Differential Risk of Incident Alzheimer’s Disease Dementia in Stable Versus Unstable Patterns of Subjective Cognitive Decline

Article type: Research Article

Authors: Wolfsgruber, Steffen^{a; b; 1; *} | Kleineidam, Luca^{a; b; 1} | Wagner, Michael^{a; b} | Mösch, Edelgard^c | Bickel, Horst^c | Lϋhmann, Dagmar^d | Ernst, Annette^d | Wiese, Birgitt^e | Steinmann, Susanne^e | König, Hans-Helmut^f | Brettschneider, Christian^f | Luck, Tobias^{g; h} | Stein, Janine^g | Weyerer, Siegfriedⁱ | Werle, Jochenⁱ | Pentzek, Michael^j | Fuchs, Angela^j | Maier, Wolfgang^{a; b} | Scherer, Martin^d | Riedel-Heller, Steffi G.^{g; 2} | Jessen, Frank^{b; k; 2} | for the AgeCoDe Study Group

Affiliations: [a] Department of Psychiatry and Psychotherapy, University of Bonn, Germany | [b] German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany | [c] Department of Psychiatry, Technical University of Munich, Munich, Germany | [d] Department of Primary Medical Care, Center for Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany | [e] WG Medical Statistics and IT-Infrastructure, Institute of General Practice, Hannover Medical School, Hannover, Germany | [f] Department of Health Economics and Health Services Research, Hamburg Center for Health Economics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany | [g] Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Germany | [h] LIFE – Leipzig Research Center for Civilization Diseases, University of Leipzig, Germany | [i] Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany | [j] Institute of General Practice, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany | [k] Department of Psychiatry, University of Cologne, Germany

Correspondence: [*] Correspondence to: Dr. phil. Steffen Wolfsgruber, Dipl.-Psych., Department of Psychiatry and Psychotherapy, University of Bonn, Sigmund-Freud-Straße 25, D-53105, Bonn, Germany. Tel.: +49 0 228 287 16946; Fax: +49 0 228 287 16371; E-mail: [email protected].

Note: [1] These authors contributed equally to the manuscript.

Note: [2] These last authors contributed equally to the manuscript.

Abstract: Background: It is unknown whether longitudinal stability versus instability in subjective cognitive decline (SCD) is a modifying factor of the association between SCD and risk of incident Alzheimer’s disease (AD) dementia. Objective: We tested the modifying role of temporal stability of the SCD report on AD dementia risk in cognitively normal elderly individuals. Methods: We analyzed data of 1,990 cognitively normal participants from the longitudinal AgeCoDe Study. We assessed SCD with/without associated worries both at baseline and first follow-up 18 months later. Participants were then classified either as (a) Controls (CO, with no SCD at both baseline and follow-up 1, n = 613), (b) inconsistent SCD (with SCD reported only at baseline or at follow-up 1, n = 637), (c) consistent SCD but without/or with inconsistent worries (n = 610) or (d) consistent SCD with worries (n = 130). We estimated incident AD dementia risk over up to 6 years for each group with Cox-Proportional Hazard Regression analyses adjusted for age, gender, education, ApoE4 status, and depression. Results: Compared to CO, inconsistent SCD was not associated with increased risk of incident AD dementia. In contrast, risk was doubled in the group of consistent SCD without/ with inconsistent worries, and almost 4-fold in the group of consistent SCD with worries. These results could be replicated when using follow-up 1 to follow-up 2 response patterns for group definition. Conclusion: These findings suggest that longitudinal stability versus instability is an important modifying factor of the association between SCD and AD dementia risk. Worrisome SCD that is also consistently reported over time is associated with greatly increased risk of AD dementia.

Keywords: Alzheimer’s disease, dementia, prognosis, subjective cognitive decline

DOI: 10.3233/JAD-160407

Journal: Journal of Alzheimer's Disease, vol. 54, no. 3, pp. 1135-1146, 2016