There is an emerging body of evidence that diabetes may accelerate age-related cognitive decline and leads to an almost twofold increase in the risk of both vascular and Alzheimer's dementia (21,22). An association with cognitive impairment has also been observed in "pre-diabetic" states of IFG (23), the metabolic syndrome (24) and insulin resistance (25). Diabetes may accelerate global cognitive decline, but psychomotor slowing has been reported as a characteristic finding in patients with diabetes (26). Although the increased prevalence of CVD may be a contributing factor, diabetes-associated dementia may occur independently of clinically significant micro or macrovascular disease (22,27). Proposed biological mechanisms for diabetes-associated central nervous system dysfunction include free radical-mediated oxidative stress, formation of advanced glycation end-products and alterations in neuronal insulin signaling pathways. In addition, a direct relationship between insulin metabolism
(via insulin degrading enzyme) and formation of beta amyloid (pathogenic for Alzheimer's dementia) has been proposed (27,28).
Regardless of its pathogenesis, the presence of cognitive impairment has substantial implications for diabetes management in affected patients. Even mild, unrecognized cognitive impairment has been associated with poor diabetes control in older adults (29). Complex tasks related to diabetes self-management, including attention to medication schedules, blood glucose monitoring and nutritional factors, become more difficult as cognition (especially memory and executive function) declines. Thus, treatment goals (i.e., less stringent glucose control in order to avoid hypoglycemia) and patient education efforts (medication reminders, pill boxes, etc.) should be modified as cognitive status declines. Ultimately, responsibility for care may need to be shifted to others.
Unrecognized depression is common among elderly diabetic patients (30) and may coexist with (or masquerade as) dementia. The presence of depression can have significant impact on diabetes control through changes in appetite, lack of attention to treatment regimen and use of psychoactive substances such as sedatives or ethanol.
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