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Background: Cognitive decline could start or get worse among elderly patients with diabetes mellitus more than elderly without diabetes mellitus. So, those diabetic elderly patients have more risk to develop Alzheimer’s disease and vascular dementia. Patients and Methods: This study included 48 elderly, grouped into three equal groups. First group included patients with diabetes mellitus and cognitive impairment. Second group included patients with diabetes mellitus and no cognitive impairment. The last group included the controls. Evaluation through Mini Mental State Examination, MRI brain, and Quantitative Electroencephalography (QEEG) recording was done for every studied elderly. Results: MRI finding revealed that hippocampal atrophy was significantly more prevalent among diabetic patients with mild cognitive impairment (MCI) (37.5%). The QEEG showed increase in the distribution of alpha 1 (low alpha) waves among control and diabetic patients without MCI groups, while there was an increase in the distribution of alpha 2 (high alpha) among diabetic patients with MCI. The QEEG results revealed increased alpha 2/alpha 1 ratio among patients with hippocampal atrophy. Conclusions: Type 2 DM was suggested to increase the risk of cognitive impairment. The cognitive impairment in patients with diabetes mellitus was associated with changes in hippocampal volume and QEEG changes. Keywords: Diabetes mellitus, Mild cognitive impairment, Hippocampal atrophy, QEEG Background memory formation take place in the hippocampus. The Diabetes mellitus is a common disease known to have hippocampus is the main source of rhythmic activity in adverse effects on all systems of the body (Kodl and EEG (Tsanov et al. 2011). It is widely accepted that the Seaquist 2008). Cognitive decline could start or get cerebral EEG rhythms reflect underlying brain network worse among elderly patients with diabetes mellitus activity. So, the modifications in these rhythms could be more than elderly without diabetes mellitus. So, those an early sign of Alzheimer’s disease. Specifically, the study diabetic elderly patients have a higher risk of developing of alpha rhythm could be a satisfying measurement for the Alzheimer’s disease and vascular dementia (Das et al. relationship between the structure and the function of 2007). Mild cognitive impairment is a stage between these brain networks (Ingber and Nunez 2011). normal cognitive changes with aging and very early de- mentia (Petersen and Negash 2008). Attention and Aim of the work The aim of this work was to assess the effect of diabetes * Correspondence: Dr.email@example.com mellitus on cognitive functions, through assessing quan- Department of Neuropsychiatry, Suez Canal University, Ismailia, Egypt 2 titative EEG changes and hippocampal atrophy in dia- Department of Neurology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt betic patients with mild cognitive impairment. © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Abo hagar et al. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2018) 54:15 Page 2 of 6 Patients and methods D. Cognitive assessment using the Mini Mental State This is a case-control study, including 32 diabetic pa- Examination (MMSE) (Folstein et al. 1975). tients with variable levels of education with at least 8 years of education selected by the attendants in the Measurement of the hippocampus neuropsychiatry outpatient clinic in Suez Canal Coronal and sagittal magnetic radiographic volumetric University Hospital, Ismailia, Egypt. Patients were scan with high-resolution T1 weight intensity was subdivided into one group of patients with diabetes done. The Philips Acheiva scanner 1.5 T, Netherlands mellitus and cognitive impairment and a second (Holland), was used. The used technique was the gra- group which included patients with diabetes mellitus dient echo 3D with repetition (TR) of 20 ms and and no cognitive impairment. The inclusion criteria echo (TE) of 5 ms. The used Flip Angle was 30 to were the following: controlled diabetic patients with view a field of 220 mm. The slice thickness was at 1. type 2 diabetes, patient aged 55–85 years old, com- 3 mm and acquisition matrix of 256 × 256. The plaint by the patient or report by a relative of mem- hippocampus was measured including the fimbria but ory or other cognitive disturbances, patients with with exclusion of the rostral gray matter. The hippo- minimal or no depression (according to Beck campal tail was included as seen by its oval shape Depression Inventory) (Beck et al. 1996), and the just medial and caudally to the lateral ventricles Arabic translated form of Mini-Mental State Examin- (Pruessner et al. 2000).Itwas carried outatSuez ation (MMSE) with score of 24–27/30 (American Canal University MRI