CIRCULATING ANGIOGENIC CELL LEVELS SHOW PROTECTIVE ASSOCIATIONS WITH MEMORY FUNCTION: INTRODUCING THE VASCULAR RESERVE HYPOTHESIS

Abstract

Vascular risk factors are known to exacerbate age-related cognitive decline and increase the risk of dementia independent of stroke. Much less is known regarding the role of protective vascular factors. Circulating bone marrow-derived progenitors are thought to survey the vasculature and home to sites of injury where they can promote healing through angiogenesis and vasculogenesis. These circulating angiogenic cells may represent a mechanism of protection against cerebrovascular injury that could modify the impact of vascular aging on cognitive decline and brain health. Here, we tested this “vascular reserve hypothesis” through an observational study in which we cultured circulating angiogenic cells, i.e. Colony Forming Unit (CFU)-Hill cells, from the blood of older adults (ages 59 to 90 years) who were free of dementia and stroke (N=23). We also examined endothelial cells from these cultures for senescence-associated β-galactosidase staining. Participants underwent memory assessment and brain MRI for evaluation of white matter lesion burden (T2-FLAIR). Pearson correlations and multiple regression examined relationships between vascular reserve markers and indicators of memory dysfunction and white matter lesion volume. Findings indicated that higher circulating angiogenic cell levels were associated with better immediate memory (Logical Memory I, r = .55, p = .006; Visual Reproduction I, r = .58, p = .006), which remained significant after controlling for age, sex and education (all p's < .05). Increased β-galactosidase staining was associated with worse recognition memory (Visual Reproduction Recognition, r = -.53, p = .025) and greater white matter lesion burden (r = .52, p = .047). Circulating angiogenic cells may protect against the effects of vascular aging on decline in immediate memory, a cognitive ability that is particularly impacted by normal aging, cerebrovascular disease and Alzheimer's disease. Increased vascular cell senescence, indexed by β-galactosidase staining, may be linked to increased white matter damage and cerebral small vessel disease. Together these findings suggest that angiogenic repair and senescence mechanisms could inform dementia risk assessment and open novel therapeutic targets for the prevention of dementia.