WHAT IS DEMENTIA
Dementia is caused by abnormal brain changes that greatly affect people’s thinking, memory, and language. The impact of dementia is persistent, leading to a disabling decline in cognitive function the core skills your brain uses to think, read, learn, remember, reason, and pay attention. As the disorder progresses, symptoms continue to worsen.
Moreover, dementia affects behaviors, emotions, and relationships, and because of this, the quality of life becomes severely compromised. Unfortunately, there are still limited options available to slow down cognitive decline associated with dementia.
According to the World Health Organization (WHO), about 47 million people worldwide were affected by dementia in 2017, and the number is increasing by around 10 million people every year.
RISK FACTORS FOR DEMENTIA
Several factors increase the risk of developing dementia, including:
• Obesity
• High blood pressure
• Diabetes
• Age (although dementia mostly affects older adults, younger individuals can also be affected. Due to advances in medicine, life expectancy has increased, leading to a larger elderly population worldwide.)
• Inflammation and oxidative stress
HOW DIABETES IS A RISK FACTOR FOR DEMENTIA
Interestingly, people with diabetes have about twice the risk of developing dementia compared to those without diabetes. This link is explained by several mechanisms.
To begin with, diabetes affects cardiovascular health, which in turn impacts brain function. High blood pressure increases the risk of stroke a known cause of dementia. However, even without stroke, diabetics can still develop dementia, suggesting that stroke is not the only contributing factor.
Furthermore, chronic diabetes damages small blood vessels, reducing oxygen and nutrient delivery to the brain. High lipid levels and persistent hypertension often seen in diabetes can also cause cerebrovascular damage, leading to vascular dementia.
In addition, hypoglycemia (low blood sugar) can harm the hippocampus the brain region responsible for memory formation. This may occur in patients who tightly control blood sugar to prevent heart disease and stroke, but at the cost of brain health.
Another important factor is insulin’s role in amyloid beta protein synthesis. High sugar levels increase amyloid production, which clumps together to form sticky plaques the hallmark of Alzheimer’s disease, the most common form of dementia.
Lastly, in diabetes, brain insulin resistance often develops. When the brain becomes resistant to insulin, glucose uptake declines, leading to impaired brain function and progressive cognitive decline.
METFORMIN USE IN DIABETES AND DEMENTIA
Metformin, the first-line treatment for type 2 diabetes, has gained attention for its potential brain-protective effects.
According to a systematic review and meta-analysis, metformin use among diabetic adults was associated with a decreased risk of dementia (hazard ratio ≈ 0.90) compared to non-users. Similarly, the Garvan Institute of Medical Research found that diabetic patients taking metformin experienced slower cognitive decline and lower dementia rates.
Moreover, a report in the Diabetes Journal revealed that older adults who used metformin for over six years had better cognitive performance than those who did not take the drug.
Taken together, these findings suggest that metformin may offer neuroprotective benefits, particularly for diabetic patients at risk of Alzheimer’s disease.
HOW METFORMIN MAY IMPROVE DEMENTIA IN DIABETIC PATIENTS
Although the exact mechanisms are not fully understood, several biological pathways have been proposed.
• Firstly, metformin activates the AMPK (adenosine monophosphate-activated protein kinase) pathway, which reduces glucose production in the liver and may exert neuroprotective effects on brain cells.
• Secondly, it enhances insulin sensitivity by increasing insulin receptor expression. This improvement in insulin signaling and glucose metabolism helps restore brain energy balance and cognitive function.
In addition, metformin’s anti-inflammatory and antioxidant properties may protect neurons from oxidative stress one of the key contributors to neurodegeneration.
Interestingly, a randomized controlled trial in patients with vascular cognitive impairment and abnormal glucose metabolism showed that a combination of metformin and donepezil improved cognitive scores and reduced vascular stiffness compared to the control group.
These findings indicate that metformin’s role goes beyond blood sugar control it may directly benefit brain metabolism and vascular health.
CAN METFORMIN BE USED AS A DRUG OF CHOICE IN DEMENTIA WITHOUT DIABETES?
This is an emerging area of research that has sparked significant scientific interest.
