Association of Circulating Caprylic Acid with Risk of Mild Cognitive Impairment and Alzheimer’s Disease in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) Cohort

Objective Medium-chain fatty acids (MCFAs) can rapidly cross the blood-brain barrier and provide an alternative energy source for the brain. This study aims to determine 1) whether plasma caprylic acid (C8:0) is associated with risk of incident mild cognitive impairment (MCI) among baseline cognitively normal (CN) participants, and incident Alzheimer’s Disease (AD) among baseline MCI participants; and 2) whether these associations differ by sex, comorbidity of cardiometabolic diseases, apolipoprotein E (APOE) ε4 alleles, and ADAS-Cog 13. Methods Within the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, plasma C8:0 was measured at baseline in 618 AD-free participants aged 55 to 91. Logistic regression models were used to estimate odds ratios (ORs) and 95% CIs with incident MCI and AD as dependent variables, separately. Results The inverse association between circulating C8:0 and risk of incident MCI was of borderline significance. The inverse association between circulating levels of C8:0 and risk of incident MCI was significant among CN participants with ≥1 cardiometabolic diseases [OR (95% CI): 0.75 (0.58–0.98) (P=0.03)], those with one copy of APOE ε4 alleles [OR (95% CI): 0.43 (0.21–0.89) (P=0.02)], female [OR (95% CI): 0.60 (0.38–0.94) (P=0.02)], and ADAS-Cog 13 above the median [OR (95%CI): 0.69 (0.50–0.97)(P=0.03)] after adjusting for all covariates. Conclusion The inverse associations were present only among subgroups of CN participants, including female individuals, those with one or more cardiometabolic diseases, or one APOE ε4 allele, or higher ADAS-Cog 13 scores. If confirmed, this finding will facilitate precision prevention of MCI, in turn, AD among CN older adults.