Protocol Report on the Transcranial Photobiomodulation for Alzheimer's Disease (TRAP-AD) Study.

BACKGROUND: Alzheimer's disease's (AD) prevalence is projected to increase as the population ages and current treatments are minimally effective. Transcranial photobiomodulation (t-PBM) with near-infrared (NIR) light penetrates into the cerebral cortex, stimulates the mitochondrial respiratory chain, and increases cerebral blood flow. Preliminary data suggests t-PBM may be efficacious in improving cognition in people with early AD and amnestic mild cognitive impairment (aMCI). METHODS: In this randomized, double-blind, placebo-controlled study with aMCI and early AD participants, we will test the efficacy, safety, and impact on cognition of 24 sessions of t-PBM delivered over 8 weeks. Brain mechanisms of t-PBM in this population will be explored by testing whether the baseline tau burden (measured with 18F-MK6240), or changes in mitochondrial function over 8 weeks (assessed with 31P-MRSI), moderates the changes observed in cognitive functions after t-PBM therapy. We will also use changes in the fMRI Blood-Oxygenation-Level-Dependent (BOLD) signal after a single treatment to demonstrate t-PBM-dependent increases in prefrontal cortex blood flow. CONCLUSION: This study will test whether t-PBM, a low-cost, accessible, and user-friendly intervention, has the potential to improve cognition and function in an aMCI and early AD population.

Does obesity-associated insulin resistance affect brain structure and function of adolescents differentially by sex?

Metabolic abnormalities affect the adolescent brain. For equivalent abnormalities in metabolism young people exhibit deficits in more cognitive domains than adults. We examine sex differences performance for adolescents with obesity/insulin resistance (IR) and evaluated how sex and IR effected frontal lobe structures and executive functioning. 125 adolescents underwent medical, cognitive, and brain-imaging assessments. Participants were categorized as insulin sensitive (IS) (QUICKI ≥ 0.350) or IR (QUICKI < 0.350). Degree of IR may affect brain and cognition differentially by sex. Females had positive associations between QUICKI and anterior cingulate cortex (ACC) volume, medial orbito-frontal cortex (OFC) thickness, and scores on the Stroop and Digit Symbol Substitution (DSST) tests. Females with IR tended to have thinner insular cortices. No such associations were found in males. In female adolescents, IR may negatively affect brain structure and function. No such effects were found for males. Although needing more development, hormonal effects and inflammation are potential contributors.

Cognitive functions among predominantly minority urban adolescents with metabolic syndrome.

The rise in the rate of adolescent obesity has led to a concurrent rise in the rate of metabolic syndrome (MetS) among young people. In addition to diabetes and cardiovascular disease, MetS has also been linked to cognitive dysfunction. The goal of this study was to assess whether cognitive differences exist between minority urban adolescents carrying excess weight who meet criteria for MetS as compared to their peers without MetS. Two hundred and ninety-six urban adolescents, predominantly Hispanic and carrying excess weight as defined by a BMI above 25 kg/m2, were screened for MetS and divided into MetS and no MetS groups. All participants completed the CNS Vital Signs (CNS-VS) computerized neurocognitive battery that assesses cognitive domains of Memory, Processing Speed, Reaction Time, Executive Function, Complex Attention, and Cognitive Flexibility. The MetS group (29.2%, n = 84) performed significantly lower on 2 of the 7 cognitive domains: Executive Function (EF) and Cognitive Flexibility. Additionally, waist circumference was determined to be a significant predictor of both these domains. These findings suggest EF is negatively impacted in adolescents with MetS, despite there being no statistical differences between MetS groups on most other measured cognitive domains. Due to the interrelated nature of obesity, waist circumference, and MetS, these findings have larger implications for the obesity epidemic as well.

Asian Adolescents with Excess Weight are at Higher Risk for Insulin Resistance than Non-Asian Peers.

OBJECTIVE: The purpose of this study was to evaluate whether Asian American adolescents have higher metabolic risk from excess weight than non-Asians. METHODS: Seven hundred thirty-three students, aged 14 to 19 years old, completed a school-based health screening. The 427 Asian and 306 non-Asian students were overall equivalent on age, sex, and family income. Height, weight, waist circumference, percent body fat, and blood pressure were measured. Fasting triglycerides, high- and low-density lipoproteins, glucose, and insulin levels were measured. Asian and non-Asians in lean or overweight/obesity groups were contrasted on the five factors that make up the metabolic syndrome. RESULTS: Asian adolescents carrying excess weight had significantly higher insulin resistance (IR), triglyceride levels, and waist-height ratios (W/H), despite a significantly lower overall BMI than corresponding non-Asians. Similarly, Asians had a stronger relationship between W/H and the degree of IR than non-Asian counterparts; 35% and 18% of the variances were explained (R2 = 0.35, R2 = 0.18) respectively, resulting in a significant W/H by racial group interaction (Fchange [1,236] = 11.56, P < 0.01). CONCLUSIONS: Despite lower overall BMI, Asians have higher IR and triglyceride levels from excess weight than their non-Asian counterparts. One-size-fits-all public health policies targeting youth should be reconsidered and attention paid to Asian adolescents, including those with mild degrees of excess weight.

Obese Adolescents Show Reduced Cognitive Processing Speed Compared with Healthy Weight Peers.

