Female Alzheimer's Disease Patients Research Articles

EEG-Based Emotion Classification for Alzheimer's Disease Patients Using Conventional Machine Learning and Recurrent Neural Network Models.

As the number of patients with Alzheimer’s disease (AD) increases, the effort needed to care for these patients increases as well. At the same time, advances in information and sensor technologies have reduced caring costs, providing a potential pathway for developing healthcare services for AD patients. For instance, if a virtual reality (VR) system can provide emotion-adaptive content, the time that AD patients spend interacting with VR content is expected to be extended, allowing caregivers to focus on other tasks. As the first step towards this goal, in this study, we develop a classification model that detects AD patients’ emotions (e.g., happy, peaceful, or bored). We first collected electroencephalography (EEG) data from 30 Korean female AD patients who watched emotion-evoking videos at a medical rehabilitation center. We applied conventional machine learning algorithms, such as a multilayer perceptron (MLP) and support vector machine, along with deep learning models of recurrent neural network (RNN) architectures. The best performance was obtained from MLP, which achieved an average accuracy of 70.97%; the RNN model’s accuracy reached only 48.18%. Our study results open a new stream of research in the field of EEG-based emotion detection for patients with neurological disorders.

Estrogen Signaling in Alzheimer's Disease: Molecular Insights and Therapeutic Targets for Alzheimer's Dementia.

Estrogens play a crucial physiological function in the brain; however, debates exist concerning the role of estrogens in Alzheimer's disease (AD). Women during pre-, peri-, or menopause periods are more susceptible for developing AD, suggesting the connection of sex factors and a decreased estrogen signaling in AD pathogenesis. Yet, the underlying mechanism of estrogen-mediated neuroprotection is unclarified and is complicated by the existence of estrogen-related factors. Consequently, a deeper analysis of estrogen receptor (ER) expression and estrogen-metabolizing enzymes could interpret the importance of estrogen in age-linked cognitive alterations. Previous studies propose that hormone replacement therapy may attenuate AD onset in postmenopausal women, demonstrating that estrogen signaling is important for the development and progression of AD. For example, ERα exerts neuroprotection against AD by maintaining intracellular signaling cascades and study reportedreduced expression of ERα in hippocampal neurons of AD patients. Similarly, reduced expression of ERβ in female AD patients has been associated with abnormal function in mitochondria and improved markers of oxidative stress. In this review, we discuss the critical interaction between estrogen signaling and AD. Moreover, we highlight the potential of targeting estrogen-related signaling for therapeutic intervention in AD.

Estrogen protects neuroblastoma cell from amyloid-β 42 (Aβ42)-induced apoptosis via TXNIP/TRX axis and AMPK signaling

Alzheimer's disease (AD), a massive challenge to global health, is featured with the extracellular plaques made up of amyloid-β 42 (Aβ42) and the intracellular neurofibrillary pathology composed of the microtubule-associated protein tau. Women seem to have a higher vulnerability to AD. In the present study, we identified Thioredoxin-interacting protein (TXNIP) as a specifically highly-expressed gene in the hippocampus in female AD patients by bioinformatics analysis. Consistently, in the hippocampus in female AD mice, apoptosis and TXNIP expression were enhanced while TRX expression was suppressed. In Aβ42-stimulated SH-SY5Y cells, the administration of estradiol significantly rescued Aβ42-suppressed cell viability and protein level of TRX while inhibited Aβ42-induced increases in ROS production, cell apoptosis, ΔΨm, and the protein levels of PERK, IREα, and TXNIP, further confirming the potential role of estrogen in AD progression and the involvement of TXNIP/TRX axis. Furthermore, the protective effects of estradiol against Aβ42-induced in vitro neurotoxicity on SH-SY5Y cells could be significantly reversed by AMPK inhibitor, Compound C, indicating that estradiol could improve Aβ42-induced AD via TXNIP/TRX and AMPK signaling. In summary, we demonstrated the cellular function of estradiol on Aβ42-induced in vitro neurotoxicity on SH-SY5Y cells and a novel mechanism of TXNIP/TRX axis involved in estradiol function via AMPK signaling.

An integration-free iPSC line, ICCSICi007-A, derived from a female Alzheimer's disease patient with the APOE-ε4/ε4 alleles.

