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Intermittent Fasting Saves Synapses: Protects Against Cognitive Decline in Vascular Dementia
Last reviewed: 09.08.2025
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Scientists from La Trobe University and partner institutes have shown that a 16-hour intermittent fasting (IF) regimen administered for three months before and after a model of chronic cerebral hypoperfusion (CCH) protects memory and synaptic integrity in mice with vascular dementia. The study is published in the journal Theranostics.
Experimental design
- VaD model: Mice undergo bilateral common carotid artery stenosis (BCAS), causing CCH and characterized by white matter loss and cognitive impairment.
- Intervention: The IF group fasted for 16 hours daily (16:00 to 08:00) for three months before and after BCAS coil placement; the control group ate ad libitum.
Key Results
- Preservation of cognitive function: In the Barnes maze, IF mice did not show impairment in spatial memory after BCAS, unlike free-feeding animals.
- Synaptic protection: Electron microscopy revealed preservation of synaptic contact density in the hippocampus even during ongoing hypoperfusion, although the underlying architecture was unchanged.
- Proteomic "reprogramming":
- Enhanced synaptic stability: increased levels of proteins that strengthen presynaptic vesicles and postsynaptic complexes.
- Enhanced GABA signaling improves inhibitory transmission, compensating for hypoperfusion.
- Reduction of neuroinflammation: suppression of inflammatory mediators and microglial synapse “eating” (complement-mediated pruning).
Mechanisms by phases
- Early phase: strengthening of synaptic structures.
- Middle phase: metabolic optimization (activation of Nrf2, PGC-1α routes).
- Late phase: long-term suppression of chronic neuroinflammation via NLRP3 and microglia.
Meaning and Prospects
These data demonstrate for the first time that intermittent fasting may serve as a potent non-pharmacological strategy for synaptic resilience in vascular dementia. IF combines metabolic support with suppression of inflammation and synaptic preservation, making it attractive for the prevention and treatment of age-related cognitive dysfunction.
“Intermittent fasting acts as a systemic ‘coach’ for the brain, strengthening synapses and curbing inflammation,” comments Professor T. V. Arumugam.
The authors highlight key observations and perspectives:
Intermittent Fasting as a Brain 'Training'
"Our data show that 16-hour daily fasting acts as a physiological stress training: it strengthens synaptic connections and increases the resistance of neurons to chronic hypoperfusion," notes Professor T. V. Arumugam.Multiphasic mechanism of protection
“IF triggers a sequential cascade of activation of protective pathways, from early upregulation of presynaptic proteins to late suppression of microglial inflammation via modulation of NLRP3 complement,” adds co-author Dr. S. Selvaraji.The Path to Clinical Trials
“Since IF is already being used in humans, the next step is to conduct controlled trials in patients at risk of vascular dementia to assess safety, optimal fasting protocols and long-term cognitive effects,” concludes Professor A.S. Fenn
Next steps include clinical trials of IF in people at risk of vascular dementia and combination regimens with traditional neuroprotectors.