瘦驼 发表于 2010-08-07 17:10 亲爱的，去超市是这个路口右转吧？领导问我。说来惭愧，虽然挺着个大肚子，我家领导仍然牢牢掌握着座驾的方向盘。论车技，领导这个飞车党远远在我之上。可是，我们几乎天天去这个超市，更何况昨天你问过我同样的问题啊。 直行，我昨天好像说过的吧？我几乎都有点Deja vu的感觉了。 哼！别怪我！怪你孩子去吧，怀个孩子傻三年，我妈说的。 不会啊，当妈这事儿这么不容易，按说脑子应该越用越好使才对嘛。 不听你的瞎理论，我只相信数据。 领导的科学素养让我感到很欣慰。不过，为了给孩子洗刷罪名，还真得拿出过硬的数据来。于是，回家之后我立即展开了文献查询的工作。 一查不要紧，这话题居然是跨文化的，英文里叫baby brain，几项调查发现高达50%-80%的妈妈抱怨自己的脑子自打怀孕以后就不好使了，最常见的症状包括记忆力下降，其次还有阅读困难和注意力减退。其中记忆力下降是最显著的问题，医生甚至专门用怀孕健忘症命名它。科学家还发现，越是职业女性，越是学历高，这种抱怨就越多。 难道怀孕傻三年是真的？可不敢这么着急下结论，因为记忆力下降这种事儿与太多的生活因素相关，不一定就是怀孕引起的。而且，有时候自己的感觉也是不太靠谱的。果然，美国科学家格林Laura M. Glynn在今年一月份的《神经心理内分泌学》PSYCHONEUROENDOCRINOLOGY杂志上发表了一篇名为《生出一个新脑》的文章。在这篇自称有史以来最翔实的探究人类怀孕分娩与记忆力之间关系的论文中，格林找到了254名孕产妇和48名未曾生育的女性，分阶段测试了她们的记忆力。格林发现，孕产妇和对照组女性在记数列和记人脸的测试中不分高下，但是孕产妇在听声音记词对组的测试中略处下风。这个不温不火的结果反而可能会让一些科学家感到十分诧异，因为孕产妇身体的变化实在是太大了，尤其是体内的激素水平更是过山车一般。比如，孕晚期女性体内的雌二醇含量是她在未怀孕时月经周期中最高水平的30倍；同时，她体内的可的松已经相当于一个抑郁症病人的水平。这仅仅是冰山之一角，更多激素的变化我就不一一罗嗦了。这些激素为胎儿的生长乃至分娩提供了必要的物质保障。但是对于准妈妈而言，就未必都是这么美妙了。在这些激素的影响下，孕妇的脑容量甚至都会下降伦敦汉默史密斯Hammersmith医院的奥特利基Angela Oatridge博士和同事们发现，妇女的脑容量在怀孕期间会降低4%。 这一切让神经生物学家们比较挠头，因为人并不是他们理想的研究对象。相比而言，他们更热爱小老鼠。小老鼠的表现更让支持怀孕傻三年的人跌碎眼镜。大多数的研究发现与处女老鼠相比，怀孕的、哺乳期的甚至断奶以后的老鼠在记忆和压力耐受方面全面飘红。美国里奇蒙德大学University of Richmond以赫斯特Naomi Hester为首的研究团队进行的一项未发表研究中，他们通过三轮实验发现，大鼠妈妈捉板球的速度比未曾交配的大鼠快5倍。而在经典的十字迷宫测试中，妈妈老鼠在明亮分支中待的时间比处女老鼠长得多，对于喜欢黑暗的老鼠来说，这意味着她们更不那么焦虑。来自加拿大不列颠哥伦比亚大学的伽利雅Liisa A.M. Galea团队的研究更加细致，他们发现大鼠妈妈在第一胎断奶后，大脑中负责记忆的海马体中神经树突的数量的确下降了，而第二次产仔的时候就增加到高于做姑娘时候的水平。但不论是初产鼠还是经产鼠，它们跑迷宫的本事都高于处女鼠，甚至初产鼠表现更好些。对此，伽利雅解释说，初产鼠海马体中神经树突数量的下降是一种再造过程，相当于修剪。 其实这些结果也同样不令人惊讶，因为相比优哉游哉的小姑娘，鼠妈妈们面临更多生活的挑战，它必须牢记那些地方能找到吃的，必须更熟练的捕食，更迅速的返回巢穴，更好的喂养和保护自己的宝宝们。如果不升级装备，它就不能很好的完成任务。 当然，与老鼠相比，人类女性的脑更复杂，在成为妈妈之前已经经历过无数的复杂挑战，这或许是人类妈妈与人类姑娘相比并没有表现出全面超越的原因。当然，与老鼠相比，人类妈妈可能会面对更多的困扰和烦恼，不仅来自身体和生理，更多来自文化和社会。我相信如果各位等待或者已经转正的爸爸们更多的帮家里的领导分担一些，她们就不会那么经常的抱怨自己的脑子不够使了。 呃，似乎我也该面壁反省反省去了。 本文见于新京报新知周刊，发表时有删改 感谢资深奶爸云无心提供文献查询的帮助！ 参考文献 Motherhood mitigates aging-related decrements in learning and memory and positively affects brain aging in the rat Jessica D. Gatewooda, Melissa D. Morgana, Mollie Eatona, Ilan M. McNamaraa, Lillian F. Stevensa, Abbe H. Macbetha, Elizabeth A.A. Meyera, Lisa M. Lomasa, Frederick J. Kozuba, Kelly G. Lambertb,and Craig Howard Kinsley Brain Research Bulletin Volume 66, Issue 2, 30 July 2005, Pages 91-98 First reproductive experience persistently affects spatial reference and working memory in the mother and these effects are not due to pregnancy or mothering alone Jodi L. Pawluski, Brandy L. Vanderbyl, Kelsey Ragan, Liisa A.M. Galea Behavioural Brain Research 175 (2006) 157165 Motherhood Induces and Maintains Behavioral and Neural Plasticity across the Lifespan in the Rat Craig Howard KinsleyMassimo BardiKate KarelinaBrandi Rima Lillian ChristonJulia FriedenbergGarrett Grif?n Arch Sex Behav (2008) 37:4356 Reproduction-Induced Neuroplasticity: Natural Behavioural and Neuronal Alterations Associated with the Production and Care of Offspring Craig H. Kinsley and Kelly G. Lambert Journal of Neuroendocrinology 20, 515525 Changes in anxiety and cognition due to reproductive experience: A review of data from rodent and human mothers Abbe H. Macbeth , Victoria N. Luine Neuroscience and Biobehavioral Reviews 34 (2010) 452467 Giving birth to a new brain: Hormone exposures of pregnancy in?uence human memory Laura M. Glynn Psychoneuroendocrinology (2010) Single or multiple reproductive experiences attenuate neurobehavioral stress and fear responses in the female rat Jennifer Wartella, Elizabeth Amorya, Abbe H. Macbetha, Ilan McNamara, Lillian Stevens,Kelly G. Lambert, Craig H. Kinsleya, Physiology Behavior 79 (2003) 373 381
