preprints.org > medicine and pharmacology > dietetics and nutrition > doi: 10.20944/preprints202304.0406.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 14 April 2023 / Approved: 17 April 2023 / Online: 17 April 2023 (05:00:06 CEST)

Background & aims It is documented that low protein and amino-acid dietary intake is related to poorer cognitive health and increased risk of dementia. Degradation of the neuromodulatory pathways, (comprising the cholinergic, dopaminergic, serotoninergic and noradrenergic systems) is observed in neurodegenerative diseases and impairs the proper biosynthesis of key neuromodulators from micro-nutrients and amino acids. How these micro-nutrients are linked to neuromodulatory pathways in healthy adults is less studied. The Locus Coeruleus–Noradrenergic System (LC-NA) is the earliest subcortical structure affected in Alzheimer’s disease, showing marked neurodegeneration, but is also sensitive for age-related changes. The LC-NA system is critical for supporting attention and cognitive control, functions that are enhanced both by tyrosine administration and chronic tyrosine intake. The purpose of this study was to 1) investigate whether the dietary intake of tyrosine, the key precursor for noradrenaline (NA), is related to LC integrity 2) whether LC integrity mediates the reported association between tyrosine intake and higher cognitive performance (measured with Trail Making Test – TMT), and 3) whether LC integrity relates to an objective measure of brain maintenance (BrainPAD). Methods The analyses included 398 3T MRIs of healthy participants from the Berlin Aging Study II to investigate the relationship between LC integrity and habitual dietary tyrosine intake-daily average (HD-Tyr-IDA). As a control procedure, the same analyses were repeated on other main seeds of the neuromdulatory subcortical system (Dorsal and Medial Raphe, Ventral Tegmental Area and Nucleus Basalis of Meynert). In the same way, the relationships between the five nuclei and BrainPAD were tested. Results Results show that HD-Tyr-IDA is positively associated with LC integrity. Similarly, LC integrity disproportionally relates to better brain maintenance (BrainPAD). Mediation analyses reveal that only LC, relative to the other nuclei tested, mediates the relationship between HD-Tyr-IDA I and performance in the TMT and between HD-Tyr-IDA and BrainPAD. Conclusions These findings provide the first evidence linking tyrosine intake with LC-NA system integrity and its correlation with neuropsychological performance. This study strengthens the role of diet for maintaining brain and cognitive health and supports the noradrenergic theory of cognitive reserve. Within this framework, adequate tyrosine intake might increase the resilience of LC-NA system functioning, by preventing degeneration and supporting noradrenergic metabolism required for LC function and neuropsychological performance.

tyrosine; Locus Coeruleus; protein intake; attention; grey matter; neuroimaging; diet; healthy aging

Medicine and Pharmacology, Dietetics and Nutrition

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