High Serum Neuron-Specific Enolase Level Is Associated with Mild Cognitive Impairment in Patients with Diabetic Retinopathy

Figures & data

Table 1 Clinical and Biochemical Characteristics Between DR Patients with Normal Cognition and DR Patients with MCI

Variables	NCF Group (N=68)	MCI Group (N=56)	P-value
Age (years)	55.50 (50.25–63.00)	57.50 (48.50–62.75)	0.964
Sex (Male,%)	39 (57.3%)	34 (60.7%)	0.705
Duration of DM (years)	10.00 (7.00–15.75)	13.00 (5.00–17.00)	0.466
Current smoking (%)	26 (38.2%)	19 (33.9%)	0.620
Habitual alcohol drinking (%)	28 (41.1%)	24 (42.8%)	0.850
BMI (kg/m2)	25.62 ± 2.47	25.64 ± 2.86	0.976
TG (mmol/L)	1.83 (1.23–2.65)	2.13 (1.49–3.24)	0.073
NSE (ng/mL)	11.80 (10.15–13.88)	14.55 (12.00–17.57)	<0.001
Fasting C-peptide(ng/mL)	1.20 (0.90–1.70)	1.40 (0.73–2.00)	0.796
HbA1C(%)	8.39 ± 1.45	9.42 ± 2.16	0.002
TC (mmol/L)	4.87 (4.28–5.67)	5.33 (4.57–6.39)	0.083
HDL (mmol/L)	1.21 (1.10–1.38)	1.28 (1.13–1.52)	0.173
LDL (mmol/L)	2.82 (2.34–3.20)	2.97 (2.65–3.50)	0.113
UA (umol/L)	310.60 (272.30–379.68)	322.25 (262.15–407.38)	0.984
Cr (umol/L)	60.85 (48.90–73.83)	62.35 (51.25–69.85)	0.898
BUN (mmol/L)	5.84 ± 1.61	6.15 ±1.99	0.340
Education level (years)	12.00 (9–15)	9.00 (7.13–12.00)	0.001
MMSE total score	28.00 (27.00 −29.00)	25.00 (25.00–26.00)	<0.001
MMSE orientation score	10.00 (9.25–10.00)	10.00 (9.00–10.00)	0.003
MMSE registration score	3.00 (3.00–3.00)	2.00 (2.00–3.00)	<0.001
MMSE attention and calculation score	5.00 (4.00–5.00)	4.00 (3.00–4.00)	<0.001
MMSE recall score	3.00 (2.25–3.00)	2.00 (2.00–3.00)	<0.001
MMSE language score	8.00 (8.00–9.00)	7.00 (7.00–8.00)	<0.001
History of hypertension(%)	30 (44.1%)	26(46.4%)	0.797
Lower limb atherosclerosis (%)	54 (79.4%)	49 (87.5%)	0.232
Carotid atherosclerosis (%)	48(70.6%)	41 (73.2%)	0.746
Diabetic peripheral neuropathy(%)	11 (16.2%)	16 (28.5%)	0.096
PDR(%)	21 (30.8%)	23 (41.0%)	0.238
Diabetic nephropathy (%)	16 (23.5%)	18 (32.1%)	0.285
Insulin use (%)	60 (88.2%)	50 (89.2%)	0.854
Metformin use (%)	43 (63.2%)	34 (60.7%)	0.773
Acarbose use (%)	9 (13.2%)	6 (10.7%)	0.668
DPP-4 inhibitor use (%)	24 (35.2%)	21 (37.5%)	0.799
Statins use (%)	33 (48.5%)	33 (58.9%)	0.248

Abbreviations: DR, diabetic retinopathy; NCF, normal cognitive function; MCI, mild cognitive impairment; DM, diabetesmellitus; BMI, body mass index; TG, triglyceride; NSE, neuron-specific enolase; HbA1c, hemoglobin A1c; TC, total cholesterol; HDL, high density lipoprotein; LDL, low density lipoprotein; UA, uric acid; Cr, creatinine; BUN, blood urea nitrogen; MMSE, Minimum Mental State Examination; PDR, proliferative diabetic retinopathy.

Table 2 Associations Between Serum NSE Levels and MMSE Scores

Variables	Spearman Correlation Analysis		Partial Correlation Analysis		Linear Regression Analysis
	r	P-value	r	P-value^a	Β(95% CI)	P-value^a
MMSE total score	−0.421	<0.001	−0.380	<0.001	−0.150(−0.217– −0.083)	<0.001
MMSE orientation score	−0.126	0.162	−0.154	0.093	−0.026(−0.057–0.004)	0.093
MMSE registration score	−0.237	0.008	−0.101	0.274	−0.013(−0.035–0.01)	0.274
MMSE recall score	−0.117	0.197	−0.050	0.587	−0.007(−0.031–0.017)	0.587
MMSE attention and calculation score	−0.294	0.001	−0.272	0.003	−0.060(−0.099– −0.021)	0.003
MMSE language score	−0.198	0.028	−0.222	0.015	−0.042(−0.076– −0.008)	0.015

Notes: ^aAdjusted for age, sex, education level,and HbA1c.

Abbreviations: NSE, neuron-specific enolase; MMSE, Minimum Mental State Examination.

Table 3 Associations Between Serum NSE Levels and MCI

	OR	95% CI	P-value
Model 1	1.428	1.220 −1.671	<0.001
Model 2	1.427	1.219–1.669	<0.001
Model 3	1.455	1.210–1.749	<0.001
Model 4	1.606	1.264–2.041	<0.001

Notes: Model 1: Crude model; Model 2: adjusted for age and sex; Model 3: Model 2 +duration of DM, HbA1c,education level,BMI, UA, TC, and fasting C-peptide; Model 4: Model 3+current smoking, habitual alcohol drinking, insulin use, metformin use, statins use, carotid atherosclerosis, diabetic nephropathy, and diabetic peripheral neuropathy.

Abbreviations: NSE, neuron-specific enolase; MCI, mild cognitive impairment; DM, diabetes mellitus; HbA1c, hemoglobin A1c; BMI, body mass index; UA, uric acid; TC, total cholesterol.

Table 4 Effects of Other Variables on the Relationship Between NSE and MCI

Characteristic	N	OR	95% CI	P-value for Interaction
Diabetes Duration (Years)
<10	50	1.426	1.127–1.804	0.934
≥10	74	1.445	1.166–1.791
HbA1c (%)
<7	22	1.307	0.896–1.908	0.745
7–9	47	1.424	1.110–1.827
≥9	55	1.567	1.172–2.094
Degree of DR
NPDR	80	1.415	1.171–1.710	0.831
PDR	44	1.469	1.104–1.953
DPN
No	97	1.441	1.199–1.731	0.993
Yes	27	1.443	1.021–2.040

Abbreviations: NSE, neuron-specific enolase; MCI, mild cognitive impairment; HbA1c, hemoglobin A1c; DR, diabetic retinopathy; NPDR, non-proliferative diabetic retinopathy; PDR, proliferative diabetic retinopathy; DPN, diabetic peripheral neuropathy.

Figure 1 ROC curves for NSE.

Note: Adjusted estimation: adjusted for age, sex, education level, and HbA1c.