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Serum Klotho Levels, Brain Structure, and Cognitive Performance.

Alec M Czaplicki1,2, Ira Frahmand Driscoll1,2, Yue Ma1,2

  • 1Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison.

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Higher klotho levels may protect cognition against brain atrophy in older adults at risk for Alzheimer disease (AD). This effect was not observed in younger adults, suggesting klotho

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Area of Science:

  • Neuroscience
  • Gerontology
  • Biochemistry

Background:

  • Ventricle-brain volume ratio (VBR) indicates cerebral atrophy and predicts Alzheimer disease (AD) progression.
  • Higher klotho concentrations are associated with better cognition, but its role in modifying the VBR-cognition link is unknown.

Purpose of the Study:

  • To investigate if serum klotho moderates the association between VBR and cognition.
  • To determine if this moderation differs between younger (≤61.6 years) and older adults.

Main Methods:

  • Cross-sectional study (2009-2023) with data from the Wisconsin AD Research Center and Registry.
  • Included 308 non-cognitively impaired middle-aged and older adults, most with a parental history of AD.
  • Measured serum soluble α-klotho, VBR, and cognitive functions (global cognition, executive function, delayed recall, immediate learning).

Main Results:

  • A significant VBR × klotho interaction was found across the entire sample: higher klotho correlated with better global cognition and executive function despite greater VBR.
  • This interaction was not significant in younger adults.
  • In older adults, higher klotho was associated with better global cognition, executive function, and immediate learning, even with increased VBR.

Conclusions:

  • Serum klotho levels appear to modify the negative association between brain atrophy and cognition in older adults at risk for AD.
  • The neuroprotective effects of klotho may be age-dependent, being more pronounced in older individuals.