Faculty Bibliography

INTRODUCTION: Test the validity and reliability of the Quick Dementia Rating System (QDRS), a rapid dementia staging tool. METHODS: The QDRS was tested in 267 patient-caregiver dyads compared with Clinical Dementia Ratings (CDR), neuropsychological testing, and gold standard measures of function, mood, and behavior. Psychometric properties including, item variability, floor and ceiling effects, concurrent and construct validity, and internal consistency were determined. The QDRS was used to derive an independent CDR and sum of boxes. Interscale reliability between QDRS and CDR was tested using intraclass correlation coefficients (ICC). Area under the receiver operator characteristic curves (AUC) tested discrimination properties of QDRS across CDR stages. RESULTS: QDRS scores increased with higher CDR staging and poorer neuropsychological performance (p's <.001). The QDRS demonstrated low floor and ceiling effects; excellent known-groups validity across CDR stages (p's<.001); construct validity against cognitive, behavioral, and functional measures (p-value's:0.004 to <0.001); and reliability (Cronbach alpha: 0.86-0.93). The QDRS demonstrated differential scores across different dementia etiologies. The AUC for the QDRS was 0.911 (95%CI 0.86-0.96) and for the CDR-SB was 0.996 (95% CI: 0.99-1.0) demonstrating comparable ability to discriminate normal controls from dementia. The QDRS-generated CDR demonstrated excellent correspondence with the CDR (ICC=0.90) and sum-of-boxes (ICC=0.92). DISCUSSION: The QDRS validly and reliably differentiates individuals with and without dementia and accurately stages dementia without extensive training or clinician input, and is highly correlated with our gold standard measures. The QDRS provides a rapid method to determine study eligibility; stage patients in clinical practice; and improve case ascertainment in population studies.

Nearly 12 % of adults 65 years and over in Europe and 9 % in the USA are current cigarette smokers. Numerous studies have demonstrated tangible benefits of smoking cessation, regardless of advanced age. However, it is unclear which pharmacotherapy strategies are most effective in the elderly population. To that end, the literature on smoking cessation in older adults was reviewed with the aim of identifying the safest and most effective cessation pharmacotherapies. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for all articles pertaining to elderly smoking cessation strategies. Randomized controlled trials and cohort studies were included. Studies were included without regard to population or intervention, as long as results were analyzed with a group of smokers aged 60 years and above and at least one arm of the study involved a pharmacotherapy. Only 12 studies were identified that met our inclusion criteria. The limited existing literature does not allow for a definitive answer to the most effective pharmacotherapy for smoking cessation in older adult smokers. Nicotine replacement therapy (NRT) is the pharmacotherapy most studied in older adults, and the limited evidence that exists suggests that NRT is effective for smoking cessation among this population. Higher-quality studies that directly compare cessation strategies, including bupropion and varenicline, are needed in the older population in order to guide treatment decision making.

Autoimmune thyroid diseases (AITD) and Type 1 diabetes (T1D) frequently occur in the same individual pointing to a strong shared genetic susceptibility. Indeed, the co-occurrence of T1D and AITD in the same individual is classified as a variant of the autoimmune polyglandular syndrome type 3 (designated APS3v). Our aim was to identify new genes and mechanisms causing the co-occurrence of T1D + AITD (APS3v) in the same individual using a genome-wide approach. For our discovery set we analyzed 346 Caucasian APS3v patients and 727 gender and ethnicity matched healthy controls. Genotyping was performed using the Illumina Human660W-Quad.v1. The replication set included 185 APS3v patients and 340 controls. Association analyses were performed using the PLINK program, and pathway analyses were performed using the MAGENTA software. We identified multiple signals within the HLA region and conditioning studies suggested that a few of them contributed independently to the strong association of the HLA locus with APS3v. Outside the HLA region, variants in GPR103, a gene not suggested by previous studies of APS3v, T1D, or AITD, showed genome-wide significance (p < 5 × 10(-8)). In addition, a locus on 1p13 containing the PTPN22 gene showed genome-wide significant associations. Pathway analysis demonstrated that cell cycle, B-cell development, CD40, and CTLA-4 signaling were the major pathways contributing to the pathogenesis of APS3v. These findings suggest that complex mechanisms involving T-cell and B-cell pathways are involved in the strong genetic association between AITD and T1D.