The epsilon4 (ε4) allele of the APOE gene, which encodes the apolipoprotein E4 (ApoE4), is the strongest genetic risk factor known for late-onset Alzheimer´s disease (LOAD). Here, we present the characterization of an iPSC line generated from dermal fibroblasts of a female AD patient using Sendai viral vectors encoding the transcription factors OCT4, SOX2, KLF4 and c-MYC. The iPSCs maintained the original genotype, a normal karyotype, were free from Sendai viral vectors and reprogramming factors, presented a normal morphology, expressed endogenous pluripotency markers, and could be differentiated into ectodermal, mesodermal and endodermal cells, confirming its pluripotency.

Altered Redox State in Whole Blood Cells from Patients with Mild Cognitive Impairment and Alzheimer's Disease.

Oxidative stress plays an essential and early role in the pathophysiology of Alzheimer's disease (AD). Alterations in the redox state in AD and in mild cognitive impairment (MCI) patients appear in the brain and at peripheral level. Given that it is easier to study the latter, most of the research has been focused on plasma. However, the analysis of redox parameters in whole blood cells (including erythrocytes and leukocytes) has not really been investigated. Moreover, the association of these parameters with Mini-Mental State Examination (MMSE) clinical scores, has scarcely been studied. Therefore, the aim of the present work was to analyze several redox markers in whole blood cells from male and female MCI and AD patients. Antioxidant (superoxide dismutase, catalase (CAT), glutathione peroxidase (GPx), and reductase (GR) activities, and reduced glutathione (GSH) concentration) together with oxidant parameters (oxidized glutathione (GSSG) and thiobarbituric acid-reactive substances (TBARS)) were investigated using MCI and AD (10 women and 10 men in each group) and their age-matched control groups (15 women and 15 men). The results show an altered redox state in whole blood cells from AD patients (higher CAT, GSSG/GSH, TBARS and lower GPx, GR, GSH). Some of these redox parameters are already affected in MCI patients (higher TBARS and lower GPx and GR activities) in both sexes and, consequently, they could be used as markers of prodromal AD. Since GR, GSH, GSSG, and GSSG/GSH were found to be associated with MMSE scores, they seem to be useful clinically to monitor cognitive decline in AD progression.

Estrogen activates Alzheimer's disease genes

IntroductionWomen are at increased risk for Alzheimer's disease (AD), but the reason why remains unknown. One hypothesis is that low estrogen levels at menopause increases vulnerability to AD, but this remains unproven. MethodsWe compared neuronal genes upregulated by estrogen in ovariectomized female rhesus macaques with a database of >17,000 diverse gene sets and applied a rare variant burden test to exome sequencing data from 1208 female AD patients with the age of onset < 75 years and 2162 female AD controls. ResultsWe found a striking overlap between genes upregulated by estrogen in macaques and genes downregulated in the human postmortem AD brain, and we found that estrogen upregulates the APOE gene and that progesterone acts antagonistically to estrogen genome-wide. We also found that female patients with AD have excess rare mutations in the early menopause gene MCM8. DiscussionWe show with genomic data that the menopausal loss of estrogen could underlie the increased risk for AD in women.

Association of OGG1 and DLST promoter methylation with Alzheimer's disease in Xinjiang population.

Alzheimer's disease (AD) is a neurodegenerative disorder leading to progressive memory and cognitive impairment. Previous studies have identified multiple genes associated with AD. The aim of the present study was to validate the association of the five AD-associated variants, 8-oxoguanine DNA glycosylase 1 (OGG1) rs1052133, bridging integrator 1 rs744373, sortilin-related receptor 1, rs1133174, presenilin 2 rs8383, and nerve growth factor rs6330, in the Xinjiang Chinese population. In addition, the present study evaluated the contribution of the promoter methylation of two genes, OGG1 and dihydrolipoamide succinyltransferase (DLST) to the risk of AD. A total of 17 AD cases and 34 controls were recruited from Xinjiang province in China. Genotyping was done by Sanger sequencing. DNA methylation assay was performed using quantitative methylation specific polymerase chain reaction. The study was unable to repeat the previous association of the five genetic polymorphisms with AD. However, DLST methylation levels were demonstrated to be significantly decreased in AD patients (P=0.027), particularly in female AD patients (P=0.025). Subgroup analysis by apolipoprotein E (APOE ε4) genotype demonstrated that OGG1 methylation levels were significantly increased in APOE non-ε4 carriers compared with APOE ε4 carriers (P=0.027). In summary, the present study reported that DLST hypomethylation was significantly associated with AD in females, and that OGG1 promoter methylation may interact with APOE ε4 genotype.

