Altered pupil light and darkness reflex and eye-blink responses in late-life depression.

BACKGROUND: Late-life depression (LLD) is a prevalent neuropsychiatric disorder in the older population. While LLD exhibits high mortality rates, depressive symptoms in older adults are often masked by physical health conditions. In younger adults, depression is associated with deficits in pupil light reflex and eye blink rate, suggesting the potential use of these responses as biomarkers for LLD. METHODS: We conducted a study using video-based eye-tracking to investigate pupil and blink responses in LLD patients (n = 25), older (OLD) healthy controls (n = 29), and younger (YOUNG) healthy controls (n = 25). The aim was to determine whether there were alterations in pupil and blink responses in LLD compared to both OLD and YOUNG groups. RESULTS: LLD patients displayed significantly higher blink rates and dampened pupil constriction responses compared to OLD and YOUNG controls. While tonic pupil size in YOUNG differed from that of OLD, LLD patients did not exhibit a significant difference compared to OLD and YOUNG controls. GDS-15 scores in older adults correlated with light and darkness reflex response variability and blink rates. PHQ-15 scores showed a correlation with blink rates, while MoCA scores correlated with tonic pupil sizes. CONCLUSIONS: The findings demonstrate that LLD patients display altered pupil and blink behavior compared to OLD and YOUNG controls. These altered responses correlated differently with the severity of depressive, somatic, and cognitive symptoms, indicating their potential as objective biomarkers for LLD.

Plasma Phosphorylated-tau181 Is a Predictor of Post-stroke Cognitive Impairment: A Longitudinal Study.

Introduction: Post-stroke cognitive impairment (PSCI) cannot be neglected because it drastically influences the daily life of patients and their families. However, there are no studies exploring the association between preclinical blood biomarkers of neurodegeneration including plasma amyloid-ß (Aß), tau, and brain-derived neurotrophic factor (BDNF) together with the risk of PSCI. This longitudinal study was to investigate whether these blood biomarkers with imaging markers of cerebral small vessel disease can improve the prediction for PSCI. In addition, we also explored the association between blood biomarkers with the trajectories of PSCI. Methods: Adult patients with first-ever acute ischemic stroke were recruited, and the cognitive and functional abilities of these patients were evaluated. Furthermore, blood biomarkers of neurodegeneration including plasma Aß-40, Aß-42, total tau, phosphorylated tau 181 (p-tau181), and BDNF levels and image markers of cerebral small vessel disease were measured. Each patient was followed up at 3 and 12 months at the outpatient department. Results: Of 136 patients, 40 and 50 patients developed PSCI at 3 and 12 months after stroke, respectively. In functional trajectories, 27 patients did not have PSCI at 3 months but did at 12 months. By contrast, the PSCI status of 17 patients at 3 months was reversed at 12 months. Patients with high-acute plasma p-tau181 had a significantly lower PSCI risk at 3 months (odds ratio [OR] = 0.62, 95% CI = 0.40-0.94, p = 0.0243) and 12 months (OR = 0.69, 95% CI = 0.47-0.99, p = 0.0443) after adjustment for covariates and image biomarkers. Discrimination and reclassification statistics indicated that the p-tau181 level can improve discrimination ability for PSCI at 3 and 12 months, respectively. In addition, the plasma p-tau181 level was the highest in subjects without PSCI followed by those with delayed-onset PSCI and early-onset PSCI with reversal, whereas the lowest plasma p-tau181 level was found among those with persistent PSCI, showing a significant trend test (p = 0.0081). Conclusion: Plasma p-tau181 is a potential biomarker for predicting early- and delayed-onset PSCI. Future studies should incorporate plasma p-tau181 as an indicator for timely cognitive intervention in the follow-up of patients with stroke.

Periodontitis is a potential risk factor for transient ischemic attack and minor ischemic stroke in young adults: A nationwide population-based cohort study.

BACKGROUND: This study aims to determine whether periodontitis is a risk factor for transient ischemic attack (TIA) in young adults. METHODS: The National Health Insurance (NHI) Research Database in Taiwan was the source of the data used in this retrospective cohort study. Individuals aged 20 to 53 years with periodontitis in 2001 and 2002 (n = 792,426) and an age- and sex-matched control group (n = 792,426) were selected. All participants were followed up until TIA diagnosis, 55 years of age, removal from the NHI program, death, or December 31, 2016. The incidence density and hazard ratio (HR) of new-onset TIA were compared between individuals with periodontitis and controls. Periodontitis was defined by dentists according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 523.3-5 with concurrent antibiotic prescription or periodontal treatment excluding scaling performed by certified dentists. TIA was defined according to the ICD-9-CM code 435.x at hospital discharge. RESULTS: After adjustment for confounding factors, the risk of developing TIA/minor ischemic stroke was calculated to be higher in participants with periodontitis (HR, 1.24; 95% confidence interval, 1.15-1.32; P <0.001) than in those without. The HR was slightly higher among people aged 20 to 40 years than among those aged 40 to 53 years. CONCLUSION: Periodontitis is associated with an increased risk of developing TIA/minor ischemic stroke. Periodontitis might be a modifiable risk factor for stroke in young adults. Clinicians must devote greater attention to this potential association to develop new preventive and therapeutic strategies for stroke in young adults.

