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 Table of Contents  
Year : 2018  |  Volume : 5  |  Issue : 1  |  Page : 1-3

Metabolic-cognitive syndrome: Is this understanding useful?

Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication27-Jun-2018

Correspondence Address:
Sandeep Grover
Department of Psychiatry, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jgmh.jgmh_14_18

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How to cite this article:
Grover S. Metabolic-cognitive syndrome: Is this understanding useful?. J Geriatr Ment Health 2018;5:1-3

How to cite this URL:
Grover S. Metabolic-cognitive syndrome: Is this understanding useful?. J Geriatr Ment Health [serial online] 2018 [cited 2023 Feb 2];5:1-3. Available from:

Metabolic syndrome (MetS) is conceptually understood as a clinical syndrome, which can help in detecting people at risk of developing diabetes mellitus, hypertension, and dyslipidemia. It is considered as a state of chronic low-grade inflammation as a consequence of complex interplay between genetic and environmental factors. There are different definitions of MetS.[1],[2],[3],[4],[5],[6] These definitions have included factors such as glucose intolerance (impaired glucose tolerance test or present of diabetes mellitus)/raised fasting blood sugar levels (mg/dl), increased blood pressure (mm Hg), raised triglycerides (mg/dl) levels, low high-density lipoprotein (HDL) (mg/dl) levels, obesity as measured in the form of increased waist circumference (in cm) or increased waist-hip ratio, high urinary albumin excretion (μg/min) and 2-h postglucose challenge. Among these factors, the five factors which have been included in most of the recent definitions include increased waist circumference (population/ethnic-specific), raised blood pressure (≥130 or ≥85 mm of Hg or diagnosed with hypertension), fasting blood glucose levels of ≥100 mg/dL or diagnosed with diabetes mellitus, triglyceride levels ≥150 mg/dL or receiving lipid-lowering agents, HDL levels <40 for men and <50 for women or receiving lipid-lowering agents.[1],[2],[3],[4],[5],[6] To consider someone as having MetS, there is a need to fulfill at least 3 out of the 5 given criteria.[1],[2],[3],[4],[5],[6] There is also some consensus on considering the ethnic/population specific waist circumference while defining MetS.[6]

It is suggested that MetS is an outcome of genetic risk factors, lack of exercise, and excessive intake, all of which lead to insulin resistance, visceral obesity, dysregulation of the hypothalamo-pituitary axis, and dyslipidemia. These factors lead to increase in the pro-inflammatory cytokines which lead to the development of MetS.[7]

It is now increasingly recognized that central obesity, diabetes mellitus, hypertension, and dyslipidemia play a crucial role in the development of dementia.[8],[9],[10],[11],[12],[13],[14],[15] These factors contribute to increased cerebral vascular resistance, decreased capillary density, and decreased cerebral autoregulation. These changes lead to the development of white matter hyperintensities and cerebral atrophy. There is evidence to suggest that obesity, diabetes mellitus, hypertension, and dyslipidemia are related to the development of mild cognitive impairment (MCI) and dementia.[8],[9],[10],[11],[12],[13],[14],[15] It is considered that the besides these factors acting as risk factors for cognitive decline, these factors also possibly share some of the risk factors, i.e., genetic factors and lifestyle factors, which are reported to be associated with the development of cognitive decline and dementia.[8],[9],[10],[11],[12],[13],[14],[15]

However, it is important to remember that, once these diagnoses are established, it is too late to intervene to prevent the development of cognitive decline. Accordingly, it can be said that MetS, which is considered as risk factor for the development of diabetes, hypertension, dyslipidemia, and coronary artery disease can also act as an important risk factor for the development of dementia. This understanding has given rise to the concept of Metabolic Cognitive Syndrome (MCS).

The concept of MCS was first given by Frisardi et al. in 2010.[16] They used this term to describe a state which included the presence of MetS and cognitive impairment of degenerative or vascular origin. They hypothesized that this entity could help us in improving our understanding about the clinical and neuropathological features of these cognitive disorders.[16] It was further suggested that the term MCS should not be considered as a clinical label but rather must be considered as pathophysiological model which can help in identifying patients with MetS plus cognitive impairment of degenerative or vascular origin, and help in understanding the neuropsychological and neuropathological features of these predementia or dementia syndromes associated to MetS.[17]

Over the past few years, attempts have been made to evaluate this entity and look at the association of MetS with cognitive decline.[18],[19] Studies have shown association of MetS with decreased capillary density, decreased cerebral arterial vasodilation response, thickening of intima-media, decreased cerebral blood flow, vasomotor reactivity, decreased cerebral blood flow in the medial and lateral aspects of frontal, and parietal lobe gray matters and increase in arterial thickness.[20],[21] In addition, evidence also suggests association of MetS with poor immediate memory, decreased fluid intelligence, reduced global cognitive functioning, impaired executive functions, poor attention, poor recall, and poor visuospatial performance.[21] MetS have also been shown to have detrimental effect on psychomotor speed, verbal memory and fluency, and attention.[20] Some of the data suggest that decrement in executive function (as well as information processing speed and verbal memory) is the most frequently reported cognitive impairment. Some of the available data from various cross-sectional studies also suggests that present of MetS is associated with higher risk of Alzheimer's dementia (AD), increased risk of developing vascular dementia, increased risk of progression from MCI to dementia.[20],[22] However, few studies contradict these associations. There are some data to suggest that in populations aged ≥75 years, having MetS was associated with a lower risk of developing AD, and associated with decelerated cognitive decline.[22] However, it is important to remember that the cross-sectional studies are not sufficient to establish a cause and effect relationship. To overcome this limitation, many population-based longitudinal studies have evaluated the cause and effect relationship of MetS with cognitive decline.[23],[24],[25],[26],[27],[28],[29],[30],[31] These studies suggest that during the follow-up period varying from 1 to 13 years, presence of MetS at the baseline is associated with increased risk of cognitive decline, higher risk of progression from MCI to dementia, higher level of cognitive and functional decline in activities of daily living and instrumental activities of daily living by 10 years. In terms of cognitive domains, presence of MetS has been shown to be associated with worst performance in the domains of information processing speed, attention, and executive functioning (inconsistently reported) and memory (inconstantly reported).[23],[24],[25],[26],[27],[28],[29],[30],[31] In terms of effect of age, available data also suggest that the MetS may be a risk factor for cognitive decline in the young and young-elderly, but the effect is not seen in those 80 or above possibly because of development of physical morbidities.[22],[23],[24],[25],[26],[27],[28],[29],[30] An interesting finding which has been noted in some studies suggests that cognitive decline may not be related to individual components of MetS, but is related to the MetS per se.[22],[23],[24],[25],[26],[27],[28],[29],[30] Occasional study also suggests the synergistic effect of MetS and Apoε4.[32] The strength of association of MetS with cognitive decline in some of these studies can be understood by the fact that, this association is present, even after controlling for confounding variables. However, these studies are criticized for not using the same set of cognitive test for assessing the association.[23],[24],[25],[26],[27],[28],[29],[30],[31] Although the exact pathophysiological mechanisms involved require further decoding, it is suggested that possibly the metabolic-hormonal changes which occur over the course of MetS may be detrimental for neuronal cells and are resultantly responsible for development of dementia.

In the last one decade or so, understanding about the concept of MCS has improved. This concept can have multiple implications, i.e., can help in prevention of dementia, early intervention and furthering the understanding about pathophysiological mechanisms associated with development of dementia. The current level of understanding suggests that the concept of MCS provides an important window for primary prevention of dementia. Changing the modifiable risk factors can reduce the incidence of dementia and also possibly delay the onset of dementia. Further, identification of a clinical profile of the MCS could be central in detecting in these patients a molecular profile of higher risk to develop predementia or dementia syndromes. The MCS model could also help us to explain the complex relationship between metabolic disorders and cognitive disturbances and the boundaries between normal and pathological conditions, with a better understanding of clinical and neuropathological features of these metabolic-based cognitive disorders.[18]

India is considered to be diabetes capital of the World [33] and recent data also suggest that the figures for hypertension in India may also be comparable to that of diabetes mellitus.[34] In the year 2013, it was estimated that 65.1 million people aged between 20 and 79 years were suffering from diabetes mellitus and it is estimated that this number is going to increase to 109 million by 2035.[35] Accordingly, in this country, there is an urgent need to prevent the development of these noncommunicable diseases (NCDs), to reduce the associated morbidity, mortality, and health-care costs. Considering the association of cognitive decline with these NCDs, it can be said that in the future, India, may also emerge as the world capital for dementia, if timely interventions are not done. At present, there is gross lack of data in terms of association of MetS and cognitive decline. There is an urgent need to study this association in community samples. Understanding the progress from MetS to overt NCDs and development of dementia can also help in identifying other associated risk and protective factors for development of dementia.

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