The incidence of Alzheimer’s disease (AD) is increasing. By 2050 the number of cases is expected to double to 13.6 million. Two factors causing the increase number of persons with AD are the aging of the population as baby boomers reach their 60s and the increasing number of adults with diabetes. Diabetes has long been associated with AD but how they were linked was unknown. Research is starting to explain the processes by which diabetes contributes to the development of AD.

Many persons with diabetes experience dementia — a sharp decline in cognitive function with age. Dementia is defined by disturbances in memory and thinking functions that interfere with daily living and even recognizing familiar people. AD is the most common cause of dementia. Diabetics are twice as likely to develop Alzheimer’s disease later in life. Up to 70% of persons with diabetes develop Alzheimer’s disease during their lifetime. These facts have led researchers to suggest that Alzheimer’s may represent the late stage of Type 2 diabetes.

Proposed mechanisms regarding how diabetes causes AD include the following. First, high blood glucose levels damage the large and small blood vessels that supply blood to the brain. Lack of adequate blood flow and oxygen delivery leads to loss of brain cells.

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Next, abnormal insulin levels effect brain function. High insulin levels (known as hyperinsulinemia) are found in overweight and obese persons, persons with prediabetes and in the early years of type 2 diabetes. Hyperinsulinemia is also found in 50% of persons with AD. The abnormally high insulin levels interfere with proper nerve function and contribute to the development of AD.

After diabetes has been present for awhile, the ability to make insulin diminishes and low levels of insulin are found in the blood. Insulin levels are 80% lower in persons with advanced Alzheimer’s than in normally functioning brains. The lack of insulin leads to cells being unable to take up the glucose they need to function. The brain cells do not get the energy they need and they literally starve — resulting in AD. (Val8)GLP-1 is a drug that is under development that improves the ability of the brain to use glucose. It has even been shown to promote the development of new brain cells in animal models.

Abnormal protein structures that are associated with AD which may be caused in part by diabetes. Neurofibrillary tangles are abnormal protein structures that are found inside the nerves of persons with AD. The tangles are made up of a protein called tau. Levels of tau proteins are higher in persons with diabetes. These abnormal structures interfere with the movement of substances within the cells that are needed for nerves to function normally.

Treatment of diabetes with a class of diabetes medicines called PPAR agonists has been shown to stabilize or improve

brain function in AD. These agents work by improving insulin responsiveness in the cells body including brain cells. Diabetes must be avoided or if it occurs, well controlled to reduce the occurrence of AD.


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