A new narrative review unpacks how coffee may sharpen thinking and protect the brain while highlighting why its true mechanisms remain elusive.
Neurocognitive and Neurological Effects of Coffee and Caffeine: A Narrative Review. Image Credit: Igor_83 / Shutterstock
In a recent review published in the journal Cureus Journal of Medical Science, researchers examined the major chemical constituents of coffee and evaluated evidence from existing animal and human studies on their pain-relieving and cognitive benefits.
They concluded that coffee may offer cognitive, anti-inflammatory, and neuroprotective benefits. However, the diverse types of coffee, dosing patterns, and preparation methods make underlying mechanisms difficult to study, and the review emphasised that most evidence is associative rather than causal, and further study is needed.
Open Questions on Coffee Benefits
Epidemiological studies suggest that habitual coffee drinkers have lower risks of several neurodegenerative and cerebrovascular conditions, including Parkinson’s disease, Alzheimer’s disease, dementia, stroke, and multiple sclerosis.
Caffeine and related purine metabolites (theobromine, theophylline, and paraxanthine) are the best-known components, yet their precise roles in neuroplasticity, synaptic development, and neuronal signaling remain underexplored.
Caffeine influences multiple receptor systems, including adenosine, phosphodiesterase, and gamma-aminobutyric acid (GABA) receptors, but other caffeinated beverages do not consistently replicate coffee’s effects, suggesting coffee-specific synergies.
Given the aging global population, interest in coffee’s potential to enhance neuroprotection, memory, and cognitive performance has grown.
Experimental research in animals shows encouraging effects on memory, attention, and neurogenesis, but translating this to humans is complicated by the heterogeneity of coffee products and dosing patterns and by species differences in caffeine metabolism that limit generalisability from rodent models.
To map the current evidence, the authors conducted a narrative review. Broad searches in three medical databases retrieved 109 relevant peer-reviewed articles published in English in the past decade.
Coffee, Neuroplasticity, and Synaptic Function
Researchers found evidence of growing scientific interest in coffee’s relationship with neuroplasticity, the brain’s capacity to reorganize neural circuits through synaptic remodeling, long-term potentiation (LTP), long-term depression (LTD), and adult neurogenesis.
Aging reduces the brain’s plastic potential, making factors that maintain or enhance plasticity particularly important. Coffee constituents, especially caffeine, appear to influence several pathways involved in plasticity, including intracellular calcium regulation, receptor modulation, and neural oscillatory activity.
Evidence from animal studies indicates that caffeine can shift synaptic activity toward LTP, which supports learning and memory. However, studies also show that high or chronic caffeine exposure can attenuate LTP in the hippocampus, suggesting dose sensitivity and highlighting mechanistic uncertainty that remains unresolved in human studies.
Coffee and Human Brain Activity
Several trials reported improvements in vigilance, response time, memory accuracy, neural efficiency, and subjective alertness after consuming coffee, coffee fruit extracts, or combinations of coffee constituents with herbal supplements. These effects often appeared independent of caffeine dose, suggesting synergistic contributions from polyphenols although some trials reported neutral findings, underscoring variability across studies.
Studies also indicated benefits such as reduced fatigue, improved mood, and enhanced positive affect following regular coffee or coffee-berry extract consumption. Some interventions that combined sage or ginseng with coffee extracts produced additional benefits.
Additionally, beverages containing coffee berry extract or apple polyphenols increased cerebral blood flow and improved mood, hinting at a vascular or antioxidant contribution. Coffee can produce significant physiological, anxiety, and stress responses.
Caffeine challenges in individuals with panic disorder induced panic symptoms in nearly half of participants, though this was not mediated by hypothalamic, pituitary, adrenal (HPA) axis activation. Conversely, coffee aroma reduced stress biomarkers and pulse rate during dental procedures.
Regarding impacts on sleep, daily caffeine consumption in habitual coffee drinkers did not significantly alter sleep architecture, suggesting that they may adapt to its effects. Imaging studies under sleep deprivation show regional grey matter changes influenced by caffeine intake or withdrawal, highlighting coffee’s interaction with sleep-related brain plasticity.
Population-based cohorts show that higher coffee or caffeine intake is associated with slower cognitive decline in older adults, especially women. The review notes that sex-specific hormonal interactions may contribute to these differences, though mechanisms remain unclear.
Animal research supports caffeine’s neuroprotective roles in models of Alzheimer’s disease, metabolic disorders, stress, and seizures but results across human studies remain mixed.
Mechanisms Involving Adenosine
Caffeine’s neuroactive properties arise largely from antagonism of adenosine receptors, particularly A1 and A2A, which influence synaptic strength, neuronal excitability, inflammation, and energy balance.
Although caffeine binds all four adenosine receptors, many neuroplastic effects align most closely with A2A blockade. The review also discussed adenosine triphosphate (ATP) and adenosine as neuromodulators involved in neuroprotection, injury response, and neurodegenerative diseases.
Dysregulation of A2A and P2 receptors is implicated in Parkinson’s and Alzheimer’s disease, thus caffeine’s modulation of these pathways may underlie some epidemiological findings.
The review also notes that caffeine’s analgesic actions, including enhanced analgesic bioavailability and modulation of nociceptive signaling, add an additional pathway through which coffee consumption may indirectly support cognitive function in people with chronic pain although this was presented as a secondary context rather than a primary mechanism of neuroprotection.
Conclusions
Current evidence suggests coffee may support cognition, neuroplasticity, and neuroprotection, but findings remain inconsistent.
Coffee’s effects are difficult to isolate because it contains many bioactive compounds, interacts with genetics and sex, and may be further modified by differences in caffeine metabolism, and is typically consumed within broader dietary patterns such as the Mediterranean diet.
Observational data show both benefits and potential risks at high intake levels, and results vary across neurodegenerative outcomes.
However, this review’s narrative nature, reliance on heterogeneous and mainly observational studies, and limited control for factors such as bean type, preparation methods, and genetic differences in caffeine metabolism restrict firm conclusions and prevent determination of causality.
Overall, coffee appears safe and possibly beneficial, but its mechanisms and optimal intake require more rigorous, controlled research.
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