Relevance of Subjective Cognitive Decline in Older Adults with a First-Degree Family History of Alzheimer’s Disease

Article type: Research Article

Authors: Wolfsgruber, Steffen^{a; b; *} | Kleineidam, Luca^{a; b} | Weyrauch, Anne-Sophie^{a; b} | Barkhoff, Miriam^a | Röske, Sandra^a | Peters, Oliver^{c; d} | Preis, Lukas^d | Gref, Daria^d | Spruth, Eike Jakob^{c; e} | Altenstein, Slawek^{c; e} | Priller, Josef^{c; e; f} | Fließbach, Klaus^{a; b} | Schneider, Anja^{a; b} | Wiltfang, Jens^{g; h; i} | Bartels, Claudia^h | Jessen, Frank^{a; j; k} | Maier, Franziska^j | Düzel, Emrah^{l; m} | Metzger, Coraline^{l; m; n} | Glanz, Wenzel^l | Buerger, Katharina^{o; p} | Janowitz, Daniel^p | Perneczky, Robert^{o; q; r; s} | Rauchmann, Boris-Stephan^q | Kilimann, Ingo^{t; u} | Teipel, Stefan^{t; u} | Laske, Christoph^{v; w} | Munk, Matthias H.^{v; w} | Roy, Nina^a | Spottke, Annika^{a; x} | Ramirez, Alfredo^{a; b; y} | Heneka, Michael T.^{a; b} | Brosseron, Frederic^{a; b} | Wagner, Michael^{a; b} | on behalf of the DELCODE study group

Affiliations: [a] German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany | [b] University of Bonn Medical Center, Department of Neurodegenerative Diseases and Geriatric Psychiatry/Psychiatry, Bonn, Germany | [c] German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany | [d] Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Department of Psychiatry, Berlin, Germany | [e] Department of Psychiatry and Psychotherapy, Charité, Berlin, Germany | [f] Department of Psychiatry and Psychotherapy, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany | [g] German Center for Neurodegenerative Diseases (DZNE), Goettingen, Germany | [h] Department of Psychiatry and Psychotherapy, University Medical Center Goettingen, University of Goettingen, Goettingen, Germany | [i] Neurosciences and Signaling Group, Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal | [j] Department of Psychiatry, Medical Faculty University of Cologne, Cologne, Germany | [k] Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany | [l] German Center for Neurodegenerative Diseases (DZNE), Magdeburg, Germany | [m] Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University, Magdeburg, Germany | [n] Department of Psychiatry and Psychotherapy, Otto-von-Guericke University, Magdeburg, Germany | [o] German Center for Neurodegenerative Diseases (DZNE) Munich, Germany | [p] Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany | [q] Department of Psychiatry and Psychotherapy, University Hospital, LMU Munich, Munich, Germany | [r] Munich Cluster for Systems Neurology (SyNergy), Munich, Germany | [s] Ageing Epidemiology Research Unit (AGE), School of Public Health, Imperial College London, London, UK | [t] German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany | [u] Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany | [v] German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany | [w] Section for Dementia Research, Hertie Institute for Clinical Brain Research and Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany | [x] University of Bonn Medical Center, Department of Neurology, Bonn, Germany | [y] Division of Neurogenetics and Molecular Psychiatry, Department of Psychiatry, Medical Faculty University of Cologne, Cologne, Germany

Correspondence: [*] Correspondence to: Dr. phil. Steffen Wolfsgruber, Dipl.-Psych., German Center for Neurodegenerative Diseases, Venusberg Campus 1, D-53127, Bonn, Germany. Tel.: +49 228 43302 816; E-mail: [email protected].

Abstract: 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.

Keywords: Alzheimer’s disease, cerebrospinal fluid, family history, subjective cognitive decline

DOI: 10.3233/JAD-215416

Journal: Journal of Alzheimer's Disease, vol. 87, no. 2, pp. 545-555, 2022