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Minor neuropsychological deficits and stage 2 of Alzheimer's disease

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Item Type:Article
Title:Minor neuropsychological deficits and stage 2 of Alzheimer's disease
Creators Name:Stark, Melina, Wagner, Michael, Kuhn, Elizabeth, Roeske, Sandra, Amthauer, Holger, Bartels, Claudia, Boecker, Henning, Brosseron, Frederic, Buchert, Ralph, Buerger, Katharina, Daamen, Marcel, Drzezga, Alexander, Düzel, Emrah, Ersözlü, Ersin, Essler, Markus, Ewers, Michael, Fliessbach, Klaus, Glanz, Wenzel, Hellmann-Regen, Julian, Incesoy, Enise I., Janowitz, Daniel, Kafali, Konstantinia, Kilimann, Ingo, Krause, Bernd Joachim, Kronmüller, Marie, Laske, Christoph, Maier, Franziska, Maurer, Angelika, Michely, Jochen, Perneczky, Robert, Peters, Oliver, Preis, Lukas, Priller, Josef, Rauchmann, Boris-Stephan, Reimold, Matthias, Rominger, Axel, Schmid, Matthias, Schneider, Anja, Sodenkamp, Sebastian, Spottke, Annika, Spruth, Eike Jakob, Teipel, Stefan, Wiltfang, Jens, Jessen, Frank and Kleineidam, Luca
Abstract: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.
Keywords:Clinical Staging, Minor Neuropsychological Deficits, Preclinical Alzheimer’s Disease, Stage 2 of Alzheimer’s Disease, Subjective Cognitive Concerns, Subjective Cognitive Decline, Subtle Cognitive Decline, Transitional Cognitive Decline
Source:Alzheimer's & Dementia
ISSN:1552-5260
Publisher:Wiley / Alzheimer's Association
Volume:22
Number:5
Page Range:e71458
Date:May 2026
Official Publication:https://doi.org/10.1002/alz.71458
PubMed:View item in PubMed

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