A novel HDAC8 inhibitor H7E exerts retinoprotective effects against glaucomatous injury via ameliorating aberrant Müller glia activation and oxidative stress.

Glaucoma is considered a neurodegenerative disease characterized by progressive visual field defects that may lead to blindness. Although controlling intraocular pressure (IOP) is the mainstay of glaucoma treatment, some glaucoma patients have unmet needs due to unclear pathogenic mechanisms. Recently, there has been growing evidence that neuroinflammation is a potential target for the development of novel antiglaucoma agents. In this study, we investigated the protective effects and cellular mechanisms of H7E, a novel small molecule inhibits HDAC8, using in vitro and in vivo glaucoma-like models. Importantly, H7E mitigated extracellular MMP-9 activity and MCP-1 levels in glutamate- or S100B-stimulated reactive Müller glia. In addition, H7E inhibited the upregulation of inflammation- and proliferation-related signaling pathways, particularly the ERK and JNK MAPK pathways. Under conditions of oxidative damage, H7E prevents retinal cell death and reduces extracellular glutamate released from stressed Müller glia. In a mouse model of NMDA-induced retinal degeneration, H7E alleviated functional and structural defects within the inner retina as assessed by electroretinography and optical coherence tomography. Our results demonstrated that the newly identified compound H7E protects against glaucoma damage by specifically targeting HDAC8 activity in the retina. This protective effect is attributed to the inhibition of Müller glial activation and the prevention of retinal cell death caused by oxidative stress.

Attenuative effects of collagen peptide from milkfish (Chanos chanos) scales on ovariectomy-induced osteoporosis.

Osteoporosis is characterized by low bone mass, bone microarchitecture disruption, and collagen loss, leading to increased fracture risk. In the current study, collagen peptides were extracted from milkfish scales (MS) to develop potential therapeutic candidates for osteoporosis. MS was used to synthesize a crude extract of fish scales (FS), collagen liquid (COL), and hydroxyapatite powder (HA). COL samples were further categorized according to the peptide size of total COL (0.1 mg/mL), COL < 1 kDa (0.1 mg/mL), COL: 1-10 kDa (0.1 mg/mL), and COL > 10 kDa (0.1 mg/mL) to determine it. Semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) and immunofluorescence labeling were used to assess the expression levels of specific mRNA and proteins in vitro. For in vivo studies, mice ovariectomy (OVX)-induced postmenopausal osteoporosis were developed, while the sham surgery (Sham) group was treated as a control. Collagen peptides (CP) from MS inhibited osteoclast differentiation in RAW264.7 cells following an insult with nuclear factor kappa-B ligand (RANKL). CP also enhanced osteoblast proliferation in MG-63 cells, possibly through downregulating NFATc1 and TRAP mRNA expression and upregulating ALP and OPG mRNA levels. Furthermore, COL1 kDa also inhibited bone density loss in osteoporotic mice. Taken together, CP may reduce RANKL-induced osteoclast activity while promoting osteoblast synthesis, and therefore may act as a potential therapeutic agent for the prevention and control of osteoporosis.

The Ratio of Plasma Amyloid-ß 1-42 over Serum Albumin Can Be a Novel Biomarker Signature for Diagnosing End-Stage Renal Disease-Associated Cognitive Impairment.

BACKGROUND: Cognitive impairment (CI) is one of the major complications in chronic kidney disease patients, especially those with end-stage renal disease (ESRD). Limited biomarkers have been found that can significantly predict ESRD-associated cognitive decline. OBJECTIVE: This cohort study aimed to investigate de novo biomarkers for diagnosis of the ESRD-associated CI. METHODS: In this cohort study, qualified samples were divided into control (with an estimated glomerular filtration rate (eGFR) of≥60 mL/min and a Mini-Mental State Examination (MMSE) score of > 27), ESRD without CI (eGFR < 15 and MMSE > 27), and ESRD with CI (eGFR < 15 and MMSE < 27) groups. Levels of plasma amyloid-ß (Aß)1 - 42, serum indoxyl sulfate, and hematologic and biochemical parameters were measured. RESULTS: Compared to the control group, levels of blood urea nitrogen, creatinine, and indoxyl sulfate were elevated in ESRD patients both without and with CI. Interestingly, ESRD patients with CI had the lowest levels of serum albumin. In contrast, levels of plasma Aß1 - 42 were significantly higher in the ESRD with CI group than in the control and ESRD without CI groups. In addition, the ratio of plasma Aß1 - 42 over serum albumin was significantly higher in the ESRD with CI group than in the control or ESRD without CI groups. Importantly, the area under the receiver operating characteristic curve (AUROC) for CI in the total population by the ratio of Aß1 - 42 over albumin was 0.785 and significant (p < 0.05). CONCLUSIONS: This cohort study has shown that the ratio of plasma Aß1 - 42 over serum albumin can be a de novo biomarker for the diagnosis and prognosis of ESRD-associated cognitive decline.

