Survival After the Diagnosis of Mild-to-Moderate Alzheimer's Disease Dementia: A 15-Year National Cohort Study in Taiwan.

OBJECTIVES: Pharmacological and non-pharmacological interventions are mostly designed for patients with early Alzheimer's disease (AD) dementia. Long-term case management and planning for the remainder of life with disability require an estimation of the survival duration. METHODS: This cohort study utilized data from the National Health Insurance Research Database, Taiwan, to identify incident cases of mild-to-moderate AD dementia diagnosed from 2000 to 2002, followed through December 31, 2017. A multivariate Cox proportional hazards regression model was constructed to compare the independent effects of age, sex, and comorbidities on all-cause mortality risk. Cumulative survival rates and survival times were estimated. RESULTS: A total of 5258 incident cases were identified, all treated with cholinesterase inhibitors after diagnosis confirmation by an expert committee. During the 15-year follow-up period, 4331 deaths occurred. The 1-, 3-, 5-, 10-, and 15-year cumulative survival rates were 95, 92, 67, 37, and 18, respectively. The median (95% CI) survival time after diagnosis was 7.69 (7.46-7.90) years overall, 6.37 (6.06-6.65) years in men, and 8.81 (8.49-9.12) years in women. After stratification by age and number of comorbidities, the median survival time ranged from 13.72 (ages 40-64) to 5.29 (ages ≥ 80) years among those without comorbidities. For those with ≥ 3 comorbidities, the median survival times decreased to 6.43 for individuals diagnosed at ages 40-64 and to 2.98 years for those diagnosed at age 80 or older. CONCLUSIONS: This nationwide, large, long-term cohort study provided survival rates and durations from diagnosis to death, varying by sex, age group, and presence/number of comorbidities. This information can serve as a foundation for further cost-effectiveness studies on new treatments, and may aid clinicians, patients, and families in shared decision-making and advance personalized care planning for early dementia cases.

Application of blood-based biomarkers of Alzheimer's disease in clinical practice: Recommendations from Taiwan Dementia Society.

Blood-based biomarkers (BBM) are potentially powerful tools that assist in the biological diagnosis of Alzheimer's disease (AD) in vivo with minimal invasiveness, relatively low cost, and good accessibility. This review summarizes current evidence for using BBMs in AD, focusing on amyloid, tau, and biomarkers for neurodegeneration. Blood-based phosphorylated tau and the Aß42/Aß40 ratio showed consistent concordance with brain pathology measured by CSF or PET in the research setting. In addition, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are neurodegenerative biomarkers that show the potential to assist in the differential diagnosis of AD. Other pathology-specific biomarkers, such as α-synuclein and TAR DNA-binding protein 43 (TDP-43), can potentially detect AD concurrent pathology. Based on current evidence, the working group from the Taiwan Dementia Society (TDS) achieved consensus recommendations on the appropriate use of BBMs for AD in clinical practice. BBMs may assist clinical diagnosis and prognosis in AD subjects with cognitive symptoms; however, the results should be interpreted by dementia specialists and combining biochemical, neuropsychological, and neuroimaging information. Further studies are needed to evaluate BBMs' real-world performance and potential impact on clinical decision-making.

More than a piece of cake: Noun classifier processing in primary progressive aphasia.

