Non-linear association between serum spermidine and mild cognitive impairment: Results from a cross-sectional and longitudinal study

Abstract

BackgroundAlthough animal studies show that spermidine (SPD) affects cognitive function, the relevant evidence among humans is limited. We aim to examine the association between serum SPD levels and cognitive performance.Materials and MethodsWe conducted a cross-sectional and longitudinal study including a baseline and one follow-up survey. The baseline survey was conducted from June 2019 to August 2019, while the follow-up survey was conducted from June 2021 to August 2021. We analyzed 3,774 adult participants aged >35 years, who had no history of dementia.ResultsThe mean (SD) age of the participants was 57.4 (9.8) years. Relative to the first tertile, the multivariate-adjusted ORs (95% CIs) of mild cognitive impairment (MCI) for the second and third tertile groups were 0.78 (0.65, 0.93) and 0.80 (0.67, 0.96), respectively. Restricted cubic spline models show that there is a non-linear association between SPD and MCI. In line with cross-sectional findings, the longitudinal study showed that a high SPD concentration may indicate a lower risk of MCI [ORs (95% CIs) for the third tertile of 0.62 (0.39, 0.99)].ConclusionOur findings suggest that SPD is favorable for cognitive function. Monitoring the SPD levels may help reduce the incidence of MCI, hence decreasing the burden of MCI.

The positive effect of spermidine in older adults suffering from dementia after 1 year

“…This fact was questioned in a letter to the editor due to too low R 2 levels in the correlation analysis carried out [ 4 ]. A recently published study with a sample size of 3774 also described a correlation between serum spermidine levels and cognitive impairments [ 5 ]. In addition, the authors concluded that monitoring the spermidine levels may be helpful for reducing the incidence of cognitive impairments.…”

The Molecular Role of Polyamines in Age-Related Diseases: An Update

“…On the one hand, one research group demonstrated that in 43 samples from American individuals over 65 years old at the Oregon Alzheimer's Disease Center, an increase in serum levels of spermidine corresponded to the progression from MCI to AD (Figure 2 and Table 1), suggesting the viability of measuring serum spermidine as a key molecule in AD pathology and as a potential biomarker for AD progression [36]. On the other hand, a study with a rural Chinese population of approximately 3,700 individuals over 35 years old with no history of dementia revealed a non-linear relationship between spermidine and MCI, implying that high levels of spermidine may decrease the burden of MCI (Table 1) [69]. These contradictory reports raise the possibility that factors such as race, diet, and geographic location could change the general perspective on the role of spermidine in AD or MCI.…”

Spermidine content of selected dietary supplements: potential for improvement?

“…years. There was an albeit non-linear, positive correlation between spermidine levels and the risk of mild cognitive impairment [20]. Higher dietary intake of spermidine was associated with greater hippocampal volume, greater mean cortical thickness, and greater cortical thickness in parietal and temporal lobes, which are common ADaffected regions, independently of cognitive performance [21].…”