Erratum to: Association between Modifiable Risk Factors and Levels of Blood-Based Biomarkers of Alzheimer's and Related Dementias in the Look AHEAD Cohort.

[This corrects the article DOI: 10.14283/jarlife.2024.1.].

Association between Modifiable Risk Factors and Levels of Blood-Based Biomarkers of Alzheimer's and Related Dementias in the Look AHEAD Cohort.

Background: Emerging evidence suggests that a number of factors can influence blood-based biomarker levels for Alzheimer's disease (AD) and Alzheimer's related dementias (ADRD). We examined the associations that demographic and clinical characteristics have with AD/ADRD blood-based biomarker levels in an observational continuation of a clinical trial cohort of older individuals with type 2 diabetes and overweight or obesity. Methods: Participants aged 45-76 years were randomized to a 10-year Intensive Lifestyle Intervention (ILI) or a diabetes support and education (DSE) condition. Stored baseline and end of intervention (8-13 years later) plasma samples were analyzed with the Quanterix Simoa HD-X Analyzer. Changes in Aß42, Aß40, Aß42/Aß40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic, and clinical characteristics. Results: In a sample of 779 participants from the Look AHEAD cohort, we found significant associations between blood-based biomarkers for AD/ADRD and 15 of 18 demographic (age, gender, race and ethnicity, education) and clinical characteristics (APOE, depression, alcohol use, smoking, body mass index, HbA1c, diabetes duration, diabetes treatment, estimated glomerular filtration rate, hypertension, and history of cardiovascular disease) . Conclusions: Blood-based biomarkers of AD/ADRD are influenced by common demographic and clinical characteristics. These factors should be considered carefully when interpreting these AD/ADRD blood biomarker values for clinical or research purposes.

Effect of Baseline BMI and IL-6 Subgroup Membership on Gait Speed Response to Caloric Restriction in Older Adults with Obesity.

BACKGROUND: Prior work shows caloric restriction (CR) can improve physical function among older adults living with obesity. However, the contribution of starting weight and inflammatory burden to CR-associated functional improvements is unclear. The primary purpose of this study was to determine if CR-associated gait speed change varied by body mass index (BMI) and plasma interleukin 6 (IL-6) at baseline and secondarily to determine the contribution of BMI change and IL-6 change to gait speed change. DESIGN, SETTING, PARTICIPANTS: Data from eight randomized control trials were pooled, with 1184 participants randomized to CR (n=661) and No CR (n=523) conditions. All studies assessed outcomes before and five or six months after assignment to CR or No CR. MEASUREMENTS: BMI and IL-6 were assessed at baseline using standard procedures. Gait speed was assessed with the six-minute walk test or 400m walk test. Baseline BMI/IL-6 subgroups were constructed using BMI≥35 kg/m2 and IL-6>2.5 pg/mL thresholds. Participants with BMI≥35 kg/m2 were grouped into class 2+ obesity and BMI<35 kg/m2 into class 1- obesity; IL-6>2.5 pg/mL were grouped into high IL-6, and <2.5 pg/mL as low IL-6 (class 2+ obesity/high IL-6: n=288, class 2+ obesity/low IL-6: n=143, class 1- obesity/high IL-6: n=354, or class 1- obesity/low IL-6: n=399). All analyses used adjusted general linear models. RESULTS: Gait speed significantly improved with CR versus non-CR [mean difference: +0.02 m/s (95% CI: 0.01, 0.04)]. CR assignment significantly interacted with BMI/IL-6 subgroup membership (p=0.03). Greatest gait speed improvement was observed in the class 2+ obesity/high IL-6 subgroup [+0.07 m/s (0.03, 0.10)]. No other subgroups observed significant gait speed change. For each unit decrease in BMI, gait speed change increased by +0.02 m/s (p<0.001; R2=0.26), while log IL-6 change did not significantly affect gait speed change [+0.01 m/s (p=0.20)]. CONCLUSIONS: Only the class 2+ obesity/high IL-6 subgroup significantly improved gait speed in response to CR. Improvement in gait speed in this subgroup was driven by a larger decrease in BMI, but not IL-6, in response to CR. Individuals with class 2+ obesity and high IL-6 are most likely to show improved gait speed in response to CR, with improvement predominantly driven by reductions in BMI.