ReviewRisk of dementia in diabetes mellitus: a systematic review
Introduction
Diabetes mellitus is associated with changes in cognition. In type 1 diabetes mellitus this association is shown by a mild to moderate slowing of mental speed and a diminished mental flexibility.1 In type 2 diabetes cognitive changes mainly affect learning and memory, mental flexibility, and mental speed.2, 3, 4 Several large longitudinal population-based studies have shown that the rate of cognitive decline is accelerated in elderly people with type 2 diabetes.5 The determinants of this accelerated cognitive decline, however, are less clear;5 some researchers suggest that hypertension could be an important mediator,6 whereas others have found associations with glycaemic control.7
Although the association between diabetes and these modest changes in cognition is now well established, the relation between diabetes and dementia is an area of controversy. Early studies that reported a low rate of diabetes in patients with Alzheimer's disease,8, 9, 10 suggested that diabetes and Alzheimer's disease might not coexist.9 However, a more recent study suggested that type 2 diabetes or impaired fasting glucose might be present in up to 80% of patients with Alzheimer's disease.11 These opposing results clearly indicate that studies of the prevalence of diabetes in people with established dementia are unlikely to provide reliable data for the risk of dementia in individuals with diabetes. These differing outcomes may be the result of methodological issues, such as survival bias of non-diabetic patients with Alzheimer's disease and the possible effects of Alzheimer's disease itself on glucose metabolism,12 which might obscure the relation with diabetes in more advanced cases of dementia. Population-based studies that compare the incidence of dementia between patients with and without diabetes provide more reliable risk estimates than studies on patients with established dementia.
Both the absolute and relative numbers of elderly people who are affected by diabetes are expected to increase over the next few decades.13 Better insight into the strength and the nature of the association between diabetes and dementia is therefore of great importance.
In this article, we systematically review studies on the incidence of dementia in patients with diabetes mellitus to determine the strength of the association between diabetes and dementia. We also examined the extent to which researchers investigated potential modulators and mediators of the risk of dementia in people with diabetes. We discuss underlying mechanisms and relevant neuropathological and neuroradiological studies.
Section snippets
Identification of studies
Studies were identified by searches of MEDLINE (1966 to August, 2005) and EMBASE (1966 to August, 2005) with the search terms “diabet* AND Alzheim* OR dement*”. Searches were restricted to papers published in English and the Embase search was restricted to “human studies”. The bibliographies of relevant original and review articles were screened. This systematic review aimed to include all published studies that provide an estimate of the incidence of dementia among patients with diabetes
Study populations
The 14 study populations included participants of different ethnic origins: white, Hispanic, black, and, Asian. Further demographic details are presented in table 1. Most studies included both individuals living in institutions and those living at home in their baseline study sample. Recruitment varied among the studies from sampling within religious orders to true population sampling. The Rochester sample simply used the population denominator and the medical records associated with that
Discussion
This systematic review of population-based studies brings together the evidence that the risk of dementia is, in general, increased in patients with diabetes mellitus. This increased risk seems to include both Alzheimer's disease and vascular dementia—although the limitations of clinical diagnostic criteria in the classification of dementia by pathological subtype should be considered, especially in a complex disorder such as diabetes. Therefore, rather than focusing the discussion on which
Conclusion
There is convincing evidence that shows an increased risk of dementia in people with diabetes, but there are few detailed epidemiological data for risk factors. There are mechanistic studies that provide pathophysiological leads, but do not indicate which of these leads are clinically relevant. This gap in evidence between epidemiological and mechanistic studies needs to be closed. The risk factors and mechanisms that drive the association between diabetes and accelerated cognitive decline and
References (94)
- et al.
The relationship between type 2 diabetes and cognitive dysfunction: longitudinal studies and their methodological limitations
Eur J Pharmacol
(2004) - et al.
Modulation of memory by insulin and glucose: neuropsychological observations in Alzheimer's disease
Eur J Pharmacol
(2004) - et al.
A systematic literature review of attrition between waves in longitudinal studies in the elderly shows a consistent pattern of dropout between differing studies
J Clin Epidemiol
(2005) - et al.