BACKGROUND: A key aspect of any intervention to improve obesity is to better understand the environment in which decisions are being made related to health behaviors, including the food environment. METHODS: Our aim was to examine the extent to which proximity to six types of food establishments is associated with BMI z-score and explore potential effect modification of this relationship. We used geographical information software to determine proximity from 49,770 pediatric patients' residences to six types of food establishments. BMI z-score obtained from the electronic health record was the primary outcome. RESULTS: In multivariable analyses, living in closest proximity to large (beta, -0.09 units; 95% confidence interval [CI], -0.13, -0.05) and small supermarkets (-0.08 units; 95% CI, -0.11, -0.04) was associated with lower BMI z-score; living in closest proximity to fast food (0.09 units; 95% CI, 0.03, 0.15) and full-service restaurants (0.07 units; 95% CI, 0.01, 0.14) was associated with a higher BMI z-score versus those living farthest away. Neighborhood median income was an effect modifier of the relationships of convenience stores and full-service restaurants with BMI z-score. In both cases, closest proximity to these establishments had more of an adverse effect on BMI z-score in lower-income neighborhoods. CONCLUSIONS: Living closer to supermarkets and farther from fast food and full-service restaurants was associated with lower BMI z-score. Neighborhood median income was an effect modifier; convenience stores and full-service restaurants had a stronger adverse effect on BMI z-score in lower-income neighborhoods.

BACKGROUND: Baseline health and functional vulnerabilities increase the risk for complications in persons with dementia and predispose family caregivers (FCGs) to increased stress. METHODS: This secondary analysis used a combined quantitative and qualitative approach. Regression analyses examined the contribution of patient and FCG characteristics to FCG anxiety. Interviews with FCGs explored the experiences and responses of FCGs during hospitalization of their family member with dementia. RESULTS: Lower patient physical function and higher caregiver strain were associated with higher FCG anxiety. FCGs described the following themes related to the hospitalization: (1) added strain, (2) care-related worries, (3) keeping vigil, (4) need to be heard, and (5) enablers of FCGs. CONCLUSIONS: Routine evaluation of caregiver strain and baseline patient function is integral to informing the transitional planning for persons with dementia. The FCG responses suggest that a multifactorial approach (family-centered policies of partnership in care, staff education addressing the specialized needs of patients and family members, and attention to promoting functional recovery) may benefit both hospitalized patients with dementia as well as FCGs and warrants future research.

Population exposures to ambient outdoor particulate matter (PM) air pollution have been assessed to represent a major burden on global health. Ambient PM is a diverse class of air pollution, with characteristics and health implications that can vary depending on a host of factors, including a particle's original source of emission or formation. The penetration of inhaled particles into the thorax is dependent on their deposition in the upper respiratory tract during inspiration, which varies with particle size, flow rate and tidal volume, and in vivo airway dimensions. All of these factors can be quite variable from person to person, depending on age, transient illness, cigarette smoke and other short-term toxicant exposures that cause transient bronchoconstriction, and occupational history associated with loss of lung function or cumulative injury. The adverse effects of inhaled PM can result from both short-term (acute) and long-term (chronic) exposures to PM, and can range from relatively minor, such as increased symptoms, to very severe effects, including increased risk of premature mortality and decreased life expectancy from long-term exposure. Control of the most toxic PM components can therefore provide major health benefits, and can help guide the selection of the most human health optimal air quality control and climate change mitigation policy measures. As such, a continued improvement in our understanding of the nature and types of PM that are most dangerous to health, and the mechanism(s) of their respective health effects, is an important public health goal.

In a population-based study, we examined the associations of maternal plasma folate concentrations at 13 weeks of gestation and prenatal folic acid supplement use with autistic traits in the offspring at the age of six years. Parent-reported autistic traits were assessed using the Social Responsiveness Scale short form. Maternal folate was not associated with autistic traits in the offspring. In contrast, prenatal folic acid use was associated with less child autistic traits. Future research should focus on the timing of the potential effect of prenatal folate on the development of autistic traits in combination with clinical diagnosis of autism in the offspring.