Insulin resistance and hippocampal volume in women at risk for Alzheimer's disease

Rasgon, Natalie; Kenna, Heather A.; Wroolie, Tonita; Kelley, Ryan; Silverman, Daniel; Brooks, John S.; Williams, Katherine E.; Powers, Bevin; Hallmayer, Joachim; Reiss, Allan L.

doi:10.1016/j.neurobiolaging.2009.12.005

Cited by 155 publications

(118 citation statements)

References 37 publications

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“…Findings were similar to those of the current study, in that results were not solely attributable to possession of the APOEe4 allele. 17,19,21 This similarity further supports our assertion that factors associated with glucose control may impart an independent contribution to AD risk.…”

supporting

confidence: 85%

“…17 Other structural MRI studies of AD risk have also demonstrated that higher levels of insulin resistance have been associated with increased total cerebral brain atrophy 20 and lower right and total hippocampal volume. 21 Furthermore, select studies also considered the genetic contribution to imaging outcomes. Findings were similar to those of the current study, in that results were not solely attributable to possession of the APOEe4 allele.…”

mentioning

confidence: 99%

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Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions

Burns¹,

Chen²,

Kaszniak³

et al. 2013

Neurology

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Objective: To investigate whether higher fasting serum glucose levels in cognitively normal, nondiabetic adults were associated with lower regional cerebral metabolic rate for glucose (rCMRgl) in brain regions preferentially affected by Alzheimer disease (AD).Methods: This is a cross-sectional study of 124 cognitively normal persons aged 64 6 6 years with a first-degree family history of AD, including 61 APOEe4 noncarriers and 63 carriers. An automated brain mapping algorithm characterized and compared correlations between higher fasting serum glucose levels and lower [18 F]-fluorodeoxyglucose-PET rCMRgl measurements.Results: As predicted, higher fasting serum glucose levels were significantly correlated with lower rCMRgl and were confined to the vicinity of brain regions preferentially affected by AD. A similar pattern of regional correlations occurred in the APOEe4 noncarriers and carriers.Conclusions: Higher fasting serum glucose levels in cognitively normal, nondiabetic adults may be associated with AD pathophysiology. Findings suggest that the risk imparted by higher serum glucose levels may be independent of APOEe4 status. This study raises additional questions about the role of the metabolic process in the predisposition to AD and supports the possibility of targeting these processes in presymptomatic AD trials. Diabetes and related metabolic disorders have been associated with an increased risk of the development of Alzheimer disease (AD).1,2 Elevated fasting serum glucose, an indicator of metabolic dysfunction, has been linked to decreased memory functioning in cognitively normal older adults 3 and may be a risk factor for cognitive impairment 4 or predisposition to AD. 5Therefore, AD prevention research may benefit from the study of elevated fasting serum glucose and the factors that regulate glucose control in cognitively normal individuals without diabetes. [18 F]-Fluorodeoxyglucose (FDG)-PET has demonstrated reduced regional cerebral metabolic rate for glucose (rCMRgl) in specific brain regions of patients with AD. 6,7 Cognitively healthy, older individuals with 1 or 2 copies of the APOEe4 allele have exhibited reductions in these same AD-affected areas, which may indicate a predisposition to AD. 8,9 As in similar studies designed to assess the genetic, nongenetic, and perhaps interacting factors contributing to AD development, 10,11 we propose the use of FDG-PET as a measure of presymptomatic risk 12 in the evaluation of the association between fasting serum glucose levels and rCMRgl in nondiabetic, healthy adults before the onset of AD.In the present study, we utilized FDG-PET to test the hypothesis that higher fasting serum glucose levels in cognitively normal adults without diabetes are associated with lower rCMRgl in brain regions previously demonstrated to be affected in AD. 6 We also characterized these associations in APOEe4 noncarriers and carriers, and tested for a predicted interaction between elevated fasting serum glucose and APOEe4 status in AD-affected brain regions.