Effectiveness of a home-based, family caregiver-administered manual massage intervention in managing dementia symptoms and reducing caregiver stress: A randomized, controlled clinical trial.

OBJECTIVES: To investigate the effectiveness of family caregiver-administered home-based manual massages in managing dementia symptoms and reducing caregiver stress. METHODS: Thirty-eight pairs of participants-patients with dementia and their family caregivers-were randomly allocated to the experimental or the control group. The caregivers underwent 3-h-long massage training. Subsequently, the patients received a 30-min-long, home-based massage from their caregivers thrice a week for 8 consecutive weeks. The Cornell Scale for Depression in Dementia (CSDD), Cohen-Mansfield Agitation Inventory (CMAI), and Perceived Stress Scale (PSS) were assessed before and after the interventions. RESULTS: After intervention, the experimental group exhibited significant improvements in CSDD and CMAI scores compared with the scores of the control group (all p < .001). Furthermore, the experimental group obtained more favorable PSS scores than did the control group (p = .013). CONCLUSIONS: Family caregiver-administered home-based massage therapy is recommended for managing dementia symptoms and reducing caregiver stress.

Altered gut microbiota in older adults with mild cognitive impairment: a case-control study.

Introduction: The microbiota-gut-brain axis is implicated in Alzheimer's disease. Gut microbiota alterations in mild cognitive impairment (MCI) are inconsistent and remain to be understood. This study aims to investigate the gut microbial composition associated with MCI, cognitive functions, and structural brain differences. Methods: A nested case-control study was conducted in a community-based prospective cohort where detailed cognitive functions and structural brain images were collected. Thirty-one individuals with MCI were matched to sixty-five cognitively normal controls by age strata, gender, and urban/rural area. Fecal samples were examined using 16S ribosomal RNA (rRNA) V3-V4 sequencing. Compositional differences between the two groups were identified and correlated with the cognitive functions and volumes/thickness of brain structures. Results: There was no significant difference in alpha and beta diversity between MCIs and cognitively normal older adults. However, the abundance of the genus Ruminococcus, Butyricimonas, and Oxalobacter decreased in MCI patients, while an increased abundance of nine other genera, such as Flavonifractor, were found in MCIs. Altered genera discriminated MCI patients well from controls (AUC = 84.0%) and were associated with attention and executive function. Conclusion: This study provides insights into the role of gut microbiota in the neurodegenerative process.

White matter hyperintensities in cholinergic pathways are associated with dementia severity in e4 carriers but not in non-carriers.

Background and objectives: Among individuals with Alzheimer's disease (AD), APOE e4 carriers with increased white matter hyperintensities (WMHs) may selectively be at increased risk of cognitive impairment. Given that the cholinergic system plays a crucial role in cognitive impairment, this study aimed to identify how APOE status modulates the associations between dementia severity and white matter hyperintensities in cholinergic pathways. Methods: From 2018 to 2022, we recruited participants (APOE e4 carriers, n = 49; non-carriers, n = 117) from the memory clinic of Cardinal Tien Hospital, Taipei, Taiwan. Participants underwent brain MRI, neuropsychological testing, and APOE genotyping. In this study, we applied the visual rating scale of the Cholinergic Pathways Hyperintensities Scale (CHIPS) to evaluate WMHs in cholinergic pathways compared with the Fazekas scale. Multiple regression was used to assess the influence of CHIPS score and APOE carrier status on dementia severity based on Clinical Dementia Rating-Sum of Boxes (CDR-SB). Results: After adjusting for age, education and sex, higher CHIPS scores tended to be associated with higher CDR-SB in APOE e4 carriers but not in the non-carrier group. Conclusions: Carriers and non-carriers present distinct associations between dementia severity and WMHs in cholinergic pathways. In APOE e4 carriers, increased white matter in cholinergic pathways are associated with greater dementia severity. In non-carriers, WMHs exhibit less predictive roles for clinical dementia severity. WMHs on the cholinergic pathway may have a different impact on APOE e4 carriers vs. non-carriers.