High thiamine diphosphate level as a protective factor for Alzheimer’s disease

Objectives Thiamine diphosphate (TDP) is an indispensable coenzyme for three key enzymes in glucose metabolism. Reduced TDP levels in patients with Alzheimer’s disease (AD) has been widely demonstrated and is a diagnostic biomarker for the disease. In this study, we further explored the correlation between altered TDP metabolism and AD along with other risk factors.Methods A 1:1 case-control study was employed with 90 AD patients and 90 control subjects with normal-range cognitive abilities as assayed by the Mini Mental Status Evaluation. Age (≤2 years variation), gender, and educational background were strictly matched. Levels of the main thiamine metabolites in whole blood samples, including TDP, thiamine monophosphate, and thiamine, were assayed using high-performance liquid chromatography. Apolipoprotein E genotypes, haemoglobin, and several metabolic factors (fasting glucose, uric acid, triglyceride, and total cholesterol) associated with AD were also measured.Results The odds ratio of TDP level for AD was 0.95 (with TDP level as a continuous variable) or 0.09 (with TDP level as a dichotomized variable with a cut-off value of 99.48 nmol/L). Blood TDP levels were significantly decreased in female AD patients compared to male AD patients. No correlations were identified between TDP levels and several metabolic factors (fasting glucose, uric acid, triglyceride, and total cholesterol).Conclusions TDP is a protective factor for AD and its protective efficacy may be independent of other metabolic factors. The difference of TDP levels between genders may be another possible explanation for the higher prevalence of AD in females.

Influence of APOE and RNF219 on Behavioral and Cognitive Features of Female Patients Affected by Mild Cognitive Impairment or Alzheimer's Disease.

The risk for Alzheimer’s disease (AD) is associated with the presence of the 𝜀4 allele of Apolipoprotein E (APOE) gene and, recently, with a novel genetic variant of the RNF219 gene. This study aimed at evaluating interactions between APOE-𝜀4 and RNF219/G variants in the modulation of behavioral and cognitive features of two cohorts of patients suffering from mild cognitive impairment (MCI) or AD. We enrolled a total of 173 female MCI or AD patients (83 MCI; 90 AD). Subjects were screened with a comprehensive set of neuropsychological evaluations and genotyped for the APOE and RNF219 polymorphic variants. Analysis of covariance was performed to assess the main and interaction effects of APOE and RNF219 genotypes on the cognitive and behavioral scores. The analysis revealed that the simultaneous presence of APOE-𝜀4 and RNF219/G variants results in significant effects on specific neuropsychiatric scores in MCI and AD patients. In MCI patients, RNF219 and APOE variants worked together to impact the levels of anxiety negatively. Similarly, in AD patients, the RNF219 variants were found to be associated with increased anxiety levels. Our data indicate a novel synergistic activity APOE and RNF219 in the modulation of behavioral traits of female MCI and AD patients.

Effects of Gender and Other Confounding Factors on Leptin Concentrations in Alzheimer's Disease: Evidence from the Combined Analysis of 27 Case-Control Studies.

Leptin, as a link between fat mass and the brain, has been reported to be associated with gender. The gender differences in leptin levels between Alzheimer's disease (AD) and healthy elderly controls are inconclusive so far. To quantitatively summarize the leptin data available from female and male patients with AD, we searched PubMed and EMBASE for articles published from inception to July 20, 2017. Data were extracted from 27 studies, consisting of 3,014 participants. The pooled results showed that the overall leptin levels were lower in AD (Hedges' g = -0.481; p = 0.002) than in controls, and the leptin levels in whole blood and serum were decreased with moderate and large effect sizes (g = -0.677, -0.839; respectively; both of p-values <0.001) in AD compared with controls. In blood, there were significantly lower concentrations of leptin in female AD than in female controls (g = -0.590; p = 0.014), but not in male case-control group (g = -0.666; p = 0.067). Meta-regression analysis demonstrated that the decreased extent of leptin levels in AD paralleled the degree of the severity of dementia symptoms, as well as the alterations of body mass index (p-values ≤0.002). The findings provide strong evidence that 1) the blood concentrations of leptin are lower in female AD patients than in female controls; and 2) the greater the severity of dementia symptoms, the greater the decreases in the blood leptin levels. But more future investigations on the blood leptin levels in male AD patients is warranted.

Anesthesia/Surgery Induces Cognitive Impairment in Female Alzheimer's Disease Transgenic Mice.

Anesthesia and/or surgery may promote Alzheimer's disease (AD) by accelerating its neuropathogenesis. Other studies showed different findings. However, the potential sex difference among these studies has not been well considered, and it is unknown whether male or female AD patients are more vulnerable to develop postoperative cognitive dysfunction. We therefore set out to perform a proof of concept study to determine whether anesthesia and surgery can have different effects in male and female AD transgenic (Tg) mice, and in female AD Tg plus Cyclophilin D knockout (CypD KO) mice. The mice received an abdominal surgery under sevoflurane anesthesia (anesthesia/surgery). Fear Conditioning System (FCS) was used to assess the cognitive function. Hippocampal levels of synaptic marker postsynaptic density 95 (PSD-95) and synaptophysin (SVP) were measured using western blot analysis. Here we showed that the anesthesia/surgery decreased the freezing time in context test of FCS at 7 days after the anesthesia/surgery in female, but not male, mice. The anesthesia/surgery reduced hippocampus levels of synaptic marker PSD-95 and SVP in female, but not male, mice. The anesthesia/surgery induced neither reduction in freezing time in FCS nor decreased hippocampus levels of PSD-95 and SVP in the AD Tg plus CypD KO mice. These data suggest that the anesthesia/surgery induced a sex-dependent cognitive impairment and reduction in hippocampus levels of synaptic markers in AD Tg mice, potentially via a mitochondria-associated mechanism. These findings could promote clinical investigations to determine whether female AD patients are more vulnerable to the development of postoperative cognitive dysfunction.

Differences between the behavioral and psychological symptoms of Alzheimer's disease and Parkinson's disease

AimWe compared the behavioral and psychological symptoms of Alzheimer's disease (AD) and Parkinson's disease (PD) in order to determine the characteristic features of each disorder. MethodsFor this retrospective cohort study, we compared the behavioral and psychological symptoms of 288AD patients and 189 PD patients (mean age, 74.6±5.9 and 73.0±8.7years respectively). Symptoms were evaluated using the geriatric depression scale (GDS), apathy scale (AS), and Abe's behavioral and psychological symptoms of dementia score (ABS). ResultsAD patients had higher AS and ABS scores than PD patients. A gender-dependent comparison showed that ABS scores were worse in female AD patients than in female PD patients (p=0.001). A subscale analysis of ABS scores revealed that male AD patients were only significantly different from male PD patients in 1 item, whereas female AD patients were significantly different from female PD patients in 4 items. Among patients with mild cognitive decline, no differences in affective scores were observed. Alternatively, among patients with moderate cognitive decline, affective scores on all 3 scales were worse in PD patients than in AD patients. ConclusionsThe present age- and gender-matched retrospective analysis identified greater behavioral and psychological disease severity in female AD patients relative to female PD patients, and greater affective severity in PD patients versus AD patients with a similar degree of cognitive decline.

Malnutrition in Alzheimer's Disease, Dementia with Lewy Bodies, and Frontotemporal Lobar Degeneration: Comparison Using Serum Albumin, Total Protein, and Hemoglobin Level.

Malnutrition among dementia patients is an important issue. However, the biochemical markers of malnutrition have not been well studied in this population. The purpose of this study was to compare biochemical blood markers among patients with Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal lobar degeneration (FTLD). A total of 339 dementia outpatients and their family caregivers participated in this study. Low serum albumin was 7.2 times more prevalent among patients with DLB and 10.1 times more prevalent among those with FTLD than among those with AD, with adjustment for age. Low hemoglobin was 9.1 times more common in female DLB patients than in female AD patients, with adjustment for age. The levels of biochemical markers were not significantly correlated with cognitive function. Family caregivers of patients with low total protein, low albumin, or low hemoglobin were asked if the patients had loss of weight or appetite; 96.4% reported no loss of weight or appetite. In conclusion, nutritional status was worse in patients with DLB and FTLD than in those with AD. A multidimensional approach, including blood testing, is needed to assess malnutrition in patients with dementia.

Oxidative stress and inflammation are associated with physical frailty in patients with Alzheimer's disease.

Dementia is closely connected with frailty, and these two conditions are common in older adults. However, the biological mechanism that causes frailty in patients with Alzheimer's disease (AD) is not fully understood. We determined whether oxidative stress and inflammatory mechanisms could be associated with physical frailty in patients with AD. We studied 140 elderly outpatients with mild-to-moderate AD. Frailty status was determined according to the presence of the following five measurable characteristics: weight loss, exhaustion, low physical activity, slowness and weakness. We measured oxidative stress markers, including plasma levels of diacron reactive oxygen metabolite and biological anti-oxidant potential, endogenous plasma anti-oxidants, such as albumin, bilirubin and uric acid, and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-epiPGF2α (8-isoprostane), and inflammatory markers, including interleukin-6 and tumor necrosis factor-α. Among patients, 44 (31%) were non-frail, 62 (44%) were prefrail and 34 (24%) were frail. Frail and prefrail patients were older, more likely to be women and had more comorbid medical conditions than non-frail patients. Frail or prefrail patients showed significantly higher diacron reactive oxygen metabolite and lower biological anti-oxidant potential levels, a significant decrease in bilirubin, a significant increase in urinary 8-OHdG and 8-isoprostane levels, and a significantly higher interleukin-6 level, in contrast to non-frail patients. Physical frailty is common in old and female AD patients with comorbid medical diseases. The present results strongly suggest that oxidative stress and inflammation are involved in the pathophysiology of frailty status in individuals with AD. Geriatr Gerontol Int 2017; 17: 913-918.

Clusters of male and female Alzheimer's disease patients in the Alzheimer's Disease Neuroimaging Initiative (ADNI) database.

This paper presents homogeneous clusters of patients, identified in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data population of 317 females and 342 males, described by a total of 243 biological and clinical descriptors. Clustering was performed with a novel methodology, which supports identification of patient subpopulations that are homogeneous regarding both clinical and biological descriptors. Properties of the constructed clusters clearly demonstrate the differences between female and male Alzheimer’s disease patient groups. The major difference is the existence of two male subpopulations with unexpected values of intracerebral and whole brain volumes.

Adipose Tissue Distribution in Patients with Alzheimer's Disease: A Whole Body MRI Case-Control Study.

Total and central adiposity have been associated with increased risk of Alzheimer's disease (AD). Visceral and subcutaneous adipose tissues have different metabolic characteristics and could therefore be differentially associated with AD. To compare regional fat distribution determined by magnetic resonance imaging (MRI) in AD patients and healthy controls and investigate associations with stage of the disease and chemical markers. The investigation was performed in a prospective case-control study. We examined thirty patients with mild to moderate AD by whole-body MRI (1.5 T) and clinical questionnaires in comparison to thirty cognitively healthy age- and gender-matched study participants. Volumes of total, subcutaneous, and visceral body fat tissue were determined by an unbiased automatic analysis algorithm. Levels of leptin, ghrelin, and adiponectin were determined in serum, amyloid-β (Aβ)(1-42) and tau protein levels in cerebrospinal fluid (CSF). Male AD patients displayed significantly more total fat tissue than male controls. This difference was not observed in women. We observed a trend toward higher volume of visceral fat tissue in all patients (p = 0.13). Severity of disease was not associated with fat distribution in our study. Increased leptin levels correlated with lower CSF Aβ(1-42) in female, but not in male, AD patients. Fat volume is increased in male, but not in female AD patients. Negative correlation of leptin levels and CSF Aβ(1-42) in females might be one co-factor for the increased AD risk of females. Further studies are required to confirm this gender difference in fat volume during AD and evaluate its pathophysiological importance.

Gender-Specific Differences in Cognitive Profiles of Patients with Alzheimer's Disease: Results of the Prospective Dementia Registry Austria (PRODEM-Austria).

Alzheimer's disease (AD) is one of the most common age-related diseases in the western world. Gender differences in neuropsychological functions are seldom evaluated in AD. Recent investigations suggested that gender may be an important modifying factor in the development and progression of AD. We examined gender-specific differences in the pattern of cognitive dysfunction of patients with mild to moderate AD. We examined 113 males (mean age 78) and 173 females (mean age 80) of the prospective registry on dementia in Austria (PRODEM). We analyzed differences in the cognitive profile between male and female AD patients on the CERAD-Plus test battery. We found gender-related differences in the neuropsychological domains of verbal learning; the women tended to perform worse than men. Controlling for depression, stage and duration of dementia, and the level of education, there was still a significant effect of gender on verbal episodic memory. There is an interaction between gender and cognitive function, most notable in verbal episodic memory; female patients in the early stage of AD performed worse on verbal episodic memory than men. This indicates that the gender-specificities of neuropsychological functions should be given careful consideration in clinical diagnosis of dementia.

Skewed X-chromosome inactivation in women affected by Alzheimer's disease.

X-chromosome instability has been a long established feature in Alzheimer's disease (AD). Premature centromere division and aneuploidy of the X-chromosome has been found in peripheral blood lymphocytes and neuronal tissue in female AD patients. Interestingly, only one chromosome of the X pair has been affected. These results raised a question, "Is the X-chromosome inactivation pattern altered in peripheral blood lymphocytes of women affected by AD?" To address this question, we analyzed the methylation status of androgen receptor promoter which may show us any deviation from the 50 : 50% X inactivation status in peripheral blood lymphocytes of women with AD. Our results showed skewed inactivation patterns (>90%). These findings suggest that an epigenetic alteration on the inactivation centers of the X-chromosome (or skewing) relates not only to aging, by might be a novel property that could account for the higher incidence of AD in women.

The correlationship study between the levels of serum Cystatin C and the cognitive dysfunction, the cerebral perfusion in Alzheimer's diesease patients

Objective To explore the correlationship between Cystatin C and the cognitive dysfunction, encephalatrophy and the cerebral perfusion in Alzheimer's disease(AD) patients, and to analyze the probable mechanisms of the Cystatin C level alterations. Methods For the 61 male and 55 female AD patients, the levels of Cystatin C, Urea, Cr and β2-microglobulin were detected by biochemistry analysis.The hypocampus volume and Evans index were measured by MRI imaging.The cerebral perfusion was evaluated by magnetic resonance perfusion imaging of arterial spin labeling technique and image processing.The cognitive level of AD patients was done by MMSE scale and MoCA scale. Results The Cystatin C levels in serum of male AD patients were dramatically different from female AD patients(male: (0.95±0.20)mg/L, female: (1.32±0.41)mg/L)(P=0.04). For male AD patients, age and Cystatin C had a correlationship among the hypocampus volume((6157.14±355.58)mm3), Evans index(0.33±0.02), MMSE score(21.66±7.97), and MoCA score(21.96±6.19)(age: P=0.040, 0.049, 0.035, 0.039; Cystatin C: P=0.035, 0.038, 0.037, 0.035), but for female only age((79.52±8.82)years) had a correlationship with the hypocampus volume((6319.53±377.74)mm3), Evans index(0.31±0.02), MMSE score(22.93±6.22), and MoCA score(23.41±8.20)(P=0.044, 0.045, 0.047, 0.046). For male AD patients, the marked correlationship was showed between Cystatin C and the index of cerebral perfusion(P=0.034), but for female patients, there's no correlationship(P=0.086). Conclusion The Cystatin C level is distinctly different in male and female AD patients. The Cystatin C level in male AD patients maybe be an index to predict the degree of the cognitive dysfunction and the level of cerebral perfusion. Key words: Alzheimer's disease; Cystatin C; Encephalatrophy; Cognitive function; Cerebral perfusion

Increased Serum Levels of Interleukin-18, -23 and -17 in Chinese Patients with Alzheimer's Disease

Aims: To evaluate the serum levels of interleukin (IL)-18, IL-23 and IL-17 in Chinese patients with Alzheimer's disease (AD), and explore correlations between the three cytokines and relevant parameters. Methods: Serum concentrations of IL-18, IL-23 and IL-17 were measured by ELISA for 53 AD patients and 53 sex- and age-matched healthy controls in a community of elderly individuals in a Shanghai suburb. Results: Serum concentrations of IL-18, IL-23 and IL-17 were significantly higher in AD patients than controls. The serum level of IL-23 was observed to be significantly higher (p = 0.049) in female AD patients than male AD patients. In addition, a significantly inverse correlation was found between IL-18 and MMSE score (r_s = -0.356, p = 0.011) for all AD patients. Conclusion: Elevated IL-18, IL-23 and IL-17 levels are observed in AD patients and differences may exist between males and females. Besides, IL-18 may correlate with the severity of AD.