Correlation between Metabolic Syndrome and Mild Cognitive Impairment

they refuse to complete investigations. This study had been approved by ethical committee of Al-Azhar University Hospitals. Patients who had dementia (MMSE score less than 24 or CDR more than 0.5), cerebrovascular stroke, aphasia or dysphasia, brain tumor, severe head trauma, parkinsonism, premorbid psychiatric illness (schizophrenia, mood disorders and mental retardation), severe sensory impairment (blindness, deafness), drug and alcohol abuse, chronic medical disease (chronic liver disease, renal disease or COPD), or patients who refused to participate in the study were excluded from the study. The patients were divided into two groups, group (A) met criteria for diagnosis of metabolic syndrome and group (B) don’t have metabolic syndrome. All patients included in the study were subjected to complete medical and neurological history regarding to detailed history about age, gender, residence, education level, weight, height, BMI (body mass index), WC (waist circumference), diabetes mellitus, hypertension, smoking, drug or alcohol abuse and family history of dementia. Detailed history of cognitive impairment (onset, duration, course and aggravating factors). Neurological examination including mental state, cranial nerves, motor, sensory systems and cerebellum. Psychometric tests including MMSE, CDR, ADLS (Activities of Daily Living Scale), Geriatric Depression Scale and Global Deterioration Scale were applied for all patients and also some laboratories were done including random blood sugar, HbA1c, serum cholesterol, triglyceride, LDLP (low density), HDLP (high density) lipoproteins, thyroid function and serum uric acid. CT or MRI brain was done for all patients. The statistical analysis was done using the Chi-squared test with the p-Value less than 0.05 considered significant. This analysis was performed using the SPSS-16 Software and the results were tabulated accordingly.


Introduction
Mild cognitive impairment (MCI) is an etiologically heterogeneous syndrome characterized by memory performance below the normal range, otherwise unimpaired intellectual functioning and well preserved activities of daily living [1]. MCI is a clinical transitional state between the cognitive changes of aging and the earliest clinical features of dementia, a prodromal phase during which slight forgetfulness might be present but other cognitive abilities are preserved [2]. MCI can affect many areas of thought and action such as language, attention, reasoning, judgment, reading and writing. However, the most common variety of MCI causes memory problems [3]. The prevalence of MCI among the population >65 years in developed countries is as high as 10-25% and the annual conversion rate of MCI to AD (Alzheimer`s Disease) has been estimated in general to be about 10-15% [4]. The metabolic syndrome is a clustering of conditions that includes obesity, hypertension, dyslipidemia and impaired glucose metabolism and associated with increase the risk of cardiovascular disease [5]. There is evidence linking the metabolic syndrome with cognitive decline and dementia, but not all studies have found an association [6][7][8]. Several studies were reported that the risk of developing cognitive impairment increase from 2 to 7 times among those with the metabolic syndrome [9,10]. While hypertension [11], diabetes [12], obesity [13], hypertriglyceridemia [14] and impaired glucose tolerance [15] have each been associated with cognitive impairment, ranging from mild cognitive changes to dementia, the relationship between each metabolic risk factor and cognition is complex [16]. The role of the metabolic syndrome on the rate of cognitive decline remains controversial [17]. Early identification of the people with metabolic syndrome and subsequent treatment of their symptoms could modify or prevent the development of cognitive impairment [18,19]. The study aimed to assess the association between metabolic syndrome and MCI in patients aged ≥ 65 years.

Results
The study was carried out on 156 patients aged ≥ 65 years old of both sex divided into two groups, group (A) met criteria for diagnosis of metabolic syndrome and group (B) don't have metabolic syndrome. Group A were 73 patients (44 male and 29 female) with mean age 70.68 ± 5.03 years while group B were 85 patients (62 male and 23 female) with mean age 70.9 ± 6.26 years. Regard education level, about 25% of patients were educated while the remaining either not educated or just read and write and also 22% of patients were smoker (  Table 4). The correlation of result of MMSE score with age of patients, sex, education level and smoking were insignificant (Tables 5 and 6). Also there is a significant correlation between MMSE score and all components of metabolic syndrome and with number of components of Metabolic syndrome, the increase in number of Metabolic syndrome components associated with low score of MMSE (Tables 7 and 8).

