2023年 · 第103卷第25期

Dementia is a neurological disorder characterized by impairment of cognition and daily life functions, and Alzheimer's disease (AD) is one of the common types. Previous studies have shown that low hemoglobin and anemia are associated with cognitive impairment and AD. However, the association of other blood cell indicators with dementia risk and the mechanism are unknown. This study was based on the UK Biobank cohort and included 313 448 middle-aged and elderly people (mean age 60.38 years) to explore the association and underlying mechanisms of multiple blood cell indicators with dementia risk. Cox regression and restricted cubic spline models were used to investigate linear and nonlinear longitudinal associations, Mendelian randomization analysis was used to determine causality, and linear regression models were used to explore underlying mechanisms driven by brain structures. The results showed that 6 833 participants developed dementia during a mean follow-up of 9.03 years. Cox regression results suggest a decrease in red blood cell levels (HR=0.90，95%CI: 0.87-0.92), increased levels of reticulocyte maturation parameters (mean reticulocyte volume:HR=1.07，95%CI：1.04~1.10； Average spherical cell volume:HR=1.07，95%CI：1.04~1.10； Immature reticulocyte fraction:HR=1.15，95%CI: 1.11-1.19) and elevated white blood cell levels (HR=1.04，95%CI: 1.03 to 1.06) were associated with a higher incidence of dementia. There was a U-shaped association between calcitonin and mean platelet volume and dementia, with risk lows of approximately 0.26% and 9.78 fL, respectively. The results of Mendelian randomization indicate that hemoglobin (P_IVW=0.03) and the width of red blood cell distribution (P_IVW=0.01) was causally related to AD. Linear regression model results showed that hemoglobin was associated with the medial orbitofrontal cortex (left hemisphere,P_HGB=0.04), lateral orbitofrontal cortex (left hemisphere:P_HGB=0.02, right hemisphere:P_HGB=0.03), middle temporal cortex (left hemisphere:P_HGB=0.02), globus pallidus (left hemisphere:P_HGB=0.001, right hemisphere:P_HGB<0.001) and most white tract brain regions, and there was a strong association between blood cell index and brain regions with abundant blood vessels. This study is the first population-based cohort to investigate the relationship between blood cell indicators and the incidence of anemia and dementia. By performing regular blood tests, blood cell abnormalities can be monitored and corrected, contributing to the reduction of the incidence of dementia.