Type 2 diabetes mellitus and cognition: An understudied issue in women's health

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Abstract

Introduction: Diabetes is a common chronic illness, affecting approximately 16 million Americans, and is slightly more common in women than men. Data from population studies demonstrate that women with diabetes are at greater risk for cardiovascular disease, the leading cause of death among women and an independent risk factor for cognitive decline. Longitudinal epidemiologic studies report an association between diabetes mellitus and vascular dementia, but conflicting data on the association between diabetes and Alzheimer's dementia. Whether type 2 diabetes has an effect on cognitive function, independent of dementia, has received much attention since the 1980s, but the question remains unresolved. Method: The literature was rigorously reviewed for studies in which cognitive functioning was measured with neuropsychological (NP) tests in participants with type 2 diabetes and a control/comparison group without diabetes. Results: Of 32 studies that reported the effects of type 2 diabetes on cognition in nondemented middle-aged and older adults, 30 included women in their samples, and two focused exclusively on women. Of studies that included women, 20 (67%) reported that participants with type 2 diabetes performed more poorly than those without diabetics on one or more NP tests, leading the authors to conclude that diabetes is positively associated with cognitive dysfunction. Conclusions: Owing to the small number of studies with adequate numbers of women to report findings by gender, little is known about the effect of type 2 diabetes on cognition in women. It is critical that studies on type 2 diabetes and cognitive functioning be designed to include women in numbers adequate for examination of gender effects. The discussion addresses issues specific to women that warrant further research.

Introduction

Diabetes mellitus is a common chronic illness characterized by defects in the body's ability to produce or use insulin. Diabetes affects nearly 16 million Americans [1], [2] and disproportionately affects women, older adults and minorities [2], [3], [4]. It also increases the risk for multisystem end organ disease [5], [6], [7], [8] with declines in functional status and concomitant dependency on others [8]. There has been considerable interest in the effects of diabetes on the brain and the extent to which the disorder contributes to cognitive dysfunction-and the effect may occur through multiple pathways.

Some longitudinal epidemiologic studies have established a direct association between diabetes mellitus and both Alzheimer's [9], [10], [11] and vascular dementias [9], [11], while others support the link between diabetes and vascular, but not Alzheimer's dementia [12]. Retrospective postmortem studies of neuropathology from people with diabetes and control subjects also report mixed results with respect to diabetes' association with Alzheimer's disease [13], [14]. Prospective population studies have determined that diabetes is a risk factor for stroke [15] and hypertension [16], [17], both of which are independent predictors of dementia [18], [19], suggesting an association between diabetes and dementia through cerebro- and cardiovascular disease. Also, the Kungsholmen Project [20], [21], [22], a prospective community-based study of elderly residents of Stockholm, Sweden, measured cognitive impairment, defined as scores <24 on the Mini-Mental State Exam (MMSE) [23], and mild dementia, by the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) criteria [24]. Participants with either cognitive impairment or mild dementia were more likely to have heart disease and diabetes than subjects with normal cognition. What is currently known about the relationship between diabetes and dementia informs but does not clarify the relationship between type 2 diabetes and cognitive functioning independent of dementia. Therefore, the critical question of whether type 2 diabetes increases the risk of cognitive dysfunction in nondemented middle-aged and older adults has not been resolved.

Adult onset, or type 2 diabetes, usually occurs in people over 30 years of age, and is marked by decreased tissue sensitivity to insulin and impaired insulin secretion so that hyperinsulinemia and hyperglycemia occur simultaneously. The association between diabetes and cognitive dysfunction is supported by a number of biologically plausible mechanisms. Since the brain is unable to store its own supply of glucose, cortical neurons are dependent on adequate and continuous blood glucose levels to maintain normal functioning. Individuals under treatment for diabetes are at risk for hypo- and hyperglycemia. Cognitive dysfunction secondary to abnormal levels of blood glucose range from mild transient symptoms [25] to cumulative permanent impairment [26]. Diabetes is also known to cause metabolic and diffuse microvascular changes in the brain and increases the risk of stroke, all of which could contribute to cognitive dysfunction [27].

Section snippets

Diabetes and cognition in women's health

Diabetes affects approximately 8.1 million women in the United States [2], and the prevalence of diabetes is higher in Native–American, African–American and Hispanic women than in White women [3]. Aside from the numbers affected, there are several issues that make diabetes particularly important to women's health and cognitive functioning. Diabetes increases the risk of cardiovascular disease, the primary cause of death among women [28] and an independent risk factor for cognitive decline [29].

Methods

Studies had to meet four criteria in order to be included in this review. First, they had to focus on the effects of type 2 diabetes on cognitive functioning assessed with at least one neuropsychological (NP) test. Second, studies were required to include control/comparison subjects without diabetes in which cognition was also tested. Third, studies had to include women in their samples. Finally, only studies translated in English were included. Electronic databases, including Medline,

Results

The English physician Thomas Willis may have been the first to register concern about cognition in diabetes when, in 1684, he suggested that mental function in people with diabetes might not be the same as others [45]. Currently, cognition is a prominent issue in women's health, particularly for postmenopausal women. Ironically, in spite of the salience of this issue in women and the higher prevalence of type 2 diabetes in women than men, of 32 studies assessing whether type 2 diabetes has an

What accounts for differences in findings?

A number of factors may account for differences in findings among studies of cognition in type 2 diabetes, and perhaps the most prominent involve the rigorous use of exclusion criteria and control conditions to reduce the number of confounding variables in the study sample. Possible confounders are numerous and include age, gender, education and previous occupation; premorbid IQ; depression; functional disorders (visual, hearing and movement) due to age and/or disease which could interfere with

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