Impaired cerebral autoregulation is associated with poststroke cognitive impairment.

OBJECTIVE: To investigate whether dynamic cerebral autoregulation (CA) and neuroimaging characteristics are determinants of poststroke cognitive impairment (PSCI). METHODS: Eighty patients within 7 days of acute ischemic stroke and 35 age- and sex-matched controls were enrolled. In the patients with stroke, brain magnetic resonance imaging and dynamic CA were obtained at baseline, and dynamic CA was followed up at 3 months and 1 year. Montreal Cognitive Assessment (MoCA) was performed at 3 months and 1 year. Patients with a MoCA score <23 at 1 year were defined as having PSCI, and those with a MoCA score that decreased by 2 points or more between the 3-month and 1-year assessments were defined as having progressive cognitive decline. RESULTS: In total, 65 patients completed the study and 16 developed PSCI. The patients with PSCI exhibited poorer results for all cognitive domains than did those without PSCI. The patients with PSCI also had poorer CA (lower phase shift between cerebral blood flow and blood pressure waveforms in the very low frequency band) compared with that of the patients without PSCI and controls at baseline and 1 year. CA was not different between the patients without PSCI and controls. In the multivariate analysis, low education level, lobar microbleeds, and impaired CA (very low frequency phase shift [≤46°] within 7 days of stroke), were independently associated with PSCI. In addition, impaired CA was associated with progressive cognitive decline. INTERPRETATION: Low education level, lobar microbleeds, and impaired CA are involved in the pathogenesis of PSCI.

Comparison of Arrhythmia Detection by 24-Hour Holter and 14-Day Continuous Electrocardiography Patch Monitoring.

BACKGROUND: Although 24-hour Holter monitoring is routinely used for patients with suspected paroxysmal arrhythmia, its sensitivity in detecting such arrhythmias is insufficient. METHODS: We compared a 14-day electrocardiography (ECG) monitor patch - a single-use, noninvasive, waterproof, continuous monitoring patch - with a 24-hour Holter monitor in 32 consecutive patients with suspected arrhythmia. RESULTS: The 14-day ECG patch was well tolerated, and its rates of detection of relevant arrhythmias on days 1, 3, 7, and 14 were 13%, 28%, 47%, and 66%, respectively. The detection rate of paroxysmal arrhythmias was significantly higher for the 14-day ECG patch than for the 24-hour Holter monitor (66% vs. 9%, p < 0.001). Among the 32 patients, 202 atrial fibrillation or atrial flutter episodes were detected in 6 patients (22%) with the 14-day ECG patch; however, only 1 atrial fibrillation episode was detected in a patient (3%, p < 0.05) with the 24-hour Holter monitor. Other clinically relevant arrhythmias recorded on the 14-day ECG patch included 21 (65.5%) episodes of supraventricular tachycardia, 2 (6.3%) long pause, and 2 (6.3%) ventricular arrhythmias. The mean dermal response score immediately after removal of the 14-day ECG patch from the patients was 0.64, which indicated minimal erythema. CONCLUSIONS: The 14-day ECG patch was well tolerated and allowed for longer continuous monitoring than the 24-hour Holter monitor, thus resulting in improved clinical accuracy in the detection of paroxysmal arrhythmias. Future studies should examine the long-term effectiveness of 14-day ECG patches for managing selected patients.

Clinical trials of new drugs for Alzheimer disease.

Alzheimer disease (AD) accounts for 60-70% of dementia cases. Given the seriousness of the disease and continual increase in patient numbers, developing effective therapies to treat AD has become urgent. Presently, the drugs available for AD treatment, including cholinesterase inhibitors and an antagonist of the N-methyl-D-aspartate receptor, can only inhibit dementia symptoms for a limited period of time but cannot stop or reverse disease progression. On the basis of the amyloid hypothesis, many global drug companies have conducted many clinical trials on amyloid clearing therapy but without success. Thus, the amyloid hypothesis may not be completely feasible. The number of anti-amyloid trials decreased in 2019, which might be a turning point. An in-depth and comprehensive understanding of the contribution of amyloid beta and other factors of AD is crucial for developing novel pharmacotherapies.In ongoing clinical trials, researchers have developed and are testing several possible interventions aimed at various targets, including anti-amyloid and anti-tau interventions, neurotransmitter modification, anti-neuroinflammation and neuroprotection interventions, and cognitive enhancement, and interventions to relieve behavioral psychological symptoms. In this article, we present the current state of clinical trials for AD at clinicaltrials.gov. We reviewed the underlying mechanisms of these trials, tried to understand the reason why prior clinical trials failed, and analyzed the future trend of AD clinical trials.

