Background Conventional multi-session genetic counseling is currently recommended when disclosing APOE genotype for risk of Alzheimer’s disease (AD) in cognitively normal individuals. Objective To evaluate the safety of brief disclosure protocols for disclosing APOE genotype for risk of Alzheimer’s disease (AD). Methods A randomized, multicenter non-inferiority trial was conducted at 4 sites. Participants were asymptomatic adults having a first-degree relative with AD. A standard disclosure protocol by genetic counselors (SP-GC) was compared to condensed protocols, with disclosures by genetic counselors (CP-GC) and by physicians (CP-MD). Pre-planned co-primary outcomes were anxiety and depression scales 12 months after disclosure. Results 343 adults (mean age 58.3, range 33–86 years, 71% female, 23% African American) were randomly assigned to the SP-GC protocol (n= 115), CP-GC protocol (n=116) or CP-MD protocol (n=112). Mean post-disclosure scores on all outcomes were well below cut-offs for clinical concern across protocols. Comparing CP-GC to SP-GC, the 97.5% upper confidence limits at 12 months after disclosure on co-primary outcomes of anxiety and depression ranged from a difference of 1.2 to 2.0 in means (all p<0.001 on non-inferiority tests), establishing non-inferiority for condensed protocols. Results were similar between European Americans and African Americans. Conclusions These data support the safety of condensed protocols for APOE disclosure for those free of severe anxiety or depression who are actively seeking such information.

Obese Zucker rats display intracranial hypertension and increased AQP1 expression in CP compared to lean controls. The mechanisms behind these changes are still unknown, but appear to be unrelated to altered pCO levels or retinol metabolism. This indicates that the increase in ICP might be related to increased AQP1 levels in CP. Although further studies are warranted, obese Zucker rats could potentially model some aspects of the IIH pathophysiology.

Intravital microscopy on a closed cranial window allows one to measure change in the diameter of cranial blood vessels after intravenous (i.v.) administration of pharmacodynamic substances. Putative targets being pursued in migraine are large vasodilating peptide molecules such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase polypeptide (PACAP)-38. High i.v. doses are required to study their craniovascular pharmacology. Unfortunately, this leads to a drop in blood pressure (BP) that subsequently causes blood vessels to dilate by autoregulation. Hence it is difficult to decipher what effect is caused by direct receptor agonist interaction or contributed by autoregulation. In the present study we infused substances with an ingenious indwelling catheter in the common carotid artery in rats. Intracarotidly seven-, 12- and 17-fold lower doses of CGRP, PACAP-38 and capsaicin were required, respectively, compared with i.v. infusion to induce the same dilation in dural artery. Dilating intracarotid (i.c.) doses caused no or a minimal fall in BP, whereas equi-responsive i.v. doses caused a marked BP reduction. The CGRP blocking potential of olcegepant was amplified by > 20 times on i.c. infusion. Pial artery responses to CGRP did not change with i.c. infusion, demonstrating that dilations after i.v. CGRP are mediated by autoregulation rather than through specific receptors. We applied CGRP topically, which induced concentration-dependent dural vasodilation, but no effect on pial artery or on BP. In conclusion, this new approach offers an improvement of the existing model by allowing more accurate assessment of effects of pharmaca on the cranial vasculature without inducing significant systemic effects.