Cognitive Impairment and Dementia in Type 2 Diabetes Mellitus

Alexandra Mastro, Physician Assistant Candidate; James B. Caputo, RPh, PharmD; Mary C. Vagula, PhD


US Pharmacist. 2014;39:33-37. 

In This Article

Translation to Clinical Practice


With T2DM being such a complex, chronic metabolic disorder, it requires intact cognition. Independent diabetic self-care is imperative for successful patient outcomes. Glycemic control relies on patient awareness of the condition even at home and is assisted by healthcare professionals with education on self-monitoring of blood glucose (SMBG), insulin dosing, and other pharmacologic interventions that depend upon compliance. Because the disease is associated with other comorbidities, it is part of diabetic care to have many annual screenings. For example, the presence of proteinuria is assessed to monitor kidney function, ophthalmoscopic examinations are performed to look for diabetic retinopathy, and monofilament tests are done to evaluate for diabetic neuropathy. In addition to the conditions already mentioned, as well as many others, CI is now on the rise as yet another commonly associated comorbidity. For clinicians, the Mini-Mental State Examination (MMSE) or another cognitive screening tool should be on the forefront of diabetic patient care. Some recommendations have been made to assist healthcare providers in treating the T2DM patient with regard to the increasing potential for cognitive impairment.

Sending written instructions and materials home for patients who are unable to remember them has been shown to be effective. For others, whose CI prevents reading comprehension, visual aids and even video depictions have been proven helpful for patient compliance with treatment.[11]

Mental Status Screenings. Different studies have shown trends between specific cognitive screening tools and forms of dementia due to the characteristics of each subtype of dementia. For example, Alzheimer's disease in the initial stage can be characterized by loss of episodic memory, while VaD has a severe impairment of executive functioning. Frontotemporal dementia has early impairments on letter fluency, and Lewy body dementia has a loss of attention and abstract reasoning. A screening tool that could pick up Alzheimer's disease might not detect frontotemporal dementia. Mental status screening tools should not only detect the CI, but also identify the most likely etiology. Although the MMSE is the most widely used, others, such as the Addenbrooke's Cognitive Examination-Revised (ACE-R), help to distinguish Alzheimer's disease specifically from other subtypes. Clinicians should take into account the many different types of screening tools to be performed (Table 3).[15]

Pharmacologic Management

For insulin-dependent diabetes mellitus (IDDM), strict glycemic control and SMBG are the preferred method of management, according to the ADA. When monitoring after an episode of hypoglycemia, a patient and provider should attempt to identify the cause and prevent any further hypoglycemic episodes due to their strong link to CI and dementia. Monitoring blood glucose before and after meals to prevent future events is recommended.[16] Overall, well-controlled glycemic levels are what give the patient the best possibility for positive outcomes.

Some studies recently have argued that insulin significantly increases the prevalence of dementia and should be avoided, if possible. A documented decrease in the incidence of dementia is seen with the use of oral hypoglycemic agents, such as metformin. The use of HMG-CoA reductase inhibitors (statins) has been proven to significantly decrease the risk for dementia as well.[12] Another drug class to consider is the peroxisome proliferator-activated receptors (PPARs) because of their efficacy in reducing inflammatory response, enhancing insulin sensitivity, and improving glucose metabolism.[17] For example, rosiglitazone, a PPAR-γ agonist, has been shown to maintain performance on attention tasks and delayed recall. Other recent studies have shown negative effects of rosiglitazone in patients with Alzheimer's disease with regard to objective cognitive performance.[17] More studies and research would benefit the medical community on this dispute.

Investigational Therapies. Another pharmacologic intervention to consider is noninvasive intranasal insulin. The administration of intranasal insulin is argued to be more efficacious because it delivers drugs directly to the brain faster.[17] It has also been demonstrated to improve memory in normal adults. Glucagon-like peptide-1 (GLP-1), a stimulator of insulin secretion via oral glucose, has been studied as well. A study in the animal-subject phase showed that cognitive deficits and insulin resistance had been improved by GLP-1. Two specific analogues were reviewed, extendin-4 and Val(8)-GLP-1(7–36). GLP-1 intranasal administration demonstrated improved glycemic control.[17] Further studies would be needed to support these claims. Weighing the risks and benefits for all diabetic patients to achieve the best glycemic control while keeping pharmacologic management to an affordable cost for the patient is the preferred treatment on an individual basis.