Is Insulin Resistant Brain State a Central Feature of the Metabolic-Cognitive Syndrome?

Frisardi, Vincenza; Solfrizzi, Vincenzo; Capurso, Cristiano; Imbimbo, Bruno P.; Vendemiale, Gianluigi; Seripa, Davide; Pilotto, Alberto; Panza, Francesco

doi:10.3233/jad-2010-100015

Cited by 74 publications

(44 citation statements)

References 69 publications

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“…Hence, a potential overlap between brain regions associated with peripheral insulin resistance and Alzheimer's disease (AD) has been proposed [5]. Among the risk factors proposed for sporadic AD, age, family history and the apolipoprotein E (APOE) ε4 allele are the only recognized to date [6], However, over the last two decades, the role of metabolic syndrome (MetS) and its components [impaired glucose tolerance, abdominal or central obesity, arterial hypertension, hypertriglyceridemia, and reduced high-density lipoprotein (HDL) cholesterol] has largely emerged in the development of CD and dementia, either from vascular or degenerative origin, so that the definition of "metabolic-cognitive syndrome" (MCS) has been proposed [7].…”

Section: Introductionmentioning

confidence: 99%

Midlife Metabolic Profile and the Risk of Late-Life Cognitive Decline

Tortelli

Lozupone

Guerra

et al. 2017

JAD

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Abstract. Among metabolic syndrome components, the effects of higher plasma glucose levels on cognitive decline (CD) have been considered in few studies. We evaluated the associations among midlife glycemia, total cholesterol, high-density lipoprotein cholesterol, triglycerides, midlife insulin resistance [homeostasis model assessment for insulin resistance (HOMAindex)], and CD in the older subjects of the population-based MICOL Study (Castellana Grotte, Italy) at baseline (M1) and at follow-ups seven (M2) and twenty years later (M3). At M1, a dementia risk score and a composite cardiovascular risk score for dementia were calculated. For 797 subjects out of 833, we obtained a Mini-Mental State Examination (MMSE) score at M3, subdividing these subjects in three cognitive functioning subgroups: normal cognition, mild CD, and moderate-severe CD. Mean fasting glycemia at baseline was significantly higher in moderate-severe CD subgroup (114.6 ± 71.4 mg/dl) than in the normal cognition subgroup (101.2 ± 20.6). Adjusting for gender, age, and other metabolic components, higher fasting glycemia values both at M1 [odds ratio (OR) = 1.31; 95% confidence interval (CI): 1.08-1.59] and M2 (OR = 1.26; 95% CI: 1.01-1.57) were associated with an increased risk of moderate-severe CD. Mean HOMA index value was significantly higher in the moderate-severe CD subgroup (5.7 ± 9.4) compared to the normal cognition subgroup (2.9 ± 1.4) at M1. The dementia risk probability (MMSE < 24) increased moving through higher categories of the dementia risk score and decreased as long as the cardiovascular score increased. The present findings highlighted the indication to control blood glucose levels, regardless of a diagnosis of diabetes mellitus, as early as midlife for prevention of late-life dementia.

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Section: Introductionmentioning

confidence: 99%

Midlife Metabolic Profile and the Risk of Late-Life Cognitive Decline

Tortelli

Lozupone

Guerra

et al. 2017

JAD

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“…A growing body of evidence points to the importance of a condition of the insulin inability to serve its physiological function in the brain, in literature described by two alternative terms, ''brain insulin resistance'' (BIR) (Su et al 2017;Talbot et al 2012; or ''insulin resistant brain state'' (IRBS) (Correia et al 2013;Frisardi et al 2010;Plaschke et al 2010a, b;SalkovicPetrisic et al 2009). At the molecular level, BIR is characterized by a reduced response to insulin signalling generally downstream the insulin receptor (IR)-insulin receptor substrate (IRS)-phosphatidyl inositol kinase-3 (PI-3) pathway in the brain, which, particularly considering the neurotrophic, neuroprotective, and neuromodulatory roles of brain insulin, may lead to neurodegeneration and cognitive impairment as seen in AD as well as metabolic alterations in hypothalamic functions, as seen in obesity and T2DM (Kullmann et al 2016).…”

Section: Glycemic Controlmentioning

confidence: 99%

The diabetic brain and cognition

et al. 2017

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The prevalence of both Alzheimer's disease (AD) and vascular dementia (VaD) is increasing with the aging of the population. Studies from the last several years have shown that people with diabetes have an increased risk for dementia and cognitive impairment. Therefore, the authors of this consensus review tried to elaborate on the role of diabetes, especially diabetes type 2 (T2DM) in both AD and VaD. Based on the clinical and experimental work of scientists from 18 countries participating in the International Congress on Vascular Disorders and on literature search using PUBMED, it can be concluded that T2DM is a risk factor for both, AD and VaD, based on a pathology of glucose utilization. This pathology is the consequence of a disturbance of insulin-related mechanisms leading to brain insulin resistance. Although the underlying pathological mechanisms for AD and VaD are different in many aspects, the contribution of T2DM and insulin resistant brain state (IRBS) to cerebrovascular disturbances in both disorders

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“…It is based on the co-existence, in patients, of metabolic syndrome and cognitive impairment of degenerative or vascular origin. 22 Insulin resistance can be manifested in peripheral tissues or directly in the brain as an insulin resistance brain state that contributes to cognitive impairment and neurodegeneration for the reason described above. 22 Many molecules participate in the regulation of the insulin signaling pathway; therefore, an alteration in the function or expression of some of these proteins causes a reduction in glucose uptake.…”

Section: Metabolic-cognitive Syndrome: Insulin and The Central Nervoumentioning

confidence: 99%

“…In particular insulin resistance might be the first step toward both disorders, constituting a bridge between AD and metabolic syndrome. 22 …”

Section: Introductionmentioning

confidence: 99%

Can Alzheimer Disease Be a Form of Type 3 Diabetes?

Accardi

Caruso

Colonna‐Romano

et al. 2012

Rejuvenation Research

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Alzheimer disease (AD) and metabolic syndrome are two highly prevalent pathological conditions of Western society due to incorrect diet, lifestyle, and vascular risk factors. Recent data have suggested metabolic syndrome as an independent risk factor for AD and pre-AD syndrome. Furthermore, biological plausibility for this relationship has been framed within the ''metabolic cognitive syndrome'' concept. Due to the increasing aging of populations, prevalence of AD in Western industrialized countries will rise in the near future. Thus, new knowledge in the area of molecular biology and epigenetics will probably help to make an early molecular diagnosis of dementia. An association between metabolic syndrome and specific single-nucleotide polylmorphisms (SNPs) in the gene INPPL1, encoding for SHIP2, a SH2 domain-containing inositol 5-phosphatase involved in insulin signaling, has been described. According to recent data suggesting that Type 2 diabetes represents an independent risk factor for AD and pre-AD, preliminary results of a case-control study performed to test the putative association between three SNPs in the SHIP2 gene and AD show a trend toward association of these SNPs with AD.

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Is Insulin Resistant Brain State a Central Feature of the Metabolic-Cognitive Syndrome?

Cited by 74 publications

References 69 publications

Midlife Metabolic Profile and the Risk of Late-Life Cognitive Decline

Midlife Metabolic Profile and the Risk of Late-Life Cognitive Decline

The diabetic brain and cognition

Can Alzheimer Disease Be a Form of Type 3 Diabetes?

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