- •
Older adults with type 2 diabetes are 50% to 100% more likely to develop dementia than those without diabetes.
- •
More research is needed to identify whether the observed association reflects a causal relationship between type 2 diabetes and dementia pathogenesis.
- •
The proposed link between type 2 diabetes and dementia includes mechanisms contributing to features of Alzheimer's disease and macrovascular and microvascular disorders in the brain.
- •
Infarcts and atrophy are more common in the brains of
Diabetes and Cognition
Section snippets
Key points
Overview of Dementia
Dementia is a syndrome defined as a decline in at least 2 cognitive domains that is severe enough to interfere with daily activities.7, 8 Alzheimer disease and vascular dementia are the two most common causes of dementia, and it is increasingly recognized that most older adults with dementia have features of both Alzheimer disease and cerebrovascular disease.9, 10, 11, 12 In addition to studying dementia, examining the rate of cognitive decline is important for understanding the effects of T2D
Potential mechanisms
The interaction between Alzheimer disease, cerebrovascular disease and cognitive reserve18 in the development of dementia9 and the complexity of metabolic dysregulation in T2D makes it difficult to identify the mechanisms linking T2D and dementia. The proposed mechanisms include the effects of hyperglycemia and insulin dysregulation (hyperinsulinemia and insulin resistance) on the features of Alzheimer disease and macrovascular and microvascular disease. Fig. 1 shows the potential mechanisms
Type 2 Diabetes and All-cause Dementia
Table 1 summarizes results from longitudinal epidemiologic studies examining the relationship between T2D and risk of dementia. Estimates of the relative risk (RR) of dementia among people with T2D compared with those without T2D from longitudinal studies range from 1.2 to 2.8, although the confidence intervals (CIs) from some studies include the null. The pooled risk estimate from a recent meta-analysis of 19 longitudinal cohort studies published through 2010 suggested that older adults with
Evidence from neuropathologic and neuroimaging studies
Neuropathologic and neuroimaging studies can help elucidate the mechanisms linking T2D and dementia. Most neuropathologic studies have found more infarcts in the brains of people with T2D, but have not found evidence of greater burden of Alzheimer disease (β-amyloid plaques and neurofibrillary tangles), with some studies reporting fewer features of Alzheimer disease in the brains of people with T2D.57, 58, 59, 60, 61 However, in contrast with these findings, evidence from a recent
Risk factors for dementia among people with type 2 diabetes
Glycemic control is a central aspect of T2D care and is typically measured by glycosylated hemoglobin A1c (A1c) levels, a measure of the amount of glucose that binds to hemoglobin in red blood cells and represents average glycemic control over several months.20 Among older adults with T2D, higher A1c levels are associated with lower cognitive function47, 55 and accelerated cognitive decline.55 Longer duration of T2D and higher A1c levels have been shown to be associated with faster cognitive
Summary
Consistent evidence exists that older adults with T2D are more likely to develop dementia than those without T2D. The literature on the effect of T2D on cognitive decline is less consistent. From a clinical perspective, it is important to know that people with T2D have an increased risk of dementia. However, understanding whether T2D has a causal effect on cognitive decline and dementia and, if so, through what mechanisms is useful for identifying potential strategies to prevent or treat
References (92)
- et al.
The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease
Alzheimers Dement
(2011) - et al.
Tracking pathophysiological processes in Alzheimer's disease: an updated hypothetical model of dynamic biomarkers
Lancet Neurol
(2013) - et al.
Classification and epidemiology of MCI
Clin Geriatr Med
(2013) - et al.
Risk factors for the progression of mild cognitive impairment to dementia
Clin Geriatr Med
(2013) - et al.
The Alzheimer's disease neuroimaging initiative: progress report and future plans
Alzheimers Dement
(2010) - et al.
Type 2 diabetes: principles of pathogenesis and therapy
Lancet
(2005) - et al.
Advanced glycation endproducts and their receptor RAGE in Alzheimer's disease
Neurobiol Aging
(2011) - et al.