研究进展： http://www.bioon.com/biology/neuroscience/449629.shtml ACER：青少年酗酒损害前瞻记忆力 知识发现平台： http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/edit_b.cgi Start A-Literature C-Literature B-list Filter Literature A-query: Memory Processing C-query: Drinking Affects The B-list contains title words and phrases (terms) that appeared in both the A and the C literature. 19 articles appeared in both literatures and were not included in the process of computing the B-list but can be viewed here . The results of this search are saved under id # 16927 and can be accessed from the start page after you leave this session. There are 502 terms on the current B-list ( 106 are predicted to be relevant), which is shown ranked according to predicted relevance. The list can be further trimmed down using the filters listed in the left margin. To assess whether there appears to be a biologically significant relationship between the AB and BC literatures for specific B-terms, please select one or more B-terms and then click the button to view the corresponding AB and BC literatures. Use Ctrl to select multiple B-terms. job id # 16927 started Wed Aug 4 03:50:44 2010 Max_citations: 50000 Stoplist: /var/www/html/arrowsmith_uic/data/stopwords_pubmed Ngram_max: 3 16927 Search ARROWSMITH A A_query_raw: Memory Processing Wed Aug 4 03:57:31 2010 A query = Memory Processing started Wed Aug 4 03:57:31 2010 A query resulted in 17488 titles 16927 Search ARROWSMITH C C_query_raw: Drinking Affects Wed Aug 4 03:57:59 2010 C: Drinking Affects 5175 A: pubmed_query_A 17488 C_query_raw: Drinking Affects Wed Aug 4 03:57:59 2010 AC: ( Memory Processing ) AND ( Drinking Affects ) 19 C: Drinking Affects 5175 A: pubmed_query_A 17488 AC: ( Memory Processing ) AND ( Drinking Affects ) 19 C query = Drinking Affects started Wed Aug 4 03:58:00 2010 C query resulted in 5175 titles A AND C query resulted in 19 titles 7656 B-terms ready on Wed Aug 4 03:59:45 2010 Sem_filter: Genes Molecular Sequences, and Gene Protein Names 502 B-terms left after filter executed Wed Aug 4 04:03:16 2010 B-list on Wed Aug 4 04:03:57 2010 1 ltp 2 5-ht1a 3 5-ht4 4 toll receptor 5 apoe 6 ca1 7 cb1 8 metabolic syndrome 9 p300 10 glutamate receptor 11 d2 receptor gene 12 drb1 13 quantitative trait loci 14 leptin 15 apolipoprotein e 16 opioid receptor 17 rem 18 single nucleotide polymorphism 19 neurotrophin 20 promoter polymorphism 21 c fos 22 niti 23 ca3 24 neuropeptide y 25 gaba a receptor 26 caspase-3 27 adhd 28 neuropeptide 29 pup 30 angiotensin receptor 31 gaba a 32 fos 33 map kinase 34 maze 35 transgene expression 36 epilepsy 37 dopamine receptor 38 gabaa 39 transgene 40 clock 41 amylin 42 diazepam binding inhibitor 43 cd8 44 tachykinin 45 il-2 46 calbindin 47 dopamine d2 receptor 48 tactile 49 race 50 emotionality 51 statin 52 alpha7 53 cue 54 transcription factor 55 alcohol enhancement 56 tea 57 olfactory 58 alzheimer disease 59 anxiety 60 dsm 61 glucocorticoid receptor 62 synapsin 63 synapsin i 64 brain volume 65 ifn gamma 66 npy 67 operant 68 protein kinase c 69 spike 70 5-ht 71 gene environment 72 pet 73 p38 74 brain protein 75 flavor 76 lobe 77 fuzzy 78 bcl-2 79 nf kappab 80 estrogen receptor 81 galanin 82 trait 83 rna binding protein 84 alcohol dehydrogenase 85 ethanol induced 86 nmdar 87 parkinson disease 88 lymphokine 89 calcium channel 90 neurotensin 91 il-6 92 tbi 93 meta 94 life span 95 pha 96 pcb 97 map 98 fear 99 na k atpase 100 receptor gene 101 huntington disease 102 erk 103 ifn 104 blind 105 iddm 106 bfgf
