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SCD‐<i>plus</i> features and AD biomarkers in cognitively unimpaired samples: A meta‐analytic approach for nine cohort studies

Elizabeth Kuhn, Hannah M Klinger, Rebecca E. Amariglio, Michael Wagner, Frank Jessen, Emrah Düzel, Michael T. Heneka, Gaël Chételat, Dorene M. Rentz, Reisa A. Sperling, Jarith L. Ebenau, Elke Butterbrod, Wiesje M. van der Flier, Sietske A.M. Sikkes, Charlotte E. Teunissen, Argonde C. van Harten, Elsmarieke van de Giessen, Lorena Rami, Adrià Tort‐Merino, Gonzalo Sánchez‐Benavides, Katherine A. Gifford, Carol Van Hulle, Rachel F. Buckley, Alzheimer's Disease Neuroimaging Initiative, Australian Imaging Biomarkers and Lifestyle flagship study of ageing, A4 Study Team, DELCODE Study, Harvard Aging Brain Study

2025Alzheimer s & Dementia11 citationsDOIOpen Access PDF

Abstract

INTRODUCTION: Specific features of subjective cognitive decline (SCD-plus) have been proposed to indicate an increased risk of preclinical Alzheimer's disease (AD). However, few studies have examined how these features relate to AD biomarkers in cognitively unimpaired (CU) older adults. METHODS: Meta-analyses were performed using cross-sectional data from nine cohorts (n = 7219, mean age (SD): 71.17 (5.9), 56.5% female) to determine associations of SCD-plus features with positron emission tomography (PET)- or cerebrospinal fluid (CSF)-derived amyloid beta (Aβ) and tau biomarkers. RESULTS: Participants with preclinical AD (community-based only) were more likely to fulfill SCD-plus features. The presence of self-reported memory decline, associated concern/worry, and a higher number of fulfilled features were all associated with high Aβ levels. Only the latter was associated with abnormal tau. DISCUSSION: Simultaneous endorsement of multiple SCD-plus features is a robust indicator of abnormal AD biomarkers in CU older adults, whereas isolated SCD features seem only sensitive to elevated Aβ, supporting their value as early behavioral markers of preclinical AD. HIGHLIGHTS: About two-tenths of our sample had abnormal amyloid beta (Aβ) levels with evidence of subjective cognitive decline (SCD). Preclinical AD subsamples (community-based) had a higher percentage of participants meeting SCD-plus features. Self-reported memory decline and concern/worry were the sole features associated with high Aβ, but not tau, burden. A higher number of fulfilled SCD-plus features are linked to high Aβ and tau burden. Use of multiple SCD-plus features may help identify early stages of biological AD.

Topics & Concepts

WorryCognitive declineMedicineDiseaseCohortBiomarkerOncologyInternal medicinePositron emission tomographyCognitionNeuroimagingPsychologyClinical psychologyDementiaPsychiatryAnxietyNeuroscienceBiologyBiochemistryDementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies
SCD‐<i>plus</i> features and AD biomarkers in cognitively unimpaired samples: A meta‐analytic approach for nine cohort studies | Litcius