center. Psychiatric Association (APA) 2013). The volume of the hippocampus was calculated by The exclusion criteria were the following: illiterate the summation of measured volumes of both right individuals or less than 8 years of education, any pa- and left hippocampus. The mean value of hippocam- tient with disturbed conscious level, history or neuro- pus volume among normal elderly was 5.75 cm with logical signs of vascular or degenerative disorder, standard deviations of ± 1.1 cm (Moretti et al. 2007). other psychiatric diseases, dementia (MMSE score The cutoff value was presented using two standard below 24), epilepsy, patient with moderate or severe deviation from the mean (3.55 cm ). So, the atrophy depression (according to Beck Depression Inventory), of hippocampus was considered in elderly with and using psychoactive drugs which included acetyl- hippocampus volume measuring less than that value. cholinesterase inhibitors and included drugs that en- hance brain cognitive functions or bias EEG activity. Digital EEG examination Also, the systemic diseases that could affect cognitive Digital EEG was recorded utilizing E-Series EEG/PSG function and the history or current intake of alcohol system © Compumedics Limited 2004, Australia. or drug addiction were excluded. Placing the electrodes was done according to the Another 16 age-, sex-, and education-matched International 10–20 system, and ear lobe electrodes healthy subjects were included as a control group. were used as reference, with a ground electrode on Thestudy wasapprovedbythe Suez CanalFaculty of the forehead. Impedance was kept below 10 kohm. Medicine Ethical Committee. Written, informed con- The high-frequency filter was 70 Hz, the time con- sent was obtained from all persons before inclusion stant was 0.3, and the paper speed was 30 mm/s. The in the study. investigation was carried out while the patient was re- cumbent in supine position in semi-dark room. Re- cording was carried out for about 20 min with 3-min Methods hyperventilation and intermittent photic stimulation All subjects underwent the following: as provocative techniques. The EEG records were visually assessed. Five artifacts’ A. Clinical assessment including thorough history free epochs while awake and resting were selected for taking, full general, and neurological examination. QEEG, each epoch of 10-s duration. The relative powers B. Routine laboratory investigations: fasting, post- of 19 electrodes (Fp1, Fp2, F7, F8, F3, F4, C3,C4, T3, T4, prandial blood sugar level and HBA1C, lipid profile, T5, T6, P3, P4, O1, O2, Fz, Cz, and Pz) were studied in liver, kidney and thyroid function tests, complete the following frequency bands: delta (0.5 to < 4 Hz), blood count, ESR, uric acid, and Na, K and calcium theta (4 to < 8 Hz), alpha 1 (8 to < 11.0 Hz), alpha 2 (11 levels. These tests were done for exclusion of any to < 14 Hz), beta 1 (14 to < 25 Hz), and beta 2 (25 to systemic diseases. 35 Hz). The relative power was the percentage of the C. Clinical diagnosis of mild cognitive impairment power of a given frequency band compared to the sum (MCI) according to DSM-V criteria (American of the power of all frequency bands (Sharbrough et al. Psychiatric Association (APA) 2013). 2002). Abo hagar et al. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2018) 54:15 Page 3 of 6 Statistical analysis Table 2 The distribution of hippocampal atrophy among the study groups Collected data were processed using SPSS IBM SPSS sta- tistics (version 22.0, 2013; IBM Corp. Armonk, New York, DM with DM without Control Chi-squared MCI MCI group test USA). Quantitative data were presented as means ± SD. P value On the other hand, qualitative data were presented as Hippocampal atrophy 6 (37.5%) 2 (12.5%) 0 (0.0%) 0.01** numbers and its percentages. The used statistical tests for significance were the following: the one-way ANOVA to DM diabetes mellitus, MCI mild cognitive impairment **Statistically highly significant test the differences between groups and the chi-squared test in testing significance of difference between qualitative data. Pearson correlation coefficient (r) was used to meas- Results of QEEG ure correlation between quantitative variables. A probabil- Predominance of alpha 2 was significantly higher ity value (P value) of less than 0.05 was considered as among DM with MCI group in comparison to other statistically significant. A probability value (P value) of less groups with a mean 30.8 ± 12.24 (P =0.01), and alpha than 0.01 was considered statistically highly significant. 