Researchers studied 2,762 people over age 60 to understand why some experience memory and thinking problems as they age. They found that people with higher levels of a chemical called methylmalonic acid (MMA) in their blood performed worse on memory and thinking tests. MMA is produced when our bodies break down certain foods. The study also looked at vitamin B12, which helps control MMA levels. While the connection between MMA and brain function isn’t fully understood yet, these findings suggest that measuring MMA levels might help doctors identify people at risk for cognitive decline and could lead to new treatments.

The Quick Take

  • What they studied: Whether a chemical in the blood called methylmalonic acid (MMA) is connected to memory and thinking problems in older people
  • Who participated: 2,762 people aged 60 and older (average age 69), about half were women. All participants completed memory and thinking tests.
  • Key finding: People with higher MMA levels were nearly twice as likely to score poorly on memory tests compared to those with lower MMA levels. This connection was stronger in men and people over 75.
  • What it means for you: If you’re over 60, your doctor might eventually be able to check your MMA levels to help predict memory problems early. However, this is early research—more studies are needed before doctors routinely use this test. Don’t worry if you haven’t heard of MMA before; it’s not something most people need to think about yet.

The Research Details

Scientists studied a large group of older adults and gave them several different memory and thinking tests. These tests measured things like how quickly people could match symbols, how many animal names they could name, and how well they could remember words. The researchers measured MMA and vitamin B12 levels in the participants’ blood and looked for connections between these chemicals and test performance.

The team also studied brain tissue from people with Alzheimer’s disease and compared it to healthy brains. They looked at which genes (the instructions that tell our cells what to do) were active in each group, focusing on genes related to MMA production and how mitochondria (the energy factories inside our cells) work.

This combination of studying real people and studying brain tissue helped the researchers understand both whether MMA matters for thinking and memory, and how it might affect the brain at a biological level.

This research approach is important because it looks at the problem from two angles. By studying a large group of real people, the researchers could see if MMA levels actually matter in everyday life. By studying brain tissue, they could start to understand the biological reasons why MMA might affect thinking and memory. This helps separate coincidence from actual cause-and-effect.

The study is fairly reliable because it included a large number of people (2,762) and used multiple different memory tests rather than just one. The researchers also looked at brain tissue to support their findings. However, this type of study can only show that MMA and cognitive problems are connected—it cannot prove that MMA causes the problems. The study was published in a peer-reviewed journal, meaning other scientists checked the work before publication.

What the Results Show

People with higher MMA levels performed worse on all four memory and thinking tests. The strongest connection was with the symbol-matching test, where people with high MMA were almost twice as likely to score in the bottom group. For animal naming and word recall tests, people with high MMA were about 50% more likely to score poorly.

The connection between MMA and poor thinking performance was stronger in certain groups. Men showed a stronger connection than women. People over 75 showed a stronger connection than those aged 60-75. Interestingly, people with high vitamin B12 levels (whether from supplements or food) showed a stronger connection between MMA and cognitive problems.

When researchers looked at brain tissue from people with Alzheimer’s disease, they found that genes related to MMA production and mitochondrial function were behaving differently compared to healthy brains. This suggests that the biological machinery involved in MMA production may not be working properly in people with cognitive decline.

An unexpected finding was that high vitamin B12 levels were associated with worse memory performance on one specific test (CERAD-IR), even though B12 is supposed to help control MMA. However, taking B12 supplements didn’t show this same connection, suggesting the relationship is more complicated than simply ‘more B12 is better.’ This finding needs more research to understand what’s really happening.

Scientists have known for decades that a rare genetic disease called methylmalonic acidemia, which causes very high MMA levels, damages the brain in children. This new study suggests that even moderately elevated MMA levels in older adults might contribute to thinking and memory problems. However, the MMA levels in this study were much lower than in the genetic disease, so the effects are likely smaller and develop more slowly. This research adds to growing evidence that mitochondrial function (how our cells produce energy) may be important for brain health in aging.

This study can show that MMA and cognitive problems are connected, but cannot prove that MMA causes cognitive decline. It’s possible that something else causes both high MMA and thinking problems. The study only measured MMA and B12 at one point in time, so we don’t know if changes in these chemicals over time matter. The study included mostly older adults, so results may not apply to younger people. Finally, the researchers didn’t measure how much of different foods people ate, which could affect MMA levels.

The Bottom Line

At this stage, there is no specific action recommended for most people based on this research. This is early-stage research that identifies a potential connection worth studying further. If you’re concerned about memory problems, talk to your doctor about standard cognitive screening tests rather than MMA testing, which is not yet a routine clinical tool. Maintaining overall brain health through exercise, healthy diet, cognitive activities, and social engagement remains the best evidence-based approach. (Confidence: Low for MMA-specific recommendations; High for general brain health recommendations)

This research is most relevant to older adults (especially men over 75) who are concerned about memory changes, and to doctors and researchers studying aging and cognitive decline. If you have a family history of Alzheimer’s disease or early memory problems, this research adds to the growing understanding of what might contribute to these conditions. You should NOT be concerned if you haven’t had your MMA levels checked—this is not yet a standard medical test.

If MMA testing eventually becomes a clinical tool, it would likely be used to identify people at higher risk for cognitive decline so they can be monitored more closely. Any actual treatment based on lowering MMA levels is years away and would need to be tested in clinical trials first. Changes in thinking and memory develop slowly over years or decades, so any preventive approach would need long-term commitment.

Want to Apply This Research?

  • Track cognitive performance monthly using simple self-assessments: time yourself naming as many animals as possible in one minute, or test how quickly you can complete word puzzles. Compare scores over time to notice any gradual changes worth discussing with your doctor.
  • Use the app to log activities that support brain health: daily walks (30+ minutes), social interactions, learning new skills, and sleep quality. These evidence-based activities support mitochondrial function and overall brain health while waiting for more research on MMA-specific interventions.
  • Set quarterly reminders to assess memory and thinking using standard tests (available free online). If you notice gradual decline, discuss with your doctor about comprehensive cognitive screening. Track any changes in energy levels, as mitochondrial dysfunction can affect both brain and body energy production.

This research describes an association between methylmalonic acid levels and cognitive performance in older adults but does not establish that MMA causes cognitive decline. MMA testing is not currently a standard clinical tool for assessing cognitive risk. If you’re experiencing memory problems or cognitive changes, consult with your healthcare provider for proper evaluation and diagnosis. This article is for educational purposes and should not replace professional medical advice. Do not start, stop, or change any supplements or medications based on this research without discussing it with your doctor first.