Serum Aβ Levels as Predictors of Conversion to Mild Cognitive Impairment/Alzheimer Disease in an ADAPT Subcohort

被引:13
作者
Abdullah, Laila [1 ]
Luis, Cheryl [1 ]
Paris, Daniel [1 ]
Mouzon, Benoit [1 ]
Ait-Ghezala, Ghania [1 ]
Keegan, Andrew P. [1 ]
Wang, Duolao [2 ]
Crawford, Fiona [1 ]
Mullan, Michael [1 ]
机构
[1] Roskamp Inst, Sarasota, FL 34243 USA
[2] London Sch Hyg & Trop Med, Med Stat Unit, London WC1, England
关键词
ALZHEIMERS-DISEASE; RISK-FACTORS; APOLIPOPROTEIN-E; DEMENTIA; HEALTH; CHOLESTEROL; MEDICATIONS; PREVENTION; STATINS; NSAIDS;
D O I
10.2119/molmed.2009.00083
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent evidence suggests an association of beta-amyloid (A beta) with vascular risk factors and the medications to treat them, which could potentially obfuscate the usefulness of A beta for prediction of mild cognitive impairment (MCI) or Alzheimer disease (AD). In a subcohort from the Alzheimer's Disease Anti-inflammatory Prevention Trial (enriched for family history of AD), we investigated whether systolic blood pressure, total cholesterol, triglycerides, serum creatinine, apolipoprotein E, and use of statins and antihypertensives influenced the predictive value of serum A beta for MCI/AD during a 2-year period. We collected blood samples to quantify serum A beta from cognitively normal participants (n = 203) at baseline and ascertained the outcome of MCI/AD (n = 24) for a period of approximately 2 years, In an unadjusted model, the lowest quartile of A beta(1-42) (hazard ratio (HR) = 2.93,95% Cl (1.02-8.32), P = 0.04) and of the A beta(1-42)/A beta(1-40) ratio (HR = 353,95% CI (1.24-10.07), P = 0.02), compared with the highest quartile, predicted conversion to MCI/AD, but no impact of A beta(1-40) was observed. No relationship between nonsteroidal antiinflammatory drug interventions and A beta on MCl/AD risk was evident. Once data were adjusted for potential confounders (age, sex, and education), vascular risk factors, and the medications listed above, the lowest quartiles of A beta(1-42) (HR = 4.47,95% Cl (1.39-14.39), P = 0.01), and of the A beta(1-42/)A beta(1-40) ratio (HR 4.87,95% CI (1.50-15.87), P = 0.01) became strong predictors of conversion to MCl/AD. In this subcohort of individuals at risk for AD, the association of All with vascular risk factors and medications to treat these conditions did not interfere with All's predictive value for MCl/AD. (C) 2009 The Feinstein Institute for Medical Research, www.feinsteininstitute.org Online address: http://www.molmed.org doi: 10.2119/molmed.2009.00083
引用
收藏
页码:432 / 437
页数:6
相关论文
共 36 条
[1]   High Serum Aβ and Vascular Risk Factors in First-Degree Relatives of Alzheimer's Disease Patients [J].
Abdullah, Laila ;
Luis, Cheryl ;
Paris, Daniel ;
Ait-ghezala, Ghania ;
Mouzon, Benoit ;
Allen, Elizabeth ;
Parrish, Julia ;
Mullan, Myles A. ;
Ferguson, Scott ;
Wood, Marcie ;
Crawford, Fiona ;
Mullan, Michael .
MOLECULAR MEDICINE, 2009, 15 (3-4) :95-100
[2]  
Benton A.L., 1983, JUDGMENT LINE ORIENT
[3]   Effects of medications on plasma amyloid beta (Aβ) 42:: Longitudinal data from the VITA cohort [J].
Blasko, Imrich ;
Jungwirth, Susanne ;
Jellinger, Kurt ;
Kemmler, Georg ;
Krampla, Wolfgang ;
Weissgram, Silvia ;
Wichart, Ildiko ;
Tragl, Karl Heinz ;
Hinterhuber, Hartmann ;
Fischer, Peter .
JOURNAL OF PSYCHIATRIC RESEARCH, 2008, 42 (11) :946-955
[4]   Risk of dementia and AD with prior exposure to NSAIDs in an elderly community-based cohort [J].
Breitner, J. C. S. ;
Haneuse, S. J. P. A. ;
Walker, R. ;
Dublin, S. ;
Crane, P. K. ;
Gray, S. L. ;
Larson, E. B. .
NEUROLOGY, 2009, 72 (22) :1899-1905
[5]   The prevention of dementia with antihypertensive treatment [J].
Forette, F ;
Seux, ML ;
Staessen, JA ;
Thijs, L ;
Babarskiene, MR ;
Babeanu, S ;
Bossini, A ;
Fagard, R ;
Gil-Extremera, B ;
Laks, T ;
Kobalava, Z ;
Sarti, C ;
Tuomilehto, J ;
Vanhanen, H ;
Webster, J ;
Yodfat, Y ;
Birkenhäger, WH .
ARCHIVES OF INTERNAL MEDICINE, 2002, 162 (18) :2046-2052
[6]   Relationships between plasma β-amyloid peptide 1-42 and atherosclerotic risk factors in community-based older populations [J].
Fujiwara, Y ;
Takahashi, M ;
Tanaka, M ;
Hoshi, T ;
Someya, T ;
Shinkai, S .
GERONTOLOGY, 2003, 49 (06) :374-379
[7]   Association of low plasma Aβ42/Aβ40 ratios with increased imminent risk for mild cognitive impairment and Alzheimer disease [J].
Graff-Radford, Neill R. ;
Crook, Julia E. ;
Lucas, John ;
Boeve, Bradley F. ;
Knopman, David S. ;
Ivnik, Robert J. ;
Smith, Glenn E. ;
Younkin, Linda H. ;
Petersen, Ronald C. ;
Younkin, Steven G. .
ARCHIVES OF NEUROLOGY, 2007, 64 (03) :354-362
[8]   Duration of antihypertensive drug use and risk of dementia A prospective cohort study [J].
Haag, M. D. M. ;
Hofman, A. ;
Koudstaal, P. J. ;
Breteler, M. M. B. ;
Stricker, B. H. C. .
NEUROLOGY, 2009, 72 (20) :1727-1734
[9]   Statins are associated with a reduced risk of Alzheimer disease regardless of lipophilicity. The Rotterdam Study [J].
Haag, M. D. M. ;
Hofman, A. ;
Koudstaal, P. J. ;
Stricker, B. H. C. ;
Breteler, M. M. B. .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 2009, 80 (01) :13-17
[10]   Apolipoprotein E ε4 allele, elevated midlife total cholesterol level, and high midlife systolic blood pressure are independent risk factors for late-life Alzheimer disease [J].
Kivipelto, M ;
Helkala, EL ;
Laakso, MP ;
Hänninen, T ;
Hallikainen, M ;
Alhainen, K ;
Iivonen, S ;
Mannermaa, A ;
Tuomilehto, J ;
Nissinen, A ;
Soininen, H .
ANNALS OF INTERNAL MEDICINE, 2002, 137 (03) :149-155