1 was significantly lower among DM with MCI group in comparison to other groups with a mean 20.42 ± Results 11.87 (P = 0.001) while theta, delta, and beta waves Demographic data was found to be insignificant (Table 3). This study was carried out on 48 subjects divided into Alpha 2/alpha 1 power ratio was distributed signifi- three groups, each one containing 16 subjects. The first cantly among DM with MCI group in comparison to group consisted of diabetic patients with mild cognitive other groups (P = 0.01) (Table 4) (Fig. 1). impairment, and their age ranged between 55 and 80 years Significant relationship was found between alpha with a mean (63.75 ± 6.83 SD); there were seven males (43. 2/alpha 1 ratio and hippocampal atrophy among 8%) and nine females (56.3%). The second group consisted DM with MCI group in comparison to other groups of diabetic patients without cognitive impairment. Their (P < 0.001) (Fig. 2). age ranged between 55 and 73 years with a mean (62.18 ± There was a high statistically significant positive 5.03 SD); there were eight males (50%) and eight females correlation between hippocampal atrophy and alpha (50%). The third group was the control group; their age 2/alpha 1 ratio among DM with MCI group, where ranged between 55 and 71 years with a mean (62.25 ± 4.87 correlation coefficient (r) = 0.535 and P = 0.001 SD). No statistically significant difference was detected be- respectively (Table 5). tween groups as regards age and sex (P >0.05). Discussion Results of cognitive assessment Previous studies support the view that individuals On comparing the results of MMSE of the three groups, with diabetes are at an increased risk for developing statistically significant lower results were found in DM with cognitive impairment (Allen et al. 2004)and dementia MCI group when compared to other groups (P = 0.001) (Biessels et al. 2006). These studies found indicators (Table 1). for the associations between MCI and type 2 diabetes mellitus. Moreover, another longitudinal cohort study emphasized the association of type 2 diabetes mellitus Results of brain imaging with so called amnestic MCI among the population Hippocampal atrophy was distributed significantly who developed both AD and vascular pathology, but among DM with MCI group in comparison to other with weak association with nonamnestic MCI (Biessels groups (P = 0.01) (Table 2). Table 3 The relative power of all frequency bands among the study groups Table 1 The results of cognitive assessment among the study DM with MCI DM without MCI Control group ANOVA test groups Mean ± SD Mean ± SD Mean ± SD P value DM with MCI DM without MCI Control group ANOVA test Delta 3.53 ± 0.57 3.42 ± 0.41 3.68 ± 0.68 0.40 Mean ± SD Mean ± SD Mean ± SD P value Theta 22.87 ± 3.04 21.54 ± 3.77 21.26 ± 3.85 0.40 Min–Max Min–Max Min–Max Alpha 1 20.44 ± 11.87 31.06 ± 12.70 37.68 ± 5.58 0.001** MMSE 25.5 ± 0.51 28.56 ± 0.81 28.62 ± 0.88) 0.001** Alpha 2 30.80 ± 12.24 20.42 ± 11.78 17.18 ± 4.40 0.01** (25–26) (28–30) (28–30) Beta 25.75 ± 1.46 24.53 ± 0.68 24.17 ± 1.95 0.33 DM diabetes mellitus, MCI mild cognitive impairment, SD standard deviation, Min minimum, Max maximum, MMSE Mini Mental State Examination DM diabetes mellitus, MCI mild cognitive impairment, SD standard deviation **Statistically highly significant **Statistically highly significant Abo hagar et al. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2018) 54:15 Page 4 of 6 Table 4 The distribution of alpha 2/alpha 1 ratio among the Table 5 Correlation between alpha 2/alpha 1 ratio and study groups hippocampal atrophy among DM with MCI group DM with DM Control ANOVA test Alpha 2/alpha 1 ratio MCI without group P value Correlation coefficient (r) P value MCI Hippocampal atrophy 0.535* 0.001** Alpha 2/alpha 1 ratio 2.6 ± 2.15 1.34 ± 1.52 1.0 ± 0.86 0.01** DM diabetes mellitus, MCI mild cognitive impairment Alpha 2/alpha 1 power ratio was expressed as mean ± SD *Significant r (correlation coefficiency) > 0.5 DM diabetes mellitus, MCI mild cognitive impairment **Correlation is highly significant at < 0.01 **Statistically highly significant et al. 2007). EEG is not a new idea to be used as an predominance of synchronized alpha 2 bands over the early detection for cognitive decline. But still, EEG is frontal, temporal, and parietal regions is due to a pro- unable to meet the National Institute on Aging gressive recruitment of many other cortical areas that in- Consensus Conference (1998) ideal parameters to be volve wider cortico-thalamic re-entry loops. They considered as a reliable biomarker. On the other specified the loop of the frontal-midline thalamic nuclei. hand, QEEG stood to debate those parameters with This explanation was confirmed by Nicolelis and Fanse- the facts of being a cost-effective, noninvasive tech- low (2002) and Klimesch et al. (2007) who considered nique for the identification of the earliest signs of the increase in the alpha power to be due to hyperpolari- brain dysfunction in patients with evolving dementia zation at thalamic level. or even MCI. That will give the opportunity for early The