Cerebral Small Vessel Disease is Associated with Mild Cognitive Impairment in Type 2 Diabetes Mellitus

Figures & data

Table 1 Clinical Characteristics of All Participants with T2DM

Variable	Total (n = 228)	Normal Cognitive Group (n = 104)	MCI Group (n = 124)	P value
Age, mean (SD), years	67.4±8.1	65.6±8.3	68.8±7.6	0.002*
Sex (male), n (%)	126 (55.3)	54 (51.9)	72 (58.1)	0.353
Education, median (IQR), years	11 (9–12)	12 (9–12)	9 (9–12)	0.059
Body mass index, median (IQR), kg/m^2	25.1 (23.3–26.8)	25.01 (23.4–27.2)	25.1 (22.9–26.7)	0.912
Current smoking, n (%)	40 (17.5)	14 (13.5)	26 (21.0)	0.138
Alcohol use, n (%)	27 (11.8)	9 (8.7)	18 (14.2)	0.194
Hypertension, n (%)	262 (71.2)	72 (69.2)	96 (77.4)	0.162
Duration of T2DM, median (IQR), year	10 (4.3–15.0)	10.0 (4.3–14.8)	10.0 (4.3–15.0)	0.674
Coronary heart disease, n (%)	54 (23.7)	20 (19.2)	34 (27.4)	0.147
History of stroke	136 (37.0)	32 (30.8)	57 (46.0)	0.019*
HbA1c, median (IQR), %	7.1 (6.5–7.9)	6.9 (6.3–7.6)	7.2 (6.5–8.1)	0.021*
TC, median (IQR), mmol/L	4.30 (3.59–5.29)	4.34 (3.55–5.37)	4.26 (3.61–5.20)	0.557
TG, median (IQR), mmol/L	1.38 (1.00–2.09)	1.31 (0.99–2.02)	1.48 (1.00–2.13)	0.585
HDL-C, median (IQR), mmol/L	1.07 (0.92–1.29)	1.08 (0.94–1.28)	1.06 (0.90–1.30)	0.785
LDL-C, median (IQR), mmol/L	2.73 (2.14–3.47)	2.76 (2.14–3.65)	2.72 (2.15–3.37)	0.560
Uric acid, mean (SD), umol/L	301.2±83.6	310.0±84.9	293.9±82.2	0.150
Serum tHcy, median (IQR), umol/L	13.8 (11.4–16.6)	12.9 (10.6–15.7)	14.5 (11.7–17.0)	0.016*

Note: *Denotes signifcance at a P value of <0.05.

Abbreviations: SD, standard deviation; IQR, interquartile range; MCI, mild cognitive impairment; T2DM, type 2 diabetes mellitus; TC, total cholesterol; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; tHcy, total homocysteine.

Table 2 Characteristics of Imaging Markers of CSVD of All Participants with T2DM

Variable	Total (n = 228)	Normal Cognitive Group (n = 104)	MCI Group (n = 124)	P value
Severity of dWMH, n (%)
Mild	113 (49.6)	75 (72.1)	38 (30.6)	<0.001*
Moderate	62 (27.2)	16 (15.4)	46 (37.1)
Severe	53 (23.2)	13 (12.5)	40 (32.3)
Severity of pWMH, n (%)
Mild	88 (38.6)	57 (54.8)	31 (25.0)	< 0.001*
Moderate	79 (34.6)	32 (30.8)	47 (37.9)
Severe	61 (26.8)	15 (14.4)	46 (37.1)
Severity of lacunes, n (%)
Absent	93 (40.8)	64 (61.5)	29 (23.4)	<0.001*
Mild	55 (24.1)	23 (22.1)	32 (25.8)
Extensive	80 (35.1)	17 (16.3)	63 (50.8)
No. of lobar CMBs, n (%)
0	168 (73.7)	82 (78.8)	86 (69.4)	0.137
1	36 (15.8)	11 (10.6)	25 (20.2)
≥2	24 (10.5)	11 (10.6)	13 (10.5)
No. of deep CMBs, n (%)
0	160 (70.2)	83 (79.8)	77 (62.1)	0.003
1	27 (11.8)	10 (9.6)	17 (13.7)
≥2	41 (18.0)	11 (10.6)	30 (24.2)
Severity of BG-EPVS, n (%)
Mild	95 (41.6)	65 (62.5)	30 (24.2)	<0.001*
Moderate	85 (37.3)	24 (23.1)	61 (49.2)
Severe	48 (21.1)	15 (14.4)	33 (26.6)
Severity of CSO-EPVS, n (%)
Mild	63 (27.6)	31 (29.8)	32 (25.8)	0.157
Moderate	93 (40.8)	46 (44.2)	47 (37.9)
Severe	72 (31.6)	27 (26.0)	45 (36.3)
Severity of total CSVD burden, n (%)
Mild	90 (39.5)	66 (63.5)	24 (19.4)	<0.001*
Moderate	48 (21.0)	20 (19.2)	28 (22.6)
Severe	90 (39.5)	18 (17.3)	72 (58.1)

Note: *Denotes significance at a P value of <0.05.

