Background: Mild cognitive impairment (MCI) represents an intermediate and modifiable stage between normal aging and dementia. There is an urgent need for simple, non-invasive testing of MCI by blood biomarkers.

Objective: This study aimed to retrospectively evaluate the association of red blood cell (RBC) indices with MCI, and select the best hematologic characteristic for detection of MCI in elderly Chinese.

Methods: Matched case-control study was carried out with 85 pairs of MCI subjects and healthy controls. The matching criteria was age, gender and education attainment. All samples were analyzed for RBC indices, including hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width-standard deviation (RDW-SD). A conditional logistic regression model was used to evaluate the association between RBC indices and MCI. The diagnostic efficacy of the biomarkers was evaluated by receiver operating characteristics (ROC).

Results: Among all RBC indices, there were significant differences in HGB (124.82 ± 7.89 vs. 133.93 ± 4.52, P < 0.001) and RDW-SD (45.29 ± 2.03 vs. 41.34 ± 4.41, P < 0.001) between two groups. In the logistic regression model, after adjustment for lifestyle factors and comorbidities, significant statistically associations have been found between higher HGB and lower risk of MCI (adjusted OR: 0.831; 95% CI: 0.773-0.893), higher RDW-SD and a higher risk of MCI (adjusted OR: 1.575; 95% CI: 1.326- 1.872). ROC analysis suggested that the largest area under the ROC curve (AUC) was found with the combination of HGB and RDW-SD (AUC = 0.842), followed by HGB(AUC = 0.795), and finally by modest RDW-SD (AUC = 0.777). Combination of HGB <131 g/L and RDW-SD >43.4 fL yielded a sensitivity of 92% and a specificity of 89%, overall diagnosis efficiency of which were better than HBG and RDW-SD alone.

Conclusion: Lower HGB and higher RDW-SD alone were significantly found to be associated with increased risk of MCI, and offered modest sensitivity and specificity as a diagnostic marker. The combination of HGB and RDW-SD was more sensitive and had higher classification accuracy for differentiating MCI from healthy controls. Further prospective research is needed to clarify whether HGB in combination with RDW-SD may be a potential diagnostic tool for early diagnosis of AD.