Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
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.
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Thomas Kelsey R, Bangen Katherine J, Rotblatt Lindsay J, Weigand Alexandra J, Edwards Lauren, Tosun Duygu, Galasko Douglas, Alzheimer's Disease Neuroimaging Initiative
Аннотация
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 (Aβ+ or Aβ-) 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, Aβ+/α-syn+ had the greatest cognitive decline. Aβ-/α-syn+ did not differ from Aβ-/α-syn- across ECog scores. Study partner-reported results had a similar pattern, but Aβ+/α-syn- and Aβ+/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, Aβ+/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 (Aβ)-/α-syn-, Aβ-/α-syn+, Aβ+/α-syn-, and Aβ+/α-syn+ biomarker groups were created. Aβ+/α-syn+ had greater subjective cognitive decline (SCD) than the other biomarker groups. Aβ-/α-syn+ did not differ from Aβ-/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.
METHODS: Alzheimer's Disease Neuroimaging Initiative participants without dementia (n = 918) were classified as positive or negative for amyloid beta (Aβ+ or Aβ-) 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, Aβ+/α-syn+ had the greatest cognitive decline. Aβ-/α-syn+ did not differ from Aβ-/α-syn- across ECog scores. Study partner-reported results had a similar pattern, but Aβ+/α-syn- and Aβ+/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, Aβ+/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 (Aβ)-/α-syn-, Aβ-/α-syn+, Aβ+/α-syn-, and Aβ+/α-syn+ biomarker groups were created. Aβ+/α-syn+ had greater subjective cognitive decline (SCD) than the other biomarker groups. Aβ-/α-syn+ did not differ from Aβ-/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.