Dementia screening for elderly in-patients and its association with nursing care satisfaction-an observational study.

Inappropriate care for patients with cognitive dysfunction in the hospital could worsen quality of care and medical service satisfaction.All elderly participants were recruited from acute wards of 5 departments in an university hospital. They were administered the Chinese version of Ascertain Dementia 8 (AD8) at admission and the Nursing Service Satisfaction Questionnaire before discharge.A total of 345 participants completed the study. There were 91 (26.4%) participants with AD8 ≥ 2, the cut-off value of high risk of dementia. The prevalence was much higher than prior community-based reports. The Nursing Service Satisfaction Score was significantly lower in AD8 ≥ 2 than in AD8 < 2 (56.99 ±â€Š0.94 vs 60.55 ±â€Š0.48, P < .01).Using AD8 in hospital-based screening might be more efficient than in the community in terms of cost-effectiveness due to higher positive rate and easier approach to diagnostic facilities. AD8 ≥ 2 is also an indicator to identify care dissatisfaction among inpatients. By identifying patients with cognitive dysfunction, such as its related communication barriers, care systems could be tailored for more friendly services.

Plasma Amyloid Beta and Tau Levels Are Predictors of Post-stroke Cognitive Impairment: A Longitudinal Study.

Objectives: Post-stroke cognitive impairment (PSCI) is a common disease that may occur within 3 months after a stroke or even later. However, the mechanism of PSCI development is unclear. The present study investigated whether the levels of plasma amyloid beta-42 (Aß42) and tau are associated with the onset of PSCI. Methods: Fifty-five patients admitted within 7 days of acute ischemic stroke were enrolled and followed up for 1 year. Montreal Cognitive Assessment (MoCA) was administered at 3 months and 1 year, and plasma Aß42 and tau levels were determined using an ultrasensitive immunoassay (immunomagnetic reduction) within 7 days of the stroke event and 3 months later. Results: In this study, 13 of 55 patients developed PSCI (MoCA score <23) at 3 months. Seven patients with PSCI at 3 months recovered to a cognitively normal state at 1 year, whereas seven cognitively normal patients developed PSCI at 1 year. The patients with PSCI at 1 year had a higher incidence of cognitive function deterioration between 3 months and 1 year compared with those without PSCI at 1 year. Plasma Aß42 and tau levels at 3 months were lower in the patients with PSCI at 1 year than in those without PSCI (Aß42: 15.1 vs. 17.2 pg/mL, P = 0.013; tau: 16.7 vs. 19.9 pg/mL, P = 0.018). Low education levels and pre-existing white matter disease were the most significant predictors of PSCI at 3 months, and poor cognitive performance at 3 months and low plasma Aß42 and tau levels at 3 months were the most significant predictors of PSCI at 1 year. Conclusion: The pathogenesis of PSCI is complex and changes with time. Ischemia-induced Aß42/tau pathology might be involved in PSCI development.

Periodontitis as a Modifiable Risk Factor for Dementia: A Nationwide Population-Based Cohort Study.

OBJECTIVES: To determine whether periodontitis is a modifiable risk factor for dementia. DESIGN: Prospective cohort study. SETTING: National Health Insurance Research Database in Taiwan. PARTICIPANTS: Individuals aged 65 and older with periodontitis (n = 3,028) and an age- and sex-matched control group (n = 3,028). MEASUREMENTS: Individuals with periodontitis were compared age- and sex-matched controls with for incidence density and hazard ratio (HR) of new-onset dementia. Periodontitis was defined according to International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes 523.3-5 diagnosed by dentists. To ensure diagnostic validity, only those who had concurrently received antibiotic therapies, periodontal treatment other than scaling, or scaling more than twice per year performed by certified dentists were included. Dementia was defined according to ICD-9-CM codes 290.0-290.4, 294.1, 331.0-331.2. RESULTS: After adjustment for confounding factors, the risk of developing dementia was calculated to be higher for participants with periodontitis (HR = 1.16, 95% confidence interval = 1.01-1.32, P = .03) than for those without. CONCLUSION: Periodontitis is associated with greater risk of developing dementia. Periodontal infection is treatable, so it might be a modifiable risk factor for dementia. Clinicians must devote greater attention to this potential association in an effort to develop new preventive and therapeutic strategies for dementia.