INTRODUCTION: Clinical understanding of primary progressive aphasia (PPA) has been primarily derived from Indo-European languages. Generalizing certain linguistic findings across languages is unfitting due to contrasting linguistic structures. While PPA patients showed noun classes impairments, Chinese languages lack noun classes. Instead, Chinese languages are classifier language, and how PPA patients manipulate classifiers is unknown. METHODS: We included 74 native Chinese speakers (22 controls, 52 PPA). For classifier production task, participants were asked to produce the classifiers of high-frequency items. In a classifier recognition task, participants were asked to choose the correct classifier. RESULTS: Both semantic variant (sv) PPA and logopenic variant (lv) PPA scored significantly lower in classifier production task. In classifier recognition task, lvPPA patients outperformed svPPA patients. The classifier production scores were correlated to cortical volume over left temporal and visual association cortices. DISCUSSION: This study highlights noun classifiers as linguistic markers to discriminate PPA syndromes in Chinese speakers. HIGHLIGHTS: Noun classifier processing varies in the different primary progressive aphasia (PPA) variants. Specifically, semantic variant PPA (svPPA) and logopenic variant PPA (lvPPA) patients showed significantly lower ability in producing specific classifiers. Compared to lvPPA, svPPA patients were less able to choose the accurate classifiers when presented with choices. In svPPA, classifier production score was positively correlated with gray matter volume over bilateral temporal and left visual association cortices in svPPA. Conversely, classifier production performance was correlated with volumetric changes over left ventral temporal and bilateral frontal regions in lvPPA. Comparable performance of mass and count classifier were noted in Chinese PPA patients, suggesting a common cognitive process between mass and count classifiers in Chinese languages.

Oral microbiome and serological analyses on association of Alzheimer's disease and periodontitis.

OBJECTIVE: To investigate the association between Alzheimer's disease (AD) and periodontitis in the aspects of periodontal status, serological markers, and oral microbiome. MATERIALS AND METHODS: Twenty AD and 20 healthy subjects were enrolled in this age- and gender-matched case-control study. Clinical periodontal parameters and serum biomarkers, including amyloid ß42 (Aß42 ), Tau, phosphorylated Tau (pTau), triglyceride, pro-inflammatory cytokines, and anti-Porphyromonas gingivalis lipopolysaccharide (LPS) antibody were examined. The saliva samples were analyzed for oral microbiome composition. RESULTS: Alzheimer's disease patients with Clinical Dementia Rating (CDR) ≥1 exhibited significantly more clinical attachment loss (CAL) than those with lower CDR. The levels of serum Tau protein, hsCRP and anti-P. gingivalis LPS antibody were markedly elevated in the AD group compared with the control group. Serum pTau protein level was positively correlated with anti-P. gingivalis LPS antibody titer. Moreover, the increased abundances of Capnocytophaga sp ora clone DZ074, Eubacterium infirmum, Prevotella buccae, and Selenomonas artemidis were detected in the AD group. Interestingly, serum levels of Aß42, pTau, and anti-P. gingivalis LPS antibody were strongly related to the gene upregulation in human pathogen septicemia. CONCLUSIONS: Our study suggested the association of periodontal infection and oral microbiome with AD. Further large-scale studies with longitudinal follow-up are warranted.

A Multicomponent Cognitive Intervention May Improve Self-Reported Daily Function of Adults With Subjective Cognitive Decline.

IMPORTANCE: Limited evidence exists to support cognitive intervention improving the daily function of adults with subjective cognitive decline (SCD). OBJECTIVE: To examine the preliminary efficacy of a group-based multicomponent cognitive intervention that integrates Lifestyle Redesign® (LR) techniques. DESIGN: Single-arm two-period crossover trial; 16-wk waiting period, 16-wk intervention, and 16-wk follow-up. SETTING: Memory clinic in a medical center, Taiwan. PARTICIPANTS: Purposive sample of adults ages >55 yr with SCD. INTERVENTION: Sixteen 1.5-hr weekly multicomponent sessions of cognitive training, cognitive rehabilitation, psychological intervention, and lifestyle intervention. OUTCOMES AND MEASURES: Primary outcomes were (1) self-reported daily function, measured with the Activities of Daily Living Questionnaire (ADLQ) and Cognitive Failure Questionnaire; (2) performance-based daily function, measured with the Brief University of California San Diego Performance-Based Skills Assessment-Traditional Chinese Version; and (3) functional cognition, measured with the Contextual Memory Test (CMT) and Miami Prospective Memory Test. Secondary outcomes included cognitive functions, anxiety, and depression. RESULTS: Seventeen participants completed the intervention; 4 missed the follow-up. The generalized estimating equations model showed significant changes from baseline to pretest (control) and pretest to posttest (intervention) on the ADLQ (p = .014) and CMT-delayed (p = .003). Effects remained at the 16-wk follow-up. After adjusting for the effects of covariates, the self-reported daily function of participants ages ≤ 63 yr improved more than that of other participants (p = .003). CONCLUSIONS AND RELEVANCE: Multicomponent cognitive interventions integrating LR techniques may improve self-reported daily function and context-dependent memory function of adults with SCD, with efficacy sustained at follow-up. What This Article Adds: A group-based multicomponent cognitive intervention consisting of cognitive training, cognitive rehabilitation, psychoeducation, and lifestyle intervention may provide benefits for the daily function and cognitive function of adults with SCD.

Rural-urban Disparities in the Prevalence of Mild Cognitive Impairment and Dementia in Taiwan: A Door-to-door Nationwide Study.

BACKGROUND: Screening or diagnosis for the elderly with dementia in rural regions might be delayed and underestimated due to limited utilization of healthcare resources. This study aimed to evaluate the disparities of prevalence and risk factors of mild cognitive impairment (MCI) and dementia between urban and rural residence. METHODS: In this nationwide door-to-door survey, 10,432 participants aged 65 years and more were selected through computerized random sampling from all administrative districts in Taiwan and were assessed using an in-person interview. We calculated the prevalence of MCI and dementia, with their risk factors examined using multivariable logistic regression. RESULTS: The prevalence of dementia in rural, suburban, and urban areas among the elderly was 8.69% (95% CI, 8.68-8.69), 6.63% (95% CI, 6.62-6.63), and 4.46% (95% CI, 4.46-4.47), respectively. A similar rural-suburban-urban gradient relationship on the dementia prevalence was observed in any age and sex group. The rural:urban ratio was higher in women than in men for both MCI and dementia. Urbanization remained to be an independent factor for both MCI and dementia after adjustment for age, gender, education, lifestyle, and health status. The beneficial effects of exercise on dementia were more evident in rural areas than in urban ones. CONCLUSION: Significantly higher prevalence of MCI and dementia were found in rural areas than in urban ones, especially for women. The odds of risk factors for MCI and dementia varied by urbanization status. Focus on the rural-urban inequality and the modification of associated factors specifically for different urbanization levels are needed.

White matter pathology in alzheimer's transgenic mice with chronic exposure to low-level ambient fine particulate matter.

BACKGROUND: Air pollution, especially fine particulate matter (PM), can cause brain damage, cognitive decline, and an increased risk of neurodegenerative disease, especially alzheimer's disease (AD). Typical pathological findings of amyloid and tau protein accumulation have been detected in the brain after exposure in animal studies. However, these observations were based on high levels of PM exposure, which were far from the WHO guidelines and those present in our environment. In addition, white matter involvement by air pollution has been less reported. Thus, this experiment was designed to simulate the true human world and to discuss the possible white matter pathology caused by air pollution. RESULTS: 6 month-old female 3xTg-AD mice were divided into exposure and control groups and housed in the Taipei Air Pollutant Exposure System (TAPES) for 5 months. The mice were subjected to the Morris water maze test after exposure and were then sacrificed with brain dissection for further analyses. The mean mass concentration of PM2.5 during the exposure period was 13.85 µg/m3. After exposure, there was no difference in spatial learning function between the two groups, but there was significant decay of memory in the exposure group. Significantly decreased total brain volume and more neuronal death in the cerebral and entorhinal cortex and demyelination of the corpus callosum were noted by histopathological staining after exposure. However, there was no difference in the accumulation of amyloid or tau on immunohistochemistry staining. For the protein analysis, amyloid was detected at significantly higher levels in the cerebral cortex, with lower expression of myelin basic protein in the white matter. A diffuse tensor image study also revealed insults in multiple white matter tracts, including the optic tract. CONCLUSIONS: In conclusion, this pilot study showed that even chronic exposure to low PM2.5 concentrations still caused brain damage, such as gross brain atrophy, cortical neuron damage, and multiple white matter tract damage. Typical amyloid cascade pathology did not appear prominently in the vulnerable brain region after exposure. These findings imply that multiple pathogenic pathways induce brain injury by air pollution, and the optic nerve may be another direct invasion route in addition to olfactory nerve.

