Neuroscience/Nutrition and the Brain (Poster Session)

(P09-013-25) Impaired Metabolism of Brain-Related Amino Acids and Early Signs of Poor Motor Control and Cognitive Dysfunction in the Pre-stage of Frailty

Saturday, May 31, 2025

11:45 AM - 12:45 PM ET

Location: Poster Board D-12

Presenting Author(s)

Minchae Chloe Kang, BS (she/her/hers)

Graduate Research Assistant
Center for Translational Research in Aging & Longevity, Texas A&M University
College Station, Texas, United States

Co-Author(s)

ND

Nicolaas E.P. Deutz, MD, PhD

Professor
Center for Translational Research in Aging & Longevity, Department of Health & Kinesiology, Texas A&M University; and Department of Geriatrics, University of Arkansas for Medical Sciences
College Station, Texas, United States
JT

John J. Thaden, PhD

Center for Translational Research in Aging & Longevity, Department of Health & Kinesiology, Texas A&M University
College Station, Texas, United States
SD

Sofie De Wandel

Texas A&M Health, United States
SH

Seona Helmi

Texas A&M University, United States
JW

Jonathan Wang

Texas A&M University, United States
ME

Marielle P.K.J. PKJ. Engelen, PhD

Professor
Center for Translational Research in Aging & Longevity, Department of Health & Kinesiology, Texas A&M University, and Department of Geriatrics, University of Arkansas for Medical Sciences
College Station, Texas, United States

Disclosure(s):

Minchae Chloe Kang, BS: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: Cognitive impairment is often found in older adults with physical frailty. Recently, perturbations in amino acid metabolism have been found in frail older adults with cognitive decline. We studied whether the early phase of frailty in older adults is already characterized by brain health decline and specific metabolic perturbations of brain-related amino acids.

Methods: In total 127 subjects (age >60) were stratified into 3 groups based on Fried frailty phenotype (FP): 18 nonfrail (13m/5f), 76 prefrail (39m/37f), and 33 frail (10m/23f) participants. Cognition assessment: Stroop Color Word Test (SCWT), Trail Making Test (TMT), and word fluency. Motor control: dual-task gait test. Mood: Hospital Anxiety and Depression Scale (HADS) and Profile of Mood States (POMS). Postabsorptive whole body amino acid kinetics: a pulse administration of stable isotope tracers of amino acids. Plasma enrichments of amino acids: LC-MS/MS to calculate whole-body production (WBP) rates. Statistics: GLM with covariate sex, age, (lean mass for metabolic data), and Charlson comorbidity index and Pearson correlation coefficient.

Results: We observed in the frail poor cognitive performance (higher TMT, lower word fluency), motor control (dual-task time (carrying water)), and mood disturbances as compared to the non- and prefrail groups (p < 0.05). Also, higher SCWT times and interference, anxiety, and anger were observed in frailty vs prefrailty (p < 0.05). In frailty, TMT interference and dual-task time (naming animals) were higher as compared to the nonfrail (p < 0.05) while single-task time was higher in prefrail and frail vs nonfrail (p < 0.02). Moreover, we found lower WBP of glutamine, glycine, taurine, and tryptophan in prefrailty vs nonfrailty (p < 0.04). A negative association was found between dual gait task times and WBP of glycine, glutamate, glutamine, taurine, and net protein breakdown (r: [-0.31, -0.22], p< 0.02).

Conclusions: Although more severe in frailty, prefrail older adults are characterized by early signs of poor motor control and cognitive dysfunction. Our data indicate metabolism of brain-related amino acids is already impaired in the prefrail. To what extent restoring metabolic perturbations via nutritional approaches may reduce the frailty-associated decline in brain health in the early phase of frailty warrants further investigation.

Funding Sources: N/A