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