Diabetes and hypertension may cause cognitive decline
Add in obesity and smoking, and patient’s risk quadruples
A patient walks into the physician’s office. Her chart information states she has Type 2 diabetes and hypertension. The doctor looks up. The patient is overweight, and there is a lingering odor of cigarette smoke.
That’s not unusual, the doctor thinks. And health care providers well know there’s a grim litany of complications associated with diabetes — hypertension, obesity, and smoking.
Now it’s time to add another comorbidity to the list: decline in cognitive function.
Cognitive function decline is yet another reason to include anti-hypertensives in a diabetic regimen for any patient with blood pressure readings of 165/90 or higher, says Merrill Elias, PhD, MPH, professor of psychology at the University of Maine in Orono and adjunct professor of medicine at Boston University. In fact, many physicians believe anti-hypertensives are warranted for anyone with a systolic pressure over 140, he says.
"We have known for some time that diabetes and hypertension independently contribute to cognitive decline," says Elias. His recent analysis of population-based data shows that when both diseases are present, they seem to have a synergistic effect on cognitive function.
It’s a double whammy, says Elias. "A person with diabetes and hypertension has double the risk of impaired cognitive function as someone with only one disease." Overweight patients who smoke open themselves up to a quadruple whammy, he explains. "A person who has both diseases and is obese and smokes, again doubles the risk of cognitive decline. That means we must control diabetes, control blood pressure, and take it very seriously."
Elias, a founding investigator of the Maine-Syracuse Study, has analyzed 25 years of data from 2,000 participants as well as the 50 years of data provided by 5,000 participants in the Framingham Heart Study. The subjects were Type 2 diabetics between the ages of 55 and 88.
He analyzed data from patients diagnosed with both diabetes and hypertension. The Framingham Heart study, in particular, provides excellent indicators of long-term effects of the diseases because the study began when there was no real treatment for hypertension and since then, medications and treatments for glucose intolerance and insulin have changed dramatically over the years of both studies, Elias says.
Each study used a different approach to cognitive function. The Framingham study uses a short battery of neuropsychological tests emphasizing memory, while the Maine-Syracuse study uses a more comprehensive battery measuring speed of performance, memory, fluid intelligence and verbal ability.
Elias’ conclusions: An increased risk of poor performance on cognitive function test scores (below the 25th percentile) occurred only in the presence of diabetes and blood pressures over 165/90.
His findings contain some daunting numbers:
• In the diabetic group, the risk of cognitive dysfunction increased by 100% for every 10 mm Hg increase in diastolic pressure over the current dividing line of 140 mm Hg.
• In the nondiabetic population, the risk of cognitive decline increased by only 26% for every 10 mm increase in blood pressure.
• Risk increased by 1.54 for every diabetic year in the presence of hypertension.
"With untreated hypertension, you have gradual destruction of the arterial wall, changes in autoregulation, altered oxygen flow to the brain, and in old age, lesions in the white matter of the brain and small areas of dead brain tissue or infarctions from lack of oxygen perfusion," explains Elias. "Pathophysiological changes in the brain associated with diabetes are similar, and thus you would expect both to exert a negative impact on cognitive ability, and they do."
Elias theorizes that obesity contributes to the effects by increasing the risk of diabetes. Hyper-tension and smoking ultimately result in decreased or intermittent changes in brain oxygenation and damage to the epithelial walls of the arteries.
Don’t confuse with Alzheimer’s disease
He emphasizes that the levels of cognitive decline are not to be confused with dementia and its best-known form, Alzheimer’s disease, although researchers are looking into the connections between diabetes and dementia. "What we’re seeing is a slowing of their abilities. They may not learn as fast. Their reaction times may be somewhat slowed."
Other researchers in the field say this slowing may affect job performance, particularly those that require sustained concentration, attention to detail, or psychomotor coordination.
Declining cognitive function also may impair a patient’s ability to manage his diabetes, leading to poor glucose control and ultimately compound the risk for all comorbidities, including the potential for an even greater cognitive impairment, says another researcher who has conducted a large body of research on the subject.
Christopher Ryan, PhD, associate professor of psychiatry at the University of Pittsburgh Medical School, agrees with Elias’ findings. Elevated triglycerides and depression also adds to cognitive decline in diabetic patients, he explains.
And in a large patient group in Pittsburgh, Ryan and his team found that the best predictor for slowing cognition is poor metabolic control as measured by HbA1c levels or the presence of complications.
He says hypoglycemia has long been thought to be the underlying cause of cognitive decline, but here is looking at a different angle. "Chronic hyperglycemia is the culprit here, and hypertension exacerbates it."
Chronic hyperglycemia affects the central nervous system (and other systems throughout the body) by triggering the development of advanced glycosylated end products, says Ryan. These oxidation products have been found in senile plaques and neurofibrillary tangles characteristic of Alzheimer’s disease.
Hyperglycemia also causes central nervous system damage through several other possible pathways including increases in aldose reductase activity and increases in the protein kinase, Ryan explains.
Some slowing of cognitive function and psychomotor skills is expected in older patients, but Ryan found a significant reduction in performance on timed tests in patients as young as 40 that correlates directly with the patient’s degree of metabolic control.
Most of the changes in cognitive function are linked to hypoglycemia, says Ryan. He suggests that tight control may not be the best approach in terms of cognitive function decline because of the possibility of swings into hypoglycemia.
But there is some evidence that suggests hyperinsulinemia also may be associated with cognitive decline. (See story, p. 43.)
The most important aspect of the association between diabetes, hypertension, and cognitive dysfunction from a public health perspective is that these problems are preventable through appropriate hypertensive and glycemic control. But there is some good news, says Ryan. "I believe some of these changes are reversible."
Three small studies show the possibility that improved metabolic control may reverse declining cognitive function, and Ryan is working on a larger study.
[For more information, contact Merrill Elias at (207) 244-9674 and Christopher Ryan at (412) 624-2963.]
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