Affiliations: [a] Department of Psychology, University of Southern California, Los Angeles, CA, USA
| [b] Department of Clinical Pharmacy, University of Southern California, Los Angeles, CA, USA
Correspondence:
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Correspondence to: Daniel A. Nation, PhD, University of Southern California, 3620 South McClintock Avenue, Room 1010, Los Angeles, CA 90089, USA. Tel.: +1 213 740 4503; Fax: +1 213 746 9082; E-mail: danation@usc.edu.
Abstract: Background:Bone marrow-derived progenitor cells survey the vasculature and home to sites of tissue injury where they can promote repair and regeneration. It has been hypothesized that these cells may play a protective role neurodegenerative and vascular cognitive impairment. Objective:To evaluate progenitor cell levels in older adults with and without mild cognitive impairment (MCI), and to relate circulating levels to memory, brain volume, white matter lesion volume, and cerebral perfusion. Method:Thirty-two older adults, free of stroke and cardiovascular disease, were recruited from the community and evaluated for diagnosis of MCI versus cognitively normal (CN). Participants underwent brain MRI and blood samples were taken to quantify progenitor reserve using flow cytometry (CD34+, CD34+CD133+, and CD34+CD133+CD309+ cells). Results:Participants with MCI (n = 10) exhibited depletion of all CPC markers relative to those who were CN (n = 22), after controlling for age, sex, and education. Post-hoc age, sex, and education matched comparisons (n = 10 MCI, n = 10 CN) also revealed the same pattern of results. Depletion of CD34+ cells correlated with memory performance, left posterior cortical thickness, and bilateral hippocampal perfusion. Participants exhibited low levels of vascular risk and white matter lesion burden that did not correlate with progenitor levels. Conclusions:Circulating progenitor cells are associated with cognitive impairment, memory, cortical atrophy, and hippocampal perfusion. We hypothesize that progenitor depletion contributes to, or is triggered by, cognitive decline and cortical atrophy. Further study of progenitor cell depletion in older adults may benefit efforts to prevent or delay dementia.
