Since apoE allele status is the predominant Alzheimer's disease (AD) genetic risk factor, functional single nucleotide polymorphisms (SNPs) in brain apoE receptors represent excellent candidates for association with AD. Recently, we identified a SNP, rs688, as modulating the splicing efficiency of low-density lipoprotein receptor (LDLR) exon 12 in female human liver and in minigene-transfected HepG2 cells. Moreover, the rs688T minor allele was associated with significantly higher LDL and total cholesterol in women within the Framingham Offspring Study cohort. Since LDLR is a major apoE receptor in the brain, we hypothesized that rs688 modulates LDLR splicing in neural tissues and associates with AD. To evaluate this hypothesis, we first transfected LDLR minigenes into SH-SY5Y neuroblastoma cells and found that the rs688T allele reduces exon 12 inclusion in this neural model. We then evaluated the association of rs688 allele with exon 12 splicing efficiency in vivo by quantifying LDLR splicing in human anterior cingulate tissue obtained at autopsy; the rs688T allele is associated with decreased LDLR exon 12 splicing efficiency in aged males, but not females. Lastly, we evaluated whether rs688 associates with AD by genotyping DNA from 1457 men and 2055 women drawn from three case-control series. The rs688T/T genotype was associated with increased AD odds in males [recessive model, odds ratio (OR) of 1.49, 95% confidence interval (CI) of 1.13-1.97, uncorrected P = 0.005], but not in females. In summary, these studies identify a functional apoE receptor SNP that is associated with AD in a sex-dependent fashion.

A fragmented workforce consisting of multiple disciplines with varying levels of training and limited ability to work as a team often provides care to older adults. Interprofessional education (IPE) is essential for preparing practitioners for the effective teamwork required for community-based, holistic, person-centered care of the older adults. Despite numerous programs and offerings to advance education and interdisciplinary patient care, there is an unmet need for geriatric IPE, especially as it relates to community-dwelling older adults and caregivers in medically underserved areas. A core group of university faculty from multiple disciplines received funding from the Health Resources and Services Administration Geriatric Workforce Enhancement Program to collaborate with community-based providers from several Area Agencies on Aging in the creation and implementation of the Interprofessional Curriculum for the Care of Older Adults (iCCOA). This geriatric curriculum is interprofessional, comprehensive, and community-based. Learners include third-year nursing students, nurse practitioner students, third-year medical students, internal medicine and family medicine residents, master’s level social work students, third-year pharmacy students, pharmacy residents, third-year dental students, dental hygiene students, community-based organization professionals, practicing community organizers, and community health navigators. This article describes the efforts, successes, and challenges experienced with this endeavor, including securing funding, ensuring equal representation of the disciplines, adding new components to already crowded curricula, building curriculum on best practices, improving faculty expertise in IPE, managing logistics, and ensuring comprehensive evaluation. The results summarize the iCCOA components, as well as the interprofessional domains, knowledge, and competencies.

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IMPORTANCE Depression is a common disorder that may go untreated or receive suboptimal care in primary care settings. Computer-assisted cognitive behavior therapy (CCBT) has been proposed as a method for improving access to effective psychotherapy, reducing cost, and increasing the convenience and efficiency of treatment for depression.OBJECTIVES To evaluate whether clinician-supported CCBT is more effective than treatment as usual (TAU) in primary care patients with depression and to examine the feasibility and implementation of CCBT in a primary care population with substantial numbers of patients with low income, limited internet access, and low levels of educational attainment. DESIGN, SETTING, AND PARTICIPANTSThis randomized clinical trial included adult primary care patients from clinical practices at the University of Louisville who scored 10 or greater on the Patient Health Questionnaire-9 (PHQ-9) and were randomly assigned to CCBT or TAU for 12 weeks of active treatment. Follow-up assessments were conducted 3 and 6 months after treatment completion.