Midlife cardiovascular risk factors and risk of dementia in late life

Kaiser Permanente Division of Research, 2000 Broadway, Oakland, CA 94612, USA.
Neurology (Impact Factor: 8.29). 02/2005; 64(2):277-81. DOI: 10.1212/01.WNL.0000149519.47454.F2
Source: PubMed


To evaluate if midlife cardiovascular risk factors are associated with risk of late-life dementia in a large, diverse cohort.
The authors conducted a retrospective cohort study of 8,845 participants of a health maintenance organization who underwent health evaluations from 1964 to 1973 when they were between the ages of 40 and 44. Midlife cardiovascular risk factors included total cholesterol, diabetes, hypertension, and smoking. Diagnoses of dementia were ascertained by medical records from January 1994 to April 2003.
The authors identified 721 participants (8.2%) with dementia. Smoking, hypertension, high cholesterol, and diabetes at midlife were each associated with a 20 to 40% increase in risk of dementia (fully adjusted Cox proportional hazards model: HR 1.24, 95% CI 1.04 to 1.48 for hypertension, HR 1.26, 95% CI 1.08 to 1.47 for smoking, HR 1.42, 95% CI 1.22 to 1.66 for high cholesterol, and HR 1.46, 95% CI 1.19 to 1.79 for diabetes). A composite cardiovascular risk score was created using all four risk factors and was associated with dementia in a dose-dependent fashion. Compared with participants having no risk factors, the risk for dementia increased from 1.27 for having one risk factor to 2.37 for having all four risk factors (fully adjusted model: HR 2.37, 95% CI 1.10 to 5.10).
The presence of multiple cardiovascular risk factors at midlife substantially increases risk of late-life dementia in a dose dependent manner.

31 Reads
  • Source
    • "The A1166C polymorphism of AGTR1 has been reported to be associated with increased risks of hypertension [1], myocardial infarction [2], and cerebral infarction [3]. There have been no prospective cohort studies in Japanese subjects regarding the association between the polymorphism of the A1166C of AGTR1 and cardiovascular events. "

  • Source
    • "years). These ages were used to define midlife and late life alcohol consumption and are consistent with the definitions of midlife and late life provided by previous studies (Kivipelto et al., 2001; Whitmer et al., 2005; Solomon et al., 2009). Subjects who received a baseline neuropsychological battery consumed more alcohol during midlife (6.8 drinks per week vs. 5.4 drinks per week, P < 0.0001) and late life (4.6 drinks per week vs. 3.4 drinks per week, P < 0.0001) compared with subjects who did not receive a neuropsychological battery. "

    • "Indeed, increasing molecular evidence points toward a mechanistic link between altered cholesterol metabolism and AD progression [3] [4]. Moreover, hypercholesterolemia is recognized to be a risk factor for sporadic AD [5] [6] [7]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease (AD) is a neurodegenerative disease that has been linked to changes in cholesterol metabolism. Neuronal cholesterol content significantly influences the pro-apoptotic effect of amyloid-β peptide42 (Aβ42), which plays a key role in AD development. We previously reported that aged mice with reduced expression of the lipolysis stimulated lipoprotein receptor (LSR+/-), demonstrate membrane cholesterol accumulation and decreased intracellular lipid droplets in several brain regions, suggesting a potential role of LSR in brain cholesterol distribution. We questioned if these changes rendered the LSR+/- mouse more susceptible to Aβ42-induced cognitive and biochemical changes. Results revealed that intracerebroventricular injection of oligomeric Aβ42 in male 15-month old LSR+/+ and LSR+/- mice led to impairment in learning and long-term memory and decreased cortical cholesterol content of both groups; these effects were significantly amplified in the Aβ42-injected LSR+/- group. Total latency of the Morris test was significantly and negatively correlated with cortical cholesterol content of the LSR+/- mice, but not of controls. Significantly lower cortical PSD95 and SNAP-25 levels were detected in Aβ42-injected LSR+/- mice as compared to Aβ42-injected LSR+/+ mice. In addition, 24S-hydroxy cholesterol metabolite levels were significantly higher in the cortex of LSR+/- mice. Taken together, these results suggest that changes in cortex cholesterol regulation as a result of the LSR+/- genotype were linked to increased susceptibility to amyloid stress, and we would therefore propose the aged LSR+/- mouse as a new model for understanding the link between modified cholesterol regulation as risk factor for AD.
    Journal of Alzheimer's disease: JAD 02/2015; 45(1). DOI:10.3233/JAD-142127 · 4.15 Impact Factor
Show more


31 Reads