Effect of Alzheimer caregiving on circulating levels of C-reactive protein and other biomarkers relevant to cardiovascular disease risk: a longitudinal study

Abstract

Background: Providing care to a spouse with Alzheimer's disease (AD) may contribute to cardiovascular disease (CVD). The acute phase reactant C-reactive protein (CRP) is a well-established biomarker of an increased CVD risk.

Objective: To investigate the hypothesis that dementia caregiving is associated with elevated circulating levels of CRP and possibly other biomarkers of CVD risk.

Methods: We examined 118 elderly spousal Alzheimer caregivers and 51 noncaregiving controls about once a year for up to 3 years. Random regression models with fixed and time-variant effects for a range of covariates known to affect biomarker levels were used to evaluate changes in CRP and in 12 additional measures of inflammation, cellular adhesion, endothelial function, and hemostasis in relation to caregiving status, years of caregiving, and major transitions in the caregiving situation.

Results: During the study period, longer duration of caregiving was associated with elevated CRP levels (p = 0.040) and caregivers showed greater tumor necrosis factor (TNF)-α levels than controls (p = 0.048). Additionally, 3 months after the death of the AD spouse, caregivers showed a significant drop in CRP levels (p = 0.003) and levels of soluble intercellular adhesion molecule (sICAM)-1 (p = 0.008).

Conclusion: Duration of caregiving and being a caregiver per se were both associated with chronic low-grade inflammation as indicated by elevated CRP and TNF-α levels, respectively. Conversely, death of the AD spouse was associated with lower CRP and sICAM-1 levels. The findings indicate that chronic caregiving of those with dementia may result in increased inflammation and, thereby, possibly increased CVD risk.

Figure 1. Parameters of dementia caregiving stress and changes in biomarker levels

All values are given as multivariate-adjusted geometric means with 95%confidence intervals. CRP, C-reactive protein; TNF, tumor necrosis factor; sICAM-1, soluble intercellular adhesion molecule-1. Panel A illustrates the association between duration of caregiving across 5-year steps and change in CRP over time (0 years of caregiving in controls). Panel B and Panel D depict lowered CRP and sICAM-1 levels, respectively, in caregivers whose spouse had deceased relative to caregivers who are continuing to provide care for their spouse and controls. Panel C shows higher TNF-alpha levels over time in caregivers than in controls.