Alzheimer’s disease; cerebrospinal fluid; family history; subjective cognitive decline; Biomarkers; Aged; Biomarkers/cerebrospinal fluid; Cross-Sectional Studies; Female; Humans; Male; Neuropsychological Tests; Alzheimer Disease/pathology; Cognitive Dysfunction/psychology; Cognitive Dysfunction; Neuroscience (all); Clinical Psychology; Geriatrics and Gerontology; Psychiatry and Mental Health; General Medicine; General Neuroscience
Abstract :
[en] [en] BACKGROUND: It is unclear whether subjective cognitive decline (SCD) is a relevant clinical marker of incipient Alzheimer's disease (AD) and future cognitive deterioration in individuals with a family history of AD (FHAD).
OBJECTIVE: To investigate the association of SCD with cross-sectional cerebrospinal fluid (CSF) AD biomarker levels and cognitive decline in cognitively normal older adults with or without a first-degree FHAD.
METHODS: We analyzed data from cognitively normal individuals with first-degree FHAD (n = 82 "AD relatives"; mean age: 65.7 years (SD = 4.47); 59% female) and a similar group of n = 236 healthy controls without FHAD from the DELCODE study. We measured SCD with an in-depth structured interview from which we derived a SCD score, capturing features proposed to increase likelihood of underlying AD ("SCD-plus score"). We tested whether higher SCD-plus scores were associated with more pathological CSF AD biomarker levels and cognitive decline over time and whether this association varied by group.
RESULTS: AD relatives showed higher SCD-plus scores than healthy controls and more cognitive decline over time. Higher SCD-plus scores also related stronger to cognitive change and abnormal CSF AD biomarker levels in the AD relatives as compared to the healthy controls group.
CONCLUSION: Quantification of specific SCD features can provide further information on the likelihood of early AD pathology and cognitive decline among AD relatives. FHAD and SCD appear as synergistically acting enrichment strategies in AD research, the first one as a permanent indicator of genetic risk, the latter one as a correlate of disease progression.
Disciplines :
Neurology
Author, co-author :
Wolfsgruber, Steffen; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry/Psychiatry, Bonn, Germany
Kleineidam, Luca; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry/Psychiatry, Bonn, Germany
Weyrauch, Anne-Sophie; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry/Psychiatry, Bonn, Germany
Barkhoff, Miriam; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Röske, Sandra; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Peters, Oliver; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Department of Psychiatry, Berlin, Germany
Preis, Lukas; Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Department of Psychiatry, Berlin, Germany
Gref, Daria; Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Department of Psychiatry, Berlin, Germany
Spruth, Eike Jakob; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany
Altenstein, Slawek; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany
Priller, Josef; German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany ; Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany ; Department of Psychiatry and Psychotherapy, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
Fließbach, Klaus; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry/Psychiatry, Bonn, Germany
Schneider, Anja; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry/Psychiatry, Bonn, Germany
Wiltfang, Jens; German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany ; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen, Germany ; Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal
Bartels, Claudia; Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen, Germany
Jessen, Frank; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department of Psychiatry, Medical Faculty University of Cologne, Cologne, Germany ; Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany
Maier, Franziska; Department of Psychiatry, Medical Faculty University of Cologne, Cologne, Germany
Düzel, Emrah; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany
Metzger, Coraline; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany ; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany ; Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany
Glanz, Wenzel; German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany
Buerger, Katharina; German Center for Neurodegenerative Diseases (DZNE) Munich, Germany ; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
Janowitz, Daniel; Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany
Perneczky, Robert; German Center for Neurodegenerative Diseases (DZNE) Munich, Germany ; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany ; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany ; Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College London, London, UK
Rauchmann, Boris-Stephan; Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany
Kilimann, Ingo; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
Teipel, Stefan; German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany ; Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany
Laske, Christoph; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany ; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
Munk, Matthias H; German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany ; Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany
Roy, Nina; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
Spottke, Annika; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurology, Bonn, Germany
Ramirez, Alfredo; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry/Psychiatry, Bonn, Germany ; Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry, Medical Faculty University of Cologne, Cologne, Germany
HENEKA, Michael ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry/Psychiatry, Bonn, Germany
Brosseron, Frederic; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry/Psychiatry, Bonn, Germany
Wagner, Michael; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry/Psychiatry, Bonn, Germany
We would like to thank all DELCODE participants and their families for their continuing efforts. DELCODE is funded by the German Center for Neurodegenerative Diseases (Deutsches Zentrum für Neurodegenerative Erkrankungen, DZNE), reference number BN012. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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