Diabetes Mellitus, Elevated Hemoglobin A_1c, and Glycated Albumin Are Associated with the Presence of All-Cause Dementia and Alzheimer’s Disease: The JPSC-AD Study

Article type: Research Article

Authors: Noguchi-Shinohara, Moeko^{a; b} | Yuki-Nozaki, Sohshi^a | Abe, Chiemi^{a; b} | Mori, Ayaka^a | Horimoto, Mai^{a; b} | Yokogawa, Masami^c | Ishida, Natsuko^d | Suga, Yukio^d | Ishizaki, Junko^d | Ishimiya, Mai^e | Nakamura, Hiroyuki^{e; f} | Komai, Kiyonobu^g | Nakamura, Hiroyuki^{h; i; j} | Shibata, Mao^k | Ohara, Tomoyuki^l | Hata, Jun^k | Ninomiya, Toshiharu^k | Yamada, Masahito^{a; m; *} | on behalf of the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) study group¹

Affiliations: [a] Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan | [b] Department of Preemptive Medicine for Dementia, Kanazawa University Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan | [c] Department of Physical Therapy, Division of Health Sciences, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan | [d] Clinical Pharmacy and Healthcare Sciences, Faculty of Pharmacy, Institute of Medical, Pharmaceutical & Health Science, Kanazawa University, Kanazawa, Japan | [e] Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan | [f] Department of Oral and Maxillofacial Surgery, Ryukyu University Graduate School of Medical Science, Nishihara, Japan | [g] Department of Neurology, Hokuriku Brain and Neuromuscular Disease Center, National Hospital Organization Iou National Hospital, Kanazawa, Japan | [h] Department of Public Health, Kanazawa University Graduate School of Advanced Preventive Medical Sciences, Kanazawa, Japan | [i] Kanazawa University Advanced Preventive Medical Sciences Research Center, Kanazawa, Japan | [j] Department of Environmental and Preventive Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan | [k] Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan | [l] Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyusyu University, Fukuoka, Japan | [m] Kudanzaka Hospital, Tokyo, Japan

Correspondence: [*] Professor Masahito Yamada, MD, PhD, Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Sciences, 13-1 Takara-machi, Kanazawa 920-8640, Japan. Tel.: +81 76 265 2290; Fax: +81 76 265 4253; E-mail: [email protected].

Note: [1] The members of the study group are listed in the Acknowledgement section.

Abstract: Background:Glucose dysmetabolism is an important risk factor for dementia. Objective:We investigated the associations of diabetes mellitus, the levels of glycemic measures, and insulin resistance and secretion measures with dementia and its subtypes in a cross-sectional study. Methods:In this study, 10,214 community-dwelling participants were enrolled. Hemoglobin A1c (HbA1c), the homeostasis model assessment (HOMA) for insulin resistance (HOMA-IR), the HOMA of percent β-cell function (HOMA-β), and the glycated albumin (GA) was evaluated. The associations of each measure with Alzheimer’s disease (AD) and vascular dementia (VaD) were investigated. Results:The multivariable-adjusted odds ratios (ORs) of AD were significantly higher in participants with diabetes mellitus than in those without diabetes (1.46 [95% CI: 1.08–1.97]). Higher HbA1c levels were significantly associated with AD at diabetes (≥6.5%) and even at prediabetes (5.7 %–6.4 %) levels; multivariable-adjusted ORs for AD in participants at the diabetes level were 1.72 (95% CI: 1.19–2.49), and those in participants at the prediabetes level were 1.30 (95% CI: 1.00–1.68), compared with those in normal participants. Moreover, higher GA levels were associated with AD. No associations were observed between the diabetic status or the levels of glycemic measures and VaD. In addition, no significant relationships were observed between insulin resistance and secretion measurements and AD and VaD. Conclusion:Our findings indicate that diabetes mellitus and hyperglycemia are significantly associated with AD, even in individuals at the prediabetes level.

Keywords: Alzheimer’s disease, diabetes mellitus, glycated albumin, hemoglobin A1c, vascular dementia

DOI: 10.3233/JAD-215153

Journal: Journal of Alzheimer's Disease, vol. 85, no. 1, pp. 235-247, 2022