Investigating the combination of plasma amyloid-beta and geroscience biomarkers on the incidence of clinically meaningful cognitive decline in older adults

Geroscience. 2022 Jun;44(3):1489-1503. doi: 10.1007/s11357-022-00554-y. Epub 2022 Apr 20.


We investigated combining a core AD neuropathology measure (plasma amyloid-beta [Aβ] 42/40) with five plasma markers of inflammation, cellular stress, and neurodegeneration to predict cognitive decline. Among 401 participants free of dementia (median [IQR] age, 76 [73-80] years) from the Multidomain Alzheimer Preventive Trial (MAPT), 28 (7.0%) participants developed dementia, and 137 (34.2%) had worsening of clinical dementia rating (CDR) scale over 4 years. In the models utilizing plasma Aβ alone, a tenfold increased risk of incident dementia (nonsignificant) and a fivefold increased risk of worsening CDR were observed as each nature log unit increased in plasma Aβ levels. Models incorporating Aβ plus multiple plasma biomarkers performed similarly to models included Aβ alone in predicting dementia and CDR progression. However, improving Aβ model performance for composite cognitive score (CCS) decline, a proxy of dementia, was observed after including plasma monocyte chemoattractant protein 1 (MCP1) and growth differentiation factor 15 (GDF15) as covariates. Participants with abnormal Aβ, GDF15, and MCP1 presented higher CCS decline (worsening cognitive function) compared to their normal-biomarker counterparts (adjusted β [95% CI], - 0.21 [- 0.35 to - 0.06], p = 0.005). In conclusion, our study found limited added values of multi-biomarkers beyond the basic Aβ models for predicting clinically meaningful cognitive decline among non-demented older adults. However, a combined assessment of inflammatory and cellular stress status with Aβ pathology through measuring plasma biomarkers may improve the evaluation of cognitive performance.

Keywords: Aging; Alzheimer’s disease; Amyloid-beta; Cognitive decline; Inflammation; Neurodegeneration.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease* / diagnosis
  • Alzheimer Disease* / metabolism
  • Amyloid beta-Peptides / metabolism
  • Biomarkers
  • Clinical Trials as Topic
  • Cognitive Dysfunction* / diagnosis
  • Cognitive Dysfunction* / epidemiology
  • Cognitive Dysfunction* / metabolism
  • Geroscience
  • Humans
  • Incidence


  • Amyloid beta-Peptides
  • Biomarkers