Midlife cardiovascular risk factors and risk of dementia in late life

Whitmer, Rachel A.; Sidney, Stephen; Selby, Joe V.; Johnston, S. Claiborne; Yaffe, Kristine

doi:10.1212/01.wnl.0000149519.47454.f2

Cited by 1,041 publications

(824 citation statements)

References 38 publications

Supporting

Mentioning

765

Contrasting

Unclassified

Order By: Relevance

“…Both PAD and diabetes duration were independent predictors of dementia in analyses that controlled for a range of potential confounders, including age and previously implicated risk factors, glycaemic control [9,13], insulin treatment [14,15] and hypertension [8,9]. The association between PAD and dementia was strong and participants with PAD had five times the risk of developing dementia.…”

Section: Discussionmentioning

confidence: 92%

“…This disparity may be explained by the small numbers of AD cases limiting statistical power in the present study. Risk factors for PAD in diabetes include hypertension, hyperglycaemia, dyslipidaemia and smoking [23,33]; hence, atherosclerosis may explain the relationship between cardiovascular risk factors and dementia in diabetes [8,9]. An important clinical implication is the possibility that the risk of dementia can be reduced by intensive risk factor management.…”

Section: Discussionmentioning

confidence: 99%

“…Cerebrovascular disease is likely to be relevant given the significant role it plays in the development of Alzheimer's disease (AD) and vascular dementia [4]. Cardiovascular risk factors and atherosclerosis are also associated with dementia and AD [5][6][7] and the combination of diabetes and hypertension confers a high risk of dementia [8,9]. In addition, non-vascular mechanisms may also contribute to dementia in diabetes [10], including excess formation of advanced glycation endproducts [11] and/or disturbed neuronal insulin signalling that may promote cerebral amyloidosis [12].…”

Section: Introductionmentioning

confidence: 99%

“…In epidemiological studies exploring risk factors for dementia, associations between hyperglycaemia [9,13] and insulin therapy [14,15] have been reported and longduration diabetes was associated with major cognitive decline [16]. However, these studies have a number of limitations that include adopting methods to diagnose diabetes subject to significant false negative rates [8,9,15,16], incomplete or absent assessments of glycaemic control [5,8,9,[14][15][16] and lack of assessment of microvascular complications [5,8,9,[14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…However, these studies have a number of limitations that include adopting methods to diagnose diabetes subject to significant false negative rates [8,9,15,16], incomplete or absent assessments of glycaemic control [5,8,9,[14][15][16] and lack of assessment of microvascular complications [5,8,9,[14][15][16]. In type 2 diabetes, glycaemic control, diabetic complications and the need for insulin treatment are strongly interrelated and in addition they are each related to the duration of diabetes.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Predictors of cognitive impairment and dementia in older people with diabetes

et al. 2007

View full text Add to dashboard Cite

Aims/hypothesis Diabetes is associated with an increased risk of dementia but the reasons for this association are unclear because there are many potential mechanisms. We explored the relative contribution of diabetes-related variables as predictors of dementia in older individuals with diabetes. Methods Survivors, aged ≥70 or more, were recruited from an existing observational cohort study 7.6±1.0 years after baseline, when they underwent a comprehensive assessment of diabetes, complications and cardiovascular risk factors. Dementia, probable Alzheimer's disease and cognitive impairment without dementia were diagnosed clinically. Logistic regression modelling determined independent predictors of cognitive diagnoses. Results Of 302 participants, aged 75.7±4.6 years, 28 (9.3%) had dementia (16 with probable Alzheimer's disease) and 60 (19.9%) had cognitive impairment without dementia. The major independent longitudinal predictors of dementia were older age (per decade; odds ratio 4.0, 95% CI 1.59-10.10), diabetes duration (for each 5 years; odds ratio 1.69, 95% CI 1.24-2.32), peripheral arterial disease (odds ratio 5.35, 95% CI 2.08-13.72) and exercise (which was protective; odds ratio 0.26, 95% CI 0.09-0.73). For Alzheimer's disease, diabetes duration was an independent predictor in addition to age and diastolic blood pressure. The results of the cross-sectional analyses were similar with respect to diabetes duration and peripheral arterial disease. Conclusions/interpretation Peripheral arterial disease is a strong independent risk factor for dementia in diabetes. After adjustment for a wide range of potential risk factors, diabetes duration remains independently associated with dementia and probable Alzheimer's disease, indicating that factors not measured in this study may be important in the pathogenesis of dementia in diabetes.

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Predictors of cognitive impairment and dementia in older people with diabetes

et al. 2007

View full text Add to dashboard Cite

show abstract

Midlife vs Late-Life Depressive Symptoms and Risk of Dementia

Barnes

Yaffe

Byers

et al. 2012

Arch Gen Psychiatry

357

114

View full text Add to dashboard Cite

Context Depression and dementia are common in older adults and often co-occur, but it is unclear whether depression is an etiologic risk factor for dementia. Objective, Design, Setting and Participants To clarify the timing and etiology of the association, we examined depressive symptoms assessed in mid-life (1964–1973) and late-life (1994–2000) and the risks of dementia, Alzheimer’s disease (AD) and vascular dementia (VaD) (2003–2009) in a retrospective cohort study of 13,535 long-term Kaiser Permanente members. Depressive symptoms were categorized as none, mid-life only, late-life only or both. Cox proportional hazards models (age as time-scale) adjusted for demographics and medical comorbidities were used to examine depressive symptom category and risk of dementia, AD or VaD. Main Outcome Measure Any medical record diagnosis of dementia; Neurology clinic diagnosis of AD or VaD. Results Subjects had a mean (standard deviation) age of 81 (5) years in 2003; 58% were women and 25% were non-white. Depressive symptoms were present in 14.1% of subjects in mid-life only, 9.2% late-life only, and 4.2% both. Over 6 years, 23.1% were diagnosed with dementia (5.5% AD, 2.3% VaD). The adjusted hazard of dementia was increased by approximately 20% for mid-life depressive symptoms only (Hazard Ratio [95% confidence interval]: 1.19 [1.07, 1.32]), 70% for late-life symptoms only (1.72 [1.54, 1.92]), and 80% for both (1.77 [1.52, 2.06]). When we examined AD and VaD separately, subjects with late-life depressive symptoms only had a two-fold increase in AD risk (2.06 [1.67, 2.55]) whereas subjects with both mid-life and late-life symptoms had more than a three-fold increase in VaD risk (3.51 [2.44, 5.05]). Conclusions Depressive symptoms in mid-life or late-life are associated with an increased risk of developing dementia. Depression that begins in late-life may be part of the AD prodrome, while recurrent depression may be etiologically associated with increased risk of VaD.

show abstract