Abstract

AbstractBackgroundThere is growing evidence that alterations in the endocannabinoid system (ECS) co‐occur with dementia pathophysiology. Currently, limited literature is available on components of the peripheral ECS as diagnostic markers for dementia.MethodsIn the present study we analysed the concentrations of the endocannabinoids (eCBs) anandamide (AEA) and 2‐Arachidonoylglycerol (2‐AG), and their lipid congeners N‐palmitoylethanolamide (PEA) and N‐oleoylethanolamide (OEA) in plasma and serum using LC‐MS/MS. Samples were collected from healthy controls, participants with mild cognitive impairment (MCI), Alzheimer’s disease (AD) and other dementia subtypes (OD).ResultsStatistical analysis revealed significantly lower concentrations of plasma AEA (p: 0.0017), PEA (p: 0.0056) and OEA (p: 0.0015) in MCI vs. OD groups, and lower OEA levels in MCI vs. healthy controls (p: 0.0099). Plasma PEA levels in AD patients were lower compared to healthy controls (p: 0.0409) and OD groups (p: 0.0307). Additionally, plasma 2‐AG levels correlated positively with age and body mass index (p<0.0001), and negatively with ACE‐III scores (p<0.0011).ConclusionsThese results suggest that peripheral levels of eCBs vary with age and cognitive decline, and may be beneficial in differential diagnosis of dementia. Further, plasma eCB levels may be indicative of early stages of cognitive impairment like MCI, which currently is difficult to diagnose.

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