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Mainly due to the slanted focus on the mechanism and regulation of neuronal aging, research on astrocyte aging and its modulation during brain aging is scarce. In this study, we established aged astrocyte culture model by long-term culturing. Cellular senescence was confirmed through SA-β-gal staining as well as through the examination of morphological, molecular, and functional markers. RNA sequencing and functional analysis of astrocytes were performed to further investigate the detailed characteristics of the aged astrocyte model. Along with aged phenotypes, decreased astrocytic proliferation, migration, mitochondrial energetic function and support for neuronal survival and differentiation has been observed in aged astrocytes. In addition, increased expression of cytokines and chemokine-related factors including plasminogen activator inhibitor -1 (PAI-1) was observed in aged astrocytes. Using the RNA sequencing results, we searched potential drugs that can normalize the dysregulated gene expression pattern observed in long-term cultured aged astrocytes. Among several candidates, minoxidil, a pyrimidine-derived anti-hypertensive and anti-pattern hair loss drug, normalized the increased number of SA-β-gal positive cells and nuclear size in aged astrocytes. In addition, minoxidil restored up-regulated activity of PAI-1 and increased mitochondrial superoxide production in aged astrocytes.We concluded that long term culture of astrocytes can be used as a reliable model for the study of astrocyte senescence and minoxidil can be a plausible candidate for the regulation of brain aging.
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Background@#and Purpose Oral administration of cholinesterase inhibitors is often associated with adverse gastrointestinal effects, and so developing an alternative administration route, such as transdermal, is urgently needed. The primary objective of this study was to determine the efficacy and safety of the IPI-301 donepezil transdermal patch compared with donepezil tablets (control) in mild-to-moderate probable Alzheimer’s disease (AD). @*Methods@#This prospective, randomized, double-blind, double-dummy, two-arm parallel, multicenter trial included 399 patients, among whom 303 completed the trial. For randomization, the patients were stratified based on previous treatment and donepezil dose; patients in each stratum were randomized to the test and control groups at a 1:1 ratio. @*Results@#The difference between the control group and the IPI-301 group, quantified as the Hodges–Lehmann estimate of location shift, was 0.00 (95% confidence interval: -1.00 to 1.33), with an upper limit of less than 2.02. The change in Alzheimer’s Disease Cooperative Study– Activities of Daily Living (ADCS-ADL) score differed significantly between the IPI-301 and control groups (p=0.02). However, the changes in the full-itemized ADCS-ADL scores at week 24 did not differ significantly between the two groups. There were no differences between the two groups regarding the scores for the Clinician Interview-Based Impression of Change (f0.9097), Mini-Mental State Examination (p=0.7018), Neuropsychiatric Inventory (p=0.7656), or Clinical Dementia Rating (p=0.9990). Adverse events, vital signs, and laboratory test results were comparable between the two groups. @*Conclusions@#IPI-301 was safe and efficacious in improving cognitive function in patients with mild-to-moderate AD.
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Objective@#This study aimed to determine whether there are regional differences in the blood-brain barrier (BBB) permeability of cognitively normal elderly participants and to identify factors influencing BBB permeability with a clinically feasible, 10-minute dynamic contrast-enhanced (DCE) MRI protocol. @*Materials and Methods@#This IRB-approved prospective study recruited 35 cognitively normal adults (26 women; mean age, 64.5 ± 5.6 years) who underwent DCE T1-weighted imaging. Permeability maps (Ktrans) were coregistered with masks to calculate the mean regional values. The paired t test and Friedman test were used to compare Ktrans between different regions. The relationships between Ktrans and the factors of age, sex, education, cognition score, vascular risk burden, vascular factors on imaging, and medial temporal lobar atrophy were assessed using Pearson correlation and the Spearman rank test. @*Results@#The mean permeability rates of the right and left hippocampi, as assessed with automatic segmentation, were 0.529 ± 0.472 and 0.585 ± 0.515 (Ktrans, x 10-3 min-1 ), respectively. Concerning the deep gray matter, the Ktrans of the thalamus was significantly greater than those of the putamen and hippocampus (p = 0.007, p = 0.041). Regarding the white matter, the Ktrans value of the occipital white matter was significantly greater than those of the frontal, cingulate, and temporal white matter (p < 0.0001, p = 0.0007, p = 0.0002). The variations in Ktrans across brain regions were not related to age, cognitive score, vascular risk burden, vascular risk factors on imaging, or medial temporal lobar atrophy in the study group. @*Conclusion@#Our study demonstrated regional differences in BBB permeability (Ktrans) in cognitively normal elderly adults using a clinically acceptable 10-minutes DCE imaging protocol. The regional differences suggest that the integrity of the BBB varies across the brains of cognitively normal elderly adults. We recommend considering regional differences in Ktrans values when evaluating BBB permeability in patients with neurodegenerative diseases.