Although metformin clearly helps diabetic patients, researchers are now exploring whether it can also benefit non-diabetic individuals with cognitive decline. For example, a pilot randomized study conducted among overweight older adults with amnestic mild cognitive impairment (aMCI) found that metformin (up to 1000 mg twice daily) was safe and showed modest improvements in memory tests.
Building on this, the Metformin in Alzheimer’s Dementia Prevention (MAP) trial a large international study including participants aged 55–90 with aMCI is currently underway. This trial aims to determine whether metformin can delay or prevent Alzheimer’s disease by assessing changes in brain structure, biomarkers, and cognition.
Furthermore, Peking University researchers have shown growing interest in understanding metformin’s effects on aging-related cognitive decline. Their recent reviews emphasize the drug’s ability to modulate oxidative stress, mitochondrial function, and neuroinflammation, which are all central to dementia progression.
However, despite these encouraging signs, the evidence remains inconclusive. As noted by the Alzheimer’s Drug Discovery Foundation, no large-scale clinical trials have yet confirmed metformin’s cognitive benefits in non-diabetic populations.
Some newer studies also suggest that long-term metformin use may have mixed effects on Alzheimer’s pathology, underscoring the need for more precise research.
In short, while metformin has strong potential for preventing or slowing dementia, it cannot yet be recommended as a routine treatment for non-diabetic patients.
CONCLUSION
In summary, metformin is not only a cornerstone therapy for diabetes but also a promising candidate for brain protection. It appears to improve diabetes-related cognitive decline by enhancing insulin sensitivity, reducing inflammation, and protecting neurons from oxidative stress.
If upcoming clinical trials confirm that metformin can benefit non-diabetic individuals, this could revolutionize the treatment and prevention of dementia. Until then, its use for dementia should be considered experimental and guided strictly by clinical research protocols.
FAQs
1. Can non-diabetic individuals take metformin to prevent dementia?
No. Although early studies are promising, there is not enough evidence to recommend metformin for dementia prevention in non-diabetics. Ongoing trials are exploring this possibility.
2. Does metformin help Alzheimer’s disease?
Metformin may reduce amyloid-β formation and inflammation, but human evidence is still limited. Current research focuses on mild cognitive impairment rather than confirmed Alzheimer’s disease.
3. Is metformin safe for older adults without diabetes?
Short-term use in research settings appears safe, but side effects like gastrointestinal upset and vitamin B12 deficiency can occur. Only take metformin under medical supervision.
4. What natural ways can help reduce dementia risk?
Regular exercise, a balanced diet, adequate sleep, managing blood sugar and blood pressure, and staying mentally and socially active can all lower dementia risk.
5. What are researchers from Peking University studying about metformin and cognition?
Peking University scientists are exploring how metformin affects oxidative stress, inflammation, and brain metabolism mechanisms believed to influence dementia progression.
DISCLAIMER
This article is for educational purposes only and does not replace professional medical advice. Do not start or stop any medication without consulting a qualified healthcare provider. Research findings mentioned here are based on ongoing studies and may evolve with new evidence.
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REFERENCES
1. Campbell JM et al. Metformin Use Associated with Reduced Risk of Dementia in Type 2 Diabetes: A Meta-analysis. Front Aging Neurosci. 2022; PMC9453211.
2. Cheng Z, Garvan Institute of Medical Research. Metformin Linked to Slower Cognitive Decline in Older Adults. Diabetologia. 2021.
3. Lv Z, Guo Y. Metformin and Neuroprotection: AMPK Activation and Cognitive Function. Endocr Rev. 2024; 45(2):210–230.
4. Luchsinger JA et al. Metformin in Amnestic Mild Cognitive Impairment: A Pilot Randomized Controlled Trial. Alzheimers Res Ther. 2016; 8:3.
5. ClinicalTrials.gov. Metformin in Alzheimer’s Dementia Prevention (MAP Trial). NCT04098666.
6. Peking University School of Pharmaceutical Sciences. Research Progress on Metformin and Cognitive Aging. 2024 Review Article. 7. Nature Mental Health. Long-term Metformin Use and Alzheimer’s Pathology. 2024; 2(5):421–432.
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