Comparison of Standing Posture Bioelectrical Impedance Analysis with DXA for Body Composition in a Large, Healthy Chinese Population.

Bioelectrical impedance analysis (BIA) is a common method for assessing body composition in research and clinical trials. BIA is convenient but when compared with other reference methods, the results have been inconclusive. The level of obesity degree in subjects is considered to be an important factor affecting the accuracy of the measurements. A total of 711 participants were recruited in Taiwan and were sub-grouped by gender and levels of adiposity. Regression analysis and Bland-Altman analysis were used to evaluate the agreement of the measured body fat percentage (BF%) between BIA and DXA. The BF% measured by the DXA and BIA methods (Tanita BC-418) were expressed as BF%DXA and BF%BIA8, respectively. A one-way ANOVA was used to test the differences in BF% measurements by gender and levels of adiposity. The estimated BF%BIA8 and BF%DXA in the all subjects, male and female groups were all highly correlated (r = 0.934, 0.901, 0.916, all P< 0.001). The average estimated BF%BIA8 (22.54 ± 9.48%) was significantly lower than the average BF%DXA (26.26 ± 11.18%). The BF%BIA8 was overestimated in the male subgroup (BF%DXA< 15%), compared to BF%DXA by 0.45%, respectively. In the other subgroups, the BF%BIA8 values were all underestimated. Standing BIA estimating body fat percentage in Chinese participants have a high correlation, but underestimated on normal and high obesity degree in both male and female subjects.

Predicting Mortality in Patients With "Malignant" Middle Cerebral Artery Infarction Using Susceptibility-Weighted Magnetic Resonance Imaging: Preliminary Findings.

To evaluate malignant middle cerebral artery (MCA) infarction (defined as space-occupying edema in more than 50% to 75% of the MCA territory) on magnetic resonance imaging (MRI) with susceptibility-weighted imaging (SWI) sequence and assess the usefulness of SWI findings, diffusion-weighted imaging (DWI) findings, and apparent diffusion coefficient (ADC) as predictors of clinical outcome.Data from 16 patients with large MCA infarction previously admitted to our institution between December 2009 and October 2012 were retrospectively collected and analyzed. Within 7 days after stroke onset, 1 neurologist and 1 neuroradiologist estimated the area of infarction on DWI/ADC and extent of prominent vessel sign (PVS) on SWI images using the Stroke Program Early MR Score (SPEMRS). The PVS on SWI was defined as a local prominence of hypointense vessels with either increased vessel number or diameter in the target area, when compared with the number or diameter of the contralateral MCA territory vessels.Six patients died and 10 survived. Although the DWI/ADC-SPEMRS and clinical profiles were similar between the nonsurvivor and survivor groups, SWI-SPEMRS was significantly lower in the nonsurvivor group (P < 0.001).The area of deoxygenation on SWI in patients with malignant MCA infarction can predict mortality. Lower SWI-SPEMRS is a potentially better predictor of poor outcome than lower DWI-SPEMRS. A larger prospective study is needed to clarify the role of SWI as a therapeutic guide in malignant MCA.

Image Quality of 256-Slice Computed Tomography for Coronary Angiography.

PURPOSE: To assess the image quality of 256-slice computed tomographic angiography (CTA) and to identify possible impact factors associated with image quality. METHODS: From November 2009 to January 2010, 506 patients underwent 256-slice CTA at our institute. A total of 451 patients were enrolled in our study, after 55 patients were excluded because of prior bypass surgery and stenting. CTA image quality was graded by two observers using a 4-point scale: excellent (score 1), good (score 2), moderate (score 3), poor and non-diagnostic (score 4). The coronary arteries were divided into 15 segments. Image quality was correlated to the subjects' age, gender, body mass index, heart rate, and calcium scores. RESULTS: We evaluated 6650 coronary segments from CTA images of our enrolled 451 patients. The mean image quality score of all coronary segments was 1.14. Most coronary segments (99.7%) were assessable, and only 21 segments (0.3%) were non-diagnostic. A total of 5824 coronary segments were classified as having excellent image quality. Forty-two patients (9.3%) required control of heart rate with beta-blockers before CTA could be performed. Male patients had better image quality than female patients. Heart rate and severity of calcification were impact factors associated with image quality. CONCLUSIONS: Examination with 256-slice CTA provides good image quality and can effectively evaluate most coronary segments. KEY WORDS: Coronary angