Metabolic Syndrome and Cognitive Impairment: Current Epidemiology and Possible Underlying Mechanisms

Abstract

A possible role of vascular and lifestyle-related factors was recently proposed for age-related changes of cognitive function, predementia syndromes, and cognitive decline of degenerative (Alzheimer's disease, AD) or vascular origin (vascular dementia, VaD). At present, cumulative evidence suggests that vascular risk factors may be important in the development of mild cognitive impairment (MCI), dementia, and AD. Among vascular-related factors, metabolic syndrome (MetS) has been associated with the risk of cognitive decline, overall dementia, and VaD, but contrasting findings also existed on the possible role of MetS in AD. If MetS is associated with increased risk of developing cognitive impairment, regardless of mechanism, then early identification and treatment of these individuals at risk might offer new avenues for disease-course modification. Strategies towards early and effective risk factor management could be of value in reducing risk of metabolic and cognitive decline. Future research is needed to confirm the association between MetS and cognitive impairment and to determine the exact mechanism linking them. Such would provide important insights into the causes and interdependencies of predementia and dementia syndromes, and inspire novel strategies for treating and preventing these disorders. At present, vascular risk factor and MetS management could be employed to delay the onset of dementia syndromes or to prevent the progression of predementia syndromes. In the future, trials could be undertaken to determine whether modifications of these risk factors, including inflammation, could lower risk of developing cognitive decline.

Angiotensin-converting enzyme inhibitors and incidence of mild cognitive impairment. The Italian Longitudinal Study on Aging

“…This is particularly relevant for MCI which is recognized to be a pathology-based condition with a high rate of progression to AD (Petersen et al 1999), and thus, the BBB may have already been compromised in our MCI patients. The inclusion in the analyses of untreated hypertensives was important to identify the risk contribution of hypertension to incident MCI (Panza et al 2010). The exclusion of this sub-sample would have reduced the risk of incident MCI.…”

“…Both longitudinal and cross-sectional studies suggested that elevated midlife blood pressure or hypertension contribute to the development of Alzheimer's disease (AD) and overall dementia, although this effect is weaker in the years preceding dementia onset (Panza et al 2010). In particular, hypertension at baseline was related to greater cognitive decline or mild cognitive impairment (MCI) (Panza et al 2010).…”

“…Both longitudinal and cross-sectional studies suggested that elevated midlife blood pressure or hypertension contribute to the development of Alzheimer's disease (AD) and overall dementia, although this effect is weaker in the years preceding dementia onset (Panza et al 2010). In particular, hypertension at baseline was related to greater cognitive decline or mild cognitive impairment (MCI) (Panza et al 2010). However, blood pressure reduction in randomized controlled trials (RCTs) demonstrated a complex association with reduced cognitive function, supporting the hypothesis that mechanisms beyond the blood-pressurelowering effect of antihypertensive medications may be involved.…”

Neurodevelopmental origin of cognitive impairment in schizophrenia

“…In recent studies, both dose reduction and guided discontinuation of SGAs were shown to lead to cognitive improvement in stable patients (Faber et al 2012;Takeuchi et al 2013). Several factors associated with cognitive dysfunction in healthy subjects, such as metabolic syndrome, chronic substance use and stress (Johnsen & Asbjørnsen, 2008;Panza et al 2010;Stavro et al 2013), are more common in schizophrenia and there is no doubt that they can contribute to cognitive impairment in schizophrenia. For example, some studies have shown that schizophrenia patients who have co-morbid metabolic syndrome, diabetes mellitus, hypertension, obesity, post-traumatic stress disorder (PTSD) and alcohol use disorder have more cognitive impairment than other patients without such comorbidities (Goodman et al 2007;Dickinson et al 2008;Fan et al 2008;Manning et al 2009;Friedman et al 2010;Lindenmayer et al 2012;Takayanagi et al 2012;Guo et al 2013).…”

Diabetes mellitus en pacientes con enfermedad de Alzheimer: descripción clínica y correlación con el genotipo APOE en una muestra de población del departamento de Antioquia, Colombia

“…Vascular factors such as arterial hypertension, dyslipidemia, hyperinsulinemia and DM2, obesity, subclinical atherosclerosis and arrhythmias have been associated with high risks of cognitive impairment and dementia (52). Studies in Latin America have also shown that metabolic syndrome doubles the risk of cognitive impairment (57). Kalaria (58) has indicated that the gradual adoption of westernized lifestyle involving excessive caloric intake, unhealthy diet, and decreased physical activity, favors the appearance of conditions such as AD.…”