Nanoparticle-based immunomagnetic assay of plasma biomarkers for differentiating dementia and prodromal states of Alzheimer's disease - A cross-validation study.

Blood-based biomarker assays of plasma ß-amyloid (Aß) and tau have the advantages of cost-effective and less invasive for the diagnosis of Alzheimer's disease (AD). We used two independent cohorts to cross-validate the clinical use of the nanoparticle-based immunomagnetic assay of plasma biomarkers to assist in the differential diagnosis of early AD. There were in total 160 subjects in the derivation cohort, and 242 in the validation cohort both containing controls, mild cognitive impairment due to AD and AD dementia diagnosed according to the 2011 NIA-AA guidelines. The cutoff value for plasma Aß1-42 (16.4 pg/ml) performed the best in differentiating between controls and patients with prodromal or clinical AD, with 92.5% for positive percent agreement (PPA), negative percent agreement (NPA), and overall rate of agreement (ORA). Aß1-42 × tau (642.58) was useful for separating patients with dementia and prodromal states of AD, with 84.9% PPA, 78.8% NPA and 83% ORA.

Predictors and associating factors of nasogastric tube removal: Clinical and brain imaging data analysis in post-stroke dysphagia.

BACKGROUND/PURPOSE: Post-stroke dysphagia is a frequent complication. Although most patients with dysphagia recover after the acute phase, some patients require long-term enteral feeding, either through a nasogastric (NG) or gastrostomy tube; the effectiveness of using either tube is still under debate. This study elucidated the natural course of NG tube installation and removal and examined the predictors and associating factors based on clinical and brain imaging data. METHODS: This retrospective cohort study with medical record reviews recruited patients received NG tube installation after their acute stroke events between January 1, 2016, and December 31, 2016. Inclusion criteria were subjects above 20 years of age and with a diagnosis of a newly onset stroke except SAH whose comprehensive clinical and imaging data were available. Survival analysis was performed for the right-censored data because some patients were lost to follow-up after discharge or transferal. RESULTS: In total we recruited 135 patients. Among these patients, the timing of their NG tube removal reached a plateau at 12-16 weeks after stroke. The modified Rankin score on discharge, representing the overall subacute disease status, was the most significant factor. Other clinical variables could be divided into 2 categories: baseline patient characteristics and stroke event severity. Moreover, semi-quantitative brain imaging scores corresponding to the aforementioned 3 categories were correlated significantly. CONCLUSION: In Taiwan, the NG tube removal rate reached a plateau at around 12-16 weeks after stroke onset. Variables related to long-term NG tube use were divided into baseline characteristics of patient and stroke event severity.

Classifications of Neurodegenerative Disorders Using a Multiplex Blood Biomarkers-Based Machine Learning Model.

Easily accessible biomarkers for Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), and related neurodegenerative disorders are urgently needed in an aging society to assist early-stage diagnoses. In this study, we aimed to develop machine learning algorithms using the multiplex blood-based biomarkers to identify patients with different neurodegenerative diseases. Plasma samples (n = 377) were obtained from healthy controls, patients with AD spectrum (including mild cognitive impairment (MCI)), PD spectrum with variable cognitive severity (including PD with dementia (PDD)), and FTD. We measured plasma levels of amyloid-beta 42 (Aß42), Aß40, total Tau, p-Tau181, and α-synuclein using an immunomagnetic reduction-based immunoassay. We observed increased levels of all biomarkers except Aß40 in the AD group when compared to the MCI and controls. The plasma α-synuclein levels increased in PDD when compared to PD with normal cognition. We applied machine learning-based frameworks, including a linear discriminant analysis (LDA), for feature extraction and several classifiers, using features from these blood-based biomarkers to classify these neurodegenerative disorders. We found that the random forest (RF) was the best classifier to separate different dementia syndromes. Using RF, the established LDA model had an average accuracy of 76% when classifying AD, PD spectrum, and FTD. Moreover, we found 83% and 63% accuracies when differentiating the individual disease severity of subgroups in the AD and PD spectrum, respectively. The developed LDA model with the RF classifier can assist clinicians in distinguishing variable neurodegenerative disorders.

