Inflammation, Amyloid, and Atrophy in The Aging Brain: Relationships with Longitudinal Changes in Cognition

J Alzheimers Dis. 2017;58(3):829-840. doi: 10.3233/JAD-161146.


Amyloid deposition occurs in aging, even in individuals free from cognitive symptoms, and is often interpreted as preclinical Alzheimer's disease (AD) pathophysiology. YKL-40 is a marker of neuroinflammation, being increased in AD, and hypothesized to interact with amyloid-β (Aβ) in causing cognitive decline early in the cascade of AD pathophysiology. Whether and how Aβ and YKL-40 affect brain and cognitive changes in cognitively healthy older adults is still unknown. We studied 89 participants (mean age: 73.1 years) with cerebrospinal fluid samples at baseline, and both MRI and cognitive assessments from two time-points separated by two years. We tested how baseline levels of Aβ42 and YKL-40 correlated with changes in cortical thickness and cognition. Thickness change correlated with Aβ42 only in Aβ42+ participants (<600 pg/mL, n = 27) in the left motor and premotor cortices. Aβ42 was unrelated to cognitive change. Increased YKL-40 was associated with less preservation of scores on the animal naming test in the total sample (r = -0.28, p = 0.012) and less preservation of a score reflecting global cognitive function for Aβ42+ participants (r = -0.58, p = 0.004). Our results suggest a role for inflammation in brain atrophy and cognitive changes in cognitively normal older adults, which partly depended on Aβ accumulation.

Keywords: Aging; MRI; YKL-40; biomarkers; cerebrospinal fluid; cognition; cortical thickness; inflammation; memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / metabolism*
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Atrophy
  • Biomarkers / cerebrospinal fluid
  • Brain / diagnostic imaging*
  • Chitinase-3-Like Protein 1 / cerebrospinal fluid
  • Cognition*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / metabolism
  • Female
  • Humans
  • Inflammation / diagnostic imaging
  • Inflammation / metabolism*
  • Magnetic Resonance Imaging
  • Male
  • Neuropsychological Tests
  • Organ Size
  • Peptide Fragments / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Biomarkers
  • CHI3L1 protein, human
  • Chitinase-3-Like Protein 1
  • Peptide Fragments
  • amyloid beta-protein (1-42)