Obesity in your 40’s-60’s increases risk for developing the dementia of Alzheimer’s disease later in life. Researchers analyzed brain scans of more than 1,300 people from the UK Biobank and found that people who were obese in midlife had already lost gray matter in the brain in the same areas as those who suffer from Alzheimer’s disease (J Alzheimer’s Dis, Jan 31, 2023;91(3):1059-1071). Alzheimer’s disease is characterized by a buildup of amyloid plaques that cause loss of brain gray matter that, in turn, causes loss of ability to think and reason, control muscles and remember things. The authors state that preventing midlife obesity may help to reduce the risk of developing diabetes and dementia later on.

Several earlier studies show that obesity is a risk factor for dementia (Neurology, May 3, 2011;76(18):1568–1574; Arch Neurol, Mar 2009;66(3):336–342). This recent report shows that the areas of brain damage in obese people are the same as the areas of brain damage in people who suffer from Alzheimer’s dementia. That study used PET scans and found that the same areas of the brain that were damaged and lost in people with Alzheimer’s disease were also damaged and lost in people who were obese, but had no evidence of brain damage. Alzheimer patients who were lean had the same loss of areas of their brains as those who were obese.

The Leptin Connection with Obesity, Diabetes and Dementia
People who are obese in midlife are 2.5 times more likely than normal-weight people to fall, to be injured and to be hospitalized (BMJ Open, 2023;13:e065707). They are also more likely to develop diabetes and dementia (Int J Mol Sci, Aug 2022;23(16):9267). New research shows that people who are obese have damage to the parts of their brains that respond to a hormone called leptin that acts on the brain to help prevent obesity by making you feel full so you eat less food and avoid gaining excess weight (Int J Mol Sci, May 2022;23(9):5202). Leptin is secreted by fat cells and acts on special brain receptors in the hypothalamus (part of the brain) and also on other regions and nuclei of the central nervous system (CNS), such as the cerebral cortex and hippocampus. These are exactly the same areas of the brain that are diminished and damaged in people who are obese, in people who are demented and fat, and in demented people who are thin. An overactive immune system, called inflammation, is associated with increased risk for obesity and for dementia (Internat J of Epid, 2020;49:1353-1365; Cureus, 2018;10:e2660).

(Note for scientists: the areas of brain damage in both obesity and dementia are the regions expressing the long form of leptin receptor LepRb, which is the unique leptin receptor capable of transmitting complete leptin signaling, and are the first regions to be affected by chronic neurocognitive deficits, such as mild cognitive impairment (MCI) and Alzheimer’s disease. Key players of leptin resistance are SOCS3, PTP1B, and TCPTP whose signaling is related to inflammation and could be worsened in Alzheimer’s Disease (Int J Mol Sci, May 2022;23(9):5202)).

My Recommendations
The rules for prevention of obesity may also apply to the prevention of dementia. Obesity appears to be a potent risk factor for dementia, so to potentially help prevent dementia, you should:
• Avoid being overweight
• Eat lots of healthful foods such as whole grains, fruits, vegetables, beans, nuts and seeds
• Restrict unhealthful foods such as refined grains, added sugars, red meat, processed meats and fried foods
• Avoid smoke, alcohol and recreational drugs
• Try to exercise every day