Thalamic Atrophy Plays a Crucial Role in the Effect of Asymptomatic Carotid Stenosis on Cognitive Impairment

Figures & data

Figure 1 Subcortical nuclei abnormalities between the ACS patients and controls.

Notes: (A) Vertex-wise shape analysis of the left and right thalamus between ACS patients and normal controls. Blue color or inward arrows indicate regional atrophy. Red color or outward arrows indicate regional expansion. Regional atrophy on the medial-dorsal aspects of the left and right thalamus is shown. TFCE-corrected, P<0.05. (B) Thalamus subfields segmentation. 3D T1-weighted images in the sagittal, coronal, and axial planes. (C) The group differences in the thalamic subfields volume at baseline. *Statistically significant after FDR correction.

Abbreviation: ACS, asymptomatic carotid stenosis.

Table 1 Baseline Characteristics and Cognitive Assessment Scores of Subjects with or Without ACS

Characteristics	Controls (n=31)	ACS Patients (n=29)	P value
Age, y	67±6	68±8	0.68
Sex, male (%)	20 (65)	23 (80)	0.21
Education, y	12±4	10±3	0.16
Current smoker (%)	8 (26)	10 (34)	0.46
Alcohol consumption (%)	9 (29)	3 (10)	0.07
Hypertension (%)	15 (48)	19 (66)	0.18
Diabetes mellitus (%)	15 (48)	10 (34)	0.28
Dyslipidemia (%)	8 (26)	10 (34)	0.46
Ischemic heart disease (%)	3 (10)	8 (28)	0.07
Peripheral arterial occlusive disease (%)	0 (0)	3 (10)	0.11
Fazekas score	2.1±1.2	2.0±1.6	0.79
Lacunar infarction (%)	7 (23)	8 (28)	0.66
Silent infarction (%)	3 (10)	4 (14)	0.70
Carotid variables
Main plaque side, left	–	12 (41)	–
Degree of stenosis (Doppler), %	–	86±11	–
PSVICA, cm/s	95±16	415±72	<0.001
EDVICA, cm/s	42±4	91±18	<0.001
PSVICA/PSVCCA	2±1	7±2	<0.001
CIMT, mm	0.6±0.1	1.2±0.1	<0.001
Clinical variables
Systolic BP, mmHg	129±15	136±17	0.08
Diastolic BP, mmHg	80±15	72±12	0.06
TG, mmol/L	1.2±0.8	1.4±0.5	0.03
TC, mmol/L	3.9±1.0	4.1±1.3	0.49
ApoB/ApoA1	0.7±0.2	1.0±0.3	<0.001
Cognitive assessment
Mini-Mental State Examination	29±1	28±1	0.006
Working memory
DST, forward	9±1	7±1	<0.001
DST, backward	6±1	4±1	<0.001
Processing time
TMT-A	26±10	52±12	<0.001
TMT-B	130±50	159±48	0.003
Verbal fluency
ANT	18±5	13±5	<0.001
BNT	56±4	47±8	<0.001
Executive time
Stroop-color	20±7	22±6	0.10
Stroop-word	24±8	30±9	0.003
Stroop-color word	33±11	53±15	<0.001

Note: Values are presented as the mean ± SD or n (%).

Abbreviations: ACS, asymptomatic carotid stenosis; BP, blood pressure; TG, triglyceride; TC, total cholesterol; ApoB, apolipoprotein B; ApoA1, apolipoprotein A1; PSV, peak systolic velocity; EDV, end-diastolic velocity; CCA, common carotid artery; ICA, internal carotid artery; CIMT, carotid intima-media thickness; DST, digit span test; TMT, trail-making test; ANT, animal naming test; BNT, Boston naming test.

Table 2 Global Measurements and Subcortical Nuclei Volumes in ACS Patients and Controls at Baseline

Volume, cm^3	Controls (n=31)	ACS Patients (n=29)	Significance		Effect Size
			F	P	Cohen’s d
Global
Intracranial volume	1482±177	1434±140	4.555	0.037	0.479
Gray matter	569±73	538±68	0.798	0.376	0.468
White matter	519±72	493±63	0.521	0.474	0.407
Cerebrospinal fluid	588±71	561±75	0.119	0.732	0.421
Subcortical
Thalamus
Left	6.5±0.7	6.0±0.7	7.412	0.009*	0.652
Right	6.3±0.7	5.7±0.8	7.826	0.007*	0.699
Caudate
Left	3.2±0.4	3.0±0.4	6.398	0.015	0.607
Right	3.3±0.4	3.0±0.6	5.078	0.029	0.440
Putamen
Left	4.5±0.9	4.2±0.5	4.088	0.049	0.442
Right	4.6±0.7	4.1±1.0	5.044	0.029	0.426
Pallidum
Left	1.6±0.5	1.4±0.4	1.390	0.244	0.289
Right	1.6±0.4	1.4±0.4	2.668	0.109	0.421
Hippocampus
Left	3.7±0.4	3.6±0.6	2.563	0.116	0.290
Right	4.1±0.5	3.8±0.6	5.753	0.020	0.544
Amygdala
Left	0.8±0.3	0.8±0.3	0.009	0.927	−0.077
Right	1.2±0.3	1.0±0.3	0.239	0.627	0.266
Nucleus Accumbens
Left	0.5±0.1	0.4±0.1	0.463	0.499	0.250
Right	0.3±0.1	0.3±0.1	0.995	0.323	0.137

Notes: Adjusted for age, sex, education, intracranial volume, hypertension, diabetes, coronary heart disease, and smoking. *Statistically significant after FDR correction.

