INTRODUCTION. Diabetes is a severe and dangerous disease in its relentless progress, with final emergence of

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1 INTRODUCTION Diabetes is a severe and dangerous disease in its relentless progress, with final emergence of serious damage, irreversible and even lethal, with a high incidence in developed countries, with refined carbohydrate-rich diet. One of the serious complications of diabetes is chronic renal failure requiring dialysis in elderly persons, or kidney transplantation in young persons. Cognitive decline is common in patients with diabetes mellitus, a serious complication, but can be accelerated requiring dialysis for chronic renal failure. Based on these considerations, in this paper we studied cognitive function in a group of dialysis patients with diabetes mellitus using noninvasive methods of exploration: MINI Mental Status Examination (MMSE) and Self Administered Gerocognitive Evaluation -SAGE, an original test, introduced in the thesis, allowed early detection of cognitive deficit. These tests were used in a broader research project was conducted at Ohio State University, USA and the University of Medicine and Pharmacy Craiova, Romania. We have correlated the results of these tests twith laboratory tests, MRI, functional MRI, CT, and EEG in order to detect early cognitive impairment. PART I 1.DIABETES MELLITUS: in this chapter are treated etiology, classification of diabetes mellitus, pathophysiology, pathogenesis of diabetes and insulin dependent insulin-independent diabetes complications, including cognitive changes. 1

2 2. DIALYSIS - Dialysis is a method of removing waste, toxins and excess water from the blood and restore the electrolyte balance, when the kidneys no longer work. This chapter discusses hemodialysis and peritoneal dialysis. 3. NON INVASIVE METHODS AND NEUROPSYCHOLOGICAL TESTS: brain mapping, evoked potentials, nuclear magnetic resonance, MRI and functional MRI, CT scan, positron emission tomography, ultrasound Doppler and cognitive tests. 4. COGNITIVE FUNCTION - Important cognitive processes, described in this chapter are: attention, orientation, memory, learning and thinking. Part II PERSONAL CREDIT - The objectives of this research were to study the relationship between adherence to dialysis, as measured by Interdialytic Weight Gain (IWG) and cognitive function as measured by cognitive tests: Mini Mental Status Examination (MMSE) and self-administered test (SAGE) in patients on dialysis; correlation between cognitive function and cerebral vascular Doppler exploration, MRI, CT, functional MRI, for the purposes of early detection of deterioration in cognitive function. 5. MATERIAL AND METHODS 5.1. The study was conducted on a number of 19 patients of type II diabetes mellitus with chronic renal failure on dialysis, 15 male subjects (79%%) and 4female subjects (21%) between the ages of years, mean age was years. The most numerous (73%) had between 12 and 14 years of education. The group was part of the Dialysis program at Ohio State University, USA, with 1-3 years of dialysis. 2

3 CLINICAL EXAMINATION A full clinical examination was performed in all patients, revealing type II diabetes, associated comorbidities - hypertension ( 100%), ischemic heart disease (40%), end stage renal disease (ESRD) requiring dialysis (100%), hyperlipidemia (58%), iron deficiency anemia (15.8%) and depression (42.1%) LABORATORY TESTS - Common laboratory tests performed, this evaluation aimed exclusion of systemic causes of cognitive decline PUPILLARY EXAM to rule out papillary stasis, signs of intracranial hypertension ELECTROENCEFALOGRAPHY Electroencephalography (EEG) was performed using XLTEK system equipped with highresolution digital video. Database is exported to MS Excel for statistical interpretations FUNCTIONAL MRI using the Philips Achieva 3T scanner apparatus (Cleveland, OH). Functional images were obtained with an isotropic spatial resolution of 3.4 mm, TR / TE 3000/22 ms, flip angle 80, matrix size, 40 slices Examination by computed tomography - In patients with suspected stroke CT was performed using a GE Lightspeed 16 xterm 2003/2004 device DOPPLER ULTRASOUND Carotid Doppler PW Doppler examination was performed by a device with transducer T2 DWL Multidop 4 MHz CW, and ultrasound (including Doppler color-coded) with a Vingmed CFM 725 device Sonotron using 6.5 MHz sector probe duplex color. 3