White matter hyperintensities in cholinergic pathways may predict poorer responsiveness to acetylcholinesterase inhibitor treatment for Alzheimer's disease.

BACKGROUND: Acetylcholinesterase inhibitor (AChEI) drug regimens are the mainstay treatment options for patients with Alzheimer's disease (AD). Herein, We examined the association between clinical response to AChEI and white matter hyperintensities on magnetic resonance imaging (MRI) scan at baseline. METHODS: Between 2020 and 2021, we recruited 101 individuals with a clinical diagnosis of probable AD. Each participant underwent complete neuropsychological testing and 3T (Telsa) brain magnetic resonance imaging. Responsiveness to AChEI, as assessed after 12 months, was designated as less than two points of regression in Mini-Mental State Examination scores (MMSE) and stable clinical dementia rating scale. We also evaluated MRI images by examining scores on the Cholinergic Pathways Hyperintensities Scale (CHIPS), Fazekas scale, and medial temporal atrophy (MTA) scale. RESULTS: In our cohort, 52 patients (51.4%) were classified as responders. We observed significantly higher CHIPS scores in the nonresponder group (21.1 ± 12.9 vs. 14.9 ± 9.2, P = 0.007). Age at baseline, education level, sex, Clinical Dementia Rating sum of boxes scores, and three neuroimaging parameters were tested in regression models. Only CHIPS scores predicted clinical response to AChEI treatment. CONCLUSION: WMHs in the cholinergic pathways, not diffuse white matter lesions or hippocampal atrophy, correlated with poorer responsiveness to AChEI treatment. Therefore, further investigation into the role of the cholinergic pathway in AD is warranted.

Renoprotective Impacts of Inonotus obliquus Ethanol-Ethyl Acetate Extract on Combined Streptozotocin and Unilateral Nephrectomy-Induced Diabetic Nephropathy in Mice.

Diabetes nephropathy (DN) is one of the most common causes of end stage renal disease (ESRD) globally. Medication options to stop or slow the progression of chronic renal disease (CKD) are limited, and patients with DN remain at a high risk of developing renal failure. Inonotus obliquus extracts (IOEs) of Chaga mushroom have been shown to have anti-glycemic, anti-hyperlipidemia, antioxidant, and anti-inflammatory effects against diabetes. In this study, we examined the potential renal protective role of an ethyl acetate layer after water-ethyl acetate separation from Inonotus obliquus ethanol crude extract (EtCE-EA) from Chaga mushrooms in diabetic nephropathy mice after preparation with 1/3 NT + STZ. Our data showed that treatment with EtCE-EA can effectively regulate blood glucose, albumin-creatinine ratio, serum creatinine, and blood urea nitrogen (BUN) levels, and it can improve the renal damage in 1/3 NT + STZ-induced CRF mice with an increase in concentration (100, 300, and 500 mg/kg). In the immunohistochemical staining test, EtCE-EA can effectively reduce the expression of TGF-ß and α-SMA after induction according to the increase in the concentration (100 mg/kg, 300 mg/kg), thereby slowing down the degree of kidney damage. Our findings demonstrate that EtCE-EA could provide renal protection in diabetes nephropathy, possibly due to the decreased expression of transforming growth factor-ß1 and α-smooth muscle actin.

Effects of manual massage given by family caregivers for patients with dementia: A preliminary investigation.

