Self- and study partner-reported cognitive decline in older adults without dementia: The role of α-synuclein and amyloid biomarkers in the Alzheimer's Disease Neuroimaging Initiative.

ABSTRACT

INTRODUCTION: Subjective cognitive decline (SCD) may be an early marker of Alzheimer's disease (AD) pathology. Until recently, it was impossible to measure biomarkers specific for α-synuclein pathology; therefore, its association with subjective reports of cognitive decline is unknown. METHODS: Alzheimer's Disease Neuroimaging Initiative participants without dementia (n = 918) were classified as positive or negative for amyloid beta (Aß+ or Aß-) and α-synuclein (α-syn+ or α-syn-) biomarkers. Self- and study partner-reported cognitive decline was measured with the Everyday Cognition (ECog) questionnaire. RESULTS: Per self-report, Aß+/α-syn+ had the greatest cognitive decline. Aß-/α-syn+ did not differ from Aß-/α-syn- across ECog scores. Study partner-reported results had a similar pattern, but Aß+/α-syn- and Aß+/α-syn+ did not differ across ECog scores. Mild cognitive impairment classification moderated the study partner-reported memory score. DISCUSSION: While α-syn+ alone did not increase subjective reports of cognitive decline, Aß+/α-syn+ had the most self- and study partner-rated cognitive decline. Therefore, the presence of multiple pathologies was associated with greater SCD. HIGHLIGHTS Cerebrospinal fluid α-synuclein (α-syn) seed amplification assay was used to determine α-syn positivity. Amyloid beta (Aß)-/α-syn-, Aß-/α-syn+, Aß+/α-syn-, and Aß+/α-syn+ biomarker groups were created. Aß+/α-syn+ had greater subjective cognitive decline (SCD) than the other biomarker groups. Aß-/α-syn+ did not differ from Aß-/α-syn- across self- or study-partner reported SCD scores. Study partner-reported subjective memory results were largely driven by participants with mild cognitive impairment.