Diabetes mellitus and risk of dementia in the Kungsholmen project

Background: Research on diabetes mellitus as a risk factor for dementia and its main subtypes has produced conflicting results. The authors investigated the relationship between diabetes mellitus and risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD). Methods: A dementia-free cohort of 1,301 community dwellers aged 75 years and older in Stockholm, Sweden, was longitudinally examined twice over 6 years to detect dementia cases (Diagnostic and Statistical Manual of Mental Disorders–III-R diagnostic criteria). Cox proportional hazards models were used to analyze the data with adjustment for several potential confounders. Results: During the 5,584 person-years of follow-up, 350 subjects developed dementia, including 260 AD and 49 VaD cases. Diabetes mellitus was associated with hazard ratios (HR) of 1.5 (95% CI 1.0 to 2.1, p = 0.04) for dementia, 2.6 (95% CI 1.2 to 6.1) for VaD, and 1.3 (95% CI 0.9 to 2.1) for AD. Patients who were treated with oral antidiabetic medications had HRs of 1.7 (95% CI 1.0 to 2.8, p = 0.04) for dementia and 3.6 (95% CI 1.3 to 9.5) for VaD. There were significant interactions of diabetes with severe systolic hypertension (≥180 mm Hg) on dementia and its main subtypes, and of diabetes with heart disease on VaD. Conclusions: Diabetes mellitus increases the risk of dementia, and VaD in particular, in very old people. The risk for dementia and VaD is especially high when diabetes mellitus occurs together with severe systolic hypertension or heart disease.

[1]  C. Brayne,et al.  Vascular Risks and Incident Dementia: Results from a Cohort Study of the Very Old , 1998, Dementia and Geriatric Cognitive Disorders.

[2]  C. Cotman,et al.  Apolipoprotein‐E Genotyping of Diabetic Dementia Patients: Is Diabetes Rare in Alzheimer's Disease? , 1996, Journal of the American Geriatrics Society.

[3]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[4]  J. Shaw,et al.  Preventing Type 2 diabetes and the dysmetabolic syndrome in the real world: a realistic view , 2003, Diabetic medicine : a journal of the British Diabetic Association.

[5]  R. Mayeux,et al.  Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort. , 2001, American journal of epidemiology.

[6]  P. O'Brien,et al.  Risk of dementia among persons with diabetes mellitus: a population-based cohort study. , 1997, American journal of epidemiology.

[7]  L. Launer,et al.  Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. , 2002, Diabetes.

[8]  B. Winblad,et al.  The influence of education on clinically diagnosed dementia incidence and mortality data from the Kungsholmen Project. , 2001, Archives of neurology.

[9]  K. Rockwood,et al.  Diabetes mellitus and the Risk of Dementia, Alzheimer’s Disease and Vascular Cognitive Impairment in the Canadian Study of Health and Aging , 2002, Dementia and Geriatric Cognitive Disorders.

[10]  Debashis Ghosh,et al.  Impact of diabetes on cognitive function among older Latinos: a population-based cohort study. , 2003, Journal of clinical epidemiology.

[11]  B. Winblad,et al.  Clinical diagnosis of Alzheimer's disease and other dementias in a population survey. Agreement and causes of disagreement in applying Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, Criteria. , 1992, Archives of neurology.

[12]  C. Jagger,et al.  Factors associated with vascular dementia in an elderly community population , 1999, International journal of geriatric psychiatry.

[13]  Thomas P. Kobylski,et al.  Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised , 1988 .

[14]  W. Jagust,et al.  The Role of APOE ∊4 in Modulating Effects of Other Risk Factors for Cognitive Decline in Elderly Persons , 1999 .

[15]  E. Nilsson,et al.  Cognitive functioning in a population-based sample of very old non-demented and non-depressed persons: the impact of diabetes. , 2002, Archives of gerontology and geriatrics.

[16]  B. Winblad,et al.  Very Old Women at Highest Risk of Dementia and Alzheimer's Disease , 1997, Neurology.

[17]  G. Mcclearn,et al.  Diabetes Mellitus Is a Risk Factor for Vascular Dementia, but Not for Alzheimer's Disease: A Population-Based Study of the Oldest Old , 2002, International Psychogeriatrics.

