Anticholinergic Drugs and Their Effects on Delirium and Mortality in the Elderly

Aim: To investigate the use of drugs with anticholinergic properties (DAPs) and their associations with delirium and mortality among elderly patients with comorbidities. Methods: 425 patients (≧70 years of age) in geriatric wards and nursing homes were assessed. The use of DAPs was retrieved from their medical records. Delirium was diagnosed according to the DSM-IV criteria. Results: Of the 341 patients (80.2%) treated with multiple DAPs (≧2), 92 patients (27.0%) suffered from delirium, whereas 14 of 84 patients (16.7%) without DAP treatment had delirium (p = 0.050). In a logistic regression analysis with age, gender, and Charlson Comorbidity Index as covariates, DAP treatment did not predict delirium (odds ratio 1.67, 95% confidence interval 0.87–3.21). The 2-year mortality was 49.3% (n = 168) in DAP users and 35.7% (n = 30) in non-users, respectively (p = 0.026). In the Cox proportional hazard model adjusted for age, gender, and comorbidity, DAPs did not predict mortality (hazard ratio 1.12, 95% confidence interval 0.75–1.68). Conclusion: The use of DAPs is very frequent among frail inpatients with comorbidities, but their use has no independent prognostic significance

APOE ϵ4, rated life experiences, and affect among centenarians

Additional authors include M. Gearing, W. R. Markesbery, J. S. Tenover, W. L. Rodgers, D. B. Hausman, & C. Rott who are involved with the Georgia Centenarian Study.Objectives: The purpose of this study was to assess the relationship between apolipoprotein E (APOE), life events and engagement, and subjective well-being (as measured by positive and negative affect) among centenarians. Based on the life stress paradigm, we predicted that higher levels of stress would allow APOE to influence positive and negative affect. Method: 196 centenarians and near-centenarians (98 years and older) of the Georgia Centenarian Study participated in this research. The APOE, positive and negative affect, the number of recent (last 2 years) and lifelong (more than 20 years prior to testing) events, as well as a number of life engagement tasks were assessed. Results: Results suggested that centenarians carrying the APOE ϵ4 allele rated lower in positive affect, the number of lifelong events, and in engaged lifestyle, when compared to centenarians without the APOE ϵ4 allele (t = 3.43, p < .01; t = 3.19, p < .01; and t = 2.33, p < .05, respectively). Blockwise multiple regressions indicated that the APOE ϵ4 predicted positive but not negative affect after controlling for demographics. Gene–environment interactions were obtained for the APOE ϵ4 and lifelong events, suggesting that carriers of the APOE ϵ4 allele had higher scores of negative affect after having experienced more events, whereas noncarriers had reduced negative affect levels after having experienced more events. Conclusion: APOE ϵ4 is directly related to positive affect and is related to negative affect in interaction with life events

In vivo pharmacodynamic interactions between two drugs used in orthostatic hypotension--midodrine and dihydroergotamine.

International audienceA combination of midodrine and dihydroergotamine (DHE) is frequently used clinically in patients suffering from severe orthostatic hypotension (OH). Whereas midodrine acts as a selective, peripheral alpha1-receptor agonist, DHE displays complex pharmacology and can behave as an alpha-adrenergic receptor agonist or antagonist. Surprisingly, the consequences of such a combination on blood pressure have never been investigated. The present study was performed in order to evaluate the pressor effects induced by the administration of both midodrine and DHE in old conscious dogs (n = 6) in experimental condition reproducing autonomic failure-related baroreflex dysfunction (atropine 0.1 mg/kg). For this purpose, we first studied the relative potency and intrinsic activity of each agonist and noradrenaline (NA) for the alpha1-adrenergic receptor. The orders of potency obtained in our study were 0.35, 11 and 400 microg/kg for NA, DHE and midodrine, and intrinsic activity: NA > midodrine > DHE. These results strongly suggest that DHE really acts in vivo as an alpha1-adrenoceptor partial agonist. Afterwards, the pressor effects of coadministration of midodrine (0.4 mg/kg) and DHE (15 microg/kg) were investigated: in one setting, midodrine was first administered, followed by DHE; in another, DHE was first administered, followed by midodrine. Our results show that in conscious dogs, the combination of midodrine and DHE leads to near-complete abolition of the pressor effect induced by the first administered drug. This in vivo proof of such antagonistic effects on blood pressure could explain clinical observations of worsening of OH in humans administered midodrine plus DHE. Although in vivo results obtained in conscious healthy dogs need to be experimentally and clinically confirmed in humans suffering from OH, these results strongly suggest that a midodrine-DHE combined treatment should be avoided in clinical practice