الفهرس 
Introduction
Brain glucose metabolismOnly 14 pages are availabe for public view
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Abstract
Alzheimer’s disease (AD) is the major age- dependent neurodegenerative disease of the brain as well as the leading cause of dementia. Type II Diabetes mellitus is a metabolic disorder that is characterized by high blood glucose because of the insulin resistance. Patients with type II DM are at increased risk of developing cognitive and memory dysfunctions which are significant symptoms of AD. Also, cognitive dysfunction would be associated with poor self care ability in diabetic patients. In the present study, cognitive function tests were done for 76 subjects; control n= 17, DM without AD = 20, AD without DM n = 19 and AD with DM n = 20. These tests include mini mental state examination (MMSE), Wechsler adult intelligence scale (WAIS)و Wechsler memory scale (WMS) and Cognitive Event related potential (P300). Circulating levels of glycosylated haemoglobin (HbA1c), insulin, insulin like growth factor-1(IGF-1), Glucagon-like peptide-1 (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP), Nitric oxide (NO), C- reactive protein (CRP), Tumor necrosis factor α (TNFα) were determined in venous blood samples of all groups. Also, Gene expression of phosphoinositide 3-kinase (PI3K) by PCR was determined in blood samples of all groups. The correlations between the levels of these substances and cognitive function tests were determined. The results of this study demonstrated that the MMSE score was significantly lower in different patient groups in comparison with control group. This means that patient groups even type II diabetes without AD had cognitive impairment with different degrees. Concerning WAIS, it was found also that no significant difference between control group and DM without AD in verbal, performance and full scale IQ. This result may suggest that WAIS is not sensitive to detect early cognitive impairment as MMSE. But AD without DM and AD with DM had significantly lower IQ than control group. Concerning WMS, it was found that immediate memory was affected in AD either with or without DM but not in DM without AD. Working memory was affected in AD either with or without DM but not in DM without AD except visual reproduction which was affected in both DM and AD. It was found that DM without AD, AD without DM and in AD with DM had significantly longer P300 latency than control group. P300 amplitude was significantly lower in DM without AD, AD without DM and in AD with DM than in control group. This indicates that the P300 latency and amplitude are highly sensitive even in early cognitive impairment as MMSE. It was found that DM without AD had significantly higher MMSE score than AD without DM and AD with DM. Concerning WAIS, performance and full scale IQ but not verbal IQ were affected significantly in AD either with or without DM more than DM without AD. Concerning WMS, immediate memory was affected in AD either with or without DM more than DM without AD. Working memory was affected significantly in AD either with or without DM more than in DM without AD. It was found that P300 latency was significantly shorter in DM without AD than in AD without DM and in AD with DM but there was no significant difference in P300 amplitude in DM without AD compared to AD without DM and AD with DM. It was found that no significant difference between AD without DM and AD with DM in any cognitive function test or ERP (P300). Although there was no significant difference between AD without DM and AD with DM, in the present study it was found that AD without DM patients had significant older age than AD with DM. Concerning biochemical measures, it was found that HbA1c is significantly higher in DM without AD and in AD with DM compared to control group but there was no significant change in AD without DM. It appears that HbA1c is not affected by AD. It was found that insulin level was significantly higher in DM without AD, AD without DM and AD with DM compared to control level. Results indicate insulin resistance in the 3 groups. However, it is more in AD with DM, DM without AD then AD without DM. It was found that IGF-1 was significantly higher in DM without AD and AD with DM compared with control level. No significant change in AD without DM compared to control level. It appears that the change in the level of IGF-1 was due to DM not due to AD, however, AD aggravates the level of IGF-1 in diabetic patients. It was found that NO level was significantly lower in DM without AD, AD without DM and AD with DM. The decrease in the level of NO is significantly more in AD without DM than other groups. It appears that NO level is affected more in AD than DM. It was found that the level of GLP-1 was significantly higher in DM without AD compared to control level. Small increase in AD with DM compared to control level. AD without DM showed significantly lower level than controls. It was found that the level of GIP was significantly higher in DM without AD (in comparison with control. No significant change in GIP in AD without DM than control value. It appears that GLP-1 and GIP are affected by DM not due AD. On the contrary AD decreases the level of GLP-1 and GIP in diabetic patients. It was found that the level of CRP was significantly higher in DM without AD as well as in AD with DM compared to control level. The level of CRP in AD without DM was significantly lower than control level. It appears that the change in the level of CRP is due to DM not due to AD. It was found that the level of TNFα was significantly higher in DM without AD and in AD without DM compared to control group. However, the increase in DM without AD is significantly more than AD without DM. Small increase in TNFα in AD with DM in comparison with control group. It appears that TNFα is affected in both conditions; DM without AD and in AD without DM. Concerning PCR detection of PI3K- DNA expression, it was found excessive activity of PI3K- signaling in human leucocytes in DM and AD in both exon 1 and 9. The activity of PI3K- signaling was depressed in AD with DM in exon 9. This study showed that patients of DM without AD share patients of AD without DM in the following aspects: MMSE and P300 latency and amplitude in cognitive function tests and insulin level, nitric oxide and PI3K in biochemical measurements. Concerning correlations between cognitive functions and biochemical measures, it was found that insulin showed significant negative correlation with verbal IQ, full scale IQ, working memory, and P300 amplitude. This means that insulin resistance may be associated with cognitive impairment. It was found that NO showed significant positive correlation with all cognitive function tests including total MMSE, IQ, all parameters of immediate, working memory and P300 amplitude. Also, it showed significant negative correlation with P300 latency. This means that low NO strongly associated with cognitive impairment. It was found that GLP-1 showed positive significant correlation with total MMSE, performance IQ, immediate and working memory. Also, it showed significant negative correlation with P300 latency. This means that low GLP-1associated with cognitive impairment. Conclusions:
1-The significant lower MMSE, longer latency of P300 and lower P300 amplitude suggested that type II diabetes mellitus associated with cognitive impairment with different degrees.
2-Although there was no significant difference between AD without DM and AD with DM in any cognitive function test or ERP, in the present study it was noticed that AD without DM had significant older age than AD with DM.
3-Type II DM is a major risk factor for AD because of:
-Toxic effects of hyperglycemia.
-Insulin resistance.
-significant low levels of NO
-significant low levels of GLP-1
-Inflammatory reaction demonstrated by changes in CRP, TNFα as well as PI3K.