Type 2 diabetes mellitus and cognition: An understudied issue in women's health
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
References (100)
Diabetes mellitus—a priority health care issue for women
J Am Diet Assoc
(1994)- et al.
Decreased cognitive function in aging non-insulin dependent diabetic patients
Am J Med
(1984) - et al.
Advanced glycation end products in Alzheimer's disease and other neurodegenerative diseases
Am J Pathol
(1998) - et al.
15-year longitudinal study of blood pressure and dementia
Lancet
(1996) - et al.
“Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician
J Psychiatr Res
(1975) - et al.
Longitudinally measured blood pressure, antihypertensive medication use, and cognitive performance: the Framingham Study
J Clin Epidemiol
(1990) - et al.
A longitudinal study of cognitive performance in noninsulin dependent (type I) diabetes men
Exp Gerontol
(1986) - et al.
Diabetes mellitus and brain atrophy: a computed tomography study in an elderly population
Neurobiol Aging
(1992) - et al.
Memory dysfunction and autonomic neuropathy in non-insulin dependent (type 2) diabetic patients
Diabetes Res Clin Pract
(1995) - et al.
Cognitive impairment in the elderly diabetics
Arch Gerontol Geriatr
(1996)
Diabetes and cognitive function: preliminary studies
Arch Gerontol Geriatr, Suppl
Cognitive dysfunction in older subjects with diabetes mellitus: impact on diabetes self-management and use of care services
Diabetes Res Clin Pract
Cognitive function in diabetes mellitus
Neurosci Biobehav Rev
Women's perspectives on chronic illness: ethnicity, ideology, and restructuring life
Soc Sci Med
Diabetics fact sheet: national estimates and general information on diabetes in the United States
Diabetes in African American women: the silent epidemic
Women's Health
Adverse effects of diabetes on multiple cardiovascular disease risk factors in women
Diabetes Care
Insulin and cognitive function in an elderly population: the Rotterdam study
Diabetes Care
Type-2 diabetes and cognitive function in a non-demented population
Acta Neurol Scand
Association of diabetes mellitus and dementia: the Rotterdam Study
Diabetologia
Risk of dementia among persons with diabetes mellitus: a population-based cohort study
Am J Epidemiol
Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study
Neurology
Longitudinal association of vascular and Alzheimer's dementias, diabetes, and glucose tolerance
Neurology
Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects
Neurology
Diabetes as a risk factor for stroke. A population perspective
Diabetologia
Type 2 diabetes and cognitive function in community-dwelling elderly women
Diabetes Care
Is diabetes associated with cognitive impairment and cognitive decline among older women?
Arch Intern Med
Brain infarction and the clinical expression of Alzheimer's disease
JAMA
Incidence of stroke in relation to cognitive function and dementia in the Kungsholmen project
Neurology
The influence of education on clinically diagnosed dementia incidence and mortality data from the Kungsholmen project
Arch Neurol
Very old women at highest risk of dementia and Alzheimer's disease: incidence data from the Kungsholmen Project Stockholm
Neurology
Diagnostic and statistical manual of mental disorders
Changes in cortical functioning with acute hypoglycemia and hyperglycemia in type I diabetes
Diabetes Care
Cumulative cognitive impairment following recurrent severe hypoglycemia in adult patients with insulin-treated diabetes mellitus
Diabetologia
Cerebral microvascular transport and metabolism: implications for diabetes
Cardiovascular disease care for women: service utilization, disability, and costs from the National Medical Care Utilization and Expenditure Survey
Epidemiologic considerations in studies of cognitive function in the elderly: methodology and nondementing acquired dysfunction
Epidemiol Rev
Risk factors that attenuate the female coronary disease advantage
Arch Intern Med
Why is diabetes mellitus a stronger risk factor for fatal ischemic heart disease in women than in men? The Rancho Bernardo Study
JAMA
Coronary heart disease prevalence and its relation to risk factors in American Indians
Am J Epidemiol
Prevalence of coronary heart disease in subjects with normal and impaired glucose tolerance and non-insulin dependent diabetes mellitus in a biethnic Colorado population: the San Luis Valley Diabetes Study
Am J Epidemiol
Sex difference in the effects of sociocultural status on diabetes and cardiovascular risk factors in Mexican Americans: the San Antonio Heart Study
Am J Epidemiol
Diabetes 1996: vital statistics
Correlates of cognitive function in middle-aged adults
Gerontology
Neuropsychological test performance, cognitive functioning, blood pressure, and age: the Framingham Heart Study
Exp Aging Res
Ovarian steroids and the brain: implications for cognitive aging
Neurology
The women's health initiative estrogen replacement therapy is neurotrophic and neuroprotective
Neurobiol Aging
A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging
Neurology
Cognitive function in nondemented older women who took estrogen after menopause
Neurology
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