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BACKGROUND@#We previously showed that aging accelerates after 3 months of exposure to hypoxia and environmental change but not genetic modifications. Here, we aimed to simply induce early-onset age-related hearing loss within a short period based on our previous method. @*METHODS@#We randomly divided 16 C57BL/6 mice into four groups that were maintained under conditions of normoxia and hypoxia with or without injected D-galactose for 2 months. Deteriorated hearing, the expression of age-related factors, and oxidative stress responses were detected using the click and tone burst auditory brainstem response test, reverse transcription-polymerase chain reaction, and by measuring superoxide dismutase (SOD). @*RESULTS@#The group maintained under hypoxia combined with D-galactose lost hearing particularly at 24 Hz and 32 Hz at 6 weeks compared with the other groups. Aging-related factors were also significantly decreased in the hypoxia and D-galactose groups. However, SOD levels did not significantly differ among the groups. @*CONCLUSION@#Age-related hearing loss is an environmental disorder induced by chronic oxidative stress associated with genetic backgrounds. Our findings suggested that D-galactose and hypoxia can induce the phenotypes of age-related hearing loss and aging-associated molecules in a murine model within a short time with environmental stimulation alone.
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Background and Objectives@#The present study aimed to explore meaningful change in the musical performance of cochlear implant (CI) users according to age after receiving music training compared to the other CI users who did not receive any music training and normal hearing (NH) listeners. @*Materials and Methods@#Article search was conducted from five journal databases. In accordance with PICOS criteria, 29 articles and 15 articles were included for the CI and NH groups, respectively. A total of 44 articles consisting of 407 CI users and 486 NH participants were then analyzed. Using the data gathered from pre- and post-training, meta-analysis was applied by the random-effects model, and then piecewise meta-regression was employed. @*Results@#CI users with music training showed better performance than those without the training across all ages. The curve change in musical performance when training showed that the CI users was similar to the general pattern of NH performance, indicating that the CI users gained benefits from music training and developed perceptual ability, even though it was not as high as the level of NH counterparts. @*Conclusions@#This finding supports the benefits of active engagement with music for both CI users and NH listeners, while noting the important role of music as one of the primary aural rehabilitation approaches.
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Congenital cutaneous candidiasis (CCC) is a rare disease caused by Candida spp. that occurs within the first six days of life. Its exact pathogenesis remains unclear; however, the suspected pathomechanisms include maternal vulvovaginal candidiasis and ascending infections. A preterm, 1,550-g male infant presented with generalized maculopapules and pustules on his whole body. The patient’s mother had undergone cervical cerclage at a gestational age (GA) of 29 weeks due to an incompetent internal os of the cervix. The pregnancy was terminated at GA 37-week because the mother developed chorioamnionitis. We performed a potassium hydroxide microscopic examination, skin biopsy, and fungal culture test on the baby. Microscopic examination of the skin scrapings revealed pseudohyphae with yeasts, and Candida albicans was identified in the culture test. Maternal placental biopsy revealed fungal organisms, and the baby was diagnosed with CCC due to an ascending infection. The skin lesions completely disappeared after intravenous liposomal amphotericin B treatment.
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Objectives@#. Otitis media is a common infection worldwide. Owing to the limited number of ear specialists and rapid development of telemedicine, several trials have been conducted to develop novel diagnostic strategies to improve the diagnostic accuracy and screening of patients with otologic diseases based on abnormal otoscopic findings. Although these strategies have demonstrated high diagnostic accuracy for the tympanic membrane (TM), the insufficient explainability of these techniques limits their deployment in clinical practice. @*Methods@#. We used a deep convolutional neural network (CNN) model based on the segmentation of a normal TM into five substructures (malleus, umbo, cone of light, pars flaccida, and annulus) to identify abnormalities in otoscopic ear images. The mask R-CNN algorithm learned the labeled images. Subsequently, we evaluated the diagnostic performance of combinations of the five substructures using a three-layer fully connected neural network to determine whether ear disease was present. @*Results@#. We obtained the receiver operating characteristic (ROC) curve of the optimal conditions for the presence or absence of eardrum diseases according to each substructure separately or combinations of substructures. The highest area under the curve (0.911) was found for a combination of the malleus, cone of light, and umbo, compared with the corresponding areas under the curve of 0.737–0.873 for each substructure. Thus, an algorithm using these five important normal anatomical structures could prove to be explainable and effective in screening abnormal TMs. @*Conclusion@#. This automated algorithm can improve diagnostic accuracy by discriminating between normal and abnormal TMs and can facilitate appropriate and timely referral consultations to improve patients’ quality of life in the context of primary care.