Abbreviations: MCI, mild cognitive impairment; CSVD, cerebral small vessel disease; dWMH, deep white matter hyperintensity; pWMH, periventricular white matter hyperintensity; CMBs, cerebral microbleeds; BG-EPVS, basal ganglia-enlarged perivascular spaces; CSO-EPVS, centrum semiovale-enlarged perivascular spaces.

Table 3 Analysis of the Association Between Different Imaging Markers of CSVD and MCI in Patients with T2DM

Variable	Model 1		Model 2		Model 3
	OR (95% CI)	P value	OR (95% CI)	P value	OR (95% CI)	P value
Severity of dWMH
Mild	Reference		Reference		Reference
Moderate	5.01 (2.47–10.15)	<0.001*	4.61 (2.24–9.48)	<0.001*	3.26 (1.43–7.41)	0.005*
Severe	5.87 (2.74–12.56)	<0.001*	5.34 (2.36–12.07)	<0.001*	2.15 (0.75–6.20)	0.157
Severity of pWMH
Mild	Reference		Reference		Reference
Moderate	2.33 (1.21–4.48)	0.011*	1.97 (0.99–3.91)	0.053	0.82 (0.35–1.93)	0.655
Severe	5.39 (2.54–11.46)	<0.001*	4.66 (2.07–10.49)	<0.001*	1.29 (0.45–3.78)	0.633
Severity of lacunes
Absent	Reference		Reference		Reference
Mild	2.88 (1.41–5.88)	0.004*	2.72 (1.27–5.83)	0.01*	2.31 (0.99–5.35)	0.051
Extensive	8.43 (4.14–17.15)	<0.001*	9.84 (4.20–23.09)	<0.001*	4.97 (1.79–13.81)	0.002*
No. of deep CMBs
0	Reference		Reference		Reference
1	1.97 (0.83–4.68)	0.127	1.98 (0.81–4.87)	0.137	2.11 (0.73–6.06)	0.166
≥2	3.34 (1.52–7.31)	0.003*	3.32 (1.47–7.49)	0.004*	1.62 (0.59–4.53)	0.359
Severity of BG-EPVS
Mild	Reference		Reference		Reference
Moderate	5.02 (2.62–9.61)	<0.001*	4.69 (2.39–9.22)	<0.001*	3.84 (1.81–8.13)	<0.001*
Severe	4.01 (1.86–8.64)	<0.001*	3.68 (1.63–8.31)	0.002*	1.43 (0.54–3.78)	0.467
Severity of total CSVD burden
Mild	Reference		Reference		-	-
Moderate	3.46 (1.63–7.38)	0.001*	3.29 (1.48–7.32)	0.004*	-	-
Severe	10.27 (5.06–20.84)	<0.001*	10.97 (4.94–24.34)	<0.001*	-	-

Note: *Denotes significance at a P value of <0.05. Results from binary logistic regression analysis. Model 1: adjusted for age and education. Model 2: adjusted for age, education, history of stroke, HbA1c and serum tHcy. Model 3: adjusted for age, education, history of stroke, HbA1c, serum tHcy and imaging markers of CSVD (ie, WMH, CMBs, lacunes, and EPVS).

Abbreviations: MCI, mild cognitive impairment; CSVD, cerebral small vessel disease; T2DM, type 2 diabetes mellitus; dWMH, deep white matter hyperintensity; pWMH, periventricular white matter hyperintensity; CMBs, cerebral microbleed; BG-EPVS, basal ganglia-enlarged perivascular spaces.

Figure 1 Distribution of mean values of MoCA scores according to WMH, lacunes, CMBs, EPVS and total CSVD burden. MoCA scores were negatively associated with the severity of WMH (both of dWMH and pWMH), lacunes, deep CMBs, BG-EPVS, and total CSVD burden ((A–E) respectively).

Notes: ^aKruskal–Wallis test; ^bJonckheere–Terpstra test.

Abbreviations: CSVD, cerebral small vessel disease; dWMH, deep white matter hyperintensity; pWMH, periventricular white matter hyperintensity; CMBs, cerebral microbleeds; BG-EPVS, basal ganglia-enlarged perivascular spaces; CSO-EPVS, centrum semiovale-enlarged perivascular spaces.