Association of Midlife Inflammatory Markers With Cognitive Performance at 10-Year Follow-up.

BACKGROUND AND OBJECTIVES: Chronic low-grade inflammation, commonly associated with cardiovascular diseases and risk factors, has been associated inconclusively with cognitive decline and dementia. The aim of our study was to evaluate whether low-grade inflammation, measured in midlife, is associated with a decline in cognitive performance after a 10-year follow-up. We hypothesized that low-grade inflammation, estimated by interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and high-sensitivity CRP (hs-CRP), is a predictor of cognitive decline in the general population. METHODS: This prospective cohort study is based on a Finnish nationwide, population-based Health 2000 Examination Survey, its supplemental examinations in 2000-2001, and the follow-up Health 2011 Survey. Cognitive performance at baseline and at follow-up was assessed with categorical verbal fluency (VF), word-list learning (WLL), and word-list delayed recall (WLDR). Baseline low-grade inflammation was measured with IL-6, TNF-α, and hs-CRP in 2001. Associations between low-grade inflammation and cognitive performance were analyzed with multivariable linear models adjusted for age, sex, education, APOE ε4 genotype, type 2 diabetes, hypertension, hypercholesterolemia, body mass index, depressive symptoms, smoking, and baseline cognition. RESULTS: Nine hundred fifteen participants aged 45-74 years (median age 54 years, 55% women) were included in the analysis. Both higher IL-6 and TNF-α at baseline predicted poorer performance in VF and WLL at 10-year follow-up (VF: IL-6 ß: -1.14, p = 0.003, TNF-α ß: -1.78, p = 0.008; WLL: IL-6 ß: -0.61, p = 0.007, TNF-α ß: -0.86, p = 0.03). Elevated IL-6 also predicted a greater decline in VF and WLL after a 10-year follow-up (VF: ß: -0.81, p = 0.01; WLL: ß: -0.53, p = 0.008). Baseline TNF-α did not predict cognitive decline, and hs-CRP did not predict cognitive performance or decline after 10-years. DISCUSSION: Our results suggest that low-grade inflammation in midlife is an independent risk factor for poorer cognitive performance later in life. Of the studied markers, IL-6 and TNF-α seem to be stronger predictors for cognitive performance and decline than hs-CRP.

Insulin resistance is associated with poorer verbal fluency performance in women.

AIMS/HYPOTHESIS: Type 2 diabetes is an independent risk factor for cognitive decline. Insulin resistance occurring during midlife may increase the risk of cognitive decline later in life. We hypothesised that insulin resistance is associated with poorer cognitive performance and that sex and APOE*E4 might modulate this association. METHODS: The association of insulin resistance and APOE*E4 genotype on cognitive function was evaluated in a nationwide Finnish population-based study (n = 5,935, mean age 52.5 years, range 30-97 years). HOMA-IR was used to measure insulin resistance. Cognitive function was tested by word-list learning, word-list delayed-recall, categorical verbal fluency and simple and visual-choice reaction-time tests. Linear regression analysis was used to determine the association between HOMA-IR and the results of the cognitive tests. RESULTS: Higher HOMA-IR was associated with poorer verbal fluency in women (p < 0.0001) but not in men (p = 0.56). Higher HOMA-IR was also associated with poorer verbal fluency in APOE*E4 -negative individuals (p = 0.0003), but not in APOE*E4 carriers (p = 0.28). Furthermore, higher HOMA-IR was associated with a slower simple reaction time in the whole study group (p = 0.02). CONCLUSIONS/INTERPRETATION: To our knowledge, this is the first comprehensive, population-based study, including both young and middle-aged adults, to report that female sex impacts the association of HOMA-IR with verbal fluency. Our study was cross-sectional, so causal effects of HOMA-IR on cognition could not be evaluated. However, our results suggest that HOMA-IR could be an early marker for an increased risk of cognitive decline in women.

Effects of oral sea buckthorn oil on tear film Fatty acids in individuals with dry eye.