Mild cognitive impairment in combination with comorbid diabetes mellitus and hypertension is negatively associated with health-related quality of life among older persons in Taiwan.

PURPOSE: To fill the gap in knowledge about associations of health-related quality of life (HRQoL) with comorbid diabetes mellitus (DM), hypertension (HTN), and/or mild cognitive impairment (MCI) in the elderly, we explored associations of comorbid DM, HTN, and/or MCI with HRQoL. METHODS: Data for this study were from a population-based cross-sectional survey of elderly Taiwanese (≥ 65 years old). Participants (N = 4,634; 47.9% male) were categorized into eight chronic-illness groups: DM only (n = 224); HTN only (n = 1226); DM and HTN (n = 365); MCI only (n = 497); DM and MCI (n = 58); HTN and MCI (n = 303); DM, HTN, and MCI (n = 101); and none (healthy; n = 1860). Associations were examined between the eight chronic-illness groups and HRQoL (measured by EQ-5D scores) using binary logistic regression analyses and generalized linear models adjusted for covariates. Index scores were calculated from EQ-5D scores using Taiwan's general population-preference weights. RESULTS: Compared to the healthy group, after adjusting covariates, MCI alone or with other comorbidities was significantly, negatively associated with HRQoL. Among all chronic-illness groups, comorbid DM, HTN, and MCI exhibited the lowest HRQoL. After adjusting covariates, between-group odds ratios for index scores were significant when comparing comorbid DM and MCI to DM only, comparing comorbid HTN and MCI to HTN only and comorbid DM, comparing HTN and MCI to comorbid DM and HTN, suggesting that MCI additively affects HRQoL. CONCLUSIONS: HRQoL of older Taiwanese adults was negatively associated with having MCI. Thus, clinicians managing older persons with chronic illnesses should assess their cognitive function to identify high-risk groups needing HRQoL assistance.

Cognitive dysfunction predicts worse health-related quality of life for older stroke survivors: a nationwide population-based survey in Taiwan.

OBJECTIVES: This study investigated the associations of cognitive status with specific/overall health-related quality of life (HRQoL) in older stroke survivors in Taiwan. METHOD: A subsample of 592 older stroke survivors in a nationwide population-based survey of cognitive-dysfunction prevalencewas analyzed. HRQoL was assessed using the EuroQol five-dimension questionnaire (EQ-5D). RESULTS: Stroke survivors with dementia were 5.60 times more likely to have mobility problems, 12.20 times to have self-care problems, 16.61 times to have problems in usual activities, 4.31 times to have pain/discomfort, and 3.28 times to have anxiety/depression than stroke survivors with normal cognitive function. Stroke survivors with mild cognitive dysfunction (MCD) were 2.57 times more likely to have mobility problems, 3.17 times to have self-care problems, 3.31 times to have problems in usual activities, 2.11 times to have pain/discomfort, and 2.35 times to have anxiety/depression than those with normal cognitive function. Both dementia (b = -15.13, p < .001) and MCD (b = -6.24, p < .001) significantly contributed to lower EQ-5D VAS; both dementia (b = -.15, p < .001) and MCD (b = -.10, p < .001) significantly contributed to lower EQ-5D index. CONCLUSION: Dementia and MCD strongly predicted worse overall and specific HRQoL dimensions, especially self-care and usual activities for older stroke survivors.

Diminution of context association memory structure in subjects with subjective cognitive decline.