OBJECTIVES: To explore the effects of a 10-week manual massage intervention given by caregivers of patients with dementia on the behavioral and psychological symptoms of dementia (BPSD) and caregiver burden. METHODS: Twelve pairs of participants-patients with dementia and their family caregivers-were recruited. Before the intervention, caregivers received a four-hour full body manual massage training course. Thereafter, the caregivers gave a 30-min massage to the patients once a week for a 10-week period. The Cornell Scale for Depression in Dementia, Cohen-Mansfield Agitation Inventory, and Zarit Burden Scale were administered pre- and post-intervention. RESULTS: Total scores on all questionnaires significantly decreased after the intervention (p < .05). Moreover, two subscale scores of the Cornell Scale for Depression in Dementia-behavioral disturbance and physical signs-reduced significantly (p < .05). CONCLUSIONS: This study provides preliminary evidence on the benefits of manual massage given by caregivers for the management of BPSD and caregiver burden.

Determinants of long-term care service use by persons with dementia: A national dementia registry study conducted in Taiwan.

BACKGROUND: This study investigated the determinants and use of Taiwan's long-term care (LTC) Plan Version 2.0 (LTC 2.0) services by persons with dementia (PWDs) and their caregivers. METHODS: In total, 1268 PWD-caregiver dyads were enrolled for analysis from a national dementia registry. Andersen's Behavioral Model of Health Services Use was used to investigate the association of LTC service use with several factors, namely the demographic data of PWDs and their caregivers, migrant caregiver employment, monthly household income, caregiver burden as determined by the Zarit Burden Interview (ZBI), Mini-Mental State Examination score, Clinical Dementia Rating scores, neuropsychiatric inventory scores for the behavioral and psychological symptoms of dementia, and PWDs' activities of daily living (ADLs). RESULTS: Among the studied family caregivers, 81.4% did not use LTC resources. A multivariable logistic analysis revealed that aberrant motor behaviors (odd ratio [OR] = 1.31, 95% confidence interval [CI] = 1.10-1.56, p = 0.003), dysfunction in ADLs (OR = 1.06, 95% CI = 1.02-1.10, p = 0.002), higher ZBI scores (OR = 1.02, 95% CI = 1.01-1.03, p = 0.004), not residing with family members (OR = 1.88, 95% CI = 1.32-2.66, p < 0.001), and not employing a migrant caregiver (OR = 4.41, 95% CI = 2.59-7.51, p < 0.001) were the factors most significantly associated with LTC service use. CONCLUSION: Factors such as whether PWDs live alone, specific neuropsychiatric symptoms, and impaired function should be considered in future policy amendments to provide required activities and care resources for PWDs and their caregivers.

Factors associated with burden among male caregivers for people with dementia.

BACKGROUND: There is a dearth of information on male dementia caregivers in Asia and, in particular, on the factors relating to caregiver burden. We aimed to identify factors that may be associated with burden among male caregivers of people with dementia (PWD). METHODS: Data were collected from a national dementia registration survey. The caregiver burden was measured with the short version of the Zarit Burden Interview (ZBI). We analyzed the correlation between ZBI scores and variables, such as demographic data of PWD and their male caregivers, caregivers' monthly income, the relationship between PWD and caregivers, the severity of dementia, physical comorbidities and activities of daily living (ADL) of PWD, and neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory (NPI). RESULTS: A total of 509 PWD and their male caregivers were included. The majority of caregivers were sons (72.1%) and husbands (22.0%). Sons had higher ZBI scores than husbands (28.5 ± 15.2 vs 22.0 ± 17.0; p < 0.001). Multivariable linear regression showed that sons as caregivers (ß = 7.44, p = 0.034), ADL (ß = 0.52, p = 0.002), and NPI_severity subscore of apathy (ß = 2.74, p = 0.001) were positively associated with ZBI scores. CONCLUSION: Poor ADL and apathy in PWD and being a patient's son were associated with higher levels of burden among male dementia caregivers. Effective interventions are needed to assist male caregivers in accomplishing their caregiving role and at the same time to alleviate their caregiver burden.

Interface Design for Products for Users with Advanced Age and Cognitive Impairment.

The aim of this study is to investigate the problems and needs of users with advanced age and cognitive impairment regarding the design and operation of daily living products. Television remote controls and an electric rice cooker were applied as the research tools, and focus group interviews with control older adults and interviews with individuals with MCI or mild dementia were conducted regarding the operation of the products. The control participants stressed that the operating procedures should not be excessively complex, the number of functions and buttons should not be overly high, and buttons and text should be enlarged. For those with MCI or mild dementia, in addition to the size and number of buttons, text size, and functions, their operation of product interfaces was affected by the complexity of the operating procedures. The solutions recommended by the participants included interface design involving direct operation and voice control.

