A decade ago, researchers from numerous countries documented the downward trend of Alzheimer’s disease among the older adults. Pointing to higher levels of education and improvements in stroke rates in this age group, the authors of a 2014 review article in a New England Journal of Medicine were optimistic this trend would continue if patients recognized that their personal choices could contribute to their risk for dementia.

But the optimistic narrative also noted the following: “A potentially ominous trend that could lead to a reversal of the decrease in risk is the growing prevalence of obesity and diabetes among middle-aged and younger people.” 

Evidence of this foreseen trend is appearing in clinicians’ offices, as well as in numerous studies, some even before the journal article. Epidemiologic research has shown the global extent of earlier onset dementia; electronic health record-driven work and other existing databases point to earlier onset of mild cognitive impairment (MCI) due to earlier diagnoses of diabetes.

One Neurology study from 2011 detailed how midlife hypertension, diabetes, smoking, and obesity can affect brain function, including executive function, a decade later. MRI scans and cerebrospinal fluid measures taken every 20 years of middle-aged and older patients who were experiencing such diseases documented the descent of the brain from normal cognition to MCI.

People are more complex, said Lydia Bazzano, MD, PhD, director of the Tulane Center for Lifespan Epidemiology Research at Tulane University School of Public Health and Tropical Medicine in New Orleans.

In the clinic, she often sees hypertension and diabetes at younger ages. “I see a lot of people in their 40s, instead of their 50s, 60s,” she said.

Bazzano is not the only one. More of the patients at Sadiya S. Khan, MD’s preventive cardiology practice — where obesity management is a focal point — are experiencing heart disease and MCI. “There are general trends increasing,” said Khan, who is the Magerstadt Professor of cardiovascular epidemiology at Northwestern Medicine in Chicago.

With more people overweight earlier “than any other generation in history, we are going to see an earlier onset of dementia,” said Suzanne Craft, PhD, professor of gerontology and geriatrics at Wake Forest University School of Medicine in Winston-Salem, North Carolina.

Her team predicted the dangers of rising obesity and dementia numbers in 2017.

Hypertension at an early age can contribute to cognitive function decline in someone’s fifties, according to Bazzano. People with hypertension often have glucose handling and insulin resistance, as well, Bazzano and Craft said.

Craft, who is also director of the Wake Forest Alzheimer’s Disease Research Center, said dementia pathology starts at least 15 years before symptoms appear. “It might not be to the level of diagnosed diabetes,” she said. “A lot of subtle changes happen over time. It is cumulative damage over many years and [which is then] being demonstrated as dementia.” 

If these various factors — too much glucose and cholesterol and too little exercise — are not altered, the constant, low-level damage inflicted on someone’s peripheral and central nervous systems can turn symptomatic, changing the risk for mortality into its inevitability.

 More is at stake here.

Besides the general concern of people with diabetes facing MCI, and perhaps dementia, in midlife, there is the fear of young brains — not fully developed until their mid-20s — being affected by insulin resistance. Again, the younger a person receives a diabetes diagnosis, the greater the risk dementia will develop at a younger age.

“Without a doubt, this is incredibly worrisome,” said Peter J. Fried, PhD, assistant professor of neurology at the Beth Israel Deaconess Medical Center in Boston. “It will interfere with natural brain development. Unchecked, it will start earlier and [stay] longer.”

“There is growing concern that diabetes in young people could affect their cognitive development,” said Xiang Qi, PhD, RN, an assistant professor at Rory Meyers College of Nursing, New York University, New York City. “Chronic high blood sugar or metabolic disturbances might interfere with that process.”

As the peripheral nervous system and central nervous system deterioration continues, each system eventually runs out of ways to compensate for those years of excess glucose. “The inflammation is causing chaos; there is a complex cycle of events that get put into place,” said Craft, who has studied the diabetes-dementia connection for two decades.

Should primary care physicians treating young and middle-aged patients with obesity and diabetes (who are not showing signs of cognitive impairment) be routinely evaluated for MCI?

“It is hard to leap from a retrospective view [of the data] to [the decision that] every single patient should be screened,” said Jason Goldman, MD, president of the American College of Physicians, adding that he was “sure people have seen” cognitive issues in middle-aged patients. “We need to know more about the risk and the incidence.” There isn’t enough information, at least not yet, to launch a full-scale research project that could lead to clinical screens, he said.

Data to Consider

• A Harvard/George Washington University trajectory study predicted that 57.3% of the children living in this country today will have obesity when they are 35.
• The CDC projects that by 2060, the US will have about 250,000 people younger than 20 years diagnosed with type 2 diabetes. As of last year, that total stood at 28,000.
• According to StatPearls, overweight and obesity increase the lifetime risk for type 2 diabetes in men from 7% to 70% and in women from 12% to 74%, as BMI increases.
• The Alzheimer’s Association, in its 2025 annual report on Alzheimer’s disease, reported that 1.9 million people between 65 and 74 years had Alzheimer’s disease. In its 2021 report, that figure was 1.72 million. In 2021, 6.2 million people aged 65 years or older had Alzheimer’s disease; by 2025, that figure is 7.2 million.
• A 2024 global prevalence study showed that dementia among people aged 70 years or younger increased to 13.14 million in 2021 from 5.91 million in 1990, especially among those aged 65 years or younger living in North America. Smoking, high fasting blood sugar, and high BMI were blamed for the increase.

In the Clinic 

At the clinical level, the tools to determine if midlife patients with diabetes have MCI do not exist. “There are no screening tools to capture the MCI,” said Fried, who is also associate director for research at Berenson-Allen Center for Noninvasive Brain Stimulation at Beth Israel Deaconess Medical Center. “With cognitive impairment, you won’t get that information unless it is volunteered.” 

Goldman said it is a concerning trend that “we need to be aware of, but the magnitude of the issue has to be explored” before diagnostic tools and treatment protocols can be devised. “It takes years to comb through data and come up with evidence-based strategies,” he said. As for whether the MCI-related data should be discussed with all younger patients with diabetes and obesity, Goldman said no. “It is patient specific. This is what I am finding with their history and through evaluation. If [patients] keep sugar under control, lose weight, and stop smoking, how would that help to discuss the risk of MCI?” 

Qi and Fried said physicians could think outside the box. Tight cardiometabolic control and addressing obesity early are critical, said Qi, adding that cognitive check-ins with high-risk patients are “reasonable.”

Qi referred to a study showing that semaglutide users had a lower 3-year risk for a first Alzheimer’s disease diagnosis than users of other diabetes drugs. On average, women were 56.8 years, with more obesity and depression. Men, at 59.5 years, had more cardiovascular disease. “These are the patient profiles to target for cognitive check-ins and aggressive control of modifiable risks,” he said.

While that semaglutide study did show promising results, it’s important to note that many patients stop taking GLP-1 receptor agonists often because of side effects.

Physicians need to think holistically, Fried said, acknowledging that many practices can’t provide the educational support for diabetes and obesity management. “Think about diabetes as a check-engine light for what is going on under the hood,” he said. “The person is exceeding safeguards that evolution has designed for them, given the environment they are in.”