Serum leptin level and cognition in the elderly: Findings from the Health ABC Study

Holden, Karen F.; Lindquist, Karla; Tylavsky, Frances A.; Rosano, Caterina; Harris, Tamara B.; Yaffe, Kristine

doi:10.1016/j.neurobiolaging.2007.11.024

Cited by 200 publications

(161 citation statements)

References 58 publications

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“…The authors found that 25% of subjects developed AD in the lowest quartile of leptin as compared to 6% in the highest quartile, and circulating leptin levels correlated with gray matter volume in the brain, specifically in the hippocampus. Further, in another study by Holden et al [47], significantly less likelihood of cognitive decline was observed in elders from the high serum leptin group. However, no correlation between serum leptin levels and cognitive decline in PwAD has been reported either [48].…”

Section: Discussionmentioning

confidence: 89%

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population

Talwar

Grover

Sinha

et al. 2017

Dement Geriatr Cogn Disord

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Background: Alzheimer disease (AD) is a progressive neurodegenerative disease with a complex multifactorial etiology. Here, we aim to identify a biomarker pool comprised of genetic variants and blood biomarkers as predictor of AD risk. Methods: We performed a case-control study involving 108 cases and 159 non-demented healthy controls to examine the association of multiple biomarkers with AD risk. Results: The APOE genotyping revealed that ε4 allele frequency was significantly high (p value = 0.0001, OR = 2.66, 95% CI 1.58-4.46) in AD as compared to controls, whereas ε2 (p = 0.0430, OR = 0.29, CI 0.07-1.10) was overrepresented in controls. In biochemical assays, significant differences in levels of total copper, free copper, zinc, copper/zinc ratio, iron, epidermal growth factor receptor (EGFR), leptin, and albumin were also observed. The AD risk score (ADRS) as a linear combination of 6 candidate markers involving age, education status, APOE ε4 allele, levels of iron, Cu/Zn ratio, and EGFR was created using stepwise linear discriminant analysis. The area under the ROC curve of the ADRS panel for predicting AD risk was significantly high (AUC = 0.84, p < 0.0001, 95% CI 0.78-0.89, sensitivity = 70.0%, specificity = 83.8%) compared to individual parameters. Conclusion: These findings support the multifactorial etiology of AD and demonstrate the ability of a panel involving 6 biomarkers to discriminate AD cases from non-demented healthy controls.

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Section: Discussionmentioning

confidence: 89%

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population

Talwar

Grover

Sinha

et al. 2017

Dement Geriatr Cogn Disord

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“…Jak-Stat, Erk, PI3K/Akt and AMPK [138,139] Leptin is known to affect satiety, food intake and body weight through its action in hypothalamus, but the hormone has more diverse neurotrophic and neuroprotective actions in the brain and also affects hippocampal neurigenesis and long-term potentiation [138,139,140]. Several case-control and large population based prospective studies have shown an inverse association of circulating leptin levels with AD or general cognitive decline [141,142,143]. In case of adiponectin the epidemiological link with AD risk is less clear.…”

Section: Adipokinesmentioning

confidence: 99%

Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment

Chakrabarti¹,

Khemka²,

Banerjee³

et al. 2015

Aging and disease

111

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Alzheimer's disease (AD), the major cause of dementia among the elderly world-wide, manifests in familial and sporadic forms, and the latter variety accounts for the majority of the patients affected by this disease. The etiopathogenesis of sporadic AD is complex and uncertain. The autopsy studies of AD brain have provided limited understanding of the antemortem pathogenesis of the disease. Experimental AD research with transgenic animal or various cell based models has so far failed to explain the complex and varied spectrum of AD dementia. The review, therefore, emphasizes the importance of AD related risk factors, especially those with metabolic implications, identified from various epidemiological studies, in providing clues to the pathogenesis of this complex disorder. Several metabolic risk factors of AD like hypercholesterolemia, hyperhomocysteinemia and type 2 diabetes have been studied extensively both in epidemiology and experimental research, while much less is known about the role of adipokines, proinflammatory cytokines and vitamin D in this context. Moreover, the results from many of these studies have shown a degree of variability which has hindered our understanding of the role of AD related risk factors in the disease progression. The review also encompasses the recent recommendations regarding clinical and neuropathological diagnosis of AD and brings out the inherent uncertainty and ambiguity in this area which may have a distinct impact on the outcome of various population-based studies on AD-related risk factors.

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“…Despite extensive animal research on leptin, there are limited studies in human populations. A subgroup of the Framingham cohort and the Health ABC Study have demonstrated that higher leptin levels were associated with lower dementia risk and higher brain volume 7,7 or 4 years after leptin was assayed, respectively (Lieb et al 2009;Holden et al 2009). On the other hand, Rajagopalan et al (2013) reported that elderly with higher leptin levels (obese) showed concomitant greater global brain atrophy, highlighting the deleterious effect of central leptin insufficiency associated with obesity.…”

Section: Leptinmentioning

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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Serum leptin level and cognition in the elderly: Findings from the Health ABC Study

Cited by 200 publications

References 58 publications

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population

Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population

Metabolic Risk Factors of Sporadic Alzheimer's Disease: Implications in the Pathology, Pathogenesis and Treatment

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

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