Thymoma Removal Improved Cognitive Function in a Patient with Alzheimer disease: A Case Report.

Purpose Alzheimer disease (AD) is an irreversible neurodegenerative disease that causes progressive cognitive decline. Co-existing thymoma should be considered when rapid deterioration of cognition was noted in AD patients and removal of thymoma may improve cognition in AD. Case report We report a 72-year-old woman with initial complaints of memory impairment for 2 years. After detailed history taking, neuropsychological tests, brain magnetic resonance imaging, and positive amyloid positron emission tomography, she was diagnosed as having dementia of the Alzheimer type. At the time of diagnosis, her dementia condition was mild (clinical dementia rating [CDR] is equal to 1, CDR sum of boxes [CDR-sb] = 4.5, Mini-Mental State Examination (MMSE) is equal to 21 divided by 30). She needed moderate assistance in performing daily life activities. One year after AD diagnosis, her condition deteriorated drastically, and she experienced frequent falls and severe weakness apart from cognitive symptoms. Concurrent myasthenia gravis (MG) with thymoma was found later, and thymectomy was performed. Her symptoms related to MG alleviated after the operation. Notably, her cognitive symptoms also improved 4 months after the operation, and her dementia reversed to mild cognitive impairment. Conclusion Although the role of neuroinflammation in AD has been widely discussed, it remains elusive. Removal of the co-existing thymoma not only alleviated the patient's MG symptoms but also improved her cognitive performance. We supposed that this effect may have been a direct result of the decrease in acetylcholine receptor antibody or reduction in the degree of neuroinflammation. Keywords Alzheimer disease, thymoma, neuroinflammation, central cholinergic effects, acetylcholine receptor antibody.

Urban-rural differences in the prevalence and correlates of mild cognitive impairment in community-dwelling older adults in Taiwan: The EMCIT study.

BACKGROUND: Taiwan is a rapidly aging society. The elderly with mild cognitive impairment (MCI) have increased risk of dementia, and this is a population-based report using standard neuropsychological tests and expert consensus diagnosis to assess the MCI prevalence and its associated factors in Taiwan. METHOD: The Epidemiology of Mild Cognitive Impairment study in Taiwan (EMCIT) is a community-based, prospective cohort study. Independently-living individuals aged ≧60 years in a rural area (n = 122) and in an urban area (n = 348) of New Taipei City, Taiwan, completed detailed neuropsychological tests at the cohort baseline. Diagnosis of MCI was ascertained through expert consensus based on 2011 NIA-AA criteria. RESULTS: Of 470 participants recruited between 2017 and 2019 (mean age 71.2 ± 5.4 years), the prevalence of MCI was higher in the rural area than in the urban area (25.1% vs. 10.8%, p < 0.001) after standardized for age, gender, and level of education. Having lower education and having depression symptoms were consistently associated with increased risk of MCI in both urban and rural areas (p < 0.05). Being male and diabetes were additionally associated with MCI prevalence in urban areas. CONCLUSION: In this community-based prospective cohort study in Taiwan, the prevalence of MCI in the rural community was much higher than that in the urban community. Different strategies may be needed to targeted different types of communities.

Predictors of caregiver burden in aged caregivers of demented older patients.

BACKGROUND: Dementia in the oldest-old is projected to increase exponentially as is the burden of their caregivers who may experience unique challenges and suffering. Thus, we aim to investigate which factors are associated with older caregivers' burden in caring demented outpatients in a multicenter cohort. METHODS: Patients and their caregivers, both aged ≧65 years, in the National Dementia Registry Study in Taiwan (T-NDRS) were included in this study. Caregiver burden was measured with the short version of the Zarit Burden Interview (ZBI). The correlations between the ZBI scores and characteristics of caregivers and patients, including severity of dementia, physical comorbidities, instrumental activities of daily living (IADL), neuropsychiatric symptoms assessed by the Neuropsychiatric Inventory (NPI), and family monthly income, were analyzed. RESULTS: We recruited 328 aged informal caregiver-patient dyads. The mean age of caregivers was 73.7 ± 7.0 years, with female predominance (66.8%), and the mean age of patients was 78.8 ± 6.9 years, with male predominance (61.0%). Multivariable linear regression showed that IADLs (ß = 0.83, p < 0.001) and NPI subscores of apathy (ß = 3.83, p < 0.001)and irritability (ß = 4.25, p < 0.001) were positively associated with ZBI scores. The highest family monthly income (ß = - 10.92, p = 0.001) and caregiver age (ß = - 0.41, p = 0.001) were negatively correlated with ZBI scores. CONCLUSIONS: Older caregivers of older demented patients experience a higher care burden when patients had greater impaired functional autonomy and the presence of NPI symptoms of apathy and irritability. Our findings provide the direction to identify risky older caregivers, and we should pay more attention to and provide support for these exhausted caregivers.

