Incidence of subjective cognitive decline is associated with amyloid‐β pathology, whereas stability relates to neurodegeneration: Neuropsychiatry and behavioral neurology/presymptomatic disease/prodromal disease/prodromal states.

Background: Subjective Cognitive Decline (SCD) is a risk factor for cognitive decline and increases the likelihood of abnormal Alzheimer's disease (AD) biomarkers. A set of SCD features (SCDplus) has been proposed to be more strongly related with AD pathology, like onset within 5 years. Limited evidence suggest that there is an association between recent SCD onset and amyloid‐β (Aβ) levels but longitudinal studies exploring this association are lacking. Our objective was to explore the association between incidence and stability of SCD and biomarkers of AD pathology, synaptic dysfunction and neurodegeneration. Method: We analyzed clinical, neuroimaging and cerebrospinal fluid (CSF)‐biomarkers data from 261 cognitively unimpaired individuals from the ALFA+ study [mean age 57(5) at baseline]. SCD status was recorded at baseline and follow‐up [mean interval 48.5(8.6) months, 80% before 60 months] using the SCD‐Q question: Do you perceive memory or cognitive difficulties? Individuals were classified as Stable‐SCD [SCD at both visits (n=28)], Incident‐SCD [SCD only at follow‐up (n=44)], Unstable‐SCD [SCD only at baseline (n=21)], and non‐SCD [no SCD at any visit (n=168)]. All remained cognitively unimpaired at follow‐up. We defined amyloid status by visual reads (Aβ+/Aβ‐) from [18F]flutemetamol PET scans. Aβ40, Aβ42, p‐tau, t‐tau, neurogranin and Neurofilament Light (NfL) were measured with Roche NeuroToolKit and Elecsys® immunoassays (Roche Diagnostics). Logistic regression models were used to predict Aβ status and ANCOVA models to explore differences in biomarkers, adjusting for age, sex and interval between visits. Result: The proportion of Aβ+ individuals was higher in Incident‐SCD as compared to non‐SCD (OR=2.5, p=0.04, Table 1). Further, Incident‐SCD group displayed lower Aβ42/Aβ40 than non‐SCD (p=0.02, partial Eta2=0.02). While Stable‐SCD did not show differences in amyloid measures as compared to controls, NfL was significantly increased (p<0.0001, p‐Eta2=0.08) and t‐tau approached significance (p=0.08). Conclusion: Recent SCD onset was associated with amyloid‐β pathology, while stable SCD, even without clinical progression, was associated to biomarkers of neurodegeneration but not to amyloid pathology. These results support the usefulness of the onset in the last 5 years as SCDplus feature to detect amyloid pathology, while also highlights the role of neurodegeneration in SCD maintenance. [ABSTRACT FROM AUTHOR]