http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/edit_b.cgi?refresh=TID=5583 Start A-Literature C-Literature B-list Filter Literature A-query: memory AND CETP C-query: Dementia The B-list contains title words and phrases (terms) that appeared in both the A and the C literature. 2 articles appeared in both literatures and were not included in the process of computing the B-list but can be viewed here . The results of this search are saved under id # 5583 and can be accessed from the start page after you leave this session. There are 18 terms on the current B-list ( 9 are predicted to be relevant), which is shown ranked according to predicted relevance. The list can be further trimmed down using the filters listed in the left margin. To assess whether there appears to be a biologically significant relationship between the AB and BC literatures for specific B-terms, please select one or more B-terms and then click the button to view the corresponding AB and BC literatures. Use Ctrl to select multiple B-terms. Rank Prob B-term 10.93cetp 20.92genotype cognitive 30.91cognitive function 40.91related cognitive 50.90cognitive change 60.89age related cognitive 70.73association cetp 80.72genotype cognitive function 90.70cognitive 100.56genotype 110.50cognitive function or 120.44age related 130.05age 140.00association 150.00related 160.00function 170.00or 180.00change Restrict by semantic categories? Start A-Literature C-Literature B-list Filter Literature AB literature B-term BC literature memory AND CETP cetp Dementia 1: No association of CETP genotype with cognitive function or age-related cognitive change.2007 Add to clipboard 1: Association of CETP polymorphisms with the risk of vascular dementia and white matter lesions.2009 Add to clipboard 2: CETP polymorphisms influence cholesterol metabolism but not Alzheimer's disease risk.2008 Add to clipboard 3: The cholesteryl ester transfer protein (CETP ) gene and the risk of Alzheimer's disease.2007 Add to clipboard 4: Cholesteryl ester transfer protein (CETP ) polymorphism modifies the Alzheimer's disease risk associated with APOE epsilon4 allele.2006 Add to clipboard 以下是发现的相关知识概念（非相关文献）比较少，科研人员可以采用相关的关键词进行检索和分析。 A-query: memory AND CETP C-query: Dementia job id # 5732 started Sun Jan 17 04:38:27 2010 Max_citations: 50000 Stoplist: /var/www/html/arrowsmith_uic/data/stopwords_pubmed Ngram_max: 3 5732 Search ARROWSMITH A A_query_raw: memory AND CETPSun Jan 17 04:38:42 2010 A query = memory AND CETP started Sun Jan 17 04:38:43 2010 A query resulted in 3 titles 5732 Search ARROWSMITH C C_query_raw: dementia Sun Jan 17 04:39:19 2010 C: dementia 110543 A: pubmed_query_A 3 AC: ( memory AND CETP ) AND ( dementia ) 2 C query = dementia started Sun Jan 17 04:39:19 2010 C query resulted in 50000 titles A AND C query resulted in 2 titles 18 B-terms ready on Sun Jan 17 04:39:47 2010 B-list on Sun Jan 17 04:40:10 2010 1 cetp 2 genotype cognitive 3 cognitive function 4 related cognitive 5 cognitive