Differential effects of blood insulin and HbA1c on cerebral amyloid burden and neurodegeneration in nondiabetic cognitively normal older adults

Byun, Min Soo; Kim, Hyun Jung; Yi, Dahyun; Choi, Hyo Jung; Baek, Hong Sun; Lee, Jun Ho; Choe, Young Min; Sohn, Bo Kyung; Lee, Jun-Young; Lee, Younghwa; Ko, Hyunwoong; Kim, Yu Kyeong; Lee, Yun Sang; Sohn, Chul‐Ho; Woo, Jong Inn; Lee, Dong Hoon

doi:10.1016/j.neurobiolaging.2017.07.004

Cited by 24 publications

(19 citation statements)

References 82 publications

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“…In the current study, higher HbA 1c was associated with incident dementia at values in the diabetic range, though low levels (,5.8%, 40 mmol/mol) also appeared associated with higher risk of incident dementia. This contrasts with prior studies that found associations between HbA 1c and brain atrophy in cognitively normal individuals (34) and with higher risk of MCI (35), though not all studies have found associations, particularly when HbA 1c was assessed in combination with other markers of glycemia and insulin resistance (36,37). This may be in part related to J-shaped associations between HbA 1c and death (and other outcomes) in adults with (38) and without (39) diabetes, which has been shown in a number of prior studies.…”

Section: Discussioncontrasting

confidence: 95%

The Association of Late-Life Diabetes Status and Hyperglycemia With Incident Mild Cognitive Impairment and Dementia: The ARIC Study

et al. 2019

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We sought to examine associations in older adults among diabetes, glycemic control, diabetes duration, and biomarkers of hyperglycemia with incident mild cognitive impairment (MCI) and incident dementia. RESEARCH DESIGN AND METHODS We conducted a prospective analysis of 5,099 participants from the Atherosclerosis Risk in Communities (ARIC) Study who attended the fifth (2011-2013) exam. Cognitive status was assessed during follow-up via telephone calls, death certificate codes, surveillance, and a follow-up examination (2016-2017). We defined incident cognitive impairment as incident MCI or incident dementia in persons dementiafree at the index examination; we also examined each outcome separately. Diabetes was defined using self-report, medications, or HbA 1c ‡6.5%; poor glycemic control in persons with diabetes was defined as HbA 1c ‡7%. We examined the following biomarkers of hyperglycemia: HbA 1c , fructosamine, glycated albumin, and 1,5-anhydroglucitol. RESULTS Mean age at baseline was 76 years, 59% were female, and 21% were black. Diabetes (hazard ratio [HR] 1.14 [95% CI 1.00, 1.31]), poor glycemic control in persons with diabetes (HR 1.31 [95% CI 1.05, 1.63]), and longer diabetes duration (‡5 vs. <5 years; HR 1.59 [95% CI 1.23, 2.07]) were significantly associated with incident cognitive impairment. We found a J-shaped association between HbA 1c and incident dementia. Glycated albumin and fructosamine were also associated with incident dementia, independently of HbA 1c. HbA 1c and fructosamine were also associated with incident MCI. CONCLUSIONS Diabetes status, poor glycemic control, and longer diabetes duration were associated with worse cognitive outcomes over a median follow-up of 5 years. The U.S. population is rapidly aging. In 2012, 14% of the U.S. population was 65 years and older, and this proportion is expected to climb to .20% by 2030, representing .70 million people (1). Among older adults, the prevalence of diabetes is 22%, and the prevalence of prediabetes is 24% (2). Studies have documented that persons with

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Section: Discussioncontrasting

confidence: 95%

The Association of Late-Life Diabetes Status and Hyperglycemia With Incident Mild Cognitive Impairment and Dementia: The ARIC Study

et al. 2019

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“… 3 , 7 This interpretation is supported by recent in vivo clinical results showing that low levels of fasting blood insulin were associated with increased β-amyloid deposition and neurodegeneration in nondiabetic, cognitively normal older adults. 34 Consistent with these findings, the association between low insulin and dementia described here was particularly strong for VD and for AD without diabetes comorbidity, i.e., when the alternative pathway through diabetes mellitus was censored. Although insulin concentrations in the CSF are generally well below serum levels, the ratio varies between 1% and 10%, depending on weight status and other factors that regulate the transport across the blood-brain barrier 8 and influence brain insulin levels in addition to absolute levels of circulating insulin.…”

