Central obesity and increased risk of dementia more than three decades later

Whitmer, Rachel A.; Gustafson, Deborah; Barrett-Connor, E.; Haan, Mary N.; Gunderson, Erica P.; Yaffe, Kristine

doi:10.1212/01.wnl.0000306313.89165.ef

Cited by 665 publications

(476 citation statements)

References 51 publications

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“…In human, there are some similar association studies: Obesity increases the likelihood of systemic inflammation (Almond, Edwards, Barclay, & Johnston, 2013), and white‐fat tissue has a high percentage of activated macrophages secreting proinflammatory cytokines (Bastard et al, 2006); thus, it is not surprising to find that midlife obesity is a risk factor for AD (Whitmer et al, 2008). Data from microbiome studies (see below) have also provided supporting evidence on this issue.…”

Section: Systems Level Events In Aging and Admentioning

confidence: 92%

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

et al. 2018

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Alzheimer's disease is the most prevalent cause of dementia, which is defined by the combined presence of amyloid and tau, but researchers are gradually moving away from the simple assumption of linear causality proposed by the original amyloid hypothesis. Aging is the main risk factor for Alzheimer's disease that cannot be explained by amyloid hypothesis. To evaluate how aging and Alzheimer's disease are intrinsically interwoven with each other, we review and summarize evidence from molecular, cellular, and system level. In particular, we focus on study designs, treatments, or interventions in Alzheimer's disease that could also be insightful in aging and vice versa.

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Section: Systems Level Events In Aging and Admentioning

confidence: 92%

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

et al. 2018

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“…While aging is still the most important risk factor for late onset sporadic Alzheimer's Disease (AD), several studies have pointed high adiposity as an independent contributor for the development of this type of dementia (Gorospe and Dave 2007;Beydoun et al 2008;Whitmer et al 2008). In fact, life-long relation between adiposity and cognition has triggered some questions about the mechanisms by which adipose tissue might influence cerebral structures related to learning and memory, namely if its action is dependent on insulin resistance state (Fig.…”

Section: Introductionmentioning

confidence: 99%

Obesity as a risk factor for Alzheimer’s disease: the role of adipocytokines

2014

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Alzheimer's disease is the leading cause of dementia and the most prevalent neurodegenerative disease. It is an aging-related multi-factorial disorder and growing evidence support the contribution of metabolic factors to what was formerly thought to be a centrally mediated process. Obesity has already been recognized as an important player in the pathogenesis of this type of dementia, independently of insulin resistance or other vascular risk factors. Although the exact underlying mechanisms are still unknown, adipocyte dysfunction and concomitant alteration in adipocyte-derived protein secretion seem to be involved, since these adipocytokines can cross the blood-brain barrier and influence cognitive-related structures. Very few studies have assessed the role of adipocytokines dysfunction on cognitive impaired patients and yielded contradictory results. Interestingly, extensive research on the central effects of leptin in Alzheimer's diseasetransgenic mice has demonstrated its capacity to enhance synaptic plasticity and strength, as well as to prevent betaamyloid deposition and tau phosphorylation. In addition, adiponectin, the most abundant adipocytokine whose levels are inversely correlated to adiposity, has shown to be neuroprotective to hippocampal cells. Many other adipose-derived cytokines have mainly pro-inflammatory properties, being able to trigger and/or enhance central inflammatory cascades and also to influence the secretion of other adipocytokines involved in cognition. This paper pretends to review the existing evidence on the contribution of adipocytokines dysfunction to the increased risk of dementia associated with midlife obesity, unraveling its insulin-independent effects on cognition.

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“…The studies done on animals have revealed that obesity leads to a reduction in insulin binding onto receptors on the endothelial cells of brain microvessels and impairs transendothelial transport across the brain-blood barrier [25]. Human and animal studies also indicate that obesity and IR are related to cognitive dysfunction [26][27][28]. In our study, we investigated cognitive functions using the WISC-R scale.…”

Section: Discussionmentioning

confidence: 94%

Relation of insulin resistance to neurocognitive function and electroencephalography in obese children

Akın

Eker

Arslan

et al. 2017

Journal of Pediatric Endocrinology and Metabolism

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Background: Childhood obesity may lead to neuronal impairment in both the peripheral and the central nervous system. This study aimed to investigate the impact of obesity and insulin resistance (IR) on the central nervous system and neurocognitive functions in children. Methods: Seventy-three obese children (38 male and 35 female) and 42 healthy children (21 male and 21 female) were recruited. Standard biochemical indices and IR were evaluated. The Wechsler Intelligence Scale for Children-Revised (WISC-R) and electroencephalography (EEG) were administered to all participants. The obese participants were divided into two groups based on the presence or absence of IR, and the data were compared between the subgroups. Results: Only verbal scores on the WISC-R in the IR+ group were significantly lower than those of the control and IRgroups. There were no differences between the groups with respect to other parameters of the WISC-R or the EEG. Verbal scores of the WISC-R were negatively correlated with obesity duration and homeostatic model assessmentinsulin resistance (HOMA-IR) values. EEGs showed significantly more frequent 'slowing during hyperventilation' (SDHs) in obese children than non-obese children.

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Central obesity and increased risk of dementia more than three decades later

Abstract: Central obesity in midlife increases risk of dementia independent of diabetes and cardiovascular comorbidities. Fifty percent of adults have central obesity; therefore, mechanisms linking central obesity to dementia need to be unveiled.

Cited by 665 publications

References 51 publications

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

Aging and Alzheimer’s disease: Comparison and associations from molecular to system level

Obesity as a risk factor for Alzheimer’s disease: the role of adipocytokines

Relation of insulin resistance to neurocognitive function and electroencephalography in obese children

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