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no abstract available.
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Background@#Pathogenesis of psoriasis is related to dysregulated keratinocyte function and immune responses. Genetic background is one of the most important factors in disease pathogenesis. However, psoriasis-associated genes have not yet been fully identified. Activating transcription factor 3 (ATF3) is a member of the cyclic adenosine monophosphate responsive element-binding protein family of transcription factors, which may regulate epidermal keratinocytes. @*Objective@#We aimed to evaluate the effects of ATF3 on inflammation and differentiation of keratinocytes. @*Methods@#We evaluated the expression of ATF3 in polyinosinic:polycytidylic acid (poly[I:C])-treated keratinocytes. Subsequently, we compared ATF3 levels in psoriatic and normal skin using immunohistochemical staining. To illustrate the role of ATF3, we generated ATF3-overexpressing keratinocytes and ATF3-knockdown keratinocytes using a recombinant adenovirus. We investigated inflammation and differentiation of keratinocytes by measuring the mRNA levels of inflammatory cytokines and differentiation markers. @*Results@#Treatment of keratinocytes with poly(I:C) increased ATF3 expression in a time-dependent manner. Immunohistochemical staining showed that ATF3 expression was increased in the epidermis of psoriatic tissues. When ATF3 was overexpressed in keratinocytes using a recombinant adenovirus, poly(I:C)-induced inflammation was reduced. Conversely, ATF3 knockdown increased poly(I:C)-induced inflammation. Thus, ATF3 overexpression inhibited keratinocyte differentiation, while ATF3 knockdown promoted it. @*Conclusion@#ATF3 may be involved in the pathogenesis of psoriasis by influencing the inflammatory response and differentiation of keratinocytes.
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Background@#Acral melanoma is the most common subtype of melanoma among Koreans, and regional or distant metastasis is an indicator of poor prognosis. Yes-associated protein (YAP), a key effector of the Hippo pathway, is known to induce tumor progression and metastasis in various cancers. @*Objective@#We aimed to analyze the clinical and histopathological characteristics of acral melanoma among Koreans and to evaluate their association with YAP expression. @*Methods@#This retrospective review included 27 patients with acral melanoma. Clinical features including age, sex, lesion site, and stage were obtained from the medical records and images. Biopsy slides of patients with acral melanoma were reviewed, and immunohistochemical staining for YAP was performed. @*Results@#The rate of YAP expression was significantly higher in patients having acral melanoma with regional or distant lymph node (LN) metastasis than in those without metastasis (n=4/5, 80.0% vs. n=2/22, 9.1%; p=0.004). Histopathologically, the rate of YAP expression was higher in patients having acral melanoma with lymphovascular invasion than in those without lymphovascular invasion (n=4/8, 50.0% vs. n=2/19, 10.5%; p=0.044). Among the 27 lesions, 14 (51.9%) were on stress-bearing sites such as the forefoot and heel. However, the rate of YAP expression did not differ significantly between weight-bearing and non-weight-bearing locations (p=0.834). @*Conclusion@#YAP expression is significantly associated with metastasis, especially LN metastasis, in patients with acral melanoma. Therefore, YAP expression may be used as a prognostic factor for LN metastasis and a target for novel treatments in patients with melanoma.