Section: Discussionsupporting

confidence: 84%

Low fasting serum insulin and dementia in nondiabetic women followed for 34 years

et al. 2018

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ObjectiveIn a representative population of women followed over 34 years, we investigated the prospective association between fasting serum insulin and dementia, taking into account the incidence of diabetes mellitus.MethodsFasting values for serum insulin and blood glucose were obtained in 1,212 nondiabetic women 38 to 60 years of age at the 1968 baseline. Risk of dementia was assessed by Cox proportional hazard regression with adjustment for insulin, glucose, and other covariates and, in a second model, after censoring for incident cases of diabetes mellitus. Incident diabetes mellitus was considered as a third endpoint for comparison with dementia.ResultsOver 34 years, we observed 142 incident cases of dementia. The low tertile of insulin displayed excess risk for dementia (hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.52–3.58) compared to the medium tertile, but the high tertile of insulin did not (HR 1.28, 95% CI 0.81–2.03). These associations were also seen for dementia without diabetes comorbidity. In contrast, high but not low insulin predicted incident diabetes mellitus (115 cases) (HR 1.70, 95% CI 1.08–2.68 and HR 0.76, 95% CI 0.43–1.37, respectively).ConclusionA previous study reported a U-shaped association between fasting insulin and dementia in a 5-year follow-up of elderly men. Our results confirmed a nonlinear association in a female population, with high risk at low insulin values that was not attributable to preclinical dementia or impaired insulin secretion. This condition suggests a new pathway to dementia, which differs from the metabolic pathway involving diabetes mellitus.

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“…Using a 3.0T Biograph mMR (PET-MR) scanner (Siemens, Germany), we conducted 3D [ 11 C] Pittsburg compound B (PiB)positron emission tomography (PET), simultaneously with 3D T1-weighted MRI. Details on imaging acquisition and related preprocessing can be found elsewhere (Byun et al, 2017a). The PiB retention level was measured in the following 4 regions of 1 http://www.law.go.kr interest (ROIs): the frontal, lateral parietal, posterior cingulateprecuneus, and lateral temporal regions.…”

Section: Measurement Of Cerebral Amyloid Depositionmentioning

confidence: 99%

Multiparity, Brain Atrophy, and Cognitive Decline

Jung

Lee

Lee³

et al. 2020

Front. Aging Neurosci.

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Background: Multiparity-grand multiparity (i.e., five or more childbirths) in particularhas been reported to have an association with increased risk of Alzheimer's disease (AD) dementia or related cognitive decline in women. However, the pathological links underlying this relationship are still unknown. This study was conducted to examine the relationships of multiparity with cerebral amyloid-beta (Aβ) deposition, brain atrophy, and white matter hyperintensities (WMHs). Methods: In this study, total of 237 older women with 148 cognitively normal and 89 mild cognitive impairment from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) were included. Participants underwent clinical and neuropsychological assessments in addition to 11 C-labeled Pittsburgh Compound B positron emission tomography, and magnetic resonance imaging. The associations of parity with Aβ deposition, hippocampal volume, cortical volume, WMH volume and mini-mental status examination (MMSE) score were examined. Results: Participants with grand multiparity showed significantly reduced adjusted hippocampal volume, spatial pattern of atrophy for recognition of AD volume and spatial pattern of atrophy for recognition of brain aging volume even after controlling for potential confounders. Furthermore, MMSE score was also significantly lower in this group. In contrast, grand multiparity did not show any association with global Aβ retention, Aβ positivity rate, or WMH volume, regardless of covariates. Conclusion: Our findings suggest that grand multiparity contributes to cognitive decline or increased dementia risk in older women by aggravating amyloid-independent hippocampal or cortical atrophy.

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Differential effects of blood insulin and HbA1c on cerebral amyloid burden and neurodegeneration in nondiabetic cognitively normal older adults

Cited by 24 publications

References 82 publications

The Association of Late-Life Diabetes Status and Hyperglycemia With Incident Mild Cognitive Impairment and Dementia: The ARIC Study

The Association of Late-Life Diabetes Status and Hyperglycemia With Incident Mild Cognitive Impairment and Dementia: The ARIC Study

Low fasting serum insulin and dementia in nondiabetic women followed for 34 years

Multiparity, Brain Atrophy, and Cognitive Decline

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