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Minor neuropsychological deficits and stage 2 of Alzheimer's disease.

Alzheimer's & dementia : the journal of the Alzheimer's Association

Authors: Melina Stark, Michael Wagner, Elizabeth Kuhn, Sandra Roeske, Holger Amthauer, Claudia Bartels, Henning Boecker, Frederic Brosseron, Ralph Buchert, Katharina Buerger, Marcel Daamen, Alexander Drzezga, Emrah Düzel, Ersin Ersözlü, Markus Essler, Michael Ewers, Klaus Fliessbach, Wenzel Glanz, Julian Hellmann-Regen, Enise I Incesoy, Daniel Janowitz, Konstantinia Kafali, Ingo Kilimann, Bernd Joachim Krause, Marie Kronmüller, Christoph Laske, Franziska Maier, Angelika Maurer, Jochen Michely, Robert Perneczky, Oliver Peters, Lukas Preis, Josef Priller, Boris-Stephan Rauchmann, Matthias Reimold, Axel Rominger, Matthias Schmid, Anja Schneider, Sebastian Sodenkamp, Annika Spottke, Eike Jakob Spruth, Stefan Teipel, Jens Wiltfang, Frank Jessen, Luca Kleineidam

INTRODUCTION: Subtle symptoms, like subjective cognitive decline (SCD) and minor neuropsychological deficits (MNPD), can improve the risk stratification in preclinical Alzheimer´s disease (AD) but their importance is insufficiently elaborated.

METHODS: We pooled data from cognitively normal individuals participating in three longitudinal cohort studies (N = 13,192, 8,359[63.3%] female, mean [SD] age 71.0[8.4]).

RESULTS: Compared to participants without SCD and MNPD (SCD-/MNPD-), SCD-/MNPD+, SCD+/MNPD-, and SCD+/MNPD+ participants had an increased risk for mild cognitive impairment (MCI) and dementia, including in amyloid-positive individuals. Focusing on SCD+/MNPD+ participants triples the positive predictive value of amyloid biomarker testing for the 5-year prediction of MCI and reduces the required samples size for trials in preclinical AD to one fourth, compared to considering all cognitively normal participants regardless of subtle symptoms.

DISCUSSION: SCD and MNPD offer a powerful approach for risk stratification in preclinical AD, which can improve clinical trial designs, risk counseling, and future case identifications for early treatment.

© 2026 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

PMID: 42129577

Participating cluster members