Abstract
Despite strong evidence for a socioeconomic gradient in many health outcomes, including cognition, substantial gaps remain in understanding these disparities. We investigated the ...biopsychosocial mechanisms underlying the associations between socioeconomic status (SES) and later-life cognitive health using the Harmonised Cognitive Assessment Protocol (HCAP), a sub-study of the English Longitudinal Study of Ageing (ELSA) which comprises of 1,273 ELSA participants aged 65+. A latent g factor was derived using 12 tests covering a broad range of cognitive domains (memory, language, executive function, and psychomotor speed). We estimated direct and indirect pathways between SES indicators, Apolipoprotein E, inflammatory markers, chronic conditions, and depression. We found that higher education was associated with better cognition, while wealth was not. Increased depressive symptoms were linked with lower cognition, while prior inflammation was indirectly associated with cognition via depressive symptoms and chronic conditions, supporting evidence for a psychosocial role in the context of a socioeconomic gradient.
The results of two single-center, two-period, open-label trials that evaluated the effects of multiple doses of desvenlafaxine on the pharmacokinetics of desipramine, a cytochrome P450 (CYP) 2D6 ...enzyme substrate, are presented. Healthy individuals aged 18-45 years were administered a single oral dose of 50 mg desipramine with and without 100 mg daily (n=34) or 400 mg daily (n=23) desvenlafaxine for 5 days. After coadministration of 100 mg desvenlafaxine, desipramine exposure, measured by peak plasma concentration (C(max)) and total area under the plasma concentration-versus-time curve (AUC), showed minimal increases of 25 and 17%, respectively; coadministration of 400 mg desvenlafaxine resulted in a 52% increase in desipramine C(max) and a 90% increase in AUC. For the 100 mg dose, the geometric least squares mean ratios and 90% confidence intervals (CIs) for desipramine AUC (117%; 90% CI 110-125%), 2-hydroxydesipramine AUC (114%; 90% CI 110-119%), and C(max) (110%; 90% CI 104-116%) were all within the 80-125% interval, showing the bioequivalence for AUC between desipramine administered alone and in combination with 100 mg desvenlafaxine. These results indicate that desvenlafaxine is a relatively weak inhibitor of CYP2D6 and that desvenlafaxine 100 mg, twice the recommended therapeutic dose of 50 mg, is unlikely to cause drug-drug interactions with CYP2D6 substrates.
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