1. MILD COGNITIVE IMPAIRMENT IN PATIENTS WITH CAROTID DISEASE Irena Martinic Popovic 1, M.D, Arijana Lovrencic-Huzjan 1, M.D, Ph. D, Ana-Maria Simundic 2, Ph.D, Vida Demarin 1, M.D, Ph.D University Department of Neurology 1 and Clinical Institute of Chemistry 2, “Sestre milosrdnice” University Hospital Center Zagreb, Croatia Referal Centre for Neurovascular Disorders of Croatian Ministry of Health 1 Referal Centre for Neurovascular Disorders of Croatian Ministry of Health Referal Centre for Headaches of Croatian Ministry of Health 1 Referal Centre for Headaches of Croatian Ministry of Health

2. Conflict of Interest Disclosure Irena Martinic Popovic, M.D. Arijana Lovrencic-Huzjan, M.D, Ph.D Ana-Maria Simundic, Ph.D Vida Demarin, M.D, Ph.D Have no real or apparent conflicts of interest to report.

3. CAROTID DISEASE Risk factor for TIA/stroke Each 10% increase in the degree of CS 26% increase in risk of TIA/stroke “Severe carotid disease” advanced stenosis (>70%) and /or occlusion of the internal carotid artery (ICA) – ICA s/o Associated with silent cerebral infarctions

4. Narrowing or occlusion of carotid arteries (ICA) State of increased risk for cerebrovascular incident Increased risk for cognitive decline ASYMPTOMATIC CAROTID DISEASE

5. ASYMPTOMATIC CAROTID DISEASE & VASCULAR RISK associated with multiple VRFs (arterial hypertension, diabetes, hyperlipoproteinaemia, increased body-mass index (BMI) and cigarette smoking) VRFs the risk for atherosclerotic disease and for brain injury VRFs detrimental effects on cognitive abilities

7. THE AIMS OF THE STUDY Besides standard MMSE, we used MoCA to investigate the association of ICA s/a and cognition in asymptomatic ICA s/o Assessment of predicitive value of ICA s/o and vascular risk factors with respect to performance on cognitive domains (covered by MoCA)

8. Clinical history Data on vascular risk factors Brain CAT scan (patients) Color Doppler Flow Imaging (CDFI) of carotid arteries Cognitive testing (MMSE and MoCA) STUDY PROTOCOL

9. Variable PATIENTS (n=70) CONTROLS (n=70) p Age/years (median, min-max)67.5 (43 -85)67.0 (42-82) 0.675** Females (proportion, n)0.37 (26)0.44 (31)0.640 Education/years (mean, SD)11.58 (2.45)11.78 (3.24)0.681 Hypertension (proportion, n)0.83 (58)0.81 (57)0.959 Diabetes (proportion, n)0.26 (18)0.29 (20)0.867 Hyperlipidaemia (proportion, n)0.74 (52)0.41 (29)0.009* Coronary disease (proportion, n)0.39(27)0.27 (19)0.356 Current smoking (proportion, n)0.23 (16)0.29 (20)0.995 Ex-smoking (proportion, n)0.31 (22)0.19 (13)0.238 Obesity (proportion, n)0.23 (16)0.19 (13)0.792 DEMOGRAPHIC & VASCULAR RISK DATA * sign. difference (z-test) ** t-test

10. INCLUSION CRITERIA PATIENTS: Asymptomatic (stroke/TIA free) patients; right-handed CAT scan normal Diagnosed with severe ICA stenosis (>70%) or with ICA occlusion CONTROLS Asymptomatic (stroke/TIA free) patients; right-handed Without severe ICA stenosis (>70%) or with ICA occlusion EXCLUSION CRITERIA BOTH PATIENTS AND CONTROLS: A history or presence of stroke/TIA Dementia (DSM-IV) Depressive disorder (DSM-IV) Inability to perform the cognitive testing CRITERIA FOR THE STUDY

11. CAROTID ARTERIES ASSESSMENT COLOR DOPPLER FLOWCOLOR DOPPLER FLOW IMAGING (CDFI) IMAGING (CDFI) (10 MHz transducer) - morphological changes of the carotid arteries – the degree of stenosis (B mode) impairment of carotid hemodynamics (M mode)

12. Proportion (n) PATIENTS Left ICA advanced stenosis0.38 (27) Right ICA advanced stenosis0.4 (28) Billateral ICA advanced stenosis0.04 (3) Left ICA occlusion0.03 (2) Right ICA occlusion0.07 (5) Billateral ICA occlusion0.03 (2) Left ICA occlusion and right ICA advanced stenosis 0.03 (2) Right ICA occlusion and left ICA advanced stenosis 0.01 (1) CAROTID PATHOLOGY: THE SIDE & THE DEGREE OF STENOSIS