[18]  Hiromitsu Iwamoto,et al.  Incidence and risk factors of vascular dementia and Alzheimer's disease in a defined elderly Japanese population , 1995, Neurology.

[19]  P Ducimetière,et al.  Changes in cognitive abilities over a 4-year period are unfavorably affected in elderly diabetic subjects: results of the Epidemiology of Vascular Aging Study. , 2001, Diabetes care.

[20]  W. Kukull,et al.  Epidemiology of dementia: concepts and overview. , 2000, Neurologic clinics.

[21]  B. Winblad,et al.  Changes in blood glucose and insulin secretion in patients with senile dementia of Alzheimer type. , 2009, Acta medica Scandinavica.

[22]  A. Hofman,et al.  Non-insulin-dependent Diabetes Mellitus (niddm) Association of Diabetes Mellitus and Dementia: the Rotterdam Study , 2022 .

[23]  S. Henderson.  Epidemiology of dementia. , 1998, Annales de medecine interne.

[24]  J. Foster,et al.  Cognitive impairment, physical disability and depressive symptoms in older diabetic patients: the Fremantle Cognition in Diabetes Study. , 2003, Diabetes research and clinical practice.

[25]  S. Fowler,et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. , 2002 .

[26]  N J Wald,et al.  A strategy to reduce cardiovascular disease by more than 80% , 2003, BMJ : British Medical Journal.

[27]  Carole Dufouil,et al.  Magnetic resonance imaging of the brain in diabetes: the Cardiovascular Determinants of Dementia (CASCADE) Study. , 2004, Diabetes.

[28]  J. Heitner,et al.  Diabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects , 1997, Neurology.

[29]  R. Stewart,et al.  Type 2 diabetes mellitus, cognitive impairment and dementia , 1999, Diabetic medicine : a journal of the British Diabetic Association.

[30]  Ian G. McKeith,et al.  Pathological correlates of late-onset dementia in a multicentre, community-based population in England and Wales , 2001, The Lancet.

[31]  B. Winblad,et al.  Occurrence of dementia in advanced age: the study design of the Kungsholmen Project. , 1992, Neuroepidemiology.

[32]  E. Nilsson,et al.  Cognitive performance in very old diabetic persons: the impact of semantic structure, preclinical dementia, and impending death. , 2002, Neuropsychology.

[33]  Anthony F Jorm,et al.  A case‐control study of Alzheimer's disease in Australia , 1990, Neurology.

[34]  J. Jolles,et al.  The relation between morbidity and cognitive performance in a normal aging population. , 1998, The journals of gerontology. Series A, Biological sciences and medical sciences.

[35]  M. D. O'Brien,et al.  Cerebral blood flow in dementia , 1986, Neurology.

[36]  B. Winblad,et al.  Association of stroke with dementia, cognitive impairment, and functional disability in the very old: a population-based study. , 1998, Stroke.

[37]  G. C. Román,et al.  Vascular dementia , 1993, Neurology.

[38]  P. Mathurin,et al.  [Magnetic resonance imaging of the brain]. , 1988, Journal belge de radiologie.

[39]  K Yaffe,et al.  Is diabetes associated with cognitive impairment and cognitive decline among older women? Study of Osteoporotic Fractures Research Group. , 2000, Archives of internal medicine.

[40]  G. Sundkvist,et al.  Incidence, prevalence, and mortality of diabetes in a large population. A report from the Skaraborg Diabetes Registry. , 1999, Diabetes care.

[41]  K. Manton,et al.  Apolipoprotein E polymorphism and stroke in a population sample aged 75 years or more. , 1996, Stroke.

[42]  A. Hofman,et al.  Silent brain infarcts and the risk of dementia and cognitive decline. , 2003, The New England journal of medicine.

[43]  G. Reaven,et al.  Relationship Between Hyperglycemia and Cognitive Function in Older NIDDM Patients , 1990, Diabetes Care.

[44]  A Hofman,et al.  Diabetes mellitus and the risk of dementia , 1999, Neurology.

[45]  W. Jagust,et al.  Prevalence of Dementia in Older Latinos: The Influence of Type 2 Diabetes Mellitus, Stroke and Genetic Factors , 2003, Journal of the American Geriatrics Society.