BACKGROUND: Childhood obesity and obesity-associated diabetes and metabolic syndrome (MetS) continue to rise. Obesity has been linked to structural and functional brain abnormalities, particularly in the frontal lobe. METHODS: One hundred sixty-two adolescents (aged 19.53 ± 1.53 years) underwent medical, neurocognitive, and brain magnetic resonance imaging assessments. Participants were either healthy weight (BMI <25.0 kg/m2 or BMI percentile <85%) or obese (BMI ≥30.0 kg/m2 or BMI percentile ≥95%). We evaluated frontal lobe cognitive functions and the size of the corpus callosum (CC). RESULTS: Groups differed on four measures of processing speed contained in four different cognitive tests, but not on executive function. A confirmatory factor analysis verified that the significant processing speed variables loaded on the same factor. We also found differences between the weight groups on the area of the anterior portion of the CC, but not the overall CC. Only the Controlled Oral Word Association Test (COWAT) was significantly correlated with the area of the anterior portion of the CC. In the obese group, 32.4% met criteria for MetS. No differences were found between obese participants with or without MetS and none of the MetS factors contributed consistently to cognitive performance. CONCLUSIONS: Obese adolescents show slower cognitive processing speed while maintaining equivalent performance on executive functioning compared with their healthy weight peers. The group differences in the anterior portion of the CC, responsible for frontal lobe interhemispheric communication, may in part explain our processing speed findings. Future studies should include a longitudinal design and diffusion tensor imaging to examine the integrity of white matter.

Impact of metabolic syndrome on cognition and brain: a selected review of the literature.

Metabolic syndrome (MetS), a clustering of risk factors for type 2 diabetes mellitus and cardiovascular disease, has been associated with cognitive dysfunction and brain abnormalities. This review describes the literature on the impact of MetS on brain and cognition and suggests directions for future research. A literature search for reports of MetS and cognition and brain imaging was conducted for both nonelderly adults and adolescents. No studies were found describing MetS and brain or cognition among adolescents; therefore, we also included studies investigating individual components of MetS in this age group. Most studies found associations between MetS and cognitive dysfunction. Multiple cognitive domains were affected by MetS in adults. In adolescents, the majority of findings were in executive functioning. Brain imaging literature in adults implicated MetS in ischemic stroke, white matter alterations, and altered brain metabolism. For adolescents, individual MetS factors were linked to volume losses in the hippocampus and frontal lobes. MetS negatively impacts cognitive performance and brain structure. Potential explanatory models include impaired vascular reactivity, neuroinflammation, oxidative stress, and abnormal brain lipid metabolism. We posit that insulin resistance-associated impairment in cerebrovascular reactivity is an important mechanism underlying brain deficits seen in MetS.

Obesity, orbitofrontal structure and function are associated with food choice: a cross-sectional study.

Objectives Obesity is on the rise in the US and is linked to the development of type 2 diabetes and cardiovascular disease. Emerging evidence over the last decade suggests that obesity may also adversely affect executive function and brain structure. Although a great deal of research focuses on how diet affects the brain and cognitive performance, no study focuses on how food choice may be associated with brain integrity. Here we investigated how lean and overweight/obese (o/o) adults differed in their food choices and how brain structure and cognition may be associated with those choices. Design As part of an ongoing study on diabetes and the brain, participants had routine blood work and a research MRI, received a battery of neurocognitive tests, and were instructed to keep a 3-day food diary. Results and conclusions The lean group ate more high quality foods and less low quality foods compared to the o/o group. In the o/o group, high quality food choices were associated with orbitofrontal cortex volume. The lean group performed better than the o/o group on neurocognitive measures of executive function, such as the Stroop Interference Test, the Wisconsin Card Sort Test and the Trail Making Test B-A, and on attention and concentration tasks such as the Digit Symbol Substitution Test. Taken together, these preliminary data suggest that in obesity poor food choices may be associated with frontal cognitive impairments that may be the result of, or contribute to, decreases in orbitofrontal cortex volume. Therefore, longitudinal studies are warranted to investigate a causal link between food choice and executive functioning.

Course of patients with histories of aggression and crime after discharge from a cognitive-behavioral program.

OBJECTIVE: Patients exhibiting aggressive or criminal behavior present a challenge to treaters and caregivers. After discharge from an inpatient facility, such patients are at high risk of rehospitalization and rearrest. A long-term behaviorally based cognitive skills program was developed and administered to a group of such high-risk inpatients. The authors report the results of a postdischarge follow-up of this group. METHODS: After patients entered the inpatient treatment program, their psychiatric and criminal histories were recorded, and a battery of psychological measures were administered, including IQ tests and the Hare Psychopathy Checklist. After discharge, multiple sources were used to obtain information about patients' outcomes. RESULTS: Eighty-five patients were followed for between six months and two years after discharge. Thirty-three of these patients (39 percent) remained stable in the community, 35 (42 percent) were rehospitalized, and 17 (20 percent) were arrested. Several variables that were ascertained before discharge predicted rehospitalization or arrest rates: comorbid antisocial personality disorder, higher score on the Psychopathy Checklist, history of arrests for violent crimes, and history of a learning disability. In addition, patients who developed substance use problems or did not adhere to medication treatment after discharge were more likely to be rehospitalized or arrested. CONCLUSIONS: Arrest rates were low compared with those observed in studies with similar populations. Although this outcome may be attributable to the treatment program, this naturalistic study could not prove that. The predictors of poor outcome may be used to develop a follow-up treatment program that focuses more resources on patients who are at the highest risk.