Implementation difficulties and solutions for a smart-clothes assisted home nursing care program for older adults with dementia or recovering from hip fracture.

BACKGROUND: Wearable devices have the advantage of always being with individuals, enabling easy detection of their movements. Smart clothing can provide feedback to family caregivers of older adults with disabilities who require in-home care. METHODS: This study describes the process of setting up a smart technology-assisted (STA) home-nursing care program, the difficulties encountered, and strategies applied to improve the program. The STA program utilized a smart-vest, designed specifically for older persons with dementia or recovering from hip-fracture surgery. The smart-vest facilitated nurses' and family caregivers' detection of a care receiver's movements via a remote-monitoring system. Movements included getting up at night, time spent in the bathroom, duration of daytime immobility, leaving the house, and daily activity. Twelve caregivers of older adults and their care receiver participated; care receivers included persons recovering from hip fracture (n = 5) and persons living with dementia (n = 7). Data about installation of the individual STA in-home systems, monitoring, and technical difficulties encountered were obtained from researchers' reports. Qualitative data about the caregivers' and care receivers' use of the system were obtained from homecare nurses' reports, which were explored with thematic analysis. RESULTS: Compiled reports from the research team identified three areas of difficulty with the system: incompatibility with the home environment, which caused extra hours of manpower and added to the cost of set-up and maintenance; interruptions in data transmissions, due to system malfunctions; and inaccuracies in data transmissions, due to sensors on the smart-vest. These difficulties contributed to frustration experienced by caregivers and care receivers. CONCLUSIONS: The difficulties encountered impeded implementation of the STA home nursing care. Each of these difficulties had their own unique problems and strategies to resolve them. Our findings can provide a reference for future implementation of similar smart-home systems, which could facilitate ease-of-use for family caregivers.

Exploring the aging process of cognitively healthy adults by analyzing cerebrospinal fluid metabolomics using liquid chromatography-tandem mass spectrometry.

BACKGROUND: During biological aging, significant metabolic dysregulation in the central nervous system may lead to cognitive decline and neurodegeneration. However, the metabolomics of the aging process in cerebrospinal fluid (CSF) has not been thoroughly explored. METHODS: In this cohort study of CSF metabolomics using liquid chromatography-mass spectrometry (LC-MS), fasting CSF samples collected from 92 cognitively unimpaired adults aged 20-87 years without obesity or diabetes were analyzed. RESULTS: We identified 37 metabolites in these CSF samples with significant positive correlations with aging, including cysteine, pantothenic acid, 5-hydroxyindoleacetic acid (5-HIAA), aspartic acid, and glutamate; and two metabolites with negative correlations, asparagine and glycerophosphocholine. The combined alterations of asparagine, cysteine, glycerophosphocholine, pantothenic acid, sucrose, and 5-HIAA showed a superior correlation with aging (AUC = 0.982). These age-correlated changes in CSF metabolites might reflect blood-brain barrier breakdown, neuroinflammation, and mitochondrial dysfunction in the aging brain. We also found sex differences in CSF metabolites with higher levels of taurine and 5-HIAA in women using propensity-matched comparison. CONCLUSIONS: Our LC-MS metabolomics of the aging process in a Taiwanese population revealed several significantly altered CSF metabolites during aging and between the sexes. These metabolic alterations in CSF might provide clues for healthy brain aging and deserve further exploration.

1H NMR metabolomic profiling of human cerebrospinal fluid in aging process.

The molecular process of biological aging might be accompanied by significant metabolic derangement, especially in the central nervous system (CNS), since the brain has an enormous energy demand. However, the metabolic signature of the aging process in cerebrospinal fluid (CSF) has not been thoroughly investigated, especially in the Asian population. In this prospective cohort study on CSF metabolomics using proton nuclear magnetic resonance (NMR) spectroscopy, fasting CSF samples from 75 cognitively unimpaired patients aged 20-92 years without diabetes or obesity, undergoing spinal anesthesia for elective surgery were analyzed. Several metabolites in CSF samples were identified as having a significant association with the aging process in cerebral circulation; among the metabolites, the levels of alanine, citrate, creatinine, lactate, leucine, tyrosine, and valine significantly increased in old patients compared to those in young patients. The combined CSF metabolite alterations in citrate, lactate, leucine, tyrosine, and valine had a superior correlation with the aging process in all age groups. In conclusion, our pilot study of aging CSF metabolomics in the Taiwanese population presents significantly altered CSF metabolites with potential relevance to the aging process. These metabolic alterations in CSF samples might imply increasing anaerobic glycolysis, mitochondrial dysfunction, and decreasing glucose utilization in cerebral circulation in aged patients.