Abbreviation: ACS, asymptomatic carotid stenosis.

Table 3 Correlations of Morphometric Abnormalities with Clinical Variables, Cognitive Scores, and Carotid Variables in ACS Patients and Controls

Group	Index	Subcortical Nuclei Volume				Subcortical Nuclei Shape Deformation				Thalamic Subregion Volume
		L_Thalamus		R_Thalamus		L_Thalamus		R_Thalamus		L_Mediodorsal		R_Mediodorsal
		r	P	r	P	r	P	r	P	r	P	r	P
ACS Patients	ApoB/ApoA1	−0.596	0.001	−0.637	<0.001	−0.402	0.031	−0.545	0.002	−0.410	0.027	−0.529	0.003
	Working memory	0.032	0.871	0.209	0.276	−0.086	0.657	−0.045	0.817	−0.110	0.570	0.068	0.728
	Processing time	−0.463	0.012	−0.598	0.001	−0.403	0.030	−0.460	0.012	−0.371	0.047	−0.304	0.109
	Verbal fluency	0.162	0.402	0.335	0.075	0.285	0.134	0.267	0.161	0.224	0.242	0.405	0.029
	Executive time	−0.474	0.009	−0.539	0.003	−0.312	0.100	−0.359	0.056	−0.151	0.434	−0.449	0.014
	CIMT	−0.512	0.004	−0.561	0.002	−0.390	0.037	−0.430	0.020	−0.468	0.010	−0.451	0.014
Controls	ApoB/ApoA1	0.005	0.980	0.021	0.911	−0.036	0.845	−0.088	0.637	−0.059	0.752	0	0.999
	Working memory	0.045	0.810	0.097	0.603	−0.073	0.696	−0.233	0.207	−0.233	0.208	0.070	0.709
	Processing time	0.182	0.327	0.116	0.535	−0.205	0.268	0.044	0.814	0.277	0.131	0.121	0.518
	Verbal fluency	−0.096	0.607	−0.024	0.898	−0.415	0.020	−0.324	0.076	−0.287	0.118	−0.061	0.746
	Executive time	0.038	0.841	−0.024	0.897	0.118	0.527	0.239	0.196	0.303	0.098	−0.034	0.856
	CIMT	−0.274	0.136	−0.213	0.249	0.100	0.593	−0.041	0.827	0.075	0.69	0.112	0.549

Notes: Spearman correlation analyses. Compound scores for each cognitive domain were calculated by averaging the z-scores of all individuals.

Abbreviations: L, left; R, right; CIMT, carotid intima-media thickness; ApoB/ApoA1, apolipoprotein B/apolipoprotein A1 ratio; ACS, asymptomatic carotid stenosis.

Table 4 Volumes of Thalamic Subregions in ACS Patients and Controls at Baseline

Volume, mm^3	Controls (n=31)	ACS Patients (n=29)	Significance		Effect Size
			F	P	Cohen’s d
Anteroventral (AV)
Left	104±16	103±15	0.009	0.923	0.048
Right	109±15	111±19	0.112	0.739	−0.182
Later posterior (LP)
Left	98±15	97±16	0.056	0.814	−0.012
Right	91±13	87±17	0.046	0.831	0.127
Centromedian (CM)
Left	209±20	205±22	4.264	0.044	0.186
Right	196±19	199±23	0.230	0.634	−0.233
Mediodorsal (MD)
Left	892±92	818±113	7.707	0.008*	0.708
Right	870±73	799±103	10.678	0.002*	0.755
Ventral lateral (VL)
Left	1211±114	1183±107	4.380	0.041	0.289
Right	1197±108	1169±132	1.249	0.269	0.114
Pulvinar (PU)
Left	1433±117	1350±178	5.294	0.026	0.491
Right	1416±136	1444±329	0.626	0.432	−0.228

Notes: Adjusted for age, sex, education, intracranial volume, hypertension, diabetes, coronary heart disease, and smoking. *Statistically significant after FDR correction.

Abbreviation: ACS, asymptomatic carotid stenosis.

Figure 2 Mediation analysis for associations among carotid stenosis, lipid/metabolic variables, thalamic volume, and cognition at baseline.

Notes: The standardized β coefficients were derived from the mediation models. Values are standardized path coefficients with 95% Cis in parentheses. (A) Association of CIMT, thalamic volume, and executive function (time). (B) Association of ApoB/ApoA1 ratio, CIMT and right thalamus volume.

Abbreviations: CIMT, carotid intima-media thickness; ApoB/ApoA1, apolipoprotein B/apolipoprotein A1 ratio.

Figure 3 The changes in cognitive assessment scores and thalamic subfield volumes in ACS patients 6 months after CEA.

Notes: (A) Cognitive scores of processing speed and executive function significantly improved 6 months after CEA; *P<0.01, Bonferroni corrected. The error bars represent the standard errors of the mean. (B) Changes in the left and right thalamic subfield volumes after CEA; *P<0.05.

Abbreviations: CEA, carotid endarterectomy; ACS, asymptomatic carotid stenosis; MMSE, Mini-Mental State Examination; AV, anteroventral; LP, later posterior; CM, centromedian; MD, mediodorsal; VL, ventral lateral; PU, pulvinar.