A comprehensive study published in Brain and Behaviour involving over 500,000 people in the UK is highlighting the overlooked cognitive effects of everyday medications.
Researchers at the UCL Institute of Neurology have introduced a new tool which is the “cognitive footprint” to better understand how drugs influence mental performance at a population level.
Defining the Cognitive Footprint Framework
Researchers are applying a familiar environmental concept to brain health, introducing the idea of a cognitive footprint to capture how interventions shape mental function at scale. Study author Martin Rossor noted:
“We have been exploring the concept of a cognitive footprint…”
Even minor drug effects can lead to significant changes across a population, prompting questions around monitoring and long-term impacts.
Methodology: Measuring Cognitive Impact at Scale
The study drew on three large-scale datasets:
- The UK Biobank (over 500,000 participants aged 37–73)
- The EPIC Norfolk study (over 8,000 participants with cognitive testing)
- The Caerphilly Prospective Study (approximately 3,000 older men)
Participants were tested on cognitive tasks targeting memory, attention, and reaction time. Researchers applied principal component analysis and Bayesian regression to make sense of the diverse testing methods. The data were further adjusted to control for variables such as age, mood, health status, and education.
Identifying Medications with Negative Cognitive Associations
Some medications showed negative associations with cognition, particularly those that act on the central nervous system. Here are the most notable:
- Valproic acid, a seizure medication, was linked to slower cognitive processing.
- Amitriptyline, a tricyclic antidepressant, was associated with reduced performance across several cognitive domains.
- Even paracetamol (acetaminophen), widely used for pain relief, showed a small but consistent negative impact on cognitive function across all three datasets.
Rossor explained:
“Drug side effects are very common—particularly cognitive ones—but often not sufficiently recognised, especially for medications that do not specifically target the central nervous system.”
Highlighting Drugs with Potential Cognitive Benefits
Surprisingly, the study also identified positive cognitive footprints for several widely used medications:
- Ibuprofen and naproxen (NSAIDs) were associated with better performance on memory and attention tasks.
- Glucosamine, a joint supplement, had small but consistent positive effects—except in the Caerphilly study, where its use was less frequent.
- Omega-3 fatty acids were linked to improved cognitive scores, particularly in the EPIC Norfolk and Caerphilly cohorts.
Rossor acknowledged the unexpected nature of these findings:
“While we anticipated negative effects, we were surprised that glucosamine and ibuprofen had a significant positive cognitive footprint.”
Benchmarking Cognitive Effects Against Ageing and Environmental Risk
The study used standardised Z-scores to compare cognitive effects to familiar benchmarks. For example:
- The positive effect of ibuprofen was equivalent to making the population, on average, two months younger.
- In contrast, the negative impact of paracetamol was more pronounced due to its extensive use, creating a disproportionately large cognitive footprint.
These comparisons help contextualise the findings in ways that are meaningful for public health decisions and risk assessments.
Recommendations for Medical Practice and Policy Reform
The study advocates for a new approach to evaluating drugs, suggesting that cognitive effects should be considered alongside physical side effects.
Exploring Broader Applications of the Cognitive Footprint
The cognitive footprint model isn’t limited to pharmaceuticals. Researchers envision applying it to:
- Environmental exposures (e.g., pollution, heatwaves)
- Occupational factors (e.g., shift work)
- Lifestyle interventions (e.g., diet, exercise)
Rossor added:
“We would like to explore the cognitive footprint of a variety of interventions and effects—such as, at an individual level, the footprint of shift work, and at a population level, the effect of heat waves.”
Conclusion
Researchers are highlighting a new dimension in drug evaluation, with a study showing the need to factor cognitive impact into assessments of drug safety and efficacy. Non-neurotropic medications, often assumed to have little effect on the brain, may subtly influence cognitive function.
The study calls for a more holistic prescribing approach, one that considers cognitive outcomes in addition to traditional clinical objectives.