Inflammation and Alzheimer's disease
Neurobiol Aging
(2000) - et al.
Inflammation: the link between insulin resistance, obesity and diabetes
Trends Immunol
(2004) - et al.
Mid-life and late-life vascular risk factors and dementia in Korean men and women
Arch Gerontol Geriatr
(2011)
Type 2 diabetes mellitus, hypertension, dyslipidemia and obesity: a systematic comparison of their impact on cognition
Biochim Biophys Acta
Fourteen-year longitudinal study of vascular risk factors, APOE genotype, and cognition: the ARIC MRI Study
Alzheimers Dement
Somatic chronic diseases and 6-year change in cognitive functioning among older persons
Arch Gerontol Geriatr
Midlife type 2 diabetes and poor glycaemic control as risk factors for cognitive decline in early old age: a post-hoc analysis of the Whitehall II cohort study
Lancet Diabetes Endocrinol
Alliance for aging research AD biomarkers work group: structural MRI
Neurobiol Aging
Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges
Lancet Neurol
Risk score for prediction of 10 year dementia risk in individuals with type 2 diabetes: a cohort study
Lancet Diabetes Endocrinol
The older population: 2010
Trends in death rates among U.S. adults with and without diabetes between 1997 and 2006: findings from the National Health Interview survey
Diabetes Care
Deaths: Leading Causes for 2010
2013 Alzheimer's disease facts and figures
Alzheimers Dement
Diagnostic and statistical manual of mental disorders
Mixed brain pathologies account for most dementia cases in community-dwelling older persons
Neurology
Neuropathological correlates of dementia in over-80-year-old brain donors from the population-based Cambridge City Over-75s Cohort (CC75C) study
J Alzheimers Dis
Co-occurrence of different pathologies in dementia: implications for dementia diagnosis
J Alzheimers Dis
Vascular contributions to cognitive impairment and dementia a statement for healthcare professionals from the American Heart Association/American Stroke Association
Stroke
Neuropathology of older persons without cognitive impairment from two community-based studies
Neurology
Cognitive reserve in aging
Curr Alzheimer Res
Standards of medical care in diabetes–2014
Diabetes Care
Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures
J Anat
Retinal vascular imaging: a new tool in microvascular disease research
Circ Cardiovasc Imaging
Cognitive function and retinal and ischemic brain changes: the Women's Health Initiative
Neurology
Retinal microvascular abnormalities and cognitive decline: the ARIC 14-year follow-up study
Neurology
Severe diabetic retinal microvascular eye disease and dementia risk in type 2 diabetes
J Alzheimers Dis
Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment
Circulation
Oxidative damage is the earliest event in Alzheimer disease
J Neuropathol Exp Neurol
Biomarkers of oxidative damage and inflammation in Alzheimer's disease
Biomark Med
Advanced glycation end products sparking the development of diabetic vascular injury
Circulation
Advanced glycation end product level diabetes, and accelerated cognitive aging
Neurology
Insulin and Alzheimer's disease: untangling the web
J Alzheimers Dis
The role of insulin dysregulation in aging and Alzheimer’s disease
Inflammatory markers and cognition in well-functioning African-American and white elders
Neurology
Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging Study
Ann Neurol
Diabetes as a risk factor for dementia and mild cognitive impairment: a meta-analysis of longitudinal studies
Intern Med J
Cited by (84)
Type 2 diabetes mellitus predicts cognitive decline: Evidence from the Irish longitudinal study on ageing (TILDA)
2022, Diabetes Epidemiology and ManagementOccurrence of mild cognitive impairment with hyperinsulinaemia in Africans with advanced type 2 diabetes mellitus
2022, IBRO Neuroscience ReportsThe Effects of Type 2 Diabetes on Cognitive Performance: A Review of Reviews
2024, International Journal of Behavioral Medicine
Disclosure: The authors were supported by funding from National Institute on Aging grant K24 AG031155, National Institute of Diabetes and Digestive and Kidney Diseases grant R01DK081796, and grant support from the BrightFocus Foundation.