Aging is the major risk factor for neurodegenerative diseases, accelerated by excessive calorie consumption and sedentary lifestyles. Bioenergetic challenges such as intermittent fasting (IF) have shown to promote lifespan and healthspan via an adaptive stress response. Activity-dependent brain-derived neurotrophic factor (BDNF) has emerged as key regulator of cognitive performance and brain health. This review aims to investigate the pathophysiological mechanisms linking IF and cognitive function with a focus on the role of BDNF, evaluating evidence from pre-clinical and human studies. A systematic literature search was performed. 82 peer-reviewed papers were accepted, critically appraised and summarised in a narrative analysis. Aging-related loss of BDNF has been associated with reduced synaptic plasticity, memory and learning as well as increased risk of cognitive impairment and Alzheimer's disease. IF was consistently reported to upregulate BDNF and improve cognitive performance in animal models. Further research is required to assess cognitive outcomes of IF in humans.
Keywords: Aging; Alzheimer’s disease; BDNF; Brain; Cognitive decline; Intermittent fasting; Learning and memory; Neurogenesis; Synaptic plasticity.
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