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For aging populations, MDD presents an even greater concern, as it significantly raises the risk of Alzheimers disease, dementia, frailty, and reduced health span, underlining its multifaceted burden on both mental and physical health in older adults [491,492,493]

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However, KYNA influences AMPAR activity predominantly through indirect mechanisms, namely its non-competitive allosteric inhibition of presynaptic 7nAChRs on glutamatergic terminals in mood-related circuits, leading to reduced glutamate release and downstream modulation of excitatory signalling [29, 30]