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Background@#Alopecia areata (AA) is an autoimmune disease characterized by chronic inflammation, the pathogenesis of which is unknown. Stress is believed to play a role; however, evidence remains insufficient. A recent study showed that substance P (SP) damaged hair follicles by causing neurogenic inflammation, activating perifollicular mast cells, and inducing keratinocyte apoptosis. @*Objective@#We aimed at studying the role of SP in AA pathogenesis. We investigated the SP levels in the lesional scalp tissues and serum. We also studied the effect of SP on the inflammatory response and hair growth in the outer root sheath (ORS) cells. @*Methods@#We compared the serum levels of SP in 58 AA patients and 28 healthy subjects.Then, we checked the expression of SP and SP receptor, neurokinin-1 receptor (NK-1R) in the scalps of AA patients and healthy controls using immunohistochemical staining.Finally, we analyzed the mRNA expression of inflammatory cytokines and hair growthrelated factors in ORS cells. @*Results@#SP and NK-1R expression were markedly higher in the hair follicles and interfollicular epidermis of the scalp lesions of AA patients. However, there was no statistically significant difference in serum SP levels between controls and patients, regardless of the type of alopecia. SP significantly increased the mRNA expression of inflammatory cytokines and decreased hair growth-related growth factors in ORS cells, but the results were not dramatic. @*Conclusion@#SP triggered a localized micro-inflammation in lesional hair follicles, provoked an inf lammatory response, and inhibited hair growth, thereby confirming the pathogenic role of SP in AA.
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Background@#Skin aging can be divided into intrinsic and extrinsic processes, and occur due to several factors. Although the interest in skin youthfulness is increasing globally, research on facial skin youthfulness and lifestyle is limited. @*Objective@#This study aimed to evaluate the association between facial skin youthfulness and biophysical facial skin parameters in Korean women over 50 years of age. We further investigated lifestyle factors that make people appear younger than their chronological age. @*Methods@#We surveyed the essential information and lifestyle of subjects by questionnaires, and measured the biophysical parameters of the facial skin. We then performed clinical facial assessments, and the values were compared with the chronologic age. The associations between age differences, biophysical parameters, and living habits were evaluated. @*Results@#We identified a positive correlation between age and melanin index (r=0.245, p＜0.001) and erythema index (r=0.119, p=0.002). The melanin index was statistically significantly lower in the group without regular outdoor activities (144.66±43.24 vs. 137.00±55.48, p=0.043). The melanin index and erythema index were the significant differences that defined younger perceived age than chronological age. The perceived age was younger in the group who wore a hat when performing outdoor activities than the group who did not (3.70±1.84 vs. 3.40±1.94, p=0.034). @*Conclusion@#To retain youthful skin, it is essential to reduce sun exposure, as this factor can affect the melanin and erythema indices by inducing photoaging. Therefore, avoiding the sun bia proper methods, such as wearing a hat and sunscreen during outdoor activities, is recommended to maintain skin youthfulness.
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Background@#Hormone therapy, which includes tamoxifen and aromatase inhibitors, is the most common adjuvant therapy used for breast cancer. However, only a few studies have reported endocrine therapy induced alopecia. @*Objective@#We investigated the effects of long-term adjuvant hormone therapy on hair in patients with breast cancer, in addition to patients’ concerns and current treatment for hair loss. @*Methods@#Patients completed a questionnaire that included information on self-perceived hair changes after each adjuvant therapy session, distress, and current treatment for hair loss. Using a folliscope, we measured hair density and thickness in each patient and in healthy controls. @*Results@#The study included 93 patients with breast cancer (mean age 51.9±9.8 years). The density and hair thickness were 106.36±21.85 hairs/cm2 and 0.07±0.01 mm in the patient group and 147.86±30.67 hairs/cm2 and 0.07±0.01 mm in the control group (n=98, mean age 52.10±8.40 years), respectively. The mean hair density was significantly lower in the patient group than in the control group; however, no statistically significant intergroup difference was observed in hair thickness. Among 76 patients who perceived hair changes after adjuvant therapy, 71.1% (n=54) were distressed with regard to hair changes. However, only 7.8% of the patients, including two who were treated by dermatologists, currently received treatment for hair changes. @*Conclusion@#Dermatologists should be familiar with hair changes in patients with breast cancer and provide appropriate education to encourage patients to consult dermatologists for hair loss and thinning after breast cancer treatment.
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Background@#Increased sebum secretion is considered the main causative factor in the pathogenesis of acne. There is an unmet pharmacological need for a novel drug that can control sebum production with a favorable adverse effect profile. @*Objective@#To investigate the effect of azidothymidine on lipid synthesis in sebocytes and to identify the underlying mechanism of the inhibitory effect of azidothymidine on insulin-like growth factor (IGF)-1-induced lipid synthesis in sebocytes. @*Methods@#Immortalized human sebocytes were used for the analysis. Thin-layer chromatography (TLC) and Oil Red O staining were performed to evaluate lipid synthesis in the sebocytes. The differentiation, lipid synthesis, mitochondrial biogenesis, and mitophagy in sebocytes were investigated. @*Results@#TLC and Oil Red O staining revealed that azidothymidine reduced IGF-1 induced lipid synthesis in the immortalized human sebocytes. Azidothymidine also reduced IGF-1-induced expression of transcriptional factors and enzymes involved in sebocyte differentiation and lipid synthesis, respectively. Moreover, we found that IGF-1 upregulated the levels of peroxisome proliferator-activated receptor-gamma coactivator-1α, LC-3B, p62, and Parkin, major regulators of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. In contrast, azidothymidine inhibited IGF-1 induced mitochondrial biogenesis and mitophagy in the sebocytes. @*Conclusion@#These results suggest that azidothymidine downregulates IGF-1-induced lipogenesis by dysregulating the quality of mitochondria through suppression of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. Our study provides early evidence that azidothymidine may be an effective candidate for a new pharmacological agent for controlling lipogenesis in sebocytes.
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Background@#Psoriasis is a chronic inflammatory skin disease. The etiology of psoriasis is not fully understood, but the genetic background is considered to be the most important factor. To date, many psoriasis-related genes have been discovered, but the role of many important genes has not been well understood. @*Objective@#The purpose of this study is to uncover possible roles of MDA5 in psoriasis. @*Methods@#Expression of MDA5 was investigated using immunohistochemistry. Then, MDA5 was overexpressed in keratinocytes using a recombinant adenovirus. @*Results@#As a result of immunohistochemical staining, the expression of MDA5 was significantly increased in the epidermis of psoriasis compared to normal skin. Similarly, the expression of MDA5 was increased in imiquimod-induced psoriasiform dermatitis model. In cultured keratinocytes, toll-like receptor 3 agonist poly(I:C) induced expression of MDA5 at both mRNA and protein levels. When MDA5 was overexpressed using a recombinant adenovirus, poly(I:C)-induced cytokine expression was significantly increased. Finally, MDA5 overexpression significantly inhibited calcium-induced differentiation of keratinocytes. @*Conclusion@#These results suggest that MDA5 increases in psoriasis and negatively regulates keratinocyte differentiation.
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In the field of tissue regeneration and tissue engineering, many years ago, various nano to macroscopic-sized materials have been used to reduce inflammation and restore damaged tissue. Whether it is safe to study the regeneration of all tissues based on the biological mechanisms of an organism composed of cells is still debated, and studies using extracellular vesicles derived from cells have become popular in the past decade. It has been reported that exosomes with a size of 100 nm or less, which plays an important role in cell–cell communication, contain various factors, such as proliferation, anti-inflammatory, and growth factors. In addition, the payload of exosomes varies depending on the parent cell and the recipient cell, and a technology to differentiate the selective payload must treat specific diseases. In this review, we examined the current trends in research using exosomes derived from cells or tissues and analyzed various research reports on factors that can affect tissue regeneration.
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Background@#Hormone therapy, which includes tamoxifen and aromatase inhibitors, is the most common adjuvant therapy used for breast cancer. However, only a few studies have reported endocrine therapy induced alopecia. @*Objective@#We investigated the effects of long-term adjuvant hormone therapy on hair in patients with breast cancer, in addition to patients’ concerns and current treatment for hair loss. @*Methods@#Patients completed a questionnaire that included information on self-perceived hair changes after each adjuvant therapy session, distress, and current treatment for hair loss. Using a folliscope, we measured hair density and thickness in each patient and in healthy controls. @*Results@#The study included 93 patients with breast cancer (mean age 51.9±9.8 years). The density and hair thickness were 106.36±21.85 hairs/cm2 and 0.07±0.01 mm in the patient group and 147.86±30.67 hairs/cm2 and 0.07±0.01 mm in the control group (n=98, mean age 52.10±8.40 years), respectively. The mean hair density was significantly lower in the patient group than in the control group; however, no statistically significant intergroup difference was observed in hair thickness. Among 76 patients who perceived hair changes after adjuvant therapy, 71.1% (n=54) were distressed with regard to hair changes. However, only 7.8% of the patients, including two who were treated by dermatologists, currently received treatment for hair changes. @*Conclusion@#Dermatologists should be familiar with hair changes in patients with breast cancer and provide appropriate education to encourage patients to consult dermatologists for hair loss and thinning after breast cancer treatment.
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Background@#Increased sebum secretion is considered the main causative factor in the pathogenesis of acne. There is an unmet pharmacological need for a novel drug that can control sebum production with a favorable adverse effect profile. @*Objective@#To investigate the effect of azidothymidine on lipid synthesis in sebocytes and to identify the underlying mechanism of the inhibitory effect of azidothymidine on insulin-like growth factor (IGF)-1-induced lipid synthesis in sebocytes. @*Methods@#Immortalized human sebocytes were used for the analysis. Thin-layer chromatography (TLC) and Oil Red O staining were performed to evaluate lipid synthesis in the sebocytes. The differentiation, lipid synthesis, mitochondrial biogenesis, and mitophagy in sebocytes were investigated. @*Results@#TLC and Oil Red O staining revealed that azidothymidine reduced IGF-1 induced lipid synthesis in the immortalized human sebocytes. Azidothymidine also reduced IGF-1-induced expression of transcriptional factors and enzymes involved in sebocyte differentiation and lipid synthesis, respectively. Moreover, we found that IGF-1 upregulated the levels of peroxisome proliferator-activated receptor-gamma coactivator-1α, LC-3B, p62, and Parkin, major regulators of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. In contrast, azidothymidine inhibited IGF-1 induced mitochondrial biogenesis and mitophagy in the sebocytes. @*Conclusion@#These results suggest that azidothymidine downregulates IGF-1-induced lipogenesis by dysregulating the quality of mitochondria through suppression of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. Our study provides early evidence that azidothymidine may be an effective candidate for a new pharmacological agent for controlling lipogenesis in sebocytes.
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Background@#Psoriasis is a chronic inflammatory skin disease. The etiology of psoriasis is not fully understood, but the genetic background is considered to be the most important factor. To date, many psoriasis-related genes have been discovered, but the role of many important genes has not been well understood. @*Objective@#The purpose of this study is to uncover possible roles of MDA5 in psoriasis. @*Methods@#Expression of MDA5 was investigated using immunohistochemistry. Then, MDA5 was overexpressed in keratinocytes using a recombinant adenovirus. @*Results@#As a result of immunohistochemical staining, the expression of MDA5 was significantly increased in the epidermis of psoriasis compared to normal skin. Similarly, the expression of MDA5 was increased in imiquimod-induced psoriasiform dermatitis model. In cultured keratinocytes, toll-like receptor 3 agonist poly(I:C) induced expression of MDA5 at both mRNA and protein levels. When MDA5 was overexpressed using a recombinant adenovirus, poly(I:C)-induced cytokine expression was significantly increased. Finally, MDA5 overexpression significantly inhibited calcium-induced differentiation of keratinocytes. @*Conclusion@#These results suggest that MDA5 increases in psoriasis and negatively regulates keratinocyte differentiation.
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In the field of tissue regeneration and tissue engineering, many years ago, various nano to macroscopic-sized materials have been used to reduce inflammation and restore damaged tissue. Whether it is safe to study the regeneration of all tissues based on the biological mechanisms of an organism composed of cells is still debated, and studies using extracellular vesicles derived from cells have become popular in the past decade. It has been reported that exosomes with a size of 100 nm or less, which plays an important role in cell–cell communication, contain various factors, such as proliferation, anti-inflammatory, and growth factors. In addition, the payload of exosomes varies depending on the parent cell and the recipient cell, and a technology to differentiate the selective payload must treat specific diseases. In this review, we examined the current trends in research using exosomes derived from cells or tissues and analyzed various research reports on factors that can affect tissue regeneration.
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This study aimed to evaluate the efficacy of music training on the improvement of musical perception among hearing-impaired listeners using a systematic review and meta-analysis. Article search was conducted from five databases, Scopus, ScienceDirect, Web of Knowledge, CINAHL, and PubMed. A total of 186 participants from 10 studies investigating the music training effects on individuals fitted with hearing assistive devices and outcome measurements were included. The meta-analysis showed standardized mean difference as a measure of the effect size, in musical improvement between the preand post-training. Although the funnel plot yielded an asymmetrical graph, the Egger’s regression showed no significant publication bias. Interestingly, subgroup analysis showed that the training effect was greater in children than in adults. With a necessity of longer training period to significantly improve their musical perception, cochlear implant only users had better effect compared to bi-modal users with both cochlear implant and hearing aids. However, the difference in the training effect between the users with and without previous musical experience was nonsignificant. The present study concludes that auditory music training brings hearing-impaired listeners into better musical perception while informing that training effects differ depending on age, duration of the training, and the type of hearing device used.
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Background@#Longitudinal melanonychia (LM) is a common clinical finding. Most cases of LM are benign, and a waitand-see approach is preferred in the management of this condition. Nevertheless, it is important for clinicians to distinguish subungual melanoma (SUM) from other benign LMs. @*Objective@#To evaluate the demographic and clinicopathologic characteristics of LM in the Korean population and to identify the predictor of SUM against other benign conditions. @*Methods@#This was a single-center retrospective cohort study including patients who underwent nail biopsy for LM from January 2000 to May 2019. To identify the predictor of SUM, receiver operating characteristic (ROC) analyses was performed. @*Results@#A total of 68 cases of biopsy-proven LM were included in the analysis. Among the 68 cases, 8 were SUM. In univariable analysis, patients diagnosed with SUM were older (p=0.035) and had a longer disease duration (p=0.004).They also showed multicolor pigmentation of LM (p=0.022),a larger width of LM (p＜0.001), and associated nail plate dystrophy (p=0.010) than patients diagnosed with benign conditions. In multivariable logistic regression, width of LM showed statistical significance (odds ratio, 1.083; 95% confidence interval, 1.018∼1.153). ROC analysis suggested that an LM width ＞28% of the whole nail was the predictor of SUM (area under the curve=0.883; p＜0.001). @*Conclusion@#SUM has distinct demographic and clinical features. The width of LM can predict SUM against other benign LMs.
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It is acknowledged that there is a negative relationship between dementia and auditory function in older adults. This study conducted a systematic review and meta-analysis based on the data of audiologic testings from patients with neurodegenerative diseases in terms of auditory eventrelated potentials and central auditory processing tests, while focusing on Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and Parkinson’s disease dementia (PDD). A total of 34765 articles were retrieved from the seven electronic databases. After being screened by Participants, Index test, Control, Outcomes, Study design (PICOS) criteria, 129 articles for AD were included and then 72 articles were applied to the meta-analysis. However, five and six ar-ticles were systematically reviewed for the auditory functions of DLB and PDD, respectively,due to a small number of articles. The results of meta-analysis showed a significant difference between patients with AD and age-matched normal subjects, for N200 and P300 latency, P300 amplitude, and the behavioral central auditory processing tests, although there was a high heterogeneity. On the other hand, the systematic review indicated that the results of mismatch negativity test might distinguish auditory performance of DLB patients from that of PDD. Furthermore, for P300 amplitude, anterior to posterior distribution of brain resulted in meaningful difference of auditory function between AD and DLB patients. In sum, current review study suggests that lesion and degree of auditory (dys)function may be different depending on the type of dementia, although future research should be followed.