Discussion
MCI is an important public health concern due to the increased risk of progression to dementia and increased mortality [20]. The concept of MCI permits timely identification of patients at high risk of developing dementia, thus opening a potentially larger therapeutic window and increasing the significance of modifiable risk factors [21,22]. Early diagnosis and intervention of MCI could postpone or prevent the onset of subsequent dementia. It is critical to identify potentially protective factors for the development of MCI and progression to dementia. One hundred and fifty eight patients aged 65 years old or more of both sex were included in the study, 73 patients (46.2%) have metabolic syndrome (group A) and 85 patients (53.8%) didn't have metabolic syndrome (group B) with no significant difference between both groups regarding age, sex, education level. In our study we found that, metabolic syndrome prevalence was 46% among general populations (56%in females and     [30] reported that cognitive function decreased in the metabolic syndrome group compared to the normal control group. Also several cross-sectional studies reported that, metabolic syndrome was associated with significantly poorer cognitive performance [31][32][33][34][35]. In our study, the metabolic risk factors, diabetes mellitus, hypertension, WC, high triglyceride and low HDL levels affected the MMSE total score and significantly associated with MCI that were agreed with several studies reported that hypertension [36][37][38], diabetes mellitus [39], obesity [14,40], high triglyceride [41,42] and low HDL [43][44][45][46][47] have each been associated with cognitive impairment, ranging from MCI to dementia. The score of MMS was inversely related with number of Metabolic syndrome components, increase in number of metabolic syndrome components associated with increasing degree of cognitive impairment, that agree with [48] who report the same results. In the Longitudinal Aging Study Amsterdam [35], hyperglycemia was a key predictor, while HDL-C was found to be the most important predictor in the current study as noted above, and this was agree with [49], while [50] concluded that, high triglycerides was the most important predictor of vascular dementia. Regarding DM and cognitive impairment, we found a significant positive correlation; these results were agreed with Brownlee [ [62], they reported same correlation, our result was disagreed with Gifford et al. [63] who found an inverse relationship between blood pressure and cognitive dysfunction. Hypertension is said to decrease the number of nicotinic receptors sensitive to acetylcholine and to cause cerebrovascular diseases, cerebral infarction and cerebral gray substances, arteriosclerosis and lower cognitive function [64]. The combination of type II diabetes and hypertension is associated with greater cognitive impairment compared to normotensive diabetic patients [65].
Large population-based studies then revealed that hyperlipidemia and particularly hypercholesterolemia in middle age are associated with the risk of subsequent occurrence of MCI [66][67][68]. Hypertriglyceridemia changes cerebral blood by increasing the viscosity of blood and lowers cognitive function by causing arteriosclerosis [69] Lower HDL-C level is associated with more severe lesions of white matter changes, leading to MCI, even AD [70]. HDL-C has been described as a negative risk factor for the development of cognitive impairment [71]. HDL-C can prevent aggregation and polymerization of β-amyloid, thus slowing or even preventing the development of AD [72,73]. HDL-C is also has anti-inflammatory properties [74]. Abdominal obesity was associated with cognitive dysfunction as defined by scores obtained on a MMSE developed for the assessment of cognitive functioning in individuals over 65 years, even after adjustment for age [75]. Adiposity has a direct effect on neuronal degradation [76]. Obesity is also associated with subclinical inflammatory status, a condition linked to dementia [77] and cognitive decline [78]. Although the association between obesity and poor cognitive function is prominent in the elderly, middle-aged, obese adults may have a greater degree of brain atrophy compared with age-matched, non-obese people [9]. Non-elderly obese people may experience subtle cognitive dysfunction and may be at greater risk of progression to significant cognitive impairment [79].

Conclusion
Patients with metabolic syndrome have a higher risk for developing cognitive impairment and this risk increase with increased number of metabolic syndrome components.