinson's disease (PD) patients without dementia, and 55 PDpatients with dementia (PDD) from 10 centers. CSF amyloid-beta42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) values were dichotomized as abnormal or normal according to locally available cut-off values. A CSF AD profile was defined as abnormal Aβ42 combined with abnormal t-tau and/or p-tau. RESULTS: A substantial proportion of DLB patients had abnormal values for CSF Aβ42, t-tau, and p-tau, while abnormal values were uncommon in PD without dementia. Patients with PDD had values in between. A CSF AD profile was observed in 25% of DLB patients, compared with only 9% of PDD and 3% of PD without dementia. Within DLB, patients with a CSF AD profile were older, more often female, performed worse on the Mini-Mental State Examination, and had shorter disease duration compared with patients with normal CSF. CONCLUSION: A CSF AD profile is more common in DLB compared with PDD and PD, and is associated with more severe cognitive impairment in DLB.
Entities:
Keywords:
Amyloid beta-protein (1-42); Lewy body disease; biomarkers; cerebrospinal fluid; dementia with zzm321990Lewy bodies; tau protein
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