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Patients with diabetes face a number of challenges as they work with their physicians to manage their disease—adopting healthy lifestyles, finding the best treatment regimens, and dealing with comorbidities and drug-related adverse effects. And while modern medicine is prolonging the lives of these patients, it is becoming apparent that these individuals face additional mental challenges as they age. Diabetes can accelerate age-related cognitive decline, making patients especially vulnerable to impairment and dementia over time.
“We tend not to routinely consider cognitive decline in our patients with diabetes, though the older our patients are, the greater the risk is,” says Katherine Samaras, MBBS, PhD, FRACP, who is Head of the Diabetes and Obesity Clinical Group at the Garvan Institute of Medical Research, in Sydney, Australia. Dr. Samaras also practices medicine in the Department of Endocrinology at St. Vincent’s Hospital, also in Sydney.
Take Note
- Diabetes detrimentally affects brain structure and function. Its effects on cognition are due at least in part to macrovascular disease, microvascular changes, hyperlipidemia, alterations in insulin homeostasis, and inflammation.
- The relationship between hypoglycemia and dementia may be bidirectional.
- Patients with diabetes and cognitive impairment may be able to continue with self-care but might benefit from receiving additional ‘one-to-one’ support services, written instructions, or visual supports. Medication regimens might also need to be simplified to minimize medication-related risks.
Diabetes is thought to account for 6% to 8% of all cases of dementia in older people.1 Studies consistently show a 2.0- to 3.4-fold increased risk of vascular dementia and a 1.8- to 2.0-fold increased risk of Alzheimer’s disease in older people with diabetes.2 The precise mechanisms involved are not clear, but numerous studies have shown that diabetes detrimentally affects brain structure and function, with more frequent structural brain lesions and greater cortical atrophy in people with diabetes compared with normoglycemic controls.2 It appears that the effects of the disease on cognition are due at least in part to macrovascular disease, microvascular changes, hyperlipidemia, alterations in insulin homeostasis, and inflammation. Researchers are teasing out the potential roles of each of these factors as they strive to decipher what is sure to be a complex process. Their current understanding suggests that very high blood glucose concentrations that are associated with mood changes and poor memory function may cause alterations in cerebral blood flow or osmotic changes in neurons. Correction of acute hyperglycemia appears beneficial, but chronic hyperglycemia may cause cerebral microvascular disease.3
The other side of the coin is that self-reported history of severe hypoglycemia has been linked with poorer late-life cognitive ability in people with type 2 diabetes.4 Recently published data from the Health, Aging, and Body Composition (Health ABC) Study, a prospective evaluation of the relationship between hypoglycemia and dementia, actually suggest a bidirectional relationship between hypoglycemic episodes and dementia. The study followed a biracial cohort of 783 patients (mean age, 74 years; approximately 50% female) with diabetes at baseline but normal cognition. During the 12-year follow-up, 8% had a hypoglycemic event, and 19% developed dementia. A hypoglycemic event doubled a patient’s risk of developing dementia, while dementia tripled the risk of a hypoglycemic event.5
Other diabetes-related conditions are also likely to play a role in cognitive decline. For example, results from a recent sibling study of cardiovascular disease in individuals with a high prevalence of type 2 diabetes show that additional cardiovascular factors—especially calcified plaque and vascular status—and not diabetes status alone are major contributors to diabetes-related cognitive decline.6 The results suggest that risk factor intervention should begin before comorbidities, particularly cardiovascular disease, become clinically apparent.
Cognitive impairment or decline can be dangerous in any situation, but it is especially worrisome in patients with diabetes. Their health relies on informed and independent self-care to achieve glycemic targets and minimize vascular risks. Unfortunately, annual screenings performed in patients with diabetes do not include an evaluation of cognition. Clinicians can identify cognitive decline by performing a standard mini-mental state exam as part of annual screenings, said Dr. Samaras. “This is very quick and simple, requires no tools, and has no cost. It can help identify patients at risk where a downward trend is noted,” she explained. “Our suspicion of declining cognitive function might also be raised by medication errors and confusion about performing some of the complex tasks of diabetes self-care, where none have been apparent previously.”
When cognitive problems are detected in patients with diabetes, it is often unclear how to intervene. Some patients may be able to continue with self-care but will benefit from receiving additional “one-to-one” support services, written instructions, or visual aids. Medication regimens might also need to be simplified to minimize medication-related risks.2
In the Action to Control Cardiovascular Risk in Diabetes—Memory in Diabetes (ACCORD-MIND) randomized trial, intensive therapy to maintain glycemic control was associated with greater total brain volume after 40 months, but there was no improvement in cognition.7 The study also revealed a link between increased mortality and tight glycemic control, suggesting that intensive therapy to merely preserve brain volume is not justified. Also, hypoglycemia in the elderly has its own set of additional morbidities, as suggested by the Health ABC Study.
More research is warranted to determine whether diabetes’ negative effects on brain structure and function are explained by direct toxic effects of glucose or are mediated by other metabolic, lipid, or inflammatory alterations. “Additional longitudinal studies are needed that track cognitive changes over time in healthy elderly populations,” says Dr. Samaras.
Until more is known about the causes of diabetes-related cognitive decline and how to treat it, clinicians involved in the care of people with diabetes must do their very best to detect it and to make appropriate treatment changes that will safeguard their patients’ health.