The age-dependent relation of blood pressure to cognitive function and dementia
Lancet Neurol
(2005) Vascular risk factors for Alzheimer's disease: an epidemiologic perspective
Neurobiol Aging
(2000)- et al.
Central nervous system findings in a tenth decade autopsy population
Prog Brain Res
(1973) - et al.
Structural magnetic resonance imaging in the practical assessment of dementia: beyond exclusion
Lancet Neurol
(2002) - et al.
Cognition and synaptic plasticity in diabetes mellitus
Trends Neurosci
(2000) - et al.
Ageing and diabetes: implications for brain function
Eur J Pharmacol
(2002) - et al.
Radical AGEing in Alzheimer's disease
Trends Neurosci
(1995)
Critically attained threshold of cerebral hypoperfusion: the CATCH hypothesis of Alzheimer's pathogenesis
Neurobiol Aging
Brain insulin and feeding: a bi-directional communication
Eur J Pharmacol
The source of cerebral insulin
Eur J Pharmacol
Signaling by insulin-like growth factor 1 in brain
Eur J Pharmacol
Role of insulin and insulin receptor in learning and memory
Mol Cell Endocrinol
Age- and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders
Neurobiol Aging
Insulin and neurodegenerative disease: shared and specific mechanisms
Lancet Neurol
Potential roles of insulin and IGF-1 in Alzheimer's disease
Trends Neurosci
Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer's disease is associated with the apolipoprotein E-epsilon4 allele
Am J Pathol
The effects of Type 1 diabetes on cognitive performance: a meta-analysis
Diabetes Care
The relationship between impaired glucose tolerance, type 2 diabetes, and cognitive function
J Clin Exp Neuropsychol
Type 2 diabetes mellitus, cognitive impairment and dementia
Diabet Med
Is type II diabetes associated with an increased risk of cognitive dysfunction? A critical review of published studies
Diabetes Care
Comorbid type 2 diabetes mellitus and hypertension exacerbates cognitive decline: evidence from a longitudinal study
Age Ageing
Change in cognitive function by glucose tolerance status in older adults: a 4-year prospective study of the Rancho Bernardo study cohort
Arch Intern Med
Apolipoprotein-E genotyping of diabetic dementia patients: is diabetes rare in Alzheimer's disease?
J Am Geriatr Soc
Changes in blood glucose and insulin secretion in patients with senile dementia of Alzheimer type
Acta Med Scand
Are Alzheimer patients healthier?
J Am Geriatr Soc
Increased risk of type 2 diabetes in Alzheimer disease
Diabetes
Global and societal implications of the diabetes epidemic
Nature
Development of dementing illnesses in an 80-year-old volunteer cohort
Ann Neurol
Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population: the Hisayama Study
Neurology
Risk of dementia among persons with diabetes mellitus: a population-based cohort study
Am J Epidemiol
Vascular risks and incident dementia: results from a cohort study of the very old
Dement Geriatr Cogn Disord
Diabetes mellitus and the risk of dementia: the Rotterdam Study
Neurology
Longitudinal association of vascular and Alzheimer's dementias, diabetes, and glucose tolerance
Neurology
Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort
Am J Epidemiol
Diabetes mellitus is a risk factor for vascular dementia, but not for Alzheimer's disease: a population-based study of the oldest old
Int Psychogeriatr
Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: the Honolulu-Asia Aging Study
Diabetes
Diabetes mellitus and the risk of dementia, Alzheimer's disease and vascular cognitive impairment in the Canadian Study of Health and Aging
Dement Geriatr Cogn Disord
Association between dementia and midlife risk factors: the Radiation Effects Research Foundation Adult Health Study
J Am Geriatr Soc
Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function
Arch Neurol
Diabetes mellitus in midlife and the risk of dementia three decades later
Neurology
Diabetes mellitus and risk of dementia in the Kungsholmen project: a 6-year follow-up study
Neurology
Aggregation of vascular risk factors and risk of incident Alzheimer disease
Neurology
Midlife cardiovascular risk factors and risk of dementia in late life
Neurology
Vascular dementia: incidence and risk factors in the Canadian Study of Health and Aging
Stroke
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