Alzheimer's disease (AD) progresses insidiously from the preclinical stage to dementia. While people with subjective cognitive decline (SCD) have normal cognitive performance, some may be in the preclinical stage of AD. Neurofibrillary tangles appear first in the transentorhinal cortex, followed by the entorhinal cortex in the clinically silent stage of AD. We expected the earliest changes in subjects with SCD to occur in medial temporal subfields other than the hippocampal proper. These selective structural changes would affect specific memory subcomponents. We used the Family Picture subtest of the Wechsler Memory Scale-III, which was modified to separately compute character, activity, and location subscores for episodic memory subcomponents. We recruited 43 subjects with SCD, 44 subjects with amnesic mild cognitive impairment, and 34 normal controls. MRI was used to assess cortical thickness, subcortical gray matter volume, and fractional anisotropy. The results demonstrated that SCD subjects showed significant cortical atrophy in their bilateral parahippocampus and perirhinal and the left entorhinal cortices but not in their hippocampal regions. SCD subjects also exhibited significantly decreased mean fractional anisotropy in their bilateral uncinate fasciculi. The diminution of cortical thickness over the mesial temporal subfields corresponded to brain areas with early tangle deposition, and early degradation of the uncinate fasciculus was in accordance with the retrogenesis hypothesis. The parahippocampus and perirhinal cortex contribute mainly to context association memory while the entorhinal cortex, along with the uncinate fasciculus, contributes to content-related contextual memory. We proposed that context association and related memory structures are vulnerable in the SCD stage.

Diagnostic accuracy of Instrumental Activities of Daily Living for dementia in community-dwelling older adults.

BACKGROUND: many people living with dementia remain underdiagnosed and unrecognised. Screening strategies are important for early detection. OBJECTIVE: to examine whether the Lawton's Instrumental Activities of Daily Living (IADL) scale, compared with other cognitive screening tools-the Mini-Mental State Examination (MMSE), and the Ascertain Dementia 8-item Informant Questionnaire (AD8)-can identify older (≥ 65 years) adults with dementia. DESIGN: population-based cross-sectional observational study. SETTING: all 19 counties in Taiwan. PARTICIPANTS: community-dwelling older adults (n = 10,340; mean age 74.87 ± 6.03). METHODS: all participants underwent a structured in-person interview. Dementia was identified using National Institute on Aging-Alzheimer's Association core clinical criteria for all-cause dementia. Receiver operator characteristic curves were used to determine the discriminant abilities of the IADL scale, MMSE and AD8 to differentiate participants with and without dementia. RESULTS: we identified 917 (8.9%) participants with dementia, and 9,423 (91.1%) participants without. The discriminant abilities of the MMSE, AD8 and IADL scale (cutoff score: 6/7; area under curve = 0.925; sensitivity = 89%; specificity = 81%; positive likelihood ratio = 4.75; accuracy = 0.82) were comparable. Combining IADL with AD8 scores significantly improved overall accuracy: specificity = 93%; positive likelihood ratio = 11.74; accuracy = 0.92. CONCLUSIONS: our findings support using IADL scale to screen older community-dwelling residents for dementia: it has discriminant power comparable to that of the AD8 and MMSE. Combining the IADL and the AD8 improves specificity.

Association between Helicobacter pylori infection and cognitive impairment in the elderly.

BACKGROUND/PURPOSE: Helicobacter pylori (H. pylori) infection has been positively associated with cognitive impairment. However, previous studies have shown inconsistent findings. METHODS: This cross-sectional study included 587 elderly participants (age ≧ 65) from the annual elderly health checkup program at the National Taiwan University Hospital from 2011 to 2013. Both global and domain-specific cognition were assessed using various neuropsychiatric tests. Multivariable linear regression and logistic regression models were utilized to assess the association between the serum H. pylori IgG level and cognitive impairment. RESULTS: Compared with the lowest quartile of H. pylori IgG (Q1), the highest quartile (Q4) was associated with lower scores on verbal fluency-vegetables (ß = -0.24), domain-specific attention [digit span-forward: ß = -0.19; odds ratio (OR) = 1.83, 95% confidence interval (CI) = 1.03-3.24], and attention factors (ß = -0.20; OR= 2.67, 95% CI = 1.51-4.73). No significant association was observed for global cognition. Stratified analyses revealed that, among men, the highest quartile of serum H. pylori IgG (Q4) was associated with impaired scores on verbal fluency-vegetables (ß = -0.38; OR = 3.01, 95% CI = 1.42-6.38). CONCLUSION: Our findings disclosed a positive association between serum H. pylori level and cognitive impairment, which provides important information for the primary prevention of cognitive impairment through the eradication of H. pylori.

