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| Item Type: | Preprint |
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| Title: | Subjective cognition trajectories, Alzheimer biomarkers, and incident mild cognitive impairment |
| Creators: |
Kuhn, Elizabeth  ORCID: https://orcid.org/0000-0002-3744-1155, Kleinedam, Luca ORCID: https://orcid.org/0009-0006-3309-6856, Stark, Melina ORCID: https://orcid.org/0009-0005-3812-023X, Peters, Oliver ORCID: https://orcid.org/0000-0003-0568-2998, Hellmann-Regen, Julian ORCID: https://orcid.org/0000-0003-0411-9204, Preis, Lukas ORCID: https://orcid.org/0000-0001-7601-6410, Gref, Daria ORCID: https://orcid.org/0000-0003-2497-9324, Priller, Josef ORCID: https://orcid.org/0000-0001-7596-0979, Jakob Spruth, Eike ORCID: https://orcid.org/0000-0002-8976-7309, Gemenetzi, Maria, Schneider, Anja ORCID: https://orcid.org/0000-0001-9540-8700, Fliessbach, Klaus ORCID: https://orcid.org/0000-0002-0183-7510, Wiltfang, Jens ORCID: https://orcid.org/0000-0003-1492-5330, Bartels, Claudia ORCID: https://orcid.org/0000-0003-3023-9971, Hansen, Niels, Rostamzadeh, Ayda ORCID: https://orcid.org/0000-0001-5189-134X, Düzel, Emrah ORCID: https://orcid.org/0000-0002-0139-5388, Glanz, Wenzel ORCID: https://orcid.org/0000-0002-5865-4176, Incesoy, Enise ORCID: https://orcid.org/0000-0003-2014-4098, Buerger, Katharina, Janowitz, Daniel, Stöcklein, Sophia ORCID: https://orcid.org/0000-0003-0325-4674, Perneczky, Robert ORCID: https://orcid.org/0000-0003-1981-7435, Rauchmann, Boris-Stephan ORCID: https://orcid.org/0000-0003-4547-6240, Teipel, Stefan J. ORCID: https://orcid.org/0000-0002-3586-3194, Kilimann, Ingo ORCID: https://orcid.org/0000-0002-3269-4452, Laske, Christoph ORCID: https://orcid.org/0009-0009-3434-936X, Sodenkamp, Sebastian ORCID: https://orcid.org/0009-0004-9118-0621, Spottke, Annika ORCID: https://orcid.org/0000-0001-9854-2972, Kronmüller, Marie ORCID: https://orcid.org/0000-0003-3630-8421, Roeske, Sandra ORCID: https://orcid.org/0000-0002-8262-4356, Brosseron, Frederic ORCID: https://orcid.org/0000-0003-3137-7516, Ramirez, Aflredo, Synofzik, Matthis ORCID: https://orcid.org/0000-0002-2280-7273, Schmid, Matthias C. ORCID: https://orcid.org/0000-0002-0788-0317, Jessen, Frank ORCID: https://orcid.org/0000-0003-1067-2102 and Wagner, Michael ORCID: https://orcid.org/0000-0002-3409-8574
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| Abstract: | Background: Subjective cognitive decline (SCD) is common in older adults and may precede mild cognitive impairment (MCI). Whether longitudinal changes in self- or study partner (SP)-reported SCD improve early identification of individuals at risk for clinical progression, particularly along the Alzheimer’s disease (AD) biological continuum, remains unclear. Methods: We pooled data from two longitudinal observational cohorts (DELCODE and ADNI). Cognitively unimpaired (CU) participants were recruited through public advertisement or memory clinics and included if baseline amyloid status, ≥ 2 SCD assessments, and clinical follow-up were available. SCD was assessed using the Everyday Cognition questionnaire (self- and SP-report). Linear mixed-effects models examined longitudinal associations between SCD trajectories, baseline AD biomarkers, and progression to incident MCI. Multivariable Cox proportional hazards models tested whether one-year changes in SCD predicted subsequent progression. Findings: Among 770 participants (median age 69·9years [IQR 66·0–74·6]; 52·6% women; median follow-up 5·0years [4·0-7·0]), amyloid-positive individuals and those who progressed to MCI showed steeper longitudinal increases in both SCD reports. In amyloid-positive participants, only increases in SP-reported SCD differentiated progressors from non-progressors. One-year increases in SP-reported SCD predicted a higher risk of subsequent MCI compared with unchanged scores (hazard ratio 3·24 [95%CI 1·73-6·07]), with effects confined to amyloidpositive participants. Interpretation: Longitudinal increases in SP-reported cognitive difficulties, particularly over short intervals, are associated with near-term progression to MCI in amyloid-positive CU older adults. SP-based longitudinal monitoring may represent a low-burden approach to support earlier clinical surveillance in aging populations. Funding: German Center for Neurodegenerative Diseases, US National Institutes of Health. |
| Keywords: | Subjective Cognitive Decline, Study Partner Report, Self-Report, Alzheimer's Pathology, Clinical Progression, Longitudinal Study |
| Source: | medRxiv |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Article Number: | 2026.01.27.26344715 |
| Date: | 28 January 2026 |
| Official Publication: | https://doi.org/10.64898/2026.01.27.26344715 |
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