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 AD ApoE

Abstract The neuropsychological research and ApoE genotype polymorphism analysis in mild cognitive impairment Postgraduate: Chen Xiao hong Advisors: Professor Wang Yin hua Tang Zhe Department of Neurology,the frist hospital,beijing University Mild cognitive impairment refers to the clinical condition between normal aging and AD in which persons have a memory impairment beyond that expected for age and education yet are not demented. Mild cognitive impairment is believed to be a high-risk condition for the development of clinically probable AD. These subjects are becoming the focus of many prediction studies and early intervention trials. Apolipoprotein E (ApoE) epsilon4 allele have been confirmed as risk factors for Alzheimer disease, patients with the epsilon4 allele may have an earlier age at onset of AD.The epsilon4 allele confers increased risk of AD in a dose-related manner. The presence of the ApoE epsilon4 allele is between in Alzheimer disease and normal elderly.the cognitive decline descent faster in carrier of epsilon4 than nocarrier risk of AD increased. In our study, we do the research of neuropsychology and ApoE genotype polymorphism in the patients of mild cognitive impairment,analysis the difference of normal elderly individuals. We

examined the neuropsychological test and ApoE phenotypes in a sample of 51 individuals: 23 with MCI, 28 with normanl controls. The neuropsychological test include MMSE, ADL, POD, FOM, RVR, DS,logical memory,geometry figures,cdt,delayed recall, CDR, GDS, HIS and CES-D. Results: MCI achieved significantly lower scores than healthy elderly in all cognitive function measures P <0.05~0.001 except ADL,POD performance and naming, especially in logical memory and semantic memory, similar with the earlier period of AD The ApoE genetype polymorphism examination shows that among the subjects who had normal cognitive function at baseline, apoe epsilon4 carriers showed a significantly greater decline (P < 0.001) in score on the MMSE compared with noncarriers. The proportion of apoe epsilon4 allele carriers of MCI was significantly higher than normal controls. Individuals with MCI appear to be at an increased risk of developing AD. Susceptible neuropsychological marker binding other biomarker, e.g. ApoE,can rise the sensibitity and Specificity in early diagnosis of AD. It is concluded that still no single marker of AD exists, which makes it necessary to rely on data from multiple sources in order to arrive at the best possible diagnosis of AD. Key words: Mild cognitive impairment Neuropsychology ApoE Alzheimer s disease

III 1 8 1 8 2 8 3 11 4 ApoE 12 5 13 15 18 24 25 34 1 34 2 ApoE 40 47 60 61 62 63

Alzheimer disease AD 60 [1] 65 4%~8% [2~7] 65 6.7% [8 9] 60 5 [10,11] 80 30% AD [7] 1990 400 AD 2050 1400 [12] 75% [13] 1989 1990 60 AD 3.46%~3.9% AD 64.7% 26.8% [14 15] 60 5.1% [16] 5 1.85 2000 2005 1.35 3.67 [17] 50%~70% AD 10 / [11] 70% 5 [18] 3.3 5~9 [19] AD AD 1998 AD 4 [12] AD 1190 [20] 2 50 2 1100 [21]

AD AD [22,23] AD AD AD 40 [24] AD AD AD AD [25] AD AD single-photon emission computed tomography SPECT AD, [26] AD [27] AD [28] AD [29,30] AD AD AD [31]

ApoE ApoE 4 AD AD 2 AD [32] AD 4 4 AD 4 2 4/4 10 [33] AD 4 94~98% AD 4 AD 5~10% [34] 4 AD 4 ApoE AD, [35] AD AD AD AD Cognitive impairment no dementia CIND 16.8% [5,36] 65 30% CIND [37] 2.8 [38] [39,40] AD

,, 3 0, 90 [41], 20 AD AD [42] - [43] Benign senescent forgefulness, BSF [44] Age-associated [45] memory impairment AAMI Aging-associated cognitive decline AACD [46] Aging-related cognitive decline ARCD [22,47] [5,48] Mild cognitive decline MCD [49] Mild neurocognitive decline MNI [50] Cognitive impairment no dementia CIND Mild cognitive impairment MCI

MCI ApoE 4 AD [51] AD AD 1 [12,52] MCI [22] 1.5 [53] MCI MCI MCI MCI [54] AD AD [55] MCI AD Petersen 53 10%~15% MCI 1 AD MCI 10 2/3AD MCI Johnson 56 2 40% MCI AD Mckelvey 57 3 53% Krasuki 58 4.5 100% AD 1%~2% [53,68] Morris 55 100% (Dementia Rating Scale CDR) 0.5 9.5

MCI AD MCI AD AD MCI MCI AD MCI AD MCI AD [59~63] [64] MCI [65] MCI MCI MCI AD MCI E Apolipoprotein E ApoE AD ApoE 4 MCI AD [66] Kurz ApoE 4 0.1 MCI 0.24 [67] MCI [68] 4 MCI MCI ApoE 4 AD

[60,69,70] Petersen [60] 66 MCI ApoE 4 4 MCI AD 24% 18 44% 36 55% 54 ApoE 4 MCI AD ApoE 4 ApoE 4 4/4 ApoE 4 2 ApoE 4 [71] Staehelin [72] ApoE MCI Bondi [73] 4 4 Caselli [74] 4/4 MCI ApoE ApoE 4 4 MCI AD MCI

2001 50 95 51 21 30 MCI Petersen MCI [53] 1 2 1.5 3 4 CDR 0.5 CT MRI Mini Mental State Examination MMSE 18-30 5ml 3.2% 1 9 4 ( )

1 MMSE [75] 11 30 MMSE 17 20 22 23 2 [76.77] ( Activities of Daily living ADL) basic ADL ADL Instrument ADL IADL ADL 16 3 Preffer (Pfeffer Outpatient Disability Questionnair POD) [78] POD 5 4 (Fuld Object Memory Evaluation FOM) [54] FOM 11 5 (Rapid Verbal Retrieve RVR) [80] 1 RVR 15 20 25 6 (Digit Span DS) [81]

DS 5 6 7 7 (Logical Memory) [82] 2 8 [83] 50-59 18.82 5.74 20.18 4.35 60-69 18.63 5.60 20.14 6.72 70-79 16.59 5.72 18.42 5.67 80-89 15.22 5.25 17.83 5.87 9 Clock Drawing Test CDT [84,85] CDT 2 10 (Delayed Recall) 30 11 (CDR) [86] CDR=0 12 (Global Deterioration Scale GDS) [87] 7 GDS 0-2 13 Hachinski Hachinski Ischemic Scale HIS [88]