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supporting

confidence: 85%

mentioning

confidence: 99%

Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions

Burns¹,

Chen²,

Kaszniak³

et al. 2013

Neurology

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“…Consequently, participants with type 2 diabetes mellitus (T2DM) typically display smaller hippocampal volumes than nondiabetic controls (den Heijer et al, 2003;Gold et al, 2007;Bruehl et al, 2009;Wrighten et al, 2009;Brundel et al, 2010;Hayashi et al, 2011). The hippocampal volume alterations may occur already in participants with impaired glucose tolerance (Convit et al, 2003) or insulin resistance (IR, Rasgon et al, 2011;Willette et al, 2013). The brain changes in T2DM or IR may not be isolated to the hippocampus, as suggested by some studies (Gold et al, 2007;Bruehl et al, 2009;Brundel et al, 2010;Rasgon et al, 2011;Willette et al, 2013), but may extend into cortical regions (Benedict et al, 2012;Moran et al, 2013;Willette et al, 2013;Garcia-Casares et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Insulin Resistance, Diabetes Mellitus, and Brain Structure in Bipolar Disorders

Hájek

Calkin

Blagdon

et al. 2014

Neuropsychopharmacol

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Type 2 diabetes mellitus (T2DM) damages the brain, especially the hippocampus, and frequently co-occurs with bipolar disorders (BD). Reduced hippocampal volumes are found only in some studies of BD subjects and may thus be secondary to the presence of certain clinical variables. Studying BD patients with abnormal glucose metabolism could help identify preventable risk factors for hippocampal atrophy in BD. We compared brain structure using optimized voxel-based morphometry of 1.5T MRI scans in 33 BD subjects with impaired glucose metabolism (19 with insulin resistance/glucose intolerance (IR/GI), 14 with T2DM), 15 euglycemic BD participants and 11 euglycemic, nonpsychiatric controls. The group of BD patients with IR, GI or T2DM had significantly smaller hippocampal volumes than the euglycemic BD participants (corrected p ¼ 0.02) or euglycemic, nonpsychiatric controls (corrected p ¼ 0.004). Already the BD subjects with IR/GI had smaller hippocampal volumes than euglycemic BD participants (t(32) ¼ À 3.15, p ¼ 0.004). Age was significantly more negatively associated with hippocampal volumes in BD subjects with IR/GI/T2DM than in the euglycemic BD participants (F(2, 44) ¼ 9.96, p ¼ 0.0003). The gray matter reductions in dysglycemic subjects extended to the cerebral cortex, including the insula. In conclusion, this is the first study demonstrating that T2DM or even prediabetes may be risk factors for smaller hippocampal and cortical volumes in BD. Abnormal glucose metabolism may accelerate the age-related decline in hippocampal volumes in BD. These findings raise the possibility that improving diabetes care among BD subjects and intervening already at the level of prediabetes could slow brain aging in BD.

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“…It was demonstrated that brain aging is associated with a decrease of central insulin concentration [64][65][66], with an impairment of insulin receptor binding ability, resulting in an increase in deterioration of glucose homeostasis in the brain. Brain insulin resistance [67] is associated to peripheral insulin resistance-a typical feature of elder ages, associated to atherogenic dyslipidemia [65], and ET influences insulin resistance in medial prefrontal gyrus metabolism.…”

Section: Hypothesis On Brain Aging and Neurodegeneration During Perimmentioning

confidence: 99%

Neuroprotection in Perimenopausal Women

Russu¹,

Antonescu²

2018

Sex Hormones in Neurodegenerative Processes and Diseases

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Endocrine and neural senescence overlap in time, by intertwined complex feedback loops. Womens' brain is genetically more prone to suffer during life, and perimenopause is a "critical period" in neuroaging, when the degenerative processes begin. Many hypotheses on the multifactorial nature of women's brain aging are elaborated, and tested in high-tech research centers. The most analyzed Alzheimer's disease (AD) is characterized not only by Aβ oligomers and fibrils accumulation, but also by metabolic and inflammatory changes, with the onset during menopausal transition and early years of menopause. Deep analysis of endocrine, neural, and metabolic pathways are giving new insights to the sequential view of Aβ-centric in AD pathogenesis, prevention, and treatment from perimenopause, for maintaining women's neurological health.

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Insulin resistance and hippocampal volume in women at risk for Alzheimer's disease

Cited by 155 publications

References 37 publications

Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions

Higher serum glucose levels are associated with cerebral hypometabolism in Alzheimer regions

Insulin Resistance, Diabetes Mellitus, and Brain Structure in Bipolar Disorders

Neuroprotection in Perimenopausal Women

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