The Empowering Role of Mobile Apps in Behavior Change Interventions: The Gray Matters Randomized Controlled Trial

BACKGROUND: Health education and behavior change programs targeting specific risk factors have demonstrated their effectiveness in reducing the development of future diseases. Alzheimer disease (AD) shares many of the same risk factors, most of which can be addressed via behavior change. It is therefore theorized that a behavior change intervention targeting these risk factors would likely result in favorable rates of AD prevention. OBJECTIVE: The objective of this study was to reduce the future risk of developing AD, while in the short term promoting vascular health, through behavior change. METHODS: The study was an interventional randomized controlled trial consisting of subjects who were randomly assigned into either treatment (n=102) or control group (n=42). Outcome measures included various blood-based biomarkers, anthropometric measures, and behaviors related to AD risk. The treatment group was provided with a bespoke “Gray Matters” mobile phone app designed to encourage and facilitate behavior change. The app presented evidence-based educational material relating to AD risk and prevention strategies, facilitated self-reporting of behaviors across 6 behavioral domains, and presented feedback on the user’s performance, calculated from reported behaviors against recommended guidelines. RESULTS: This paper explores the rationale for a mobile phone–led intervention and details the app’s effect on behavior change and subsequent clinical outcomes. Via the app, the average participant submitted 7.3 (SD 3.2) behavioral logs/day (n=122,719). Analysis of these logs against primary outcome measures revealed that participants who improved their high-density lipoprotein cholesterol levels during the study duration answered a statistically significant higher number of questions per day (mean 8.30, SD 2.29) than those with no improvement (mean 6.52, SD 3.612), t(97.74)=−3.051, P=.003. Participants who decreased their body mass index (BMI) performed significantly better in attaining their recommended daily goals (mean 56.21 SD 30.4%) than those who increased their BMI (mean 40.12 SD 29.1%), t(80) = −2.449, P=.017. In total, 69.2% (n=18) of those who achieved a mean performance percentage of 60% or higher, across all domains, reduced their BMI during the study, whereas 60.7% (n=34) who did not, increased their BMI. One-way analysis of variance of systolic blood pressure category changes showed a significant correlation between reported efforts to reduce stress and category change as a whole, P=.035. An exit survey highlighted that respondents (n=83) reported that the app motivated them to perform physical activity (85.4%) and make healthier food choices (87.5%). CONCLUSIONS: In this study, the ubiquitous nature of the mobile phone excelled as a delivery platform for the intervention, enabling the dissemination of educational intervention material while simultaneously monitoring and encouraging positive behavior change, resulting in desirable clinical effects. Sustained effort to maintain the achieved behaviors is expected to mitigate future AD risk. TRIAL REGISTRATION: ClinicalTrails.gov NCT02290912; https://clinicaltrials.gov/ct2/show/NCT02290912 (Archived by WebCite at http://www.webcitation.org/6ictUEwnm

Common DNA Variants Accurately Rank an Individual of Extreme Height

Polygenic scores (or genetic risk scores) quantify the aggregate of small effects from many common genetic loci that have been associated with a trait through genome-wide association. Polygenic scores were first used successfully in schizophrenia and have since been applied to multiple phenotypes including multiple sclerosis, rheumatoid arthritis, and height. Because human height is an easily-measured and complex polygenic trait, polygenic height scores provide exciting insights into the predictability of aggregate common variant effect on the phenotype. Shawn Bradley is an extremely tall former professional basketball player from Brigham Young University and the National Basketball Association (NBA), measuring 2.29 meters (7′6″, 99.99999th percentile for height) tall, with no known medical conditions. Here, we present a case where a rare combination of common SNPs in one individual results in an extremely high polygenic height score that is correlated with an extreme phenotype. While polygenic scores are not clinically significant in the average case, our findings suggest that for extreme phenotypes, polygenic scores may be more successful for the prediction of individuals

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Atypical Antipsychotic Drugs Block Selective Components of Amphetamine-Induced Stereotypy

Individual items of behavior produced by 1.0 or 5.0 mg/kg d-amphetamine were monitored in rats pretreated 15 minutes earlier with vehicle or with behaviorally relevant doses of haloperidol (0.1 or 0.25 mg/kg), clozapine (1.0 or 5.0 mg/kg), or thioridazine (1.0 or 5.0 mg/kg). Unlike haloperidol, the atypical antipsychotics failed to block all components of either the low- or high-dose response to amphetamine. These drugs, however, did block selective items of amphetamine-induced stereotyped behavior. Clozapine significantly attenuated the sniffing produced by 1.0 mg/kg d-amphetamine as well as the oral behavior (licking and/or biting) produced by 5.0 mg/kg d-amphetamine. Thioridazine, at a dose 5.0 mg/kg, also reduced oral behavior and selectively blocked repetitive head bobbing. Taken together, these results suggest that although atypical antipsychotic drugs exert some common effects on the amphetamine behavioral response, these drugs do not influence all amphetamine-induced behaviors equally

Alzheimer\u27s Disease: Risk Factors and Preventive Strategies

The renowned Principles and Practice of Geriatric Psychiatry, now in its third edition, addresses the social and biological concepts of geriatric mental health from an international perspective. Featuring contributions by distinguished authors from around the world, the book offers a distinctive angle on issues in this continually developing discipline

Amphetamine-Induced Excitations Predominate in Single Neostriatal Neurons Showing Motor-Related Activity

Neostriatal single-unit activity was recorded in freely moving rats. A majority (62%) of the 24 recorded neurons were activated during motor behavior such as locomotion (n = 11) or head movements (n = 4). The behavioral response to amphetamine (1.0 mg/kg) was associated with increases (n = 17) or decreases (n = 7) in firing rate. A significantly greater proportion of motor-related neurons were excited by the drug compared to nonmotor-related cells. These results, which confirm the heterogeneity of amphetamine-induced effects in the neostriatum, indicate that the baseline motor-response characteristics of neostriatal neurons may determine their response to amphetamine

Bilateral Cortical Ablations Attenuate Amphetamine-Induced Excitations of Neostriatal Motor-Related Neurons in Freely Moving Rats

Single-unit recordings from neostriatal neurons showing movement-related excitations were obtained in freely moving, cortically ablated rats and sham-lesioned controls. d-Amphetamine (AMPH, 1.0 mg/kg s.c.) increased neuronal activity relative to resting baseline firing rates in both groups of animals, but cortical ablation significantly attenuated this effect. A behavioral clamping analysis, which compared neuronal activity during identically rated pre- and post-AMPH behaviors, revealed that: (a) AMPH enhanced movement-related neuronal activity in sham-lesioned controls, but not in cortically ablated rats; and (b) the drug-induced neuronal activation in control rats was not simply secondary to the behavioral activation produced by AMPH. In contrast to its neuronal effects, cortical ablation did not affect ratings of AMPH-induced locomotion, rearing, or head movements, though sniffing scores showed a postive correlation with lesion size. Thus, corticostriatal projections are critically involved in AMPH-induced excitations of neostriatal motor-related neurons