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A Multimodal Risk Network Predicts Executive Function Trajectories in Non-demented Aging.

ABSTRACT: Background: Multiple modalities of Alzheimer's disease (AD) risk factors may operate through interacting networks to predict differential cognitive trajectories in asymptomatic aging. We test such a network in a series of three analytic steps. First, we test independent associations between three risk scores (functional-health, lifestyle-reserve, and a combined multimodal risk score) and cognitive [executive function (EF)] trajectories. Second, we test whether all three associations are moderated by the most penetrant AD genetic risk [Apolipoprotein E (APOE) ε4+ allele]. Third, we test whether a non-APOE AD genetic risk score further moderates these APOE × multimodal risk score associations. Methods: We assembled a longitudinal data set (spanning a 40-year band of aging, 53-95 years) with non-demented older adults (baseline n = 602; Mage = 70.63(8.70) years; 66% female) from the Victoria Longitudinal Study (VLS). The measures included for each modifiable risk score were: (1) functional-health [pulse pressure (PP), grip strength, and body mass index], (2) lifestyle-reserve (physical, social, cognitive-integrative, cognitive-novel activities, and education), and (3) the combination of functional-health and lifestyle-reserve risk scores. Two AD genetic risk markers included (1) APOE and (2) a combined AD-genetic risk score (AD-GRS) comprised of three single nucleotide polymorphisms (SNPs; Clusterin[rs11136000], Complement receptor 1[rs6656401], Phosphatidylinositol binding clathrin assembly protein[rs3851179]). The analytics included confirmatory factor analysis (CFA), longitudinal invariance testing, and latent growth curve modeling. Structural path analyses were deployed to test and compare prediction models for EF performance and change. Results: First, separate analyses showed that higher functional-health risk scores, lifestyle-reserve risk scores, and the combined score, predicted poorer EF performance and steeper decline. Second, APOE and AD-GRS moderated the association between functional-health risk score and the combined risk score, on EF performance and change. Specifically, only older adults in the APOEε4- group showed steeper EF decline with high risk scores on both functional-health and combined risk score. Both associations were further magnified for adults with high AD-GRS. Conclusion: The present multimodal AD risk network approach incorporated both modifiable and genetic risk scores to predict EF trajectories. The results add an additional degree of precision to risk profile calculations for asymptomatic aging populations.

SUBMITTER: Sapkota S

PROVIDER: S-EPMC8482841 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Recent work suggests that the brain can be conceptualized as a network comprised of groups of sub-networks or modules. The extent of segregation between modules can be quantified with a modularity metric, where networks with high modularity have dense connections within modules and sparser connections between modules. Previous work has shown that higher modularity predicts greater improvements after cognitive training in patients with traumatic brain injury and in healthy older and young adults. It is not known, however, whether modularity can also predict cognitive gains after a physical exercise intervention. Here, we quantified modularity in older adults (N = 128, mean age = 64.74) who underwent one of the following interventions for 6 months (NCT01472744 on ClinicalTrials.gov): (1) aerobic exercise in the form of brisk walking (Walk), (2) aerobic exercise in the form of brisk walking plus nutritional supplement (Walk+), (3) stretching, strengthening and stability (SSS), or (4) dance instruction. After the intervention, the Walk, Walk+ and SSS groups showed gains in cardiorespiratory fitness (CRF), with larger effects in both walking groups compared to the SSS and Dance groups. The Walk, Walk+ and SSS groups also improved in executive function (EF) as measured by reasoning, working memory, and task-switching tests. In the Walk, Walk+, and SSS groups that improved in EF, higher baseline modularity was positively related to EF gains, even after controlling for age, in-scanner motion and baseline EF. No relationship between modularity and EF gains was observed in the Dance group, which did not show training-related gains in CRF or EF control. These results are consistent with previous studies demonstrating that individuals with a more modular brain network organization are more responsive to cognitive training. These findings suggest that the predictive power of modularity may be generalizable across interventions aimed to enhance aspects of cognition and that, especially in low-performing individuals, global network properties can capture individual differences in neuroplasticity.

Project description:ImportanceExecutive functions are critical for school and social success. Although these functions are adversely affected by pediatric traumatic brain injury (TBI), recovery patterns are not well established.ObjectiveTo examine 3-year trajectories of selected children's executive functions after TBI.Design, setting, and participantsThis prospective cohort study was conducted from January 22, 2013, to September 30, 2015, with 3-year follow-up at the level I pediatric trauma centers Primary Children's Hospital in Salt Lake City, Utah and Children's Memorial Hermann Hospital in Houston, Texas. Study participants included children aged 2 to 15 years with TBI or orthopedic injury (OI) who were treated at the participating hospitals. Children were consecutively recruited and stratified by injury severity and age group. A total of 625 children consented and completed a baseline survey; 559 (89%) children completed at least 1 follow-up and composed the analysis cohort. It was hypothesized that recovery would differ by injury severity, age at injury, and sex. Data analyses were performed from June to October 2019.Main outcomes and measuresGrowth curve models examined the pattern of change in the Emotional Control, Inhibit, Working Memory, and Plan-Organize subscales of the Behavior Rating Inventory of Executive Function (BRIEF) or BRIEF-Preschool. For all BRIEF subscales, higher scores indicate worse symptoms, and a score of 65 or greater represents clinical impairment.ResultsA total of 559 children (mean [SD] age, 8.6 [4.4] years; 356 boys [64%], 328 non-Hispanic White children [59%]) were included in the study: 155 (28%) children had mild TBI, 162 (29%) had complicated mild or moderate TBI, 90 (16%) had severe TBI, and 152 (27%) had OI. Growth curve trajectories varied by BRIEF subscale and injury severity. Overall, children with TBI did not return to their preinjury baseline, with a stepwise worsening of each outcome at 36 months by TBI severity compared with OI. Among children with severe TBI, trajectories accelerated fastest, indicating increased problems, from injury to 12 months for the Emotional Control (9.0 points; 95% CI, 6.0-11.9 points), Inhibit (3.6 points; 95% CI, 1.6-5.6 points), and Working Memory (7.0 points; 95% CI, 4.1-9.9 points) subscales. Their trajectories plateaued, with a secondary acceleration before 36 months for the Emotional Control and Working Memory subscales. Children with mild TBI had worse 36-month scores on all subscales except Inhibit compared with OI. Recovery patterns were similar for boys and girls.Conclusions and relevanceIn this longitudinal cohort study of children with TBI, trajectory analysis revealed that some children worsen after a recovery plateau, suggesting a need for longitudinal reassessment beyond 1 year postinjury.

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A Multimodal Risk Network Predicts Executive Function Trajectories in Non-demented Aging.

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