Glucose Intolerance, Insulin Resistance, and Pathological Features of Alzheimer Disease in the Baltimore Longitudinal Study of Aging

被引：133

作者：

Thambisetty, Madhav ^{[1
]}

Metter, Jeffrey ^{[1
]}

Yang, An ^{[1
]}

Dolan, Hillary ^{[2
]}

Marano, Christopher ^{[3
]}

Zonderman, Alan B. ^{[1
]}

Troncoso, Juan C. ^{[4
]}

Zhou, Yun ^{[5
]}

Wong, Dean F. ^{[5
]}

Ferrucci, Luigi ^{[1
]}

Egan, Josephine ^{[1
]}

Resnick, Susan M. ^{[1
]}

O'Brien, Richard J. ^{[2
]}

机构：

[1] NIA, Res Program, Baltimore, MD 21224 USA

[2] Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD 21224 USA

[3] Johns Hopkins Bayview Med Ctr, Dept Psychiat, Baltimore, MD 21224 USA

[4] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA

来源：

JAMA NEUROLOGY | 2013年 / 70卷 / 09期

基金：

美国国家卫生研究院;

关键词：

COGNITIVE DECLINE; DIABETES-MELLITUS; TOLERANCE TEST; RISK; DEMENTIA; COMMUNITY; BRAIN; IMPAIRMENT; ROTTERDAM; HISAYAMA;

D O I：

10.1001/jamaneurol.2013.284

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

IMPORTANCE Peripheral glucose homeostasis has been implicated in the pathogenesis of Alzheimer disease (AD). The relationship among diabetes mellitus, insulin, and AD is an important area of investigation. However, whether cognitive impairment seen in those with diabetes is mediated by excess pathological features of AD or other related abnormalities, such as vascular disease, remains unclear. OBJECTIVE To investigate the association between serial measures of glucose intolerance and insulin resistance and in vivo brain beta-amyloid burden, measured with carbon 11-labeled Pittsburgh Compound B (11C-PiB), and AD pathology at autopsy. DESIGN Scores calculated from the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and Braak criteria were correlated with measures of hyperglycemia, hyperinsulinemia, glucose intolerance, and insulin resistance in 197 participants who underwent autopsy after death and who had undergone 2 or more oral glucose tolerance tests (OGTT) using grouped analyses and a continuous mixed-models analysis. The same measures of glucose intolerance and insulin resistance were also correlated with brain 11C-PiB retention in an additional 53 living subjects from the Baltimore Longitudinal Study of Aging neuroimaging study. SETTING Prospective, serially assessed cohort of community-dwelling subjects. PARTICIPANTS Cohort 1 consisted of 197 participants enrolled in the Baltimore Longitudinal Study of Aging who had 2 or more OGTTs during life and a complete brain autopsy after death. Cohort 2 consisted of 53 living subjects who had 2 or more OGTTs and underwent brain 11C-PiB positron emission tomography. EXPOSURES Autopsy and 11C-PiB positron emission tomography. MAIN OUTCOMES AND MEASURES The correlation of brain markers of AD, including CERAD score, Braak score, and 11C-PiB retention, with serum markers of glucose homeostasis using grouped and continuous mixed-models analyses. RESULTS We found no significant correlations between measures of brain AD pathology or 11C-PiB beta-amyloid load and glucose intolerance or insulin resistance in subjects who had a mean (SD) of 6.4 (3.2) OGTTs during 22.1 (8.0) years of follow-up. Thirty subjects with frank diabetes mellitus who received medications also had AD pathology scores that were similar to those of the cohort as a whole. CONCLUSIONS AND RELEVANCE In this prospective cohort with multiple assessments of glucose intolerance and insulin resistance, measures of glucose and insulin homeostasis are not associated with AD pathology and likely play little role in AD pathogenesis. Long-term therapeutic trials are important to elucidate this issue.

引用

页码：1167 / 1172

页数：6

共 35 条

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