Relevance of Cardiovascular Risk Factors and Ischemic Cerebrovascular Disease to the Pathogenesis of Alzheimer Disease

White, Lon R.; Launer, Lenore J.

doi:10.1097/00002093-200607001-00012

Cited by 27 publications

(21 citation statements)

References 16 publications

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“…Because we excluded prevalent dementia and possible dementia cases, we expected that there would be some baseline differences between the analytical and excluded samples on the risk factors for dementia based on studies previously reported. 14 The mean follow-up was 6.1 years, with an incidence rate for dementia of 9.2 per 1000 person-years.…”

Section: Methodsmentioning

confidence: 99%

Apolipoprotein E ε4 Allele Genotype and the Effect of Depressive Symptoms on the Risk of Dementia in Men

Irie

Masaki²,

Petrovitch³

et al. 2008

Arch Gen Psychiatry

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Context The apolipoprotein E ε4 (APOE ε4) allele is a genetic risk factor for Alzheimer disease. Recently, depression has also become recognized as a risk factor for dementia. However, the possible effect of the APOE genotype on the association between depression and dementia is unexamined. Objective To examine the independent and combined effects of depression and APOE ε4 on the risk of dementia and its subtypes. Design The Honolulu-Asia Aging Study, a population-based prospective cohort study of Japanese American men. Settings and Participants Depressive symptoms and presence of the APOE ε4 allele were assessed between March 1991 and October 1993 in 1932 cognitively healthy men aged 71 to 90 years. Incident cases of dementia were diagnosed during approximately 6 years of follow-up based on neurologic assessment at 2 repeated examinations (April 1994–April 1996 and October 1997–February 1999). Main Outcome Measures Overall dementia, Alzheimer disease, and vascular dementia. Results The interaction of depression and APOE ε4 was statistically significant in the analytical models. Compared with men with neither APOE ε4 nor depression, the risk of dementia in nondepressed men with APOE ε4 was not significant (hazard ratio, 1.1; 95% confidence interval [CI], 0.6–1.8); however, depressed men without APOE ε4 had a 1.6-fold greater risk (95% CI, 0.8–3.0), whereas depressed men with APOE ε4 had a 7.1-fold greater risk (95% CI, 3.0–16.7) of dementia. For subtypes, we found similar increased risks of Alzheimer disease. Conclusions The APOE ε4 status modifies the association between depressive symptoms and dementia in elderly men. Because individuals with depressive symptoms and the APOE ε4 allele had a markedly increased risk of dementia, one might be especially watchful for early signs of dementia in the older person with depression who is also positive for the APOE ε4 allele. Because this cohort includes only men, further investigation in women is required.

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Section: Methodsmentioning

confidence: 99%

Apolipoprotein E ε4 Allele Genotype and the Effect of Depressive Symptoms on the Risk of Dementia in Men

Irie

Masaki²,

Petrovitch³

et al. 2008

Arch Gen Psychiatry

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“…10 Established vascular risk factors (heart disease, stroke, hypertension, obesity, diabetes, and elevated plasma homocysteine and cholesterol concentrations) increase the risk for both vascular dementia and Alzheimer's disease and accelerate the associated cognitive decline. [11][12][13][14][15][16] A history of depression, asthma, and repeated exposure to herpes simplex type I virus in the presence of an ApoE ε4 allele have also been observed to increase the risk of dementia. [17][18][19] With regard to treatments, the use of non-steroidal anti-inflammatory agents and hormonal replacement therapy in menopausal women has been found by most studies to reduce the risk for dementia and also to diminish the risk effect of ApoE ε4, [20][21][22] whereas exposure to anaesthesia and use of drugs with anticholinergic effects have been shown to increase risk.…”

Section: Candidate Exposuresmentioning

confidence: 99%

Designing prevention programmes to reduce incidence of dementia: prospective cohort study of modifiable risk factors

Ritchie

Carrière

Ritchie

et al. 2010

BMJ

198

171

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Objective To estimate the percentage reduction in incidence of dementia that would be obtained if specific risk factors were eliminated. Design Prospective seven year cohort study. Setting General population, Montpellier, France. Participants 1433 people aged over 65 with a mean baseline age of 72.5 (SD 5.1) years. Main outcome measures Diagnosis of mild cognitive impairment or dementia established by a standardised neurological examination. Results Cox models were constructed to derive hazard ratios and determine confounding and interaction effects for potentially modifiable risk factors for dementia. Mean percentage population attributable fractions were calculated with 95% confidence intervals derived from bootstrapping for seven year incidence of mild cognitive impairment or dementia. The final model retained crystallised intelligence (population attributable fraction 18.11%, 95% confidence interval 10.91% to 25.42%), depression (10.31%, 3.66% to 17.17%), fruit and vegetable consumption (6.46%, 0.15% to 13.06%), diabetes (4.88%, 1.87% to 7.98%), and apolipoprotein E ε4 allele (7.11%, 2.44% to 11.98%). Conclusions Increasing crystallised intelligence and fruit and vegetable consumption and eliminating depression and diabetes are likely to have the biggest impact on reducing the incidence of dementia, outweighing even the effect of removing the principal known genetic risk factor. Although causal relations cannot be concluded with certainty, the study suggests priorities that may inform public health programmes. INTRODUCTIONThe past 30 years have seen the proliferation of methodologically well constructed prospective population studies of dementia that have pointed to multiple risk factors. Although the exact cause of the dementias remains unknown, these studies together suggest a complex interaction of exposures that contribute differentially to the probability and timing of onset of disease. The contribution of epidemiology to dementia research has, however, been principally in the areas

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“…In fact, Alzheimer's and microvascular disease may overlap pathogenetically, a hypothesis supported by epidemiological evidence suggesting that well-recognized risk factors for atherosclerotic disease, including hypertension, diabetes, smoking and hyperlipidaemia, play a role not only in vascular dementia but also in Alzheimer's disease as well (6)(7)(8)(9)(10) .…”

mentioning

confidence: 99%

Diet, physical activity and cognitive impairment among elders: the EPIC–Greece cohort (European Prospective Investigation into Cancer and Nutrition)

Ψαλτοπούλου

Kyrozis

Stathopoulos

et al. 2008

Public Health Nutr.

152

112

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Relevance of Cardiovascular Risk Factors and Ischemic Cerebrovascular Disease to the Pathogenesis of Alzheimer Disease

Cited by 27 publications

References 16 publications

Apolipoprotein E ε4 Allele Genotype and the Effect of Depressive Symptoms on the Risk of Dementia in Men

Apolipoprotein E ε4 Allele Genotype and the Effect of Depressive Symptoms on the Risk of Dementia in Men

Designing prevention programmes to reduce incidence of dementia: prospective cohort study of modifiable risk factors

Diet, physical activity and cognitive impairment among elders: the EPIC–Greece cohort (European Prospective Investigation into Cancer and Nutrition)

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