A cross-sectional study of 308 cognitively unimpaired older adults enriched for Alzheimer's risk found that higher serum klotho levels significantly moderated the negative relationship between brain atrophy (ventricle-brain volume ratio) and cognitive performance. Notably, individuals with both greater brain atrophy and higher klotho still performed well on global cognition and executive function tests. This protective effect was observed only in adults older than 61.6 years—not in younger participants—suggesting klotho's neuroprotective benefits may be age-dependent. The findings support klotho as a promising target for interventions aimed at preserving cognition during aging and against Alzheimer's disease progression.