Eight-Channel AC Magnetosusceptometer of Magnetic Nanoparticles for High-Throughput and Ultra-High-Sensitivity Immunoassay.

An alternating-current magnetosusceptometer of antibody-functionalized magnetic nanoparticles (MNPs) was developed for immunomagnetic reduction (IMR). A high-sensitivity, high-critical-temperature superconducting quantum interference device was used in the magnetosusceptometer. Minute levels of biomarkers of early-stage neurodegeneration diseases were detectable in serum, but measuring each biomarker required approximately 4 h. Hence, an eight-channel platform was developed in this study to fit minimal screening requirements for Alzheimer's disease. Two consistent results were measured for three biomarkers, namely Aß40, Aß42, and tau protein, per human specimen. This paper presents the instrument configuration as well as critical characteristics, such as the low noise level variations among channels, a high signal-to-noise ratio, and the coefficient of variation for the biomarkers' IMR values. The instrument's ultrahigh sensitivity levels for the three biomarkers and the substantially shorter total measurement time in comparison with the previous single- and four-channels platforms were also demonstrated in this study. Thus, the eight-channel instrument may serve as a powerful tool for clinical high-throughput screening of Alzheimer's disease.

Plasma α-synuclein predicts cognitive decline in Parkinson's disease.

OBJECTIVE: α-Synuclein is critical to the pathogenesis of Parkinson's disease (PD). Few studies examined the plasma levels of α-synuclein due to the exceptionally low level of α-synuclein in plasma compared with cerebrospinal fluid. We aimed to investigate plasma α-synuclein in patients with PD of different disease severity. METHODS: There were total 114 participants, including 80 patients with PD and 34 controls, in the study. Participants received a complete evaluation of motor and non-motor symptoms, including cognitive function. We applied immunomagnetic reduction-based immunoassay to measure plasma levels of α-synuclein. RESULTS: Plasma levels of α-synuclein were significantly higher in patients with PD compared with controls (median: 1.56 pg/mL, 95% CI 1.02 to 1.98 pg/mL vs 0.02 pg/mL, 95% CI 0.01 to 0.03 pg/mL; p<0.0001). Although there was a significant increase in plasma α-synuclein levels in PD patients with a higher Hoehn-Yahr (H-Y) stage, there was no correlation with motor symptom severity, as assessed by Unified Parkinson's Disease Rating Scale part III scores, after confounders (age, gender, and disease duration) were taken into account. However, plasma α-synuclein levels were significantly higher in PD patients with dementia (PDD) than in PD patients with mild cognitive impairment (PD-MCI) or normal cognition (0.42 pg/mL, (95% CI 0.25 to 0.93) for PD with normal cognition; 1.29 pg/mL (95% CI 0.76 to 1.93) for PD-MCI and 4.09 pg/mL (95% CI 1.99 to 6.19) for PDD, p<0.01) and were negatively correlated with Mini-Mental State Examination scores (R2-adjusted=0.3004, p<0.001), even after confounder adjustment. CONCLUSIONS: Our data suggest that plasma α-synuclein level correlates with cognitive decline but not motor severity in patients with PD. Plasma α-synuclein could serve as a surrogate biomarker for patients at risk of cognitive decline.

Development of an ultra-high sensitive immunoassay with plasma biomarker for differentiating Parkinson disease dementia from Parkinson disease using antibody functionalized magnetic nanoparticles.