Detection of cognitive impairment using self-rated AD8 and informant-reported AD8.

BACKGROUND/PURPOSE: Screening of dementia can help to initiate proper management of the disorder. The use of the Ascertain Dementia 8-item Questionnaire (AD8) in screening has been promoted in Taiwan recently. The purpose of this study was to compare the psychometric properties and appropriateness of informant-reported and self-rated AD8 in cognitive impairment screening in Taiwan. METHODS: The AD8 were administered to 153 participants and their informants recruited from two neurology out-patient clinics. The discriminative abilities for early cognitive impairment [Clinical Dementia Rating scale (CDR) 0.5 and 1] of informant-based and self-rating AD8 were determined and compared with their areas under the receiver operating curve. κ coefficients representing the agreement between self-rated and informant-reported AD8 scores were also calculated. RESULTS: Participants and their informants were aged 76.9 years and 56.0 years on average, respectively. Only informant-reported AD8 was significantly associated with CDR level (Spearman ρ=0.469, p<0.001) and Cognitive Abilities Screening Instrument score (Spearman ρ=-0.458, p<0.001). The item-by-item agreements between self-rated and informant-reported AD8 were poor (κ coefficients: -0.030 to 0.206). The area under the receiver-operator characteristic curve was 0.59 for self-rated AD8 scores, and 0.77 for informant-reported AD8 scores, indicating that the discriminating ability of AD8 scores between CDR 0 and CDR 0.5 or greater is better when reported by informant than when rated by self. CONCLUSION: Informant-rated AD8 gave more accurate screening results than self-reported AD8 in an out-patient clinic setting.

Depression and Dementia in Old-Old Population: History of Depression May Be Associated with Dementia Onset. The Tome Project.

Background: In this study, we investigated the relationship among a history of depression, depressive states, and dementia in a community-based old-old cohort. Methods: From 2012 to 2013, we recruited 200 subjects residing in Tome, Japan. Ultimately, 181 subjects were enrolled in our study and completed the whole study protocol. We used the World Mental Health-Composite International Diagnostic Interview 3.0 to evaluate whether subjects had a history of depression or other affective disorders. Simultaneously, 3.0 Tesla brain magnetic resonance imaging (MRI) was performed for each subject. Results: Of 181 subjects, 66 were normal (clinical dementia rating [CDR] = 0), 88 had MCI (CDR = 0.5), and 27 had dementia (CDR = 1 or above). Nine of the 181 subjects (4.9%) had a history of depressive episodes. CDR was significantly higher in subjects with a history of depression (0.9 vs. 0.4, p = 0.046) than in those without it. Seventy-two of the 181 subjects (39.7%) exhibited depressive symptoms. Subjects with depression exhibited lower Mini-Mental State Examination scores (21.6 vs. 23.3, p = 0.008), higher CDR scores (0.6 vs. 0.3, p = 0.004), and more atrophy of the medial temporal lobe (4.4 vs. 3.7, p = 0.036). Conclusion: A history of depression should be considered a risk factor for all-cause dementia. In the old-old population, depression is associated with a higher prevalence of dementia, lower cognitive performance, and a smaller hippocampus.

Language background in early life may be related to neuropsychiatry symptoms in patients with Alzheimer disease.