PURPOSE: Evaporative dry eye is associated with meibomian gland dysfunction and abnormalities of the tear film lipids. Dry eye is known to be affected positively by intake of linoleic and γ-linolenic acids and n-3 fatty acids. Oral sea buckthorn (Hippophaë rhamnoides) (SB) oil, which contains linoleic and α-linolenic acids and antioxidants, has shown beneficial effects on dry eye. The objective was to investigate whether supplementation with SB oil affects the composition of the tear film fatty acids in individuals reporting dry eye. METHODS: One hundred participants were randomized to this parallel, double-blind, placebo-controlled study, which 86 of them completed. The participants daily consumed 2 g of SB or placebo oil for 3 months. Tear film samples were collected at the beginning, during, and at the end of the intervention and 1 to 2 months later. Tear film fatty acids were analyzed as methyl esters by gas chromatography. RESULTS: There were no group differences in the changes in fatty acid proportions during the intervention (branched-chain fatty acids: P = 0.49, saturated fatty acids: P = 0.59, monounsaturated fatty acids: P = 0.53, and polyunsaturated fatty acids: P = 0.16). CONCLUSIONS: The results indicate that the positive effects of SB oil on dry eye are not mediated through direct effects on the tear film fatty acids. Carotenoids and tocopherols in the oil or eicosanoids produced from the fatty acids of the oil may have a positive effect on inflammation and differentiation of the meibomian gland cells.

Oral sea buckthorn oil attenuates tear film osmolarity and symptoms in individuals with dry eye.

Dry eye is a common condition that can severely impair the quality of life. We aimed to find out whether oral sea buckthorn (SB) oil, containing (n-3) and (n-6) fatty acids and antioxidants, affects dry eye. In this double-blind, randomized, parallel trial, 20- to 75-y-old women and men experiencing dry eye symptoms consumed 2 g of SB or placebo oil daily for 3 mo from fall to winter. One hundred participants were recruited and 86 completed the study. Clinical dry eye tests and symptom follow-ups were performed. Tear film hyperosmolarity is a focal factor in dry eye. There was a general increase in the osmolarity from baseline to the end of the intervention. Compared with the placebo group, the increase was significantly less in the SB group when all participants were included [intention to treat (ITT), P = 0.04] and when only participants consuming the study products for at least 80% of the intervention days were included [per protocol (PP), P = 0.02]. The maximum intensities of redness and burning tended to be lower in the SB group. In the ITT participants, the group difference was significant for redness (P = 0.04) but not for burning (P = 0.05). In the PP participants, the group difference was significant for burning (P = 0.04) but not for redness (P = 0.11). In conclusion, SB oil attenuated the increase in tear film osmolarity during the cold season and positively affected the dry eye symptoms.

Regio-distribution of stearic acid is not conserved in chylomicrons after ingestion of randomised, stearic acid-rich fat in a single meal.

Stearic acid from conventional food is well absorbed, but the fate of synthetic randomized stearic acid in fat absorption and subsequent metabolism is unclear. In this study, we examined the postprandial triglyceridemia following an ingestion of randomized stearic acid-rich fat. Following a 12-h fast, nine healthy young males ate a hamburger meal with 16.7 g of stearic acid (30% in triacylglycerol (TAG) sn-2 position, fully randomized). Postprandial blood samples were collected for 450 min, and the stearic acid content in chylomicron (CM, Svedberg flotation rate >400) TAG and the proportion of stearic acid in the sn-2 position were measured by tandem mass spectrometry at peak (180 min) and late (360 min) triglyceridemia. Of all stearic acid in CM TAG, 23% and 22% were in the sn-2 position at peak and late triglyceridemia (P<.004 and P<.001, respectively). This suggests a 68% and 62% conservation of sn-2 stearic acid, respectively. Peak postprandial TAG concentration and incremental area under the TAG curve showed a higher correlation with the fasting CM TAG (r=0.88, P<.01 and r=0.72, P<.05, respectively) than with total fasting plasma TAG (r=0.73, P<.05 and r=0.24, nonsignificant, respectively). In an earlier study, we showed that the absorption efficiency of the stearic acid of the meal was normal, with only marginal amounts of mainly sn-1,3 stearic acid found in the feces. In conclusion, we showed that sn-2 stearic acid is underrepresented in the postprandial CM TAG following an ingestion of fully randomized fat.