13. MMSE score < 24 proportion (n) MoCA score ≤ 26 proportion (n) P Patients0.185 (13)0.871 (61)P < 0.001* Controls0.086 (6)0.271 (19)P = 0.008* Proportion of abnormal scores (indicating cognitive impairment) in patients and controls when tested by MMSE and MoCA * z-test COGNITIVE IMPAIRMENT: patients vs. controls

14. PATIENTS (n=70) CONTROLS (n=70) p Median Q1 Q3 MoCA (total score) 23 20 25 24.5 23 26<0.001** MMSE 27.5 25 29 27 26 280.575 Patients and controls did not differ significantly in MMSE scores. Median total MoCA scores were significantly lower in patients. TOTAL COGNITIVE TESTING SCORES: patients vs. controls

15. MoCA subtests scores PATIENTS (n=70) CONTROLS (n=70) P Median Q1 Q3 VSE*3 2 44 3 50.018** Naming3 3 3 0.662 Attention5 4 6 0.723 Language2 2 3 0.204 Abstraction1 1 12 1 2<0.001** Delayed recall2 0 33 2 4<0.001** Orientation6 6 6 0.451 MoCA SUBTESTS SCORES: patients vs. controls

16. ParameterUnivariate regression analysis Multivariate regression analysis OR (95% CI)P P Age0.87 (0.794 - 0.955)0.00340.86 (0.780 - 0.956) 6.41 (1.277 - 32.220) 0.004 0.024 Gender1.85 (0.482 - 7.152)0.3682 Hypertension0.80 (0.147 - 4.343)0.7960 Diabetes6.00 (1.458 - 24.687)0.0130 Hyperlipidemia3.56 (0.418 - 30.271)0.2453 Coronary disease 1.73 (0.449 - 6.638)0.4262 Smoking1.26 (0.552 - 2.8790.5824 Obesity0.95 (0.672 - 1.352)0.7907 Left ICA s/o1.18 (0.415 - 3.339)0.7582 Right ICA s/o0.96 (0.335 - 2.752)0.9391 Regression model for prediction of cognitive impairment (defined as MoCA cutoff score ≤26) with respect to vascular risk factors and the side of ICA s/o COGNITIVE IMPAIRMENT & VASCULAR RISK

17.  Patients with ICA s/o AND diabetes performed worse (p <0.001) at delayed recall  Patients with ICA s/o AND increased BMI performed worse at delayed recall (p=0.02)*  Patients with diabetes had lower attention (p=0.065)* and naming (p=0.06)* MoCA subtests scores  Hyperlipemic patients scored worse at attention (p=0.064)*  Patients with hypertension scored lower at naming MoCA subtests (p=0.04)*  The side of stenosis was not associated with lower performance on MoCA subtests COGNITIVE IMPAIRMENT & VASCULAR RISK * Differences not statistically significant

18. No neuroimaging in controls ? Influence of potential cofounders (antihypertensive drugs, statin therapy...) not analyzed ? Duration of exposure to vascular risk factors ? What were THE LIMITATIONS OF OUR STUDY?

19. Patients with severe carotid disease often do have subtle cognitive abnormalities MoCA is far more suitable for cognitive assessment in patients with carotid disease than MMSE Decreased median MoCA scores in controls is probably due to the presence of vascular risk and likely to the silent brain injury (no neuroimaging was done in controls!) What are OUR PRINCIPAL FINDINGS?

20. Patients with severe carotid disease had impaired multiple cognitive domains when MoCA subtests were analyzed:... VISUOSPATIAL, EXECUTIVE, ATTENTION... Our results are similar to those of other researchers (who mostly used extensive neuropsychological testing batteries!) What are OUR PRINCIPAL FINDINGS?

21. Decreased total MoCA scores in older patients with ICA s/o Decreased total MoCA scores in diabetic patients with carotid disease in line with previous research (diabetes is well known indipendent factor for cognitive decline) What are OUR PRINCIPAL FINDINGS?

22. Stroke/TIA free patients with advanced carotid disease are routinely considered asymptomatic Cognitive impairment in patients with ICA s/o is not questioned during routine clinical visits The use of MoCA could facilitate early recognition of cognitive problems in patients with carotid disease What can we CONCLUDE ?

23. THANK YOU!