CCM1 and CCM2 variants in patients with cerebral cavernous malformation in an ethnically Chinese population in Taiwan.

Cerebral cavernous malformation (CCM) is a vascular malformation characterized by clustered enlarged capillary-like channels in the central nervous system. The genes harboring variants in patients with CCM include CCM1/Krev interaction trapped-1, CCM2/MGC4607, and CCM3/programmed cell death protein 10. We aimed to identify pathogenic variants in an ethnic Chinese population in Taiwan. We recruited 95 patients with multiple CCMs or a single lesion with a relevant family history. Sanger sequencing was performed for 41 patients. Variants were identified using sequence alignment tools, and the clinical significance of these variants was determined using American College of Medical Genetics and Genomics standards and guidelines. Several pathogenic variants were found in six patients, including three unrelated patients and three affected members of one family. Two novel pathogenic variants leading to early truncation comprised a deletion variant in exon 18 of CCM1 (c.1846delA; p.Glu617LysfsTer44) and an insertion variant in exon 4 of CCM2 (c.401_402insGCCC; p.Ile136AlafsTer4). One novel pathogenic splice site variant was c.485 + 1G > C at the beginning of intron 8 of CCM1. In this study, we identified novel variants related to CCM in an ethnically Chinese population in Taiwan.

Indole Compound NC009-1 Augments APOE and TRKA in Alzheimer's Disease Cell and Mouse Models for Neuroprotection and Cognitive Improvement.

Alzheimer's disease (AD), associated with abnormal accumulation of amyloid-ß (Aß), is the most common cause of dementia among older people. A few studies have identified substantial AD biomarkers in blood but their results were inconsistent. Here we screened gene expression alterations on Aß-GFP SH-SY5Y neuronal model for AD, and evaluated the findings on peripheral leukocytes from 78 patients with AD and 56 healthy controls. The therapeutic responses of identified biomarker candidates were further examined in Aß-GFP SH-SY5Y neuronal and APP/PS1/Tau triple transgenic (3×Tg-AD) mouse models. Downregulation of apolipoprotein E (APOE) and tropomyosin receptor kinase A (TRKA) were detected in Aß-GFP SH-SY5Y cells and validated by peripheral leukocytes from AD patients. Treatment with an in-house indole compound NC009-1 upregulated the expression of APOE and TRKA accompanied with improvement of neurite outgrowth in Aß-GFP SH-SY5Y cells. NC009-1 further rescued the downregulated APOE and TRKA and reduced Aß and tau levels in hippocampus and cortex, and ameliorated cognitive deficits in streptozocin-induced hyperglycemic 3×Tg-AD mice. These results suggest the role of APOE and TRKA as potential peripheral biomarkers in AD, and offer a new drug development target of AD treatment. Further studies of a large series of AD patients will be warranted to verify the findings and confirm the correlation between these markers and therapeutic efficacy.

Predictors of advance directives among nursing home residents with dementia.

ABSTRACTBackground:Advance directives are important for nursing home residents with dementia; for those with advanced dementia, surrogates determine medical decisions. However, in Taiwan, little is known about what influences the completion of these advance directives. The purpose of this study was to identify factors, which influence the presence of advance directives for nursing home residents with dementia in Taiwan. METHOD: Our cross-sectional study analyzed a convenience sample of 143 nursing home dyads comprised of residents with dementia and family surrogates. Documentation of residents' advance directives, physical and cognitive status was obtained from medical charts. Surrogates completed the stress of end-of-life care decision scale and a questionnaire regarding their demographic characteristics. Nursing home characteristics were obtained from each chief administrator. RESULTS: Less than half of the nursing home residents (39.2%) had advance directives and most (96.4%) had been completed by family surrogates. The following were predictors of an advance directive: surrogates had previously signed a do-not-resuscitate as a proxy and had been informed of advance directives by a healthcare provider; nursing homes had policies for advance directives and a religious affiliation. CONCLUSIONS: Advance directives were uncommon for nursing home residents with dementia. Presence of an advance directive was associated with surrogate characteristics and the nursing home facilities; there was no association with characteristics of the nursing home resident. Our findings emphasize the need to develop policies and strategies, which ensure that all residents of nursing homes and their surrogates are aware of their right to an advance directive.