current study found significant predominance intervention and better chance for therapy to these of alpha 1(low alpha) among subjects without cogni- patients (Prichep 2007). Another study adopted the tive impairment, and that was in agreement with that same concept of considering electroencephalogram as reported by Jelic et al. (2000) and considered these an ideal noninvasive and economic procedure (Rossini changes as a predictor of future conversion from MCI et al. 2006). to AD. Moreover, Klimesch et al. (2003)statedthat The current study showed predominance of hippo- induction of large alpha 1 power by neurofeedback campal atrophy among DM with MCI group with sig- training or repetitive transcranial magnetic stimulation nificant statistical difference (P < 0.05), while it was (rTMS) at alpha frequency range is typical for good 12.5% of diabetic patient without MCI and 0.0% in memory performance under normal situations enhan- normal control group. That was supported by other cing the cognitive performance. studies (Moretti et al. 2011;Frisoni 2012;Albertetal. That also was confirmed by Holschneider et al. 2011; McKhann et al. 2011). (1998)andSarter andBruno (1997, 1999, 2000)who In the current study, peak power frequency of alpha 2 reported that the efferent projections of the fore- was found high with predominance with hippocampal brain are the main providers of the low alpha power. atrophy among DM with MCI group. That was sup- They regarded that to the cholinergic tone of the ported by other studies (Moretti et al. 2011; Frisoni base of cortex especially in the nucleus basalis of 2012). O’Donnell and Grace (1995) explained that Meyner. But some studies actually considered that Fig. 1 Distribution of alpha 2/alpha 1 power ratio among the study groups. DM = diabetes mellitus, MCI = mild cognitive impairment Abo hagar et al. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (2018) 54:15 Page 5 of 6 Fig. 2 Distribution of hippocampal atrophy and alpha 2/alpha 1 ratio among the study groups. DM = diabetes mellitus, MCI = mild cognitive impairment alpha 1 is related to hippocampal atrophy (Rossini et proper glycemic control may have a good prognostic al. 2006). In the current study, alpha 2/alpha 1 value in cognitive performance in diabetic patients. power ratio was found significant among patient Funding with hippocampal atrophy and this was supported by The authors were responsible for the cost of this study including the design Moretti et al. (2011) and Frisoni (2012). of the study and collection, analysis, and interpretation of data and in Finally, type 2 DM was suggested by Roberts et al. writing the manuscript. (2014) to be the factor of increasing the risk of cog- nitive impairment acceleration and development of Availability of data and materials The data can be publicly available at the Faculty of Medicine, Suez Canal MCI into dementia, furthermore resulting in hippo- University. campal atrophy which may end in QEEG changes (Ganguli et al. 2004; Hussain 2007;Xuet al. 2010). Authors’ contributions But unfortunately, there were no available data about AA carried out the study conception and design and coordination of the the effect of DM on QEEG. So the current study study and drafted the manuscript. AY contributed to the analysis and interpretation of data and helped to draft the manuscript. AR participated in points out that DM could directly result in QEEG the study design and the sequence alignment and helped to draft the changesaswellasresulting in hippocampal atrophy manuscript. EM participated in the study design and coordination and which may open the door to enrich the idea for fur- helped to draft the manuscript. SO carried out the design of the study, participated in the acquisition of data, and performed the statistical analysis. ther studies to consider using QEEG as an alterna- All authors read and approved the final manuscript. tive predictor of hippocampal atrophy for mild cognitive impairment. Ethics approval and consent to participate The study was approved by the Ethics Committee of Suez Canal Faculty of Medicine on April 14, 2015. The committee number is 2399. An informed consent was taken from all the participants in the study. Conclusions Type 2 DM was suggested to increase the risk of cogni- Consent for publication tive impairment. The cognitive impairment in patients All participants had signed an informed consent to participate and for the with diabetes mellitus was associated with changes in data to be published. hippocampal volume and QEEG changes. Follow-up as- sessment of cognitive function of diabetic patients is rec- Competing interests ommended to detect early cognitive dysfunction, and The authors declare that they have no competing interests. Abo hagar et al. 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