Citations

Objectives This naturalistic prospective observation study examines the efficacy of electroconvulsive therapy (ECT) in treating dementia-related agitation. Methods Patients with dementia-related agitation who received ECT were compared with patients with the same condition who did not receive ECT using Cohen-Mansfield Agitation Inventory (CMAI), Neuropsychiatric Inventory (NPI)—nursing home version, and Clinical Global Impression Scale (CGI). Outcomes were compared between ECT-treated and non–ECT-treated patients. Results A total of 9 patients were included in the study. Six received ECT, and 3 did not. Patients in the ECT and non–ECT-treated groups had comparable baseline scores (CMAI, P = 0.880; NPI, P = 0.814; and CGI, P = 0.445). The CMAI, NPI, and CGI scores were lower on final assessment in both groups with no statistically significant difference (CMAI, P = 0.771; NPI, P = 0.243; and CGI, P = 0.519). Conclusions Electroconvulsive therapy should be considered as a treatment option in the management of severe treatment refractory dementia-related agitation.

DNA damage is an important contributor to endothelial dysfunction and age-related vascular disease. Recently, we demonstrated in a DNA repair-deficient, prematurely aging mouse model (Ercc1Δ/− mice) that dietary restriction (DR) strongly increases life- and health span, including ameliorating endothelial dysfunction, by preserving genomic integrity. In this mouse mutant displaying prominent accelerated, age-dependent endothelial dysfunction we investigated the signaling pathways involved in improved endothelium-mediated vasodilation by DR, and explore the potential role of the renin-angiotensin system (RAS). Ercc1Δ/− mice showed increased blood pressure and decreased aortic relaxations to acetylcholine (ACh) in organ bath experiments. Nitric oxide (NO) signaling and phospho-Ser1177-eNOS were compromised in Ercc1Δ/−. DR improved relaxations by increasing prostaglandin-mediated responses. Increase of cyclo-oxygenase 2 and decrease of phosphodiesterase 4B were identified as potential mechanisms. DR also prevented loss of NO signaling in vascular smooth muscle cells and normalized angiotensin II (Ang II) vasoconstrictions, which were increased in Ercc1Δ/− mice. Ercc1Δ/− mutants showed a loss of Ang II type 2 receptor-mediated counter-regulation of Ang II type 1 receptor-induced vasoconstrictions. Chronic losartan treatment effectively decreased blood pressure, but did not improve endothelium-dependent relaxations. This result might relate to the aging-associated loss of treatment efficacy of RAS blockade with respect to endothelial function improvement. In summary, DR effectively prevents endothelium-dependent vasodilator dysfunction by augmenting prostaglandin-mediated responses, whereas chronic Ang II type 1 receptor blockade is ineffective.