한빛사논문
- 조회1,030
Hyemin Jang, MD, PhD*, Sungjoo Lee, MS*, Sungsik An, MD, Yuhyun Park, PhD, Soo-Jong Kim, MS, Bo Kyoung Cheon, PhD, Ji Hyun Kim, MS, Hee Jin Kim, MD, PhD, Duk L. Na, MD, PhD, Jun Pyo Kim, MD, Kyunga Kim, PhD†, and Sang Won Seo, MD, PhD†
From the Alzheimer's Disease Convergence Research Center (H.J., S.A., Y.P., S.-J.K., B.K.C., J.H.K., H.J.K., D.L.N., J.P.K., S.W.S.), Samsung Medical Center; Department of Digital Health (H.J., S.L., K.K., S.W.S.), Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University; Department of Neurology (H.J., H.J.K., J.P.K., S.W.S.), Samsung Medical Center, Sungkyunkwan University School of Medicine; Neuroscience Center (H.J., H.J.K., J.P.K., S.W.S.), Samsung Medical Center; Happymind Clinic (D.L.N.); Biomedical Statistics Center (K.K.), Research Institute for Future Medicine, Samsung Medical Center; and Department of Data Convergence and Future Medicine (K.K.), Sungkyunkwan University School of Medicine, Seoul, Korea. Dr. Jang is currently at the Department of Neurology, Seoul National University Hospital, Korea.
*These authors contributed equally to this work as cofirst authors.
†These authors contributed equally to this work as cocorresponding authors.
Correspondence : Kyunga Kim, PhD, Sang Won Seo, MD, PhD
Abstract
Background and objective: We aimed to investigate the association between glycemic variability (GV) and neuroimaging markers of white matter hyperintensities (WMH), beta-amyloid (Aβ), brain atrophy, and cognitive impairment.
Methods: This was a retrospective cohort study that included participants without dementia from a memory clinic. They all had Aβ PET, brain MRI, and standardized neuropsychological tests and had fasting glucose (FG) levels tested more than twice during the study period. We defined GV as the intraindividual visit-to-visit variability in FG levels. Multivariable linear regression and logistic regression were used to identify whether GV was associated with the presence of severe WMH and Aβ uptake with DM, mean FG levels, age, sex, hypertension, and presence of APOE4 allele as covariates. Mediation analyses were used to investigate the mediating effect of WMH and Aβ uptake on the relationship between GV and brain atrophy and cognition.
Results: Among the 688 participants, the mean age was 72.2 years, and the proportion of female participants was 51.9%. Increase in GV was predictive of the presence of severe WMH (coefficient [95% CI] 1.032 [1.012-1.054]; p = 0.002) and increased Aβ uptake (1.005 [1.001-1.008]; p = 0.007). Both WMH and increased Aβ uptake partially mediated the relationship between GV and frontal-executive dysfunction (GV → WMH → frontal-executive; direct effect, -0.319 [-0.557 to -0.080]; indirect effect, -0.050 [-0.091 to -0.008]) and memory dysfunction (GV → Aβ → memory; direct effect, -0.182 [-0.338 to -0.026]; indirect effect, -0.067 [-0.119 to -0.015]), respectively. In addition, increased Aβ uptake completely mediated the relationship between GV and hippocampal volume (indirect effect, -1.091 [-2.078 to -0.103]) and partially mediated the relationship between GV and parietal thickness (direct effect, -0.00101 [-0.00185 to -0.00016]; indirect effect, -0.00016 [-0.00032 to -0.000002]).
Discussion: Our findings suggest that increased GV is related to vascular and Alzheimer risk factors and neurodegenerative markers, which in turn leads to subsequent cognitive impairment. Furthermore, GV can be considered a potentially modifiable risk factor for dementia prevention.
논문정보
- Research article
- 2024년 01월 (BRIC 등록일 2024-01-03)
- 국내 연구진
- 의약학 > 신경의학
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