4 6. RESULTS The results obtained on the dialysis group were compared with values obtained in the control group of same age group with diabetes mellitus type II without kidney involvement. 6.1 RESULTS ON NEUROPSYCHOLOGICAL TEST Two neuropsychological tests were performed: Mini Mental test and SAGE-test, the original test, TEST REZULTATE obtained MMSE MMSE test was performed in all patients at rest and relaxation, proper lighting for the test, before the dialysis session The results obtained in self-managed TEST - SAGE Patients considered for study completed SAGE test without the intervention of a psychometrician and with no time limit. The test included the following steps: orientation, picture recognition, similarities, calculation, memory, the construction of a three-dimensional figure, clock construction, verbal fluency, executive-solving test, and the trail test Comparisons between results obtained in psychological tests THE two cognitive tests correlated SAGE MMSE and statistically significant, indicating their use in evaluating psychiatric patients in the clinic. Because a small group of patients, the Spearman correlation is more sensitive in this case. We obtained a p-value with statistical significance, justifying the use of SAGE in clinical testing as a complement to the MMSE in assessing executive function. 4

5 6.4. RESULTS FROM MRI, fmri AND CT - functional MRI and MRI revealed diffuse cerebral atrophy, age-appropriate and excluded the diagnosis of hydrocephalus. In dialysis patients, MRI excluded the diagnosis of cerebral edema that can occur as a complication of dialysis process. There was a diffuse cerebral atrophy without changes in ventricular volume. On fmri study we noticed that patients have a lower cognitive performance on verbal fluency test, and attention problems, compared with controls. There was a reduction in the visual cortex activation during attention test and problem solving test and in frontal cortex during verbal fluency test DISCUSSION ON IMAGING Hyperglycemia can have a toxic effect, reflected by the overall cortical atrophy. Volumetric MRI analysis revealed correlations between structural brain changes and cognitive deficits in diabetic patients (Reaven GM, et al, 1995). In this study we noted that most patients showed diffuse cortical atrophy without white matter changes, thus excluding the possibility of a stroke. The functional MRI has revealed changes in activity of the prefrontal area and temporoparietal corresponding cognitive deficit. Processing statistical program used functional MRI results of regression and correlation analysis. The function of this program is to statistically compare images obtained during an activity, the increase or decrease the light signal can be correlated with the stimulus application. These sections were superimposed on anatomical image obtaining a map of activation (D. Scharre et al, 2011). In the literature there are few references to the MRI imaging and functional MRI in patients with diabetes mellitus, cognitive deficits, probably due to high costs of these investigations. 5

6 . DISCUSSIONS ON PSYCHOLOGICAL TESTS In recent years an increased attention is paid to cognitive deficits, including dementia, in patients with end stage renal disease. In his study, Dr. Tamura Kurella in 2011 from the Faculty of Medicine Stanfort, California, reaffirms the importance of diagnosis of cognitive deficit in this population, dementia is associated with an increased risk of death due to refusal of patients to perform dialysis. MMSE is the most common method to test cognitive deficits. From this test, executive function is poorly assessed, new investigations being needed. We found a statistically significant correlation between increased blood potassium levels and cognitive, electrolyte imbalances influencing the cognitive function. 2. In assessing cognitive function have used two psychological tests: MMSE Mini-mental test, and test self-assessment -SAGE, original test (Douglas Scharre et al., 2010) introduced in this study as part of an extensive research study. 3. MMSE psychological test results and SAGE (which were statistically significantly correlated with each other) showed a cognitive deficit in the studied group compared with controls. 4. Cardiologic examination revealed: mean systolic and diastolic blood pressure (SBP and DBP) before dialysis were between 127 and 186 mmhg, diastolic from 62 to 119 mm Hg after dialysis SBP values were between 103 and 177 mmhg and DBP between 61 and 97 mmhg compared with controls, showing that patients were decompensated before dialysis. ECG showed in 52% of patients signs of heart disease. Echocardiography showed a left ventricular failure in 70% of patient. 6

7 5. Exploration of biochemical values noted increased serum potassium level and a decreased serum albumin values in most of dialysis patients. 6. MRI showed a diffuse cerebral atrophy, characteristic of advanced ages. 7. The analysis of EEG showed a reduction in the incidence of alpha waves and theta waves increased incidence of 7%, with no direct significance in connection with the study, interpreted as a consequence of electrolyte imbalances in patients on dialysis. 8. The cognitive impairment occurred either as a complication of diabetes, favored by older age, or because dialysis, or because of all these causes. It is difficult to dissociate and chose only one diagnosis. 10. The final conclusion The present research, broad, complex clinical and preclinical assessment of a group of type II diabetes patients on dialysis, using non-invasive method of neurophysiologic and psychological exploration as MMSE tests and SAGE, is less mentioned in the literature. SAGE test introduced in this study, was patented in 2010 by D. Scharre, proved to be a more accurate diagnosis to assess executive function. Cognitive function decline in patients with diabetes on dialysis is less mentioned in the literature, early detection of mild cognitive impairment (MCI) preventing a higher risk of hospitalization, increased resource utilization, and a decline in quality of life. 7

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