Journal Article

DZNE-2026-00529

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Minor neuropsychological deficits and stage 2 of Alzheimer's disease.

Stark, M. (First author)DZNE* ; Wagner, M.DZNE* ; Kuhn, E.DZNE* ; Roeske, S.DZNE* ; Amthauer, H. ; Bartels, C. ; Boecker, H.DZNE* ; Brosseron, F.DZNE* ; Buchert, R. ; Buerger, K.DZNE* ; Daamen, M.DZNE* ; Drzezga, A.DZNE* ; Düzel, E.DZNE* ; Ersözlü, E.DZNE* ; Essler, M. ; Ewers, M.DZNE* ; Fliessbach, K.DZNE* ; Glanz, W.DZNE* ; Hellmann-Regen, J.DZNE* ; Incesoy, E. I.DZNE* ; Janowitz, D.DZNE* ; Kafali, K.DZNE* ; Kilimann, I.DZNE* ; Krause, B. J. ; Kronmüller, M.DZNE* ; Laske, C.DZNE* ; Maier, F. ; Maurer, A.DZNE* ; Michely, J.DZNE* ; Perneczky, R.DZNE* ; Peters, O.DZNE* ; Preis, L.Extern* ; Priller, J.DZNE* ; Rauchmann, B. S.Extern* ; Reimold, M. ; Rominger, A. ; Schmid, M.DZNE* ; Schneider, A.DZNE* ; Sodenkamp, S.DZNE* ; Spottke, A.DZNE* ; Spruth, E. J.DZNE* ; Teipel, S.DZNE* ; Wiltfang, J.DZNE* ; Initiative, A. D. N. (Collaboration Author) ; Jessen, F.DZNE* ; Kleineidam, L. (Last author)DZNE*

2026
Wiley Hoboken, NJ

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Please use a persistent id in citations: doi:10.1002/alz.71458

Abstract: 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.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]).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.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.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: diagnosis (MeSH) ; Alzheimer Disease: psychology (MeSH) ; Female (MeSH) ; Aged (MeSH) ; Neuropsychological Tests: statistics & numerical data (MeSH) ; Male (MeSH) ; Cognitive Dysfunction: diagnosis (MeSH) ; Longitudinal Studies (MeSH) ; Biomarkers (MeSH) ; Aged, 80 and over (MeSH) ; 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 ; Biomarkers

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Contributing Institute(s):

1. Neuropsychology (AG Wagner)
2. Positron Emissions Tomography (PET) (AG Boecker)
3. Neuroinflammation, Biomarker (AG Heneka)
4. Clinical Research (Munich) (Clinical Research (Munich))
5. Clinical Neurophysiology and Memory (AG Düzel)
6. Interdisciplinary Dementia Research (AG Endres)
7. Patient Studies (Bonn) (Patient Studies (Bonn))
8. Clinical Dementia Research (Rostock /Greifswald) (AG Teipel)
9. Clinical Research Platform (CRP) (AG Spottke)
10. Parkinson Genetics (AG Gasser)
11. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)
12. Mathematics, statistics and informatics methods for support of population studies and clinical research (AG Schmid Bonn)
13. Translational Neuropsychiatry (AG Priller)
14. Molecular biomarkers for predictive diagnostics of neurodegenerative diseases (AG Wiltfang)
15. Clinical Alzheimer’s Disease Research (AG Jessen)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Wiley ; Essential Science Indicators ; IF >= 10 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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