Circulating Endocannabinoids and Cognitive Function in Older Adults

Area of Science:

• Neuroscience
• Biochemistry
• Gerontology

Background:

• Endogenous cannabinoids (endocannabinoids; eCBs) are implicated in cognitive processes, primarily from preclinical data.
• Observational studies linking circulating eCBs to cognitive function in humans are limited.

Purpose of the Study:

• To investigate the associations between multiple circulating endocannabinoids (eCBs) and eCB-like molecules and cognitive function in dementia-free older adults.
• To explore potential effect modification by sex and apolipoprotein ε4 (ApoEε4) genotype.

Main Methods:

• Cross-sectional analysis of serum eCB levels in 237 older participants from the Framingham Heart Study Offspring cohort.
• Linear regression models were used to assess associations between 44 eCBs and cognitive performance, adjusting for confounders and correcting for multiple testing.

Main Results:

• Increased levels of linoleic acid, linolenic acid, oleic acid, oleoyl alanine, and palmitoyl alanine were associated with poorer executive function.
• Elevated linolenoyl amide and linoleoyl amide correlated with diminished verbal memory and attention.
• Most associations were significant only in women, and some eCBs showed associations with perceptual organization specifically in ApoEε4 carriers.

Conclusions:

• Novel endocannabinoid compounds are identified as potentially related to cognitive function in older adults.
• Findings highlight the importance of considering sex and ApoEε4 genotype in future research on eCBs and cognition.
• Further validation studies are warranted to confirm these exploratory findings.