ApoE Apolipoprotein E E AD Alzhemier s Disease CDI Cognitive Decline Index 4 Apolipoprotein E 4 E 4 allele EDTA Ethylene Diamine Tetra-acetic Acid POC

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2 ApoE Apolipoprotein E E AD Alzhemier s Disease CDI Cognitive Decline Index 4 Apolipoprotein E 4 E 4 allele EDTA Ethylene Diamine Tetra-acetic Acid POCD Postoperative Cognitive Dysfunction PCR Polymerase Chain Reaction RFLP Restriction Fragment Length Polymorphism Z Z score 2

3 ApoE ApoE POCD 230 PCR-RFLP ApoE 9 20% 20% POCD Z Z ApoE POCD POCD POCD 59.1% 21.0% % 4 POCD POCD 4 3 E 3

4 Abstract Relationship between the apolipoprotein E polymorphism and cognitive dysfunction after cardiac operation. Objective To study the relationship between apolipoprotein E polymorphism and early cognitive dysfunction after cardiac operation. To investigate predictors of cognitive decline after cardiac operation. Methods Apolipoprotein E genotyping was performed on 230 patients undergoing coronary artery bypass grafting. Cognitive function was evaluated with a battery of nine neuropsychological tests before operation, at 1week and 3 months after operation. Cognitive decline was defined as a decline 20% decrement in 20% or more of completed tests. Change of z-based scores and cognitive decline index were used to evaluate the severity of cognitive decline. Multiple linear regression were used to investigate the relationship between ApoE genotype and cognitive decline and to investigate the predictors of POCD after cardiac operation. Results The incidence of cognitive decline was as high as 51.9% and 21.0% 1 week and 3 months after operation respectively. Cognitve decline assessed by both continuous Z score and categoric measures of cognitive deficit, was not significantly associated with either individual apolipoprotein E genotypes or categorization by the presence or absence of the 4 allele. The 4 allele was associated with poor baseline performance and the 3 allele had protective effect against the cognitive decline. Age, the usage of cardiopulmonary bypass, duration of endotracheal intubation were preditors of cognitive impairment after cardiac operation. The low neuropsychological tests scores 1 week after operation predicted poor cognitive function 3 months postoperatively. Conclusion This study suggests that age, the usage of cardiopulmonary bypass, duration of endotracheal intubation are preditors of cognitive impairment 1 week after operation. The low neuropsychological tests scores 1 week after operation predict poor cognitive function 3 months postoperatively. The 4 allele is not associated 4

5 with cognitive decline in one week after coronary artery bypass grafting. The 4 allele is associated with poor baseline performance and the 3 allele has protective effect against the cognitive decline 1 week after operation. keywords Coronary artery bypass grafting ApoE Cognitive Dysfunction 5

6 ApoE Bedford [1] 10-50% 44 [2] ISPOCD 1998 Moller [3] % 1 POCD, 3 9.9% 3.4% 2.8% POCD 65 POCD [4] POCD POCD POCD 2. 6

7 WAIS WMS WAIS POCD 1 digit symbol test 2 trail making test 3 grooved pegboard test WMS, visual reproduction test : 3 paried associate verbal learning 4 digit span test WAIS WMS [5] POCD POCD SD SD POCD 20% 20 4 POCD POCD POCD POCD 1. POCD [6-8] 7

8 [9-15] POCD POCD Blauth [16] POCD Stump [17] POCD 2. POCD POCD 1 Feldman [18] 2 Gruber Reed [19] POCD 2 Karhunen 20, Huge [21] Rasmussen [22] 35 POCD Kalman [23] 3 Bruce Bach [24] 500ppm 15ppm 4 (20%-30%) % ppm [27] 8

9 3. POCD [28 29] 1 [21] 4 [30] 1 [31] [29] Campbell [32] Riis [30] Hole [33] 4. POCD 1 Wollman [34] 3 6 [35 36] 2 Gruvstad Kebbon [37] Eckenchoff [38] [3 39] 9

10 3 [40] Weiskopf [39] 60g/L [41] [42] Prior [43 44] Drummon [45] 5 5 Sung [46] 5 5 Eger [47] 2 [48] [8] [49] Knill [50] POCD 10

11 Moller [3] POCD 25.8% 7 9.9% 3 POCD POCD POCD POCD POCD POCD POCD 50% 80% 20% 50% 10% 30% [ ] POCD POCD POCD POCD 1 Newman [55,66] POCD Alzheimer s 2 POCD Shaw [56] 7 61% 11

12 38% 18% 31% Andrew [57] POCD 6 McSPI [58] 3 POCD 1987 Shaw [56] % 2002 Vandijk [59] P= Stroobant [60] ( 7 ), 6 Diegeler [61] POCD 4 <20 o C CABG [62] 1-3 o C Grimm [63] [64,65] Newman [66]

13 >41 o C [67] [68] >38 o C 2001 Rees [69] Croughwell [70] 23% POCD Yoshitani [71] Sjvo2 Robson [72] 5 POCD <200 m Pugsley [73] Stump [17] Hammon 395 POCD Browndyke [74] POCD 6 [90] 13

14 316 CABG Murkin [91] CPB ph- Stephen CPB ph- ph Gilman [75] [76-78] POCD [79-81] MAP mmhg L min -1 m -2 [82] Newman [66] 237 MAP 50mmHg POCD MAP 50 mmhg MAP POCD 8. POCD 1 Lee [83] Blachly [84] [85] [86] 2 [87] 3 Katz [88] 25% 2% 4 [85 89] 5 14

15 POCD [92] [93] [94] POCD 2000 Van-Dijk [4] 256 POCD 22.5% 2 POCD, POCD 1997 Tardiff [95] E ApoE POCD POCD ApoE POCD 1 ApoE E ApoE 1973 shore ApoE kb 4 ApoE 37Kda 299 ApoE ApoE-E2/2 E3/3 E4/4 ApoE-E2/3 E2/4 E3/ ApoE 2 ApoE ApoE 4 3 ApoE E3/3 ApoE 2 ApoE % 88.4% 6.3% E3/3, 78.8% [96] ApoE ApoE 1 ApoE LDL ApoE ApoE 15

16 , LDL ApoE 4 2 [97] 2 ApoE ApoE ApoE [98] ApoE 3 HDL ApoE HDL LDL ApoE 4 ApoE ApoE T ApoE ApoB 2 3 Zannis [99] ApoE ApoE 2 ApoE 3 ApoE 4 ApoE 4 2 ApoE 4 ApoE ApoE 4 1 [97] ApoE-E2/ [98] ApoE 4 [100] 4 4 ApoE 4 LDL LDL 4 Albert ApoE 4 [102] 3 ApoE 4 16

ApoE MCI MCI AD ApoE 4 AD 4 MCI AD 4 AD MCI ApoE 23 MCI 28 MMSE (ADL) Preffer (POD) (FOM) (RVR) (DS) CDT (CDR) (GDS) Hachinski HIS (CES-D) ApoE MCI P

ApoE S99017123 ApoE MCI MCI AD ApoE 4 AD 4 MCI AD 4 AD MCI ApoE 23 MCI 28 MMSE (ADL) Preffer (POD) (FOM) (RVR) (DS) CDT (CDR) (GDS) Hachinski HIS (CES-D) ApoE MCI P 0.05~0.001 AD ApoE MCI 4 MCI AD ApoE