Update: Elucidating the link between diabetes and dementia

By Naveed Saleh, MD, MS
Published April 1, 2022

Key Takeaways

  • Individuals with earlier-onset diabetes have an increasing risk of developing dementia. Several studies have linked higher levels of blood sugar to dementia biomarkers.

  • Various mechanisms have been proposed connecting dementia and diabetes, including microvascular alterations and changes caused by the interrelationship of peripheral and cerebral insulin resistance.

  • Lifestyle intervention is key to reducing the risk of dementia in individuals with diabetes. Encourage patients to incrementally change lifestyle patterns to boost their health.

The burden of diabetes in the United States is great, with 25% of those aged 65+ years having the disease and 50% having prediabetes. On its own, diabetes is destructive, but excessive blood sugar levels are linked to damage of various organs, including the brain. 

Sugar can damage blood vessels in the brain, which can trigger cognitive decline. Furthermore, high insulin levels secondary to type 2 diabetes can imbalance other brain chemicals, contributing to dementia. Moreover, high blood sugar causes inflammation, damaging brain cells and triggering dementia.

Although the full relationship between diabetes and dementia needs to be further studied, enlightening research does exist. It’s also important to understand diabetes and dementia as potential comorbidities when managing patients.

Examining risk

Results from a longitudinal study published in JAMA indicated that in patients aged between 35 and 75 years, for every onset of diabetes 5 years earlier, there was a higher hazard of dementia.[] Late-onset diabetes, however, was not related to dementia onset.

In other findings, there was no significant association between prediabetes and dementia, although stroke and diabetes comorbidity led to an additional dementia risk.

The Alzheimer’s Association cited the following research findings related to the increased risk of dementia in people with diabetes.[]

  • There’s a strong association between high blood sugar levels and increased beta-amyloid protein, which is a marker for Alzheimer disease.

  • Individuals with type 2 diabetes exhibit signs of accelerated cognitive decline such as impairments in executive function and information-processing speeds.

  • Difficulties with memory, related to the hippocampus region of the brain, already occur in patients who’ve had diabetes for less than 10 years. The hippocampus is smaller in patients with diabetes than in those without.

  • Even in early diabetes, higher levels of insulin resistance can occur in the brain, along with a decreased ability to utilize glucose as a brain fuel.

  • The amyloid precursor gene, operative in Alzheimer disease, could potentially disrupt insulin pathways. This could shed light on potential new drug targets.

Possible mechanisms

The JAMA study researchers proposed possible mechanisms tying diabetes and dementia. For instance, decreased transport of insulin via the blood-brain barrier could lead to deficiencies in insulin signaling and lowered cerebral glucose use, thereby contributing to brain metabolic dysfunction that mediates dementia.

Another hypothesis links peripheral and cerebral insulin resistance. Higher levels of systemic resistance lead to glucose neurotoxicity, vascular injury, and accumulation of advanced glycation end products, which could contribute to dementia.

The link between dementia and diabetes could be microvascular in nature. Dysfunction of the microvasculature could trigger inflammatory and immune responses, oxidative stress, increased blood-brain permeability and changes in blood flow regulation, contributing to cognitive decline.

A last hypothesis implicates the effects of periods of hypoglycemia, which can occur with use of insulin. Cumulative effects of hypoglycemia in insulin-dependent type 2 diabetes could contribute to dementia over the long term.

Managing comorbid diabetes and dementia

Given the coexistence of diabetes and dementia, the Alzheimer’s Association encourages patients to act upon Life’s Simple 7®—seven modifiable risk factors—as a strategy to both manage their diabetes and reduce their risk of cognitive decline:

  1. Blood pressure control

  2. Cholesterol control

  3. Decreasing blood sugar

  4. Becoming physically active

  5. Eating better

  6. Dropping excess weight

  7. Smoking cessation[]

This list was originally developed by the American Heart Association, which advises that individuals start by targeting one or two risk factors and ramping up from there.

In other guidance, drug maker Abbott suggests the following regarding diet in individuals with dementia and diabetes: “Mealtimes require adjustment as memory and cognition fade. Your family member may not recognize common foods, and they may forget to eat, eat too often or eat too much of the same foods, complicating efforts to manage their diabetes.”[]

Continuous glucose monitoring may be a good idea to gauge eating patterns in elderly patients with both diagnoses.

What this means for you

Diabetes and dementia are common diagnoses. These diseases likely share various mechanistic foundations. For patients with both conditions, preventive treatment is exceedingly important. It’s also a good idea to counsel patients and caregivers on the importance of healthy nutrition and continuous glucose monitoring to further improve patient outcomes.

Related: Precision treatment for Alzheimer's disease reduces phosphorylated tau
Share with emailShare to FacebookShare to LinkedInShare to Twitter