Daniela Bertens1, Dirk L Knol2, Philip Scheltens3, Pieter Jelle Visser4. 1. Department of Neurology/Alzheimer Centre, VU Medical Centre, Amsterdam, The Netherlands. Electronic address: d.bertens@vumc.nl. 2. Department of Epidemiology and Biostatistics, VU Medical Centre, Amsterdam, The Netherlands. 3. Department of Neurology/Alzheimer Centre, VU Medical Centre, Amsterdam, The Netherlands. 4. Department of Neurology/Alzheimer Centre, VU Medical Centre, Amsterdam, The Netherlands; Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience (MHeNS), Alzheimer Centre Limburg, University Medical Centre, Maastricht, The Netherlands.
Abstract
BACKGROUND: We investigated the pattern of disease progression in the asymptomatic, mild cognitive impairment (MCI), and dementia stage of Alzheimer's disease (AD). METHODS: We selected 284 subjects with AD pathology, defined as abnormal levels of amyloid beta 1-42 (Aβ1-42) in cerebrospinal fluid (CSF). Disease outcome measures included six biomarkers and five cognitive markers. We compared differences in baseline measures and decline over 4 years between the AD stages and tested whether these changes differed from subjects, without AD pathology (N = 132). RESULTS: CSF Aβ1-42 reached the maximum abnormality level in the asymptomatic stage and tau in the MCI stage. The imaging and cognitive markers started to decline in the asymptomatic stage, and decline accelerated with advancing clinical stage. CONCLUSION: This study provides further evidence for a temporal evolution of AD biomarkers. Our findings may be helpful to determine stage specific outcome measures for clinical trials.
BACKGROUND: We investigated the pattern of disease progression in the asymptomatic, mild cognitive impairment (MCI), and dementia stage of Alzheimer's disease (AD). METHODS: We selected 284 subjects with AD pathology, defined as abnormal levels of amyloid beta 1-42 (Aβ1-42) in cerebrospinal fluid (CSF). Disease outcome measures included six biomarkers and five cognitive markers. We compared differences in baseline measures and decline over 4 years between the AD stages and tested whether these changes differed from subjects, without AD pathology (N = 132). RESULTS: CSF Aβ1-42 reached the maximum abnormality level in the asymptomatic stage and tau in the MCI stage. The imaging and cognitive markers started to decline in the asymptomatic stage, and decline accelerated with advancing clinical stage. CONCLUSION: This study provides further evidence for a temporal evolution of AD biomarkers. Our findings may be helpful to determine stage specific outcome measures for clinical trials.
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