Diabetes and Alzheimer's

I was sorry to hear that Paula Martinac’s father died last month. As she writes in Dementia Blues, he had both diabetes and dementia. Gail Rae Hudson’s (The Mom and Me Journals) mom is a Type 2 diabetic, and has had what Gail refers to as “dementia-lite” since suffering a mini-stroke. “I think that her diabetes is definitely linked to her mental acuity,” Gail emailed me. “The better control we have of her blood glucose levels, the better her mental acuity.”

Bad for your memory?

These connections between insulin problems and dementia in real life are reflected in recent scientific theories and study results:

- Diabetes may increase the risk of Alzheimer’s

- Diet-induced insulin resistance [a condition in which the body fails to properly use insulin] increases beta amyloid production in mice, and is associated with increased memory problems and increased levels of plaque in the brains of these mice

- Alzheimer’s might be a “type 3 diabetes”

- Mutations in the IDE (insulin degrading enzyme) gene are associated with a higher risk of both diabetes and Alzheimer’s

- IDE degrades or decreases both insulin and beta amyloid [the protein thought to cause Alzheimer’s].

Diabetes and insulin resistance are clearly linked to dementia, but no one knows exactly how. Theories about the mechanism by which insulin problems may cause dementia include:

- Insulin affects glucose utilization in the brain [glucose provides the brain’s energy]

- Insulin modulates acetylcholine [a neurotransmitter involved in learning and memory] levels in the brain

- Insulin increases abnormal changes in tau, the protein that makes up the tangles found in neurons in Alzheimer’s brains

- Insulin makes cortisol [a stress hormone, chronically high levels of which are sometimes linked to cognitive impairment] more toxic to neurons

- Insulin increases inflammation in the brain, damaging cells and increasing production of beta-amyloid, which further increases inflammation

- Insulin problems may increase vascular disease, clogging blood vessels, and reducing blood flow to the brain

- Increased insulin uses more IDE, so less IDE is available to degrade the beta amyloid thought to cause Alzheimer’s.

Even before they can understand how insulin problems contribute to dementia, researchers are studying whether diabetes medicines can help treat or prevent Alzheimer’s and dementia. Scientists at the Veterans Affairs Puget Sound Health Care System and the University of Washington found that raising insulin levels in some patients [those without the APOE4 genetic mutation associated with Alzheimer’s] improved their memories. These researchers are also testing nasal insulin in people diagnosed with early Alzheimer’s or Mild Cognitive Impairment. In a small trial, “nasal insulin improved the ability to retain story details about 25 percent,” says Dr. Suzanne Craft, one of the researchers and Professor of Psychiatry and Behavioral Sciences at the University of Washington.

The idea of increasing insulin levels to improve memory seems counterintuitive, since high insulin levels may damage the brain. “In a healthy physiology, optimal levels of insulin that are secreted and cleared quickly are likely beneficial,” Dr. Craft explains. “But excessive or prolonged elevations are likely detrimental because of induction of insulin resistance and inflammation.” So we may need just the right level of insulin to keep our brains humming along.

Scientists are also studying drugs that increase sensitivity to insulin, instead of increasing insulin levels. “It’s too early to tell about the comparative benefits of the two approaches,” says Dr. Craft. Results of one study using this approach were disappointing. A twenty-four week trial of Rosaglitazone, a drug that increases sensitivity to insulin, in people diagnosed with mild to moderate Alzheimer’s disease showed no benefit over placebo. (Trial results did show that the drug may have helped participants who did not have the APOE gene mutation, but this needs further study.)

Even if it’s not clearly effective in treating Alzheimer’s, perhaps this approach will work to prevent mild memory problems from progressing to full-blown dementia. A preliminary study of Rosiglitazone in 30 people diagnosed with Mild Cognitive Impairment showed improvements in memory and attention. Researchers are now recruiting for a larger trial of the drug in people with Mild Cognitive Impairment. The study will measure the drug’s effects on attention and memory in 120 people 55 and older.

Whether or not diabetes drugs are useful in preventing or treating Alzheimer’s, this research shows how important it is to prevent insulin resistance and diabetes. “Our work strongly suggests that preventing insulin resistance by increasing physical activity, optimizing diet and preventing obesity will ameliorate the risk of Alzheimer’s disease, or at least delay onset,” Dr. Craft says.

Comments

[Gail Rae Hudson]

Provocative post. Set me to wondering about exenatide, the derivative insulin regulator courtesy of gila monster venom, that not only keeps insulin levels from becoming too high, but appears to also keep them from plummeting too low. As you know, Mona, I've been waiting for this post...and I'm thoroughly satisfied, despite the fact that medical research on this topic is in its infancy.
Good, good post, as usual. Thank you...as usual!

[Karma]

Its interesting. My mom also suffered from diabetes before Alzheimer's and controling her blood sugar is important still. Thanks for keeping me thinking about these things.

[Paula]

Mona - A very interesting post - I always appreciate your lucid condensing and analysis of research. Thanks!

[Sarah]

Excellent post. Thank you.

[Tony Grieco]

Before I was diagnosed with type II diabetes (at age 50), my mental acuity was going downhill fast- I couldn't read a book because I could not remember the plot, and it was getting so that I could not even watch a movie or TV show for the same reason. It took a good 6 months of slow recovery after my diabetes was controlled before I felt like I could think again. I believe that the same thing happened to my father and possibly his mother. I know people who have diabetes that was far worse than mine at diagnosis, as well as people whose diabetes is far less well controlled than mine who do not suffer any mental deficiencies. I am of the opinion that there may well be a genetic basis for the variation of response to high blood sugar. Whether that is true or not, I feel in my heart that my mind is literally at stake when I work to keep my glucose under control!

Other medications commonly prescribed for high cholesterol (a common problem in diabetics) can also have an adverse effect on memory- it is my understanding that these changes are not reversible.

The most important thing I have learned about diabetes is that it is a highly individualistic disease- things that other diabetics can eat or do that do not affect their blood sugar levels will send mine to the moon and vice-versa.