change 6 age related cognitive 7 association cetp 8 genotype cognitive function 9 cognitive 10 genotype 11 cognitive function or 12 age related 13 age 14 association 15 related 16 function 17 or 18 change http://www.gopubmed.org/web/gopubmed/1?WEB011ngmf2w487fI1pI1I00f01000j10040001rl memory AND CETP AND Dementia 3 documents semantically analyzed top author statistics documents Title: Association of a functional polymorphism in the cholesteryl ester transfer protein ( CETP ) gene with memory decline and incidence of dementia. PMID: 20068209 Related Articles Authors: Sanders, Amy E , Wang, Cuiling , Katz, Mindy , Derby, Carol A , Barzilai, Nir , Ozelius, Laurie , Lipton, Richard B Journal: JAMA , Vol. 303 (2): 150-8 , 2010 Abstract: CONTEXT: Polymorphisms in the cholesteryl ester transfer protein ( CETP ) gene have been associated with exceptional longevity and lower cardiovascular risk, but associations with memory decline and dementia risk are unclear. OBJECTIVE: To test the hypothesis that a single-nucleotide polymorphism (SNP) at CETP codon 405 ( isoleucine to valine V405; SNP rs5882) is associated with a lower rate of memory decline and lower risk of incident dementia, including Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study comprising 608 community-dwelling adults without dementia aged 70 years or older from the Einstein Aging Study with CETP genotype available. Fifteen participants with prevalent dementia were excluded, and 70 without follow-up--63 lost to follow-up and 7 new to the study--were excluded from the Cox proportional hazards model, which included 523 participants in the analysis. Standardized neuropsychological and neurological measures were administered annually from 1994-2009. Linear mixed-effects models adjusted for sex, education, race, medical comorbidities, and apolipoprotein ( APOE ) epsilon4 examined associations of V405 genotype with longitudinal performance on cognitive tests of episodic memory (Free and Cued Selective Reminding Test , possible scores of 0-48), attention (Digit Span), and psychomotor speed (Digit Symbol Substitution). The V405 genotype was the main predictor of incident dementia or AD in similarly adjusted Cox proportional hazards models with age as the time scale. MAIN OUTCOME MEASURES: Memory decline and incident dementia. RESULTS: Valine allele frequency was 43.5%. A total of 40 cases of incident dementia occurred during follow-up (mean , 4.3 years). Compared with isoleucine homozygotes, valine homozygotes had significantly slower memory decline on the FCSRT (0.43 points per year of age for isoleucine; 95% confidence interval , -0.58 to -0.29 vs 0.21 points per year of age for valine; 95% CI, -0.39 to -0.04; difference in linear age slope, 0.22; 95% CI, 0.02 to 0.41; P = .03) and no significant differences on the Digit Span or Digit Symbol Substitution tests. Valine homozygotes also had lower risk of dementia (hazard ratio, 0.28; 95% CI, 0.10-0.85; P = .02) and AD (hazard ratio, 0.31; 95% CI, 0.10-0.95; P = .04). CONCLUSION: This preliminary report suggests that CETP V405 valine homozygosity is associated with slower memory decline and lower incident dementia and AD risk. Affiliation: Department of Neurology, Albert Einstein College of Medicine, Yeshiva University, Bronx, NY 10461, USA . Wikipedia: Adult , Allele , Allele frequencies , Allele frequency , Allelomorph , Alzheimer's Disease , Alzheimer disease , Apolipoprotein , Cholesterol esters , Cholesteryl ester transfer protein , Cholesteryl esters , Cistron , Codon , Cohort Analysis , Cohort studies , Cohort study , Comorbidities , Comorbidity , Confidence Interval , Confidence intervals , Cox Models , Dementia , Early onset Alzheimer disease , Esters , Frontotemporal lobar degeneration , Gene , Gene frequencies , Gene frequency , Genetic equilibrium , Genetic material , Genotype , Hazard model , High-Density Lipoprotein , Homozygote , Incidence , Isoleucine , L-Isoleucine , L-Valine , Linear Models , Linear Regression , Linear model , Log-linear model , Longevity , Low-Density Lipoprotein , Presenile dementia , Prevalence , Proportional hazards model , Prospective studies , Prospective study , Proteins , Race , Semantic Dementia , Senile Dementia , Sex Education , Valine , Very-low-density lipoprotein Title: No association of CETP genotype with cognitive function or age-related cognitive change. PMID: 17531380 Related Articles Authors: Johnson, W , Harris, S E , Collins, P , Starr, J M , Whalley, L J , Deary, I J Journal: Neurosci Lett , Vol. 420 (2): 189-92 , 2007 Abstract: A cholesteryl ester transfer protein ( CETP ) genotype (V/V homozygosity for I405V, NCBI dbSNP rs5882) has been associated with preservation of cognitive function in old age, in addition to its associations with exceptional longevity and cardiovascular disease. We tested the hypotheses that this polymorphism was associated with either level of cognitive function or lifetime cognitive change in 525 participants who took part in the Scottish Mental Survey of 1932. Participants took the same well-validated mental ability test at ages 11 and 79. Scores were also available for several other mental ability tests at age 79, and history of cardiovascular disease was available. Frequency of the V/I genotype was slightly greater than expected in the sample, possibly consistent with some role for the V polymorphism in longevity, and the V/V genotype was associated with a lower rate of cardiovascular disease history. There were, however, no significant associations of CETP genotype with either childhood IQ or current cognitive function in old age, or with lifetime change in cognitive function. Affiliation: Department of Psychology, University of Edinburgh, Edinburgh , UK . wendy.johnson@ed.ac.uk Pubmed MeSH: Aged , Aging , Brain , Child , Cholesterol, HDL , Cognition Disorders , DNA Mutational Analysis , Disease Progression , Genetic Predisposition to Disease , Genetic Screening , Humans , Intelligence , Intelligence Tests , Memory Disorders , Neuropsychological Tests Wikipedia: Cardiovascular Disease , Cardiovascular diseases , Cholesterol esters , Cholesteryl ester transfer protein , Cholesteryl esters , Data collection , Data source , Esters , Genotype , Longevity , Proteins , Respondent , Survey , Survey Methodology Title: A genotype of exceptional longevity is associated with preservation of cognitive function. PMID: 17190939 Related Articles Authors: Barzilai, N , Atzmon, G , Derby, C A , Bauman, J M , Lipton, R B Journal: Neurology , Vol. 67 (12): 2170-5 , 2006 Abstract: OBJECTIVE: To test whether cholesterol ester transfer protein ( CETP ) genotype (VV homozygosity for I405V) is associated with preservation of cognitive function in addition to its association with exceptional longevity. METHODS: We studied Ashkenazi Jews with exceptional longevity (n = 158; age 99.2 +/- 0.3 years) for the associations of CETP VV genotype and lipoprotein phenotype, using the Mini-Mental State Examination (MMSE). To confirm the role of CETP in a younger cohort, we studied subjects from the Einstein Aging Study (EAS) for associations between CETP VV and cognitive impairment. RESULTS: Subjects with MMSE 25 were twice as likely to have the CETP VV genotype (29% vs 14%, p = 0.02), and those with the VV genotype were more likely (61% vs 30%, p = 0.02) to have MMSE 25. Subjects with the VV genotype had lower levels of CETP (1.73 +/- 0.11 vs 2.12 +/- 0.10 mug/mL, p = 0.01), higher high-density lipoprotein ( HDL ) levels (p = 0.02), and larger lipoprotein particles (p = 0.03). In the EAS cohort, an approximately fivefold increase in the VV genotype (21% vs 4%, p = 0.02), higher HDL levels, and larger lipoprotein particle sizes were associated with less dementia and improved memory . CONCLUSIONS: Using two independent cohorts, we implicate the longevity CETP gene as a modulator of age-related cognitive function. A specific CETP genotype is associated with lower CETP levels and a favorable lipoprotein profile. It has not been determined whether modulation of this gene prevents age-related decline or AD. Affiliation: Institute for Aging Research, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA . barzilai@aecom.yu.edu Pubmed MeSH: Age Distribution , Age Factors , Aged, 80 and over , Cognition , Cognition Disorders , Genetic Predisposition to Disease , Humans , New York , Polymorphism, Single Nucleotide , Prevalence , Risk Assessment , Risk Factors Wikipedia: Apolipoprotein , Cholesterol , Cholesterol esters , Cholesteryl ester transfer protein , Cholesteryl esters , Cistron , Cohort Analysis , Cohort studies , Cohort study , Dementia , Esters , Frontotemporal lobar degeneration , Gene , Genetic material , Genotype , High-Density Lipoprotein , Jew , Lipoprotein , Longevity , Low-Density Lipoprotein , Particle size , Phenotype , Proteins , Semantic Dementia , Very-low-density lipoprotein http://news.sciencenet.cn/htmlnews/2010/1/227325.shtm 科学家发现长寿基因 能够减缓记忆力减退 据国外媒体报道，美国叶史瓦大学阿尔伯特爱因斯坦医学院的科学家发现一种被称作胆固醇酯转运蛋白(CETP)基因的长寿基因，这种长寿基因可以帮助减缓记忆力减退和降低老年痴呆症发病率。科学家正在开发类似长寿基因效果的药物，此药物将有助于预防老年痴呆症。 研究者指出，正在开发的类似长寿基因效果的药物有助于预防老年痴呆症。 据报道，该发现的论文第一作者理查德B利普顿（Richard B. Lipton）博士和他的同事在2003年就对德国裔犹太人进行了研究，发现了这种称为胆固醇酯转运蛋白(CETP)基因变异的长寿基因。胆固醇酯转运蛋白(CETP)基因变异可以增加血液中高密度脂蛋白（HDL)水平，并大大高于平均水平，故又称为好胆固醇。 研究者接着对523名70岁以上，具有健全认知能力的布朗士居民进行了测试。研究者分析了他们的血液样品，以便确认出他们所携带的CETP基因变异类型。然后对每个受测试者随访4年，每年都会测试他们的认知能力下降率、老年痴呆症发病率以及其它疾病。 论文作者艾米E桑德斯(Amy E. Sanders)博士说：具有CETP基因变异长寿基因的人群记忆力下降较慢，患痴呆和老年性痴呆症的几率也小很多。具体来说，携带有利的胆固醇酯转运蛋白基因变异长寿基因的测试者比没有携带的人群患老年性痴呆症的几率小70%。 利普顿博士同时指出，目前正在开发和长寿基因有类似预防老年痴呆症的药物。他说：通过测试确定药物的剂量，可达到预防老年痴呆症的效果。 据悉，这项研究由国家老龄化研究所资助，详述这项研究成果的论文已经发表在1月13日出版的《美国医学协会期刊》（ JAMA ）上。 更多阅读 《美国医学协会期刊》发表论文摘要（英文） http://jama.ama-assn.org/cgi/content/short/303/2/150?home Vol. 303 No. 2, January 13, 2010 JAMA Online Features Preliminary Communication This Article Full text PDF Send to a friend Save in My Folder Save to citation manager Permissions Citing Articles Citation map Contact me when this article is cited Related Content Similar articles in JAMA Topic Collections Neurology Alzheimer Disease Behavioral Neurology Dementias Neurogenetics Genetics Genetic Disorders Alert me on articles by topic Social Bookmarking What's this? Association of a Functional Polymorphism in the Cholesteryl Ester Transfer Protein ( CETP ) Gene With Memory Decline and Incidence of Dementia Amy E. Sanders, MD ; Cuiling Wang, PhD ; Mindy Katz, MPH ; Carol A. Derby, PhD ; Nir Barzilai, MD ; Laurie Ozelius, PhD ; Richard B. Lipton, MD JAMA. 2010;303(2):150-158. Context Polymorphisms in the cholesteryl ester transfer protein ( CETP ) gene have been associated with exceptional longevity and lower cardiovascular risk, but associations with memory decline and dementia risk are unclear. Author Affiliations: Departments of Neurology (Drs Sanders, Derby, and Lipton and Ms Katz) and Epidemiology and Population Health (Drs Wang, Derby, and Lipton) and Institute for Aging Research (Drs Barzilai and Lipton), Albert Einstein College of Medicine, Yeshiva University, Bronx, New York; and Departments of Genetics and Genomic Sciences and Neurology, Mount Sinai School of Medicine, New York, New York (Dr Ozelius). Objective To test the hypothesis that a single-nucleotide polymorphism (SNP) at CETP codon 405 (isoleucine to valine V405; SNP rs5882 ) is associated with a lower rate of memory decline and lower risk of incident dementia, including Alzheimer disease (AD). Design, Setting, and Participants Prospective cohort study comprising 608 community-dwelling adults without dementia aged 70 years or older from the Einstein Aging Study with CETP genotype available. Fifteen participants with prevalent dementia were excluded, and 70 without follow-up63 lost to follow-up and 7 new to the studywere excluded from the Cox proportional hazards model, which included 523 participants in the analysis. Standardized neuropsychological and neurological measures were administered annually from 1994-2009. Linear mixed-effects models adjusted for sex, education, race, medical comorbidities, and apolipoprotein ( APOE ) 4 examined associations of V405 genotype with longitudinal performance on cognitive tests of episodic memory (Free and Cued Selective Reminding Test , possible scores of 0-48), attention (Digit Span), and psychomotor speed (Digit Symbol Substitution). The V405 genotype was the main predictor of incident dementia or AD in similarly adjusted Cox proportional hazards models with age as the time scale. Main Outcome Measures Memory decline and incident dementia. Results Valine allele frequency was 43.5%. A total of 40 cases of incident dementia occurred during follow-up (mean , 4.3 years). Compared with isoleucine homozygotes, valine homozygotes had significantly slower memory decline on the FCSRT (0.43 points per year of age for isoleucine; 95% confidence interval , 0.58 to 0.29 vs 0.21 points per year of age for valine; 95% CI, 0.39 to 0.04; difference in linear age slope, 0.22; 95% CI, 0.02 to 0.41; P =.03) and no significant differences on the Digit Span or Digit Symbol Substitution tests. Valine homozygotes also had lower risk of dementia (hazard ratio, 0.28; 95% CI, 0.10-0.85; P =.02) and AD (hazard ratio, 0.31; 95% CI, 0.10-0.95; P =.04). Conclusion This preliminary report suggests that CETP V405 valine homozygosity is associated with slower memory decline and lower incident dementia and AD risk.
标签: 记忆力
