Objective:To determine the nature and extent of minor neuropsychological deficits in patients with subjective cognitive decline (SCD) and their association with cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD).Method:We analyzed data from n=449 cognitively normal participants (n=209 healthy controls, n=240 SCD patients) from an interim data release of the German Center for Neurodegenerative Diseases Longitudinal Cognitive Impairment and Dementia Study (DELCODE). An extensive neuropsychological test battery was applied at baseline for which we established a latent, five cognitive domain factor structure comprising learning & memory, executive functions, language abilities, working memory and visuospatial functions. We compared groups regarding global and domain-specific performance and correlated performance with different CSF markers of AD pathology.Results:We observed worse performance (Cohen’s d≈0.25-0.5, adjusted for age-, sex differences with ANCOVA) in global performance, memory, executive functions and language abilities for the SCD group compared to healthy controls. In addition, worse performance in these domains was moderately (r≈0.3) associated with lower CSF-Aβ42/40 and CSF-Aβ42/ptau181 in the whole sample and specifically in the SCD subgroup.Conclusions:Within the spectrum of clinically unimpaired (i.e., “pre- mild cognitive impairment”) cognitive performance, SCD is associated with minor deficits in memory, executive function and language abilities. The association of these subtle cognitive deficits with AD CSF biomarkers speaks to their validity and potential use for the early detection of underlying preclinical AD.

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Introduction Subjective cognitive decline (SCD) and depressive symptoms (DS) frequently co‐occur prior to dementia. However, the temporal sequence of their emergence and their combined prognostic value for cognitive decline and dementia is unclear. Methods Temporal relationships of SCD, DS and memory decline were examined by latent difference score modeling in a high‐aged, population‐based cohort (N = 3217) and validated using Cox‐regression of dementia‐conversion. In 334 cognitively unimpaired SCD‐patients from memory‐clinics, we examined the association of DS with cognitive decline and with cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers. Results In the population‐based cohort, SCD preceded DS. High DS were associated with increased risk of dementia conversion in individuals with SCD. In SCD‐patients from memory‐clinics, high DS were associated with greater cognitive decline. CSF Aß42 predicted increasing DS. Discussion SCD typically precedes DS in the evolution to dementia. SCD‐patients from memory‐clinics with DS may constitute a high‐risk group for cognitive decline. Highlights Subjective cognitive decline (SCD) precedes depressive symptoms (DS) as memory declines. Emerging or persistent DS after SCD reports predict dementia. In SCD patients, more amyloid pathology relates to increasing DS. SCD patients with DS are at high risk for symptomatic progression.

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