Regional amyloid deposition in amnestic mild cognitive impairment and Alzheimer's disease evaluated by [18F]AV-45 positron emission tomography in Chinese population.

BACKGROUND: To compare the neocortical amyloid loads among cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and Alzheimer's disease (AD) subjects with [(18)F]AV-45 positron emission tomography (PET). MATERIALS AND METHODS: [(18)F]AV-45 PET was performed in 11 CN, 13 aMCI, and 12 AD subjects to compare the cerebral cortex-to-whole cerebellum standard uptake value ratios (SUVRs) of global and individual volumes of interest (VOIs) cerebral cortex. The correlation between global cortical [(18)F]AV-45 SUVRs and Mini-Mental State Examination (MMSE) scores was analyzed. RESULTS: The global cortical [(18)F]AV-45 SUVRs were significantly different among the CN (1.08±0.08), aMCI (1.27±0.06), and AD groups (1.34±0.13) (p = 0.0003) with amyloidosis positivity rates of 9%, 62%, and 92% in the three groups respectively. Compared to CN subjects, AD subjects had higher SUVRs in the global cortical, precuneus, frontal, parietal, occipital, temporal, and posterior cingulate areas; while aMCI subjects had higher values in the global cortical, precuneus, frontal, occipital and posterior cingulate areas. There were negative correlations of MMSE scores with SUVRs in the global cortical, precuneus, frontal, parietal, occipital, temporal, posterior cingulate and anterior cingulate areas on a combined subject pool of the three groups after age and education attainment adjustment. CONCLUSIONS: Amyloid deposition occurs relatively early in precuneus, frontal and posterior cingulate in aMCI subjects. Higher [(18)F]AV-45 accumulation is present in parietal, occipital and temporal gyri in AD subjects compared to the aMCI group. Significant correlation between MMSE scores and [(18)F]AV-45 SUVRs can be observed among CN, aMCI and AD subjects.

The association of stroke and family history of stroke depends on its subtypes and gender: a family history study in Taiwan.

OBJECTIVE: Family history is a risk factor for stroke. The objective of this study was to investigate whether stroke subtypes and gender might have a familial contribution to stroke. METHODS: Detailed family history analysis was used to investigate the parents or siblings of the probands and controls who were classified into 3 groups: probands, outpatient controls, and spouse controls. The lifetime risk (LTR) of stroke was estimated using a Cox proportional hazard model. RESULTS: The 684 probands and controls yielded 1066 parents and 3247 siblings. Compared to the parents and siblings of the controls, those of the stroke patients had a significantly higher LTR. The findings were consistent between probands with cerebral infarction (CI) or cerebral hemorrhage (CH), independent of diabetes, hypertension, and smoking. With regard to gender, family history of stroke was significant for both parents and siblings of the CH or CI patients, but not for the fathers of CI patients and sisters of CH patients. The family history of stroke was associated with an increased risk of stroke of all subtypes, except cardioembolism. CONCLUSIONS: This study supported the familial contribution to stroke in the case of both CI and CH but not cardioembolism, independent of the established risk factors for stroke. Gender differences in familial clustering of stroke subtypes were also revealed. These results warrant further molecular genetic studies.

PPP2R2B CAG repeat length in the Han Chinese in Taiwan: Association analyses in neurological and psychiatric disorders and potential functional implications.