BACKGROUND: It is difficult to discriminate healthy subjects and patients with Parkinson disease (PD) or Parkinson disease dementia (PDD) by assaying plasma α-synuclein because the concentrations of circulating α-synuclein in the blood are almost the same as the low-detection limit using current immunoassays, such as enzyme-linked immunosorbent assay. In this work, an ultra-sensitive immunoassay utilizing immunomagnetic reduction (IMR) is developed. The reagent for IMR consists of magnetic nanoparticles functionalized with antibodies against α-synuclein and dispersed in pH-7.2 phosphate-buffered saline. A high-Tc superconducting-quantum-interference-device (SQUID) alternative-current magnetosusceptometer is used to measure the IMR signal of the reagent due to the association between magnetic nanoparticles and α-synuclein molecules. RESULTS: According to the experimental α-synuclein concentration dependent IMR signal, the low-detection limit is 0.3 fg/ml and the dynamic range is 310 pg/ml. The preliminary results show the plasma α-synuclein for PD patients distributes from 6 to 30 fg/ml. For PDD patients, the concentration of plasma α-synuclein varies from 0.1 to 100 pg/ml. Whereas the concentration of plasma α-synuclein for healthy subjects is significantly lower than that of PD patients. CONCLUSIONS: The ultra-sensitive IMR by utilizing antibody-functionalized magnetic nanoparticles and high-Tc SQUID magnetometer is promising as a method to assay plasma α-synuclein, which is a potential biomarker for discriminating patients with PD or PDD.

Distinct Patterns and Clinical Implications of Semantic Memory Deterioration Among Patients With MCI.

Limited research has investigated the effects of executive dysfunction on semantic memory deterioration among patients with amnestic mild cognitive impairment (aMCI). This study examined the cognitive performance of 181 participants from various MCI subgroups, a group of mildly impaired individuals with dementia of the Alzheimer type (DAT) and a group of individuals with subjective memory impairment on various semantic memory tasks. The aMCI-single domain (aMCI-sd) group displayed poor performance on a semantic memory task requiring relatively higher degrees of effortful retrieval, and participants in the aMCI-multiple domain (aMCI-md) group, who also suffered with mild executive dysfunction displayed poor performance on all semantic memory tasks, similar to the DAT group. The nonamnestic MCI (non-a-MCI)-single domain group displayed normal performance across all semantic tasks, whereas the non-a-MCI-multiple domain group displayed a pattern similar to that of the aMCI-sd group. aMCI-sd patients who displayed poor performance on the semantic memory task had higher risk of conversion to DAT, whereas poor performance on tasks requiring relatively less effortful retrieval was associated with higher risk of conversion in the aMCI-md group. Thus, executive function may relate to deterioration of semantic memory retrieval processes. Such patterns of semantic memory impairment could be valuable for characterization of cognitive differences among MCI patients.

Delirium, subsyndromal delirium, and cognitive changes in individuals undergoing elective coronary artery bypass graft surgery.

BACKGROUND: The course of incident delirium and subsyndromal delirium (SSD) after cardiac surgery is not well studied. OBJECTIVE: The aim of this study was to evaluate the course of incident delirium and SSD, their risk factors, and impact on patients' cognitive function after elective coronary artery bypass graft (CABG) surgery. METHODS: Consecutive patients scheduled for an isolated CABG at a tertiary medical center in Taiwan were enrolled if they had no preoperative delirium symptoms. Delirium was assessed daily for 1 week after surgery using the Confusion Assessment Method. Subsyndromal delirium was defined as presenting with any core symptom below the diagnostic threshold for delirium. Cognitive function was assessed by the Mini-mental State Examination. RESULTS: Of 38 participants, 7 had incident (first-time) delirium (18.4% incidence) and 13 had incident SSD (34.2% incidence). Whereas SSD usually lasted 1 day, delirium changed gradually to SSD to recovery and its symptomatology lasted longer. We identified 6 delirium risk factors: older age, more comorbidities, cardiac pulmonary bypass, blood transfusion, larger transfusion volume, and longer duration of intraoperative blood pressure less than 60 mm Hg. The frequencies of these risk factors for SSD were often intermediate between those of risk factors in groups with and without delirium. By hospital discharge, participants with delirium had the longest hospital stays and lowest cognitive scores, those with SSD had intermediate stays and scores, and those without delirium had the lowest stays and scores. CONCLUSION: Delirium and SSD after CABG are common. Greater number and severity of risk factors for delirium may predict increasingly poor outcomes, with the dose-response relationship between risk factors and outcomes for SSD intermediate between that for no symptoms and full delirium. Intervention trials are indicated, particularly for patients with a greater number and severity of predisposing and precipitating risk factors.