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Objective@#This study aimed to determine whether there are regional differences in the blood-brain barrier (BBB) permeability of cognitively normal elderly participants and to identify factors influencing BBB permeability with a clinically feasible, 10-minute dynamic contrast-enhanced (DCE) MRI protocol. @*Materials and Methods@#This IRB-approved prospective study recruited 35 cognitively normal adults (26 women; mean age, 64.5 ± 5.6 years) who underwent DCE T1-weighted imaging. Permeability maps (Ktrans) were coregistered with masks to calculate the mean regional values. The paired t test and Friedman test were used to compare Ktrans between different regions. The relationships between Ktrans and the factors of age, sex, education, cognition score, vascular risk burden, vascular factors on imaging, and medial temporal lobar atrophy were assessed using Pearson correlation and the Spearman rank test. @*Results@#The mean permeability rates of the right and left hippocampi, as assessed with automatic segmentation, were 0.529 ± 0.472 and 0.585 ± 0.515 (Ktrans, x 10-3 min-1 ), respectively. Concerning the deep gray matter, the Ktrans of the thalamus was significantly greater than those of the putamen and hippocampus (p = 0.007, p = 0.041). Regarding the white matter, the Ktrans value of the occipital white matter was significantly greater than those of the frontal, cingulate, and temporal white matter (p < 0.0001, p = 0.0007, p = 0.0002). The variations in Ktrans across brain regions were not related to age, cognitive score, vascular risk burden, vascular risk factors on imaging, or medial temporal lobar atrophy in the study group. @*Conclusion@#Our study demonstrated regional differences in BBB permeability (Ktrans) in cognitively normal elderly adults using a clinically acceptable 10-minutes DCE imaging protocol. The regional differences suggest that the integrity of the BBB varies across the brains of cognitively normal elderly adults. We recommend considering regional differences in Ktrans values when evaluating BBB permeability in patients with neurodegenerative diseases.
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BACKGROUND@#The 48/6 Model of Care is an integrative care initiative for improving the health outcomes of hospitalized older patients; however, its applicability in community-dwelling older adults as a health screening tool has not been investigated. The present study aimed to examine the applicability of this model, prevalence of dysfunction in 6 care areas, and its relationship with self-reported mobility in community-dwelling older adults.@*METHODS@#This was a cross-sectional survey study of community-dwelling adults aged 65 or older. Participants were screened for problems using 9 items corresponding to the 6 care areas of the 48/6 Model of Care (cognitive functioning, functional mobility, pain management, nutrition and hydration, bladder and bowel management, and medication management). Mobility was assessed via the Life-Space Assessment (LSA). We examined the correlation between each screening item and the LSA.@*RESULTS@#A total of 444 older adults (260 women, 58.6%) participated. The mean number of health problems was 2.3 ± 2.1, with the most common being pain, cognitive impairment, and urinary incontinence. These problems and LSA scores were significantly different by age groups. A multiple regression analysis showed that polypharmacy (β = −10.567, P < 0.001), dysphagia (β = −9.610, P = 0.021), and pain (β = −7.369, P = 0.004) were significantly associated with life-space mobility after controlling for age.@*CONCLUSION@#The 48/6 Model of Care is applicable to community-dwelling older adults, who show high prevalence of dysfunction in the 6 care areas. This study supports the role of the model in screening for the health status of older adults living in the community, and in estimating mobility.
