LOW DENSITY LIPOPROTEIN RECEPTOR AND ALZHEIMERS DISEASE

Since apoE allele status is the predominant Alzheimers disease (AD) genetic risk factor, functional single nucleotide polymorphisms (SNPs) in brain apoE receptors represent excellent candidates for association with AD. Therefore, three low density lipoprotein receptor (LDLR) SNPs were evaluated by TaqMan allelic discrimination assays for association with AD and I found that certain haplotypes alter the odds of AD. A SNP within LDLR exon 12, rs688, was identified in silico as neutralizing a putative exon splicing enhancer (ESE). Since LDLR is a major apoE receptor in the brain, I hypothesized that rs688 modulates LDLR splicing in neural tissues and associates with AD. To evaluate this hypothesis, I analyzed splicing patterns in human hippocampus samples and established that this SNP was associated with significantly decreased LDLR exon 12 splicing efficiency when the minor allele T is present in vivo. Lastly, I evaluated whether rs688 associates with AD by genotyping DNA from the Religious Orders Study (ROS) series. The rs688T/T genotype was associated with increased AD odds in males, but not in females, in a dataset consisting of 1,457 men and 2,055 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

Effect of Computer-Assisted Cognitive Behavior Therapy vs Usual Care on Depression Among Adults in Primary Care: A Randomized Clinical Trial

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 Participants This 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. Enrollment occurred from June 24, 2016, to May 13, 2019. The last follow-up assessment was conducted on January 30, 2020. Interventions CCBT included use of the 9-lesson computer program Good Days Ahead, along with as many as 12 weekly telephonic support sessions of approximately 20 minutes with a master’s level therapist, in addition to TAU, which consisted of the standard clinical management procedures at the primary care sites. TAU was uncontrolled, but use of antidepressants and psychotherapy other than CCBT was recorded. Main Outcomes and Measures The primary outcome measure (PHQ-9) and secondary outcome measures (Automatic Thoughts Questionnaire for negative cognitions, Generalized Anxiety Disorder–7, and the Satisfaction with Life Scale for quality of life) were administered at baseline, 12 weeks, and 3 and 6 months after treatment completion. Satisfaction with treatment was assessed with the Client Satisfaction Questionnaire–8. Results The sample of 175 patients was predominately female (147 of 174 [84.5%]) and had a high proportion of individuals who identified as racial and ethnic minority groups (African American, 44 of 162 patients who reported [27.2%]; American Indian or Alaska Native, 2 [1.2%]; Hispanic, 4 [2.5%]; multiracial, 14 [8.6%]). An annual income of less than $30 000 was reported by 88 of 143 patients (61.5%). Overall, 95 patients (54.3%) were randomly assigned to CCBT and 80 (45.7%) to TAU. Dropout rates were 22.1% for CCBT (21 patients) and 30.0% for TAU (24 patients). An intent-to-treat analysis found that CCBT led to significantly greater improvement in PHQ-9 scores than TAU at posttreatment (mean difference, −2.5; 95% CI, −4.5 to −0.8; P = .005) and 3 month (mean difference, −2.3; 95% CI, −4.5 to −0.8; P = .006) and 6 month (mean difference, −3.2; 95% CI, −4.5 to −0.8; P = .007) follow-up points. Posttreatment response and remission rates were also significantly higher for CCBT (response, 58.4% [95% CI, 46.4-70.4%]; remission, 27.3% [95% CI, 16.4%-38.2%]) than TAU (response, 33.1% [95% CI, 20.7%-45.5%]; remission, 12.0% [95% CI, 3.3%- 20.7%]). Conclusions and Relevance In this randomized clinical trial, CCBT was found to have significantly greater effects on depressive symptoms than TAU in primary care patients with depression. Because the study population included people with lower income and lack of internet access who typically have been underrepresented or not included in earlier investigations of CCBT, results suggest that this form of treatment can be acceptable and useful in diverse primary care settings. Additional studies with larger samples are needed to address implementation procedures that could enhance the effectiveness of CCBT and to examine potential factors associated with treatment outcome

Implementing Chief Resident Immersion Training (CRIT) in the Care of Older Adults: Overcoming Barriers and Promoting Facilitators

The Chief Resident Immersion Training (CRIT) in the Care of Older Adults curriculum was developed at Boston University School of Medicine to improve the care of older adults through an educational intervention. The curriculum targeted chief residents (CRs) because their role as mediators between learners and faculty provides the greatest potential impact for transmitting knowledge. The goals of CRIT are to: (1) provide education on geriatric principles and on teaching/leadership skills, (2) foster interdisciplinary collaboration, and (3) complete an action project. This study demonstrates successful implementation of CRIT at a different academic institution in a rural state. The CRs indicated that their confidence in their ability to apply and teach geriatrics improved after CRIT. In addition, the CRs indicated that CRIT improved their confidence in their overall skills as CRs. The barriers and facilitators to implementation are addressed in order to promote successful adoption of CRIT at other institutions, including those in rural states