A new narrative review reveals how coffee can 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 Scienceresearchers examined the main chemical components of coffee and evaluated evidence from existing animal and human studies regarding their analgesic and cognitive benefits.
They concluded that coffee may provide cognitive, anti-inflammatory and neuroprotective benefits. However, different coffee types, dosage patterns and preparation methods make it difficult to study the underlying mechanisms, and the review highlighted that most of the evidence is associative rather than causal and further study is needed.
Open questions about the benefits of coffee
Epidemiological studies indicate that coffee drinkers have a lower risk 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 most well-known components, yet their precise roles in neuroplasticity, synaptic development, and neuronal signaling remain unexplored.
Caffeine affects multiple receptor systems, including adenosine, phosphodiesterase, and gamma-aminobutyric acid (GABA) receptors, but other caffeinated beverages do not consistently replicate the effects of coffee, suggesting coffee-specific synergies.
Given the aging world population, interest in coffee’s potential to enhance neuroprotection, memory and cognitive performance has increased.
Experimental animal research shows encouraging results on memory, attention, and neurogenesis, but translation to humans is complicated by the heterogeneity of coffee products and dosage patterns and by species differences in caffeine metabolism that limit generalizability from rodent models.
To map the current evidence, the authors conducted a narrative review. Broad searches of three medical databases retrieved 109 relevant peer-reviewed articles published in English in the last decade.
Coffee, Neuroplasticity and Synaptic Function
Researchers have found evidence of growing scientific interest in coffee’s relationship to neuroplasticity, the brain’s ability 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 especially important. Coffee components, especially caffeine, appear to affect several pathways involved in plasticity, including intracellular calcium regulation, receptor regulation, and neural oscillatory activity.
Evidence from animal studies shows that caffeine can shift synaptic activity toward LTP, which supports learning and memory. However, studies also show that high or chronic caffeine exposure can reduce LTP in the hippocampus, suggesting dose sensitivity and highlighting mechanistic uncertainty that remains unresolved in human studies.
Coffee and human brain activity
Several trials have reported improvements in alertness, response time, memory accuracy, neural efficiency, and subjective alertness after consuming coffee, coffee fruit extracts, or combinations of coffee components with herbal supplements. These effects often occurred regardless of caffeine dose, suggesting a synergistic contribution from polyphenols, although some trials reported neutral findings, highlighting interstudy variability.
Studies have also shown benefits such as reduced fatigue, improved mood and enhanced positive affect after regular consumption of coffee or coffee-berry extract. Some interventions combining 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, suggesting a vascular or antioxidant contribution. Coffee can cause significant physiological reactions, anxiety and stress.
Caffeine challenges in people with panic disorder caused panic symptoms in almost half of the participants, although this was not caused by activation of the hypothalamic-pituitary-adrenal (HPA) axis. In contrast, the aroma of coffee reduced stress biomarkers and heart rates during dental procedures.
Regarding effects on sleep, daily caffeine consumption in habitual coffee drinkers did not significantly alter sleep architecture, suggesting that they may adapt to its effects. Sleep deprivation imaging studies show local gray matter changes affected by caffeine intake or withdrawal, highlighting the interaction of coffee with sleep-related brain plasticity.
Population-based cohorts show that higher coffee or caffeine intake is associated with slower cognitive decline in older adults, particularly women. The review notes that sex-related hormonal interactions may contribute to these differences, although the mechanisms remain unclear.
Animal research supports the neuroprotective roles of caffeine in models of Alzheimer’s disease, metabolic disorders, stress, and seizures, but results in human studies remain mixed.
Mechanisms involving adenosine
Caffeine’s neuroactive properties result largely from antagonizing adenosine receptors, particularly A1 and A2A, which affect synaptic strength, neuronal excitability, inflammation, and energy balance.
Although caffeine binds all four adenosine receptors, many neuroplastic effects are more aligned 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, so the modulation of these pathways by caffeine may underlie some epidemiological findings.
The review also notes that caffeine’s analgesic actions, including enhanced analgesic bioavailability and modulation of sensory signaling, add an additional pathway through which coffee consumption may indirectly support cognition in people with chronic pain, although this was shown to be a secondary context rather than a primary mechanism of neuroprotection.
conclusions
Current evidence suggests that coffee may support cognition, neuroplasticity, and neuroprotection, but findings remain inconsistent.
The effects of coffee are difficult to isolate because it contains many bioactive compounds, interacts with genetics and gender, and can be further modified by differences in caffeine metabolism, and is commonly consumed in broader dietary patterns such as the Mediterranean diet.
Observational data show both benefits and potential risks at high levels of intake, and results vary with respect to neurodegenerative effects.
However, the narrative nature of this review, the reliance on heterogeneous and mostly observational studies, and the limited control for factors such as bean type, preparation methods, and genetic differences in caffeine metabolism limit 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.