BACKGROUND: The relationship between early life experience and the occurrence of neuropsychiatry symptoms (NPSs) in patients with Alzheimer disease (AD) is unclear. METHODS: From 2012 to 2014, we prospectively recruited 250 patients with probable AD from the memory clinic of Taipei Veterans General Hospital. All patients underwent standard assessments, including brain magnetic resonance imaging or computed tomography, neuropsychological tests, neuropsychiatry inventory (NPI-Q) and related blood tests. A linear regression analysis was performed to investigate the relationship between NPSs and age, gender, disease severity, depression, language background (with or without Japanese education). RESULTS: Among the 250 participants, 113 (45.2%) were women. Their average age was 82.6 years. Of all the participants, 93 (37.2%) had received formal Japanese education, whereas 157 (62.8%) did not receive Japanese education. The participants with Japanese education were slightly younger (83.1 ± 3.6 vs. 81.4 ± 3.4, P = 0.006), with a higher proportion of them were women (30.5% vs. 69.8%, P < 0.001) and fewer years of total education (10.8 ± 4.5 vs. 7.7 ± 3.2, P < 0.001), compared to the participants without Japanese education. NPI-Q scores significantly differed between the two groups (15.8 vs. 24.1, P = 0.024). Both disease severity and language background predicted NPI-Q scores. CONCLUSIONS: Language background in early life may be related to NPSs in patients with AD, and this effect is more significant in patients with a lower education level than in those with a higher education level. More NPSs may be the result of negative effects on dominant language or early life experiences.

Speaking one more language in early life has only minor effects on cognition in Taiwanese with low education level: the Taishan Project.

BACKGROUND: Increasing evidence shows that bilingualism or multilingualism may have beneficial effects on preventing dementia. We performed a cross-sectional, community-based study in Taiwan. Some elders (older than 70 years) in Taiwan can speak Japanese because of the formal Japanese education they received before World War II, when Taiwan was under Japanese rule. After the war, Mandarin Chinese was adopted as the official language of Taiwan. We assessed whether constantly using three languages had an effect on dementia prevalence and cognitive function. METHODS: We defined multilingualism as the ability to fluently speak Taiwanese (T), Japanese (J), and Mandarin Chinese (C) in daily life. We evaluated the Mini-Mental State Examination and AD8 questionnaire results of 514 community-dwelling people older than 70 years in Taishan, Taiwan. RESULTS: Seventy-three of the subjects (14.2%) were multilingual (T, J, C) and 441 (85.8%) were bilingual (T, C). No difference was noted in dementia prevalence between multilingual (6.8%) and bilingual (7.4%) populations, but multilinguals were older than bilinguals (mean age: 79.9 vs 77.3 years). Multilinguals had higher Mini-Mental State Examination scores than bilinguals (mean: 24.6 vs. 22.7). However, after the subjects were stratified into low and high education level groups, the Mini-Mental State Examination difference was found to be significant in only the low education level group. CONCLUSIONS: Dementia prevalence did not significantly differ between the multilingual (T, J, C) and bilingual (T, C) groups. However, given that the average age of the multilingual group was approximately 2 years older than that of the bilingual group, there may have been minor effects in the multilingual group.

Mutational analysis of TBK1 in Taiwanese patients with amyotrophic lateral sclerosis.

Mutations in the TBK1 gene were just recently identified to cause amyotrophic lateral sclerosis (ALS), and their role in ALS in various populations remains unclear. The aim of this study was to determine the frequency and spectrum of mutations in TBK1 in a Taiwanese ALS cohort of Han Chinese origin. Mutational analyses of TBK1 were carried out by direct nucleotide sequencing in a cohort of 207 unrelated patients with ALS. Among them, the genetic diagnoses of 168 patients remained elusive after mutations in SOD1, C9ORF72, TARDBP, FUS, ATXN2, OPTN, VCP, UBQLN2, SQSTM1, PFN1, HNRNPA1, HNRNPA2B1, MATR3, CHCHD10, and TUBA4A had been excluded. We identified one nonsense mutation, p.R444X (c.1330C>T), in one patient with apparently sporadic ALS-frontotemporal dementia. In vitro functional study demonstrated the p.R444X mutation resulting in a truncated TANK-binding kinase 1 (TBK1) protein product, low protein expression, and loss of kinase function and interaction with optineurin. The frequency of TBK1 mutations in ALS patients in Taiwan is, therefore, approximately 0.5% (1/207). This study reports a novel TBK1 mutation and stresses on the importance to consider TBK1 mutation as a possible etiology of ALS.