Minor neuropsychological deficits in patients with subjective cognitive decline
Steffen Wolfsgruber, Luca Kleineidam, Jannis Guski, Alexandra Polcher, Ingo Frommann, Sandra Roeske, Eike Jakob Spruth, Christiana Franke, Josef Priller, Ingo Kilimann, Stefan Teipel, Katharina Büerger, Daniel Janowitz, Christoph Laske, Martina Buchmann, Oliver Peters, Felix Menne, Manuel Fuentes, Jens Wiltfang, Claudia Bartels, Emrah Düzel, Coraline D. Metzger, Wenzel Glanz, Manuela Thelen, Annika Spottke, Alfredo Ramı́rez, Barbara Kofler, Klaus Fließbach, Anja Schneider, Michael T. Heneka, Frederic Brosseron, Dix Meiberth, Frank Jessen, Michael Wagner, on behalf of the DELCODE Study Group
Abstract
<h3>Objective</h3> To determine the nature and extent of minor neuropsychological deficits in patients with subjective cognitive decline (SCD) and their association with CSF biomarkers of Alzheimer disease (AD). <h3>Method</h3> We analyzed data from n = 449 cognitively normal participants (n = 209 healthy controls, n = 240 patients with SCD) 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, 5 cognitive domain factor structure comprising learning and memory, executive functions, language abilities, working memory, and visuospatial functions. We compared groups in terms of global and domain-specific performance and correlated performance with different CSF markers of AD pathology. <h3>Results</h3> We observed worse performance (Cohen d = ≈0.25–0.5, adjusted for age, sex differences with analysis of covariance) 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 (<i>r</i> = ≈0.3) associated with lower CSF β-amyloid<sub>42/40</sub> and CSF β-amyloid<sub>42</sub>/phosphorylated tau181 in the whole sample and specifically in the SCD subgroup. <h3>Conclusions</h3> Within the spectrum of clinically unimpaired (i.e., before 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.