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Systemic inflammation and modifiable risk factors for cognitive impairment in older persons: Findings from a British birth cohort.

ABSTRACT: Serum pro-inflammatory markers may contribute to dementia pathophysiology and cognitive impairment. In a population-representative birth cohort, serum C-reactive protein (CRP), interleukin-6 (IL-6), and white cell count (WCC) were measured at age 60-64 years and cognition was assessed using the Addenbrooke's Cognitive Examination (ACE-III) at age 69 years. Higher baseline CRP and IL-6 were associated with lower ACE-III scores, but associations were attenuated on adjustment for educational attainment, sex, and other modifiable life course factors. No associations were found for CRP, IL-6, and WCC with visual search speed or verbal memory. In conclusion, the relationship between increased baseline systemic inflammation and poorer cognition in later life may be explained by, or share pathways with, education and other modifiable life course factors.

SUBMITTER: Tsui A

PROVIDER: S-EPMC6640037 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Systemic inflammation and modifiable risk factors for cognitive impairment in older persons: Findings from a British birth cohort.

Tsui Alex A Richards Marcus M Davis Daniel D

Aging medicine (Milton (N.S.W)) 20181113 3

Serum pro-inflammatory markers may contribute to dementia pathophysiology and cognitive impairment. In a population-representative birth cohort, serum C-reactive protein (CRP), interleukin-6 (IL-6), and white cell count (WCC) were measured at age 60-64 years and cognition was assessed using the Addenbrooke's Cognitive Examination (ACE-III) at age 69 years. Higher baseline CRP and IL-6 were associated with lower ACE-III scores, but associations were attenuated on adjustment for educational attain ...[more]

PMID: 31328177

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Project description:Investigating associations between metabolites and late midlife cognitive function could reveal potential markers and mechanisms relevant to early dementia. Here, we systematically explored the metabolic correlates of cognitive outcomes measured across the seventh decade of life, while untangling influencing life course factors. Using levels of 1019 metabolites profiled by liquid chromatography-mass spectrometry (age 60-64), we evaluated relationships between metabolites and cognitive outcomes in the British 1946 Birth Cohort (N = 1740). We additionally conducted pathway and network analyses to allow for greater insight into potential mechanisms, and sequentially adjusted for life course factors across four models, including sex and blood collection (Model 1), Model 1 + body mass index and lipid medication (Model 2), Model 2 + social factors and childhood cognition (Model 3) and Model 3 + lifestyle influences (Model 4). After adjusting for multiple tests, 155 metabolites, 10 pathways and 5 network modules were associated with cognitive outcomes. Of the 155, 35 metabolites were highly connected in their network module (termed 'hub' metabolites), presenting as promising marker candidates. Notably, we report relationships between a module comprised of acylcarnitines and processing speed which remained robust to life course adjustment, revealing palmitoylcarnitine (C16) as a hub (Model 4: β = -0.10, 95% confidence interval = -0.15 to -0.052, P = 5.99 × 10-5). Most associations were sensitive to adjustment for social factors and childhood cognition; in the final model, four metabolites remained after multiple testing correction, and 80 at P < 0.05. Two modules demonstrated associations that were partly or largely attenuated by life course factors: one enriched in modified nucleosides and amino acids (overall attenuation = 39.2-55.5%), and another in vitamin A and C metabolites (overall attenuation = 68.6-92.6%). Our other findings, including a module enriched in sphingolipid pathways, were entirely explained by life course factors, particularly childhood cognition and education. Using a large birth cohort study with information across the life course, we highlighted potential metabolic mechanisms associated with cognitive function in late midlife, suggesting marker candidates and life course relationships for further study.

Dataset Information

Systemic inflammation and modifiable risk factors for cognitive impairment in older persons: Findings from a British birth cohort.

Publications

Systemic inflammation and modifiable risk factors for cognitive impairment in older persons: Findings from a British birth cohort.

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