Metabolic syndrome and the risk of vascular dementia: the Italian Longitudinal Study on Ageing

Solfrizzi, Vincenzo; Scafato, Emanuele; Capurso, Cristiano; D’Introno, Alessia; Colacicco, Anna M.; Frisardi, Vincenza; Vendemiale, Gianluigi; Baldereschi, Marzia; Crepaldi, Gaetano; Carlo, Antonio Di; Galluzzo, Lucia; Gandin, Claudia; Inzitari, Domenico; Maggi, S.; Capurso, Antonio; Panza, Francesco

doi:10.1136/jnnp.2009.181743

Cited by 117 publications

(69 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recent work from Stepp's group clearly demonstrated an increase in stroke infarct severity in OZR (39,40). Given that cognitive impairments and vascular dementia have also been linked to impairments of cerebral blood flow regulation, the cerebrovascular adaptations in MetS may represent key contributors to multiple cerebral pathologies (45,46,48). We previously reported a decrease in cerebral cortical microvascular density associated with MetS and suggested that this rarefaction may contribute to either accumulated stroke risk or poor health outcomes in afflicted individuals (7).…”

Section: Discussionmentioning

confidence: 97%

Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats

Brooks

DeVallance

d’Audiffret

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

-The metabolic syndrome (MetS) is highly prevalent in the North American population and is associated with increased risk for development of cerebrovascular disease. This study determined the structural and functional changes in the middle cerebral arteries (MCA) during the progression of MetS and the effects of chronic pharmacological interventions on mitigating vascular alterations in obese Zucker rats (OZR), a translationally relevant model of MetS. The reactivity and wall mechanics of ex vivo pressurized MCA from lean Zucker rats (LZR) and OZR were determined at 7-8, 12-13, and 16 -17 wk of age under control conditions and following chronic treatment with pharmacological agents targeting specific systemic pathologies. With increasing age, control OZR demonstrated reduced nitric oxide bioavailability, impaired dilator (acetylcholine) reactivity, elevated myogenic properties, structural narrowing, and wall stiffening compared with LZR. Antihypertensive therapy (e.g., captopril or hydralazine) starting at 7-8 wk of age blunted the progression of arterial stiffening compared with OZR controls, while treatments that reduced inflammation and oxidative stress (e.g., atorvastatin, rosiglitazone, and captopril) improved NO bioavailability and vascular reactivity compared with OZR controls and had mixed effects on structural remodeling. These data identify specific functional and structural cerebral adaptations that limit cerebrovascular blood flow in MetS patients, contributing to increased risk of cognitive decline, cerebral hypoperfusion, and ischemic stroke; however, these pathological adaptations could potentially be blunted if treated early in the progression of MetS. metabolic syndrome; cerebrovascular remodeling; arterial stiffness; reactive oxygen species NEW & NOTEWORTHY We describe the temporal development of alterations in wall mechanics and vascular reactivity of middle cerebral arteries of obese Zucker rats through evolution of the metabolic syndrome. While novel, this study is particularly noteworthy, as we also use clinically relevant agents against the metabolic syndrome given from an early age to determine vascular outcomes.THE METABOLIC SYNDROME (MetS), a clustering of metabolic abnormalities such as obesity, impaired glycemic control, atherogenic dyslipidemia, and hypertension, with the additional contributing conditions of a prooxidant, prothrombotic, and proinflammatory state, is prevalent in ϳ56 million adults in the United States (21). Correspondingly, MetS is associated with a threefold increased risk of cardiovascular mortality (21) and a 50% increased risk of stroke (5) and is a known risk factor for cognitive decline with aging (41). It is therefore imperative that translationally relevant models of MetS be effectively interrogated to guide our understanding of the cerebrovascular adaptations that are associated with the development of MetS, its physiological, molecular, and genomic mechanistic underpinnings, and the effectiveness of established and novel therapeutic agents in either blunti...

show abstract

Section: Discussionmentioning

confidence: 97%

Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats

Brooks

DeVallance

d’Audiffret

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Several population-based studies suggested that the presence of MetS increased the risk of developing age-related CD, mild cognitive impairment (MCI), AD, and vascular dementia (VaD) [8][9][10][11] and the risk of progression from MCI to dementia [11]. Furthermore, individual components of MetS have been linked to the risk of developing CD and dementia.…”

Section: Introductionmentioning

confidence: 99%

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

Tortelli

Lozupone

Guerra

et al. 2017

JAD

View full text Add to dashboard Cite

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.

show abstract

“…Importantly, the above conditions have a prolonged occurrence during aging (Seshadri and Wolf 2007;Debette et al 2011;DeCarli 2013;DeCarli et al 1995;Jack et al 2013;Swan et al 1998). A synergistic interaction between the above comorbid conditions and the ongoing dysfunction of BFB and LC may exert several deleterious impacts and enhance cognitive decline and promote MCI and AD (Sloane et al 1999;Benveniste et al 2001;Nakanishi 2003;Dik et al 2007;Solfrizzi et al 2010Solfrizzi et al , 2011Misiak et al 2012;Birdsill et al 2013).…”

Section: Commentsmentioning

confidence: 99%

Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer’s Disease

Daulatzai

2016

Neurotox Res

View full text Add to dashboard Cite

Sporadic Alzheimer's disease (AD) is a devastating neurodegenerative disorder. It is essential to unravel its etiology and pathogenesis. This should enable us to study the presymptomatic stages of the disease and to analyze and reverse the antemortem behavioral, memory, and cognitive dysfunction. Prima facie, an ongoing chronic vulnerability involving neural insult may lead normal elderly to mild cognitive impairment (MCI) and then to AD. Development of effective preventive and therapeutic strategies to thwart the disease pathology obviously requires a thorough delineation of underlying disruptive neuropathological processes. Our sensory capacity for touch, smell, taste, hearing, and vision declines with advancing age. Declines in different sensory attributes are considered here to be the primary "first-tier pathologies." Olfactory loss is among the first clinical signs of neurodegenerative diseases including AD and Parkinson's disease (PD). Sensory dysfunction in the aged promotes pathological disturbances in the locus coeruleus, basal forebrain, entorhinal cortex, hippocampus, and several key areas of neocortex and brainstem. Hence, sensory dysfunction is the pivotal factor that may upregulate cognitive and memory dysfunction. The age-related constellation of comorbid pathological factors may include apolipoprotein E (APOE) genotype, obesity, diabetes, hypertension, alcohol abuse, head trauma, and obstructive sleep apnea. The concepts and trajectories delineated here are the dynamic pillars of the current hypothesis presented-it postulates that the sensory decline, in conjunction with the above pathologies, is crucial in triggering neurodegeneration and promoting cognitive/memory dysfunction in aging and AD. The application of this thesis can be important in formulating new multifactorial preventive and treatment strategies (suggested here) in order to attenuate cognitive and memory decline and ameliorate pathological dysfunction in aging, MCI, and AD.

show abstract

Metabolic syndrome and the risk of vascular dementia: the Italian Longitudinal Study on Ageing

Abstract: In our population, MetS subjects had an elevated risk of VaD that increased after excluding patients with baseline undernutrition and selecting MetS subjects with high inflammation.

Cited by 117 publications

References 30 publications

Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats

Metabolic syndrome impairs reactivity and wall mechanics of cerebral resistance arteries in obese Zucker rats

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

Dysfunctional Sensory Modalities, Locus Coeruleus, and Basal Forebrain: Early Determinants that Promote Neuropathogenesis of Cognitive and Memory Decline and Alzheimer’s Disease

Contact Info

Product

Resources

About