PPP2R2B, a protein widely expressed in neurons throughout the brain, regulates the protein phosphatase 2A (PP2A) activity for the microtubule-associated protein tau and other substrates. Altered PP2A activity has been implicated in spinocerebellar ataxia 12, Alzheimer's disease (AD), and other tauopathies. Through a case-control study and a reporter assay, we investigated the association of PPP2R2B CAG repeat polymorphism with Taiwanese AD, essential tremor (ET), Parkinson's disease (PD), and schizophrenia and clarified the functional implication of this polymorphism. The distribution of the alleles was not significantly different between patients and controls, with 68.6-76.1% alleles at lengths of 10, 13, and 16 triplets. No expanded alleles were detected in either group. However, the frequency of the individuals carrying the short 5-, 6-, and 7-triplet alleles was notably higher in patients with AD (5/180 [2.8%], Fisher's exact test, P = 0.003; including 2 homozygotes) and ET (4/132 [3.0%], Fisher's exact test, P < 0.001) than in the controls (1/625 [0.2%]). The PPP2R2B transcriptional activity was significantly lower in the luciferase reporter constructs containing the (CAG)(5-7) allele than in those containing the common 10-, 13-, and 16-triplet alleles in both neuroblastoma and embryonic kidney cells. Therefore, our preliminary results suggest that the PPP2R2B gene CAG repeat polymorphism may be functional and may, in part, play a role in conferring susceptibility to AD and ET in Taiwan.

Risk factors for vascular dementia: a hospital-based study in Taiwan.

BACKGROUND: In Taiwan, next to Alsheimer's, vascular dementia (VD) is the second leading cause of dementia in the elderly. Few studies have examined cardiovascular risk factors and their association with VD in Taiwan. METHODS: This is a case-control study using a sampling of subjects from the outpatient memory clinics of two hospitals. Identified cases were those patients diagnosed with VD based on the DSM-IV criteria. The controls were subjects with Clinical Dementia Rating Scale as 0, i.e. no dementia from the same dementia registry database. Exposure was recorded by means of a risk factor questionnaire or medical examination. RESULTS: There were a total of 190 patients with VD and 155 controls in this study. Significant risk factors were age, hypertension, diabetes and hyperlipidemia. There was no correlation with sex, education, cigarette smoking or alcohol consumption. CONCLUSIONS: This study confirmed reported cardiovascular risk factors contributing to VD as in Western countries.

Basal Ganglia-thalamic hemorrhage in young adults: a hospital-based study.

BACKGROUND: The causes of basal ganglia-thalamic hemorrhage in the young are not well established. Therefore, its clinical profile, etiology, and risk factors were studied. METHODS: Retrospectively, collected data were evaluated using the chi(2) test and logistic regression analysis. RESULTS: Gender differences occurred in the clinical profile, risk factors, and etiological spectrum. Large hematoma, Glasgow Coma Scale

Etiologic study of young ischemic stroke in Taiwan.

BACKGROUND AND PURPOSE: The etiologic mechanisms of young ischemic stroke in Chinese are largely unknown. This work thus studied the etiologies of young ischemic stroke in Taiwan Chinese and made a comparison with previous reports. METHODS: From January 1997 to October 2001, a total of 264 consecutive young ischemic stroke patients (18 to 45 years old) were admitted to the Department of Neurology in our hospital. The risk factors for stroke and the distribution of stroke subtype were studied. The vascular ultrasound and angiographic findings of these patients were also studied. RESULTS: The sample contained 188 men and 76 women. Cerebral infarction was diagnosed in 241 patients and transient ischemic attack in 23 (8.7%). Regarding stroke subtype, stroke of small-vessel occlusion was diagnosed in 20.5% of cases, large-artery atherosclerosis in 7.2%, cardioembolism in 17.8%, other determined etiology in 22.3%, and undetermined etiology in 23.5%. The 4 most common risk factors were hyperlipidemia (53.1%), smoking (49.8%), hypertension (45.8%), and family history of stroke (29.3%). Twenty-three patients (9.6%) had significant stenosis (> or =50%) of the carotid (7.5%) and vertebral arteries (2.1%), the most common cause of which was dissection (60.9%). Forty-five patients (26.5%) had significant intracranial stenosis with 18.8% in the carotid and 10.6% in the vertebrobasilar system, and 5 (2.9%) had stenosis in both systems. Premature atherosclerosis (33.3%) was the most common cause of intracranial stenosis. CONCLUSIONS: Our study found that strokes of other determined etiology and undetermined etiology were most common among the sample group, and a battery of extensive examinations is indicated to elucidate the etiology for further stroke prevention. Intracranial stenosis is more common than extracranial stenosis in both the carotid and vertebrobasilar systems.