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BACKGROUND@#The 48/6 Model of Care is an integrative care initiative for improving the health outcomes of hospitalized older patients; however, its applicability in community-dwelling older adults as a health screening tool has not been investigated. The present study aimed to examine the applicability of this model, prevalence of dysfunction in 6 care areas, and its relationship with self-reported mobility in community-dwelling older adults.@*METHODS@#This was a cross-sectional survey study of community-dwelling adults aged 65 or older. Participants were screened for problems using 9 items corresponding to the 6 care areas of the 48/6 Model of Care (cognitive functioning, functional mobility, pain management, nutrition and hydration, bladder and bowel management, and medication management). Mobility was assessed via the Life-Space Assessment (LSA). We examined the correlation between each screening item and the LSA.@*RESULTS@#A total of 444 older adults (260 women, 58.6%) participated. The mean number of health problems was 2.3 ± 2.1, with the most common being pain, cognitive impairment, and urinary incontinence. These problems and LSA scores were significantly different by age groups. A multiple regression analysis showed that polypharmacy (β = −10.567, P < 0.001), dysphagia (β = −9.610, P = 0.021), and pain (β = −7.369, P = 0.004) were significantly associated with life-space mobility after controlling for age.@*CONCLUSION@#The 48/6 Model of Care is applicable to community-dwelling older adults, who show high prevalence of dysfunction in the 6 care areas. This study supports the role of the model in screening for the health status of older adults living in the community, and in estimating mobility.
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Background@#This study aimed to describe the experience of providing older adult patients with transitional care from an acute care hospital to home in cooperation with a public health center, in order to present the barriers to that care and suggest better organizational methods. @*Methods@#This was a cross-sectional study to show the results of the Geriatric Screening for Care-10 (GSC-10) and outcomes of transitional care. Among 659 hospitalized patients aged 65 years or above who lived in an administrative district, forty-five subjects were enrolled between June 24, 2019 and January 23, 2020. Within 48 hours of admission, using the 10 areas of GSC-10, they were assessed for cognitive impairment, depression, polypharmacy (5 or more medications), functional mobility, dysphagia, malnutrition, pain, and incontinence, and were reassessed before discharge. The transitional care plan (containing the treatment summary, the results of the GSC-10 assessment, and the post-discharge plan) was forwarded to a representative of the public health center, who provided continued disease management and various health care services, such as chronic disease and frailty care, and physical rehabilitation. @*Results@#Of all the participants, 64.4% had more than 1 GSC-10 concern. The most prevalent concerns were functional immobility (35.6%) and polypharmacy (22.2%). About 15.6% of the participants were readmitted to a nursing home or hospital. A total of 38 participants received the transitional care intervention. They received an average of 2.7 administered interventions. However, the rate of rejection was high (30.1%) and patients were visited an average of 16.5 days after discharge. @*Conclusion@#Through our experience of providing transitional care from an acute care hospital to home in cooperation with a public health center, we expect that the transitional care suitable for the Korean medical situation could be established and successful.
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BACKGROUND: The 48/6 Model of Care is an integrative care initiative for improving the health outcomes of hospitalized older patients; however, its applicability in community-dwelling older adults as a health screening tool has not been investigated. The present study aimed to examine the applicability of this model, prevalence of dysfunction in 6 care areas, and its relationship with self-reported mobility in community-dwelling older adults.METHODS: This was a cross-sectional survey study of community-dwelling adults aged 65 or older. Participants were screened for problems using 9 items corresponding to the 6 care areas of the 48/6 Model of Care (cognitive functioning, functional mobility, pain management, nutrition and hydration, bladder and bowel management, and medication management). Mobility was assessed via the Life-Space Assessment (LSA). We examined the correlation between each screening item and the LSA.RESULTS: A total of 444 older adults (260 women, 58.6%) participated. The mean number of health problems was 2.3 ± 2.1, with the most common being pain, cognitive impairment, and urinary incontinence. These problems and LSA scores were significantly different by age groups. A multiple regression analysis showed that polypharmacy (β = −10.567, P < 0.001), dysphagia (β = −9.610, P = 0.021), and pain (β = −7.369, P = 0.004) were significantly associated with life-space mobility after controlling for age.CONCLUSION: The 48/6 Model of Care is applicable to community-dwelling older adults, who show high prevalence of dysfunction in the 6 care areas. This study supports the role of the model in screening for the health status of older adults living in the community, and in estimating mobility.
