Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals

被引：118

作者：

Beeri, Michal Schnaider ^{[1
,5
]}

Moshier, Erin ^{[2
]}

Schmeidler, James ^{[1
]}

Godbold, James ^{[2
]}

Uribarri, Jaime ^{[3
]}

Reddy, Sarah ^{[1
]}

Sano, Mary ^{[1
,5
]}

Grossman, Hillel T. ^{[1
]}

Cai, Weijing ^{[4
]}

Vlassara, Helen ^{[4
]}

Silverman, Jeremy M. ^{[1
]}

机构：

[1] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA

[2] Mt Sinai Sch Med, Dept Biostat, New York, NY 10029 USA

[3] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA

[4] Mt Sinai Sch Med, Dept Geriatr, New York, NY 10029 USA

[5] James J Peters Vet Affairs Med Ctr, Bronx, NY USA

来源：

MECHANISMS OF AGEING AND DEVELOPMENT | 2011年 / 132卷 / 11-12期

关键词：

Methylglyoxal; Advanced glycation end products; Type; 2; diabetes; Cognitive decline; Alzheimer's disease; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; PROTEIN GLYCATION; OXIDATIVE STRESS; GLYCOSYLATION; PENTOSIDINE; GLYCOLYSIS; MEDIATORS; IMPAIRS; AGE;

D O I：

10.1016/j.mad.2011.10.007

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background: Advanced glycations end products increase oxidant stress, inflammation, and neurotoxicity. Serum levels are increased in diabetes and aging. We examined the relationship between serum methylglyoxal derivatives (sMG), and cognitive decline, in 267 non-demented elderly. Methods: Tobit mixed regression models assessed the association of baseline sMG with cognitive decline in the Mini Mental State Exam (MMSE) over time, controlling for sociodemographic factors (age, sex, and years of education), cardiovascular risk factors (diabetes and presence of an ApoE4 allele), and kidney function. sMG was assessed by ELISA. Results: The fully adjusted model showed an annual decline of 0.26 MMSE points per unit increase in baseline sMG (p = 0.03). Significance was unchanged as additional risk factors were added to the model. The interactions of sMG with diabetes, sex, age, kidney function, and ApoE4 genotype were not significant. Conclusions: Higher levels of baseline sMG were associated with a faster rate of cognitive decline, after adjusting for several sociodemographic and clinical characteristics. This relationship did not differ by sex, ApoE4 genotype, or diabetes status suggesting its generality. Since subjects were cognitively normal at the beginning of the study, elevated sMG may be indicative of brain cell injury initiated before clinically evident cognitive compromise. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

引用

页码：583 / 587

页数：5

共 39 条

[1] Protein glycation, oxidation and nitration adduct residues and free adducts of cerebrospinal fluid in Alzheimer's disease and link to cognitive impairment [J].

Ahmed, N ;

Ahmed, U ;

Thornalley, PJ ;

Hager, K ;

Fleischer, G ;

Münch, G .

JOURNAL OF NEUROCHEMISTRY, 2005, 92 (02) :255-263

[2] Pentosidine and Nε-(carboxymethyl)-lysine in Alzheimer's disease and vascular dementia [J].

Bär, KJ ;

Franke, S ;

Wenda, B ;

Müller, S ;

Kientsch-Engel, R ;

Stein, G ;

Sauer, H .

NEUROBIOLOGY OF AGING, 2003, 24 (02) :333-338

[3] Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology [J].

Beeri, M. S. ;

Schmeidler, J. ;

Silverman, J. M. ;

Gandy, S. ;

Wysocki, M. ;

Hannigan, C. M. ;

Purohit, D. P. ;

Lesser, G. ;

Grossman, H. T. ;

Haroutunian, V. .

NEUROLOGY, 2008, 71 (10) :750-757

[4] Age, gender, and education norms on the CERAD neuropsychological battery in the oldest old [J].

Beeri, M. S. ;

Schmeidler, J. ;

Sano, M. ;

Wang, J. ;

Lally, R. ;

Grossman, H. ;

Silverman, J. M. .

NEUROLOGY, 2006, 67 (06) :1006-1010

[5] Coronary artery disease is associated with Alzheimer disease neuropathology in APOE4 carriers [J].

Beeri, MS ;

Rapp, M ;

Silverman, JM ;

Schmeidler, J ;

Grossman, HT ;

Fallon, JT ;

Purohit, DP ;

Perl, DP ;

Siddiqui, A ;

Lesser, G ;

Rosendorff, C ;

Haroutunian, V .

NEUROLOGY, 2006, 66 (09) :1399-1404

[6] Diabetes mellitus in midlife and the risk of dementia three decades later [J].

Beeri, MS ;

Goldbourt, U ;

Silverman, JM ;

Noy, S ;

Schmeidler, J ;

Ravona-Springer, R ;

Sverdlick, A ;

Davidson, M .

NEUROLOGY, 2004, 63 (10) :1902-1907

[7] Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress [J].

Brouwers, O. ;

Niessen, P. M. ;

Haenen, G. ;

Miyata, T. ;

Brownlee, M. ;

Stehouwer, C. D. ;

De Mey, J. G. ;

Schalkwijk, C. G. .

DIABETOLOGIA, 2010, 53 (05) :989-1000

[8] Oxidative stress-inducing carbonyl compounds from common foods: Novel mediators of cellular dysfunction [J].

Cai, WJ ;

Gao, QD ;

Zhu, L ;

Peppa, M ;

He, CJ ;

Vlassara, H .

MOLECULAR MEDICINE, 2002, 8 (07) :337-346

[9] Impact of APOE ε4 on the Cognitive Performance of a Sample of Non-Demented Puerto Rican Nonagenarians [J].

Carrion-Baralt, Jose R. ;

Melendez-Cabrero, Josefina ;

Rodriguez-Ubinas, Heide ;

Schmeidler, James ;

Beeri, Michal Schnaider ;

Angelo, Gary ;

Sano, Mary ;

Silverman, Jeremy M. .

JOURNAL OF ALZHEIMERS DISEASE, 2009, 18 (03) :533-540

[10] PROTEIN GLYCOSYLATION AND THE PATHOGENESIS OF ATHEROSCLEROSIS [J].

CERAMI, A ;

VLASSARA, H ;

BROWNLEE, M .

METABOLISM-CLINICAL AND EXPERIMENTAL, 1985, 34 (12) :37-44

← 1 2 3 4 →