Insulin resistance is associated with the pathology of Alzheimer disease

The Hisayama study

T. Matsuzaki, K. Sasaki, Y. Tanizaki, Jun Hata, K. Fujimi, Y. Matsui, A. Sekita, Satoshi Suzuki, Shigenobu Kanba, Y. Kiyohara, Toru Iwaki

Research output: Contribution to journalArticle

238 Citations (Scopus)

Abstract

Objective: We examined the association between diabetes-related factors and pathology of Alzheimer disease (AD) to evaluate how diabetes affects the pathogenic process of AD. Methods: This study included specimens from a series of 135 autopsies of residents of the town of Hisayama in Fukuoka prefecture (74 men and 61 women) performed between 1998 and 2003, who underwent a 75-g oral glucose tolerance test in clinical examinations in 1988. We measured diabetes-related factors including fasting glucose, 2-hour post-load plasma glucose, fasting insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) in 1988. Neuritic plaques (NPs) were assessed according to the Consortium to Establish a Registry for Alzheimer's Disease guidelines and neurofibrillary tangles (NFTs) were assessed according to Braak stage. The associations between each factor and AD pathology were examined by analysis of covariance and logistic regression analyses. Results: Higher levels of 2-hour post-load plasma glucose, fasting insulin, and HOMA-IR were associated with increased risk for NPs after adjustment for age, sex, systolic blood pressure, total cholesterol, body mass index, habitual smoking, regular exercise, and cerebrovascular disease. However, there were no relationships between diabetes-related factors and NFTs. Regarding the effects of APOE genotype on the risk of AD pathology, the coexistence of hyperglycemia and APOE ε4 increased the risk for NP formation. A similar enhancement was observed for hyperinsulinemia and high HOMA-IR. Conclusion: The results of this study suggest that hyperinsulinemia and hyperglycemia caused by insulin resistance accelerate NP formation in combination with the effects of APOE ε4.

Original languageEnglish
Pages (from-to)764-770
Number of pages7
JournalNeurology
Volume75
Issue number9
DOIs
Publication statusPublished - Aug 31 2010

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Amyloid Plaques
Insulin Resistance
Alzheimer Disease
Pathology
Fasting
Neurofibrillary Tangles
Homeostasis
Hyperinsulinism
Glucose
Hyperglycemia
Insulin
Blood Pressure
Cerebrovascular Disorders
Glucose Tolerance Test
Registries
Autopsy
Body Mass Index
Logistic Models
Smoking
Cholesterol

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

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Insulin resistance is associated with the pathology of Alzheimer disease : The Hisayama study. / Matsuzaki, T.; Sasaki, K.; Tanizaki, Y.; Hata, Jun; Fujimi, K.; Matsui, Y.; Sekita, A.; Suzuki, Satoshi; Kanba, Shigenobu; Kiyohara, Y.; Iwaki, Toru.

In: Neurology, Vol. 75, No. 9, 31.08.2010, p. 764-770.

Research output: Contribution to journalArticle

Matsuzaki, T, Sasaki, K, Tanizaki, Y, Hata, J, Fujimi, K, Matsui, Y, Sekita, A, Suzuki, S, Kanba, S, Kiyohara, Y & Iwaki, T 2010, 'Insulin resistance is associated with the pathology of Alzheimer disease: The Hisayama study', Neurology, vol. 75, no. 9, pp. 764-770. https://doi.org/10.1212/WNL.0b013e3181eee25f
Matsuzaki, T. ; Sasaki, K. ; Tanizaki, Y. ; Hata, Jun ; Fujimi, K. ; Matsui, Y. ; Sekita, A. ; Suzuki, Satoshi ; Kanba, Shigenobu ; Kiyohara, Y. ; Iwaki, Toru. / Insulin resistance is associated with the pathology of Alzheimer disease : The Hisayama study. In: Neurology. 2010 ; Vol. 75, No. 9. pp. 764-770.
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