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Adulto , Feminino , Humanos , Transtornos Cognitivos , Estudos Transversais , Transtornos de Deglutição , Programas de Rastreamento , Manejo da Dor , Polimedicação , Prevalência , Bexiga Urinária , Incontinência UrináriaRESUMO
BACKGROUND: Few studies have evaluated risk factors for behavioral and psychological symptoms of dementia at the initial assessment for Alzheimer disease in large patient samples. In this study, the factors influencing Alzheimer disease were examined using the Clinical Research of Dementia of South Korea data. METHODS: This cross-sectional study was conducted using data of 1,128 patients with Alzheimer disease. The behavioral and psychological symptoms of dementia were examined using the Korean version of the Neuropsychiatric Inventory. Demographic characteristics, health-related behavior, neuropsychological tests, comorbidities, blood test results, and caregiver characteristics were assessed. Median logistic regression analysis with adjustment for covariates was conducted. RESULTS: The behavioral and psychological symptoms of dementia were negatively associated with memory (P=0.022) and frontal/executive (P < 0.001) function in the Seoul Neuropsychological Screening Battery-dementia, Barthel Index for Activities of Daily Living (P < 0.001), Korean version of the Mini-Mental State Examination score (P=0.003), and caregiver age (P=0.005) after adjustment for confounding factors, and positively associated with the Seoul-Instrumental Activities of Daily Living score (P < 0.001), Clinical Dementia Rating Sum of Box (P < 0.001), Global Deterioration Scale score (P < 0.001), abnormality of free T4 level (P < 0.001), anemia (P < 0.001), and family history of stroke (P=0.001). Patients with female caregivers exhibited more severe behavioral and psychological symptoms of dementia than those with male caregivers. CONCLUSION: Behavioral and psychological symptoms of dementia in Alzheimer disease patients were associated with various risk factors including the inability to live independently and Alzheimer disease severity. These findings suggest that prevention and treatment strategies for the behavioral and psychological symptoms of dementia should be comprehensive.
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Feminino , Humanos , Masculino , Atividades Cotidianas , Doença de Alzheimer , Anemia , Sintomas Comportamentais , Cuidadores , Comorbidade , Estudos Transversais , Demência , Testes Hematológicos , Coreia (Geográfico) , Modelos Logísticos , Programas de Rastreamento , Memória , Testes Neuropsicológicos , Fatores de Risco , Seul , Acidente Vascular CerebralRESUMO
Brain aging induces neuropsychological changes, such as decreased memory capacity, language ability, and attention; and is also associated with neurodegenerative diseases. However, most of the studies on brain aging are focused on neurons, while senescence in astrocytes has received less attention. Astrocytes constitute the majority of cell types in the brain and perform various functions in the brain such as supporting brain structures, regulating blood-brain barrier permeability, transmitter uptake and regulation, and immunity modulation. Recent studies have shown that SIRT1 and SIRT2 play certain roles in cellular senescence in peripheral systems. Both SIRT1 and SIRT2 inhibitors delay tumor growth in vivo without significant general toxicity. In this study, we investigated the role of tenovin-1, an inhibitor of SIRT1 and SIRT2, on rat primary astrocytes where we observed senescence and other functional changes. Cellular senescence usually is characterized by irreversible cell cycle arrest and induces senescence-associated β-galactosidase (SA-β-gal) activity. Tenovin-1-treated astrocytes showed increased SA-β-gal-positive cell number, senescence-associated secretory phenotypes, including IL-6 and IL-1β, and cell cycle-related proteins like phospho-histone H3 and CDK2. Along with the molecular changes, tenovin-1 impaired the wound-healing activity of cultured primary astrocytes. These data suggest that tenovin-1 can induce cellular senescence in astrocytes possibly by inhibiting SIRT1 and SIRT2, which may play particular roles in brain aging and neurodegenerative conditions.
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Animais , Ratos , Envelhecimento , Astrócitos , Barreira Hematoencefálica , Encéfalo , Senescência Celular , Contagem de Células , Pontos de Checagem do Ciclo Celular , Interleucina-6 , Idioma , Memória , Doenças Neurodegenerativas , Neurônios , Permeabilidade , Fenótipo , CicatrizaçãoRESUMO
Air pollution is a growing global health concern estimated to contribute to as many as 4.2 million premature deaths worldwide per year. So it poses the greatest environmental risk to human health. A strong and rapidly expanding body of evidence links ambient air pollution to respiratory and cardiovascular conditions that eventually may also affect cognition in the elderly. Among various ambient air pollutants, particulate matter (PM) has been implicated as a chronic source of neuroinflammation and reactive oxygen species that produce neuropathology resulting in neurodevelopmental disorders and neurodegenerative disease. The current review will briefly discuss the clinical features and underlying mechanism of PM induced cognitive dysfunction, more specifically, dementia.
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Idoso , Humanos , Poluição do Ar , Doença de Alzheimer , Cognição , Demência , Poeira , Saúde Global , Mortalidade Prematura , Doenças Neurodegenerativas , Transtornos do Neurodesenvolvimento , Neuropatologia , Material Particulado , Espécies Reativas de OxigênioRESUMO
BACKGROUND: Geriatric syndromes are associated with morbidity and poor quality of life (QOL). Urinary incontinence (UI) is one of the most prevalent geriatric syndromes. However, there is little research on the association of UI and UI-related QOL with other geriatric syndromes. We investigated the relationship between geriatric syndromes and UI according to gender and UI-related QOL among older inpatients. METHODS: This study was conducted among 444 older inpatients (aged 65 years and older) between October 2016 and July 2017. We examined geriatric syndromes and related factors involving cognitive impairment, delirium, depression, mobility decline, polypharmacy, undernutrition, pain, and fecal incontinence. UI-related QOL was assessed using the International Consultation on Incontinence Questionnaire-Short Form. Multiple logistic regression analysis was used to evaluate these associations. RESULTS: Geriatric syndromes and related factors were associated with UI. Mobility decline (odds ratio [OR], 4.16; 95% confidence interval [CI], 2.29–7.56), polypharmacy (OR, 3.35; 95% CI, 1.89–5.92), and pain (OR, 6.80; 95% CI, 3.53–13.09) were related to UI in both genders. Especially, delirium (OR, 7.55; 95% CI, 1.61–35.44) and fecal incontinence (OR, 10.15; 95% CI, 2.50–41.17) were associated with UI in men, while cognitive impairment (OR, 4.19; 95% CI, 1.14–15.44) was significantly associated with UI in women. Patients with depression were more likely to have poor UI-related QOL (OR, 8.54; 95% CI, 1.43–51.15). CONCLUSION: UI was associated with different geriatric syndromes and related factors according to gender. Care for patients with depression, related to poor UI-related QOL, should be considered in primary care to improve the UIrelated QOL of these individuals.
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Feminino , Humanos , Masculino , Transtornos Cognitivos , Estudos Transversais , Delírio , Depressão , Incontinência Fecal , Pacientes Internados , Modelos Logísticos , Desnutrição , Polimedicação , Atenção Primária à Saúde , Qualidade de Vida , Incontinência UrináriaRESUMO
BACKGROUND AND PURPOSE: Visual assessment of medial temporal-lobe atrophy (MTA) has been quick, reliable, and easy to apply in routine clinical practice. However, one of the limitations in visual assessments of MTA is the lack of widely accepted age-adjusted norms and cutoff scores for MTA for a diagnosis of Alzheimer's disease (AD). This study aimed to determine the optimal cutoff score on a T1-weighted axial MTA Visual Rating Scale (VRS) for differentiating patients with AD from cognitively normal elderly people. METHODS: The 3,430 recruited subjects comprising 1,427 with no cognitive impairment (NC) and 2003 AD patients were divided into age ranges of 50–59, 60–69, 70–79, and 80–89 years. Of these, 446 participants (218 in the NC group and 228 in the AD group) were chosen by random sampling for inclusion in this study. Each decade age group included 57 individuals, with the exception of 47 subjects being included in the 80- to 89-year NC group. The scores on the T1-weighted axial MTA VRS were graded by two neurologists. The cutoff values were evaluated from the area under the receiver operating characteristic curve. RESULTS: The optimal axial MTA VRS cutoff score from discriminating AD from NC increased with age: it was ≥as ≥1, ≥2, and ≥3 in subjects aged 50–59, 60–69, 70–79, and 80–89 years, respectively (all p < 0.001). CONCLUSIONS: These results show that the optimal cutoff score on the axial MTA VRS for diagnosing of AD differed according to the decade age group. This information could be of practical usefulness in the clinical setting.
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Idoso , Humanos , Doença de Alzheimer , Atrofia , Transtornos Cognitivos , Demência , Diagnóstico , Coreia (Geográfico) , Pemetrexede , Curva ROCRESUMO
In the ‘Acknowledgements’ section on page 263 of the original article, the grant number was incorrectly stated.
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OBJECTIVE: We aimed to find the sex differences of the way how educational attainment influence on cognitive function in patients with Alzheimer's disease (AD). METHODS: We recruited 424 patients with AD from a large hospital-based multi-center cohort. We evaluated cognitive subdomains using the Seoul Neuropsychological Screening Battery-Dementia version. We employed multiple linear regression analysis to compare the score of cognitive subdomains between the groups with high versus low educational attainment based on the high school graduate. Interaction between educational attainment and sex was also included in the analysis. RESULTS: High and low educational attainment group had 33.0% and 67.0% of patients in the study population. In the multiple regression analysis, score of all cognitive subdomains were significantly higher in the high educational attainment group. The score of attention was also significantly affected by interaction between educational attainment and sex. This result may be helpful to develop cognitive intervention therapy. CONCLUSION: In the female patients with AD, educational attainment showed higher influence on the attention score.
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Feminino , Humanos , Doença de Alzheimer , Cognição , Estudos de Coortes , Demência , Educação , Coreia (Geográfico) , Modelos Lineares , Programas de Rastreamento , Seul , Caracteres SexuaisRESUMO
Sarcopenia (Greek ‘sarx’ or flesh+‘penia’ or loss) originally is proposed as the term to describe age-related decrease of muscle mass. These days, sarcopenia is defined as a syndrome characterized by progressive loss of skeletal muscle mass and strength with a risk of adverse outcomes such as poor quality of life, physical disability, and death. In the recent decade, there are a few of consensus; European, international, and Asian consensus panels have published definitions. Additionally, measurement techniques that can be used for research and clinical practice settings according to their suitability are suggested. Many studies are reported about the association with sarcopenia and neurologic diseases, however, the results are heterogenous due to lack of sufficient studies. Some pharmacologic and non-pharmacologic methods are suggested as the intervention of sarcopenia, although there are not enough studies, yet. In this review, we summarize current understanding of the diagnostic sarcopenia and neurological point of view of sarcopenia.
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Humanos , Povo Asiático , Consenso , Diagnóstico , Músculo Esquelético , Qualidade de Vida , SarcopeniaRESUMO
Pain is often associated with a more rapid progression of cognitive and functional decline, and behavioral disturbance in dementia. Therefore, it is essential to accurately assesses pain for proper intervention in patients with dementia. The Face, Legs, Activity, Cry, and Consolability (FLACC) scale is an excellent behaviour scale which includes most of the domains that are recommended by the American Geriatrics Society to evaluate when assessing pain in patients with dementia. The purpose of this study was to develop the Korean version of the FLACC (K-FLACC) and to verify its reliability and validity in assessing pain of elderly patients with dementia. We developed the K-FLACC to consist of the five domains (face, legs, activity, cry, and consolability) with scores of 0, 1, and 2 for each domain and a total score ranging from 0 to 10 as in the original FLACC. Eighty-eight patients with dementia who visited Konkuk University Medical Center were evaluated. The K-FLACC revealed good validity as compared to the Numeric Rating Scale (NRS; r = 0.617, P < 0.001) and the Face Pain Scale (FPS; r = 0.350, P = 0.001). All of the five domains of the K-FLACC were related to the NRS and FPS, in which the activity domain showed the highest correlation. Test-retest reliability was excellent, as the intra-class correlation coefficient comparing the retest to test was 0.73 (95% confidence interval, 0.59–0.82). Our results show that the K-FLACC is a suitable and valuable scale to assess pain in patients with dementia in Korea.
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Idoso , Humanos , Centros Médicos Acadêmicos , Demência , Dor Facial , Geriatria , Coreia (Geográfico) , Perna (Membro) , Programas de Rastreamento , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: Extrapyramidal signs (EPS) are common in patients with mild cognitive impairment (MCI). However, few studies have assessed the effect of EPS on the clinical course of MCI. We aimed to evaluate whether patients with EPS show more frequent progression from MCI to Alzheimer's disease (AD) and to other types of dementia. METHODS: Participants (n=882) with MCI were recruited, and were followed for up to 5 years. The EPS positive group was defined by the presence of at least one EPS based on a focused neurologic examination at baseline. RESULTS: A total of 234 converted to dementia during the follow-up period. The risk of progression to AD was lower in the patients with EPS after adjusting for potential confounders [hazard ratio (HR)=0.70, 95% confidence interval (CI)=0.53–0.93, p=0.01]. In contrast, the patients with EPS had a six-fold elevated risk of progression to dementia other than AD (HR=6.33, 95%CI=2.30–17.39, p < 0.001). CONCLUSION: EPS in patients with MCI is a strong risk factor for progression of MCI to non-Alzheimer dementia. The careful neurologic examination for EPS in patients with MCI can yield important clinical information for prognosis.
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Humanos , Doença de Alzheimer , Demência , Seguimentos , Coreia (Geográfico) , Disfunção Cognitiva , Exame Neurológico , Prognóstico , Fatores de RiscoRESUMO
Autism spectrum disorder (ASD) remains unexplained and untreated despite the high attention of research in recent years. Aside from its various characteristics is the baffling male preponderance over the female population. Using a validated animal model of ASD which is the telomerase reverse transcriptase overexpressing mice (TERT-tg), we conducted ASD-related behavioral assessments and protein expression experiments to mark the difference between male and females of this animal model. After statistically analyzing the results, we found significant effects of TERT overexpression in sociability, social novelty preference, anxiety, nest building, and electroseizure threshold in the males but not their female littermates. Along these differences are the male-specific increased expressions of postsynaptic proteins which are the NMDA and AMPA receptors in the prefrontal cortex. The vGluT1 presynaptic proteins, but not GAD, were upregulated in both sexes of TERT-tg mice, although it is more significantly pronounced in the male group. Here, we confirmed that the behavioral effect of TERT overexpression in mice was male-specific, suggesting that the aberration of this gene and its downstream pathways preferentially affect the functional development of the male brain, consistent with the male preponderance in ASD.
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Animais , Feminino , Humanos , Masculino , Camundongos , Ansiedade , Transtorno do Espectro Autista , Encéfalo , Camundongos Transgênicos , Modelos Animais , N-Metilaspartato , Fenótipo , Córtex Pré-Frontal , Receptores de AMPA , Caracteres Sexuais , Sinapses , TelomeraseRESUMO
Autism spectrum disorder (ASD) remains unexplained and untreated despite the high attention of research in recent years. Aside from its various characteristics is the baffling male preponderance over the female population. Using a validated animal model of ASD which is the telomerase reverse transcriptase overexpressing mice (TERT-tg), we conducted ASD-related behavioral assessments and protein expression experiments to mark the difference between male and females of this animal model. After statistically analyzing the results, we found significant effects of TERT overexpression in sociability, social novelty preference, anxiety, nest building, and electroseizure threshold in the males but not their female littermates. Along these differences are the male-specific increased expressions of postsynaptic proteins which are the NMDA and AMPA receptors in the prefrontal cortex. The vGluT1 presynaptic proteins, but not GAD, were upregulated in both sexes of TERT-tg mice, although it is more significantly pronounced in the male group. Here, we confirmed that the behavioral effect of TERT overexpression in mice was male-specific, suggesting that the aberration of this gene and its downstream pathways preferentially affect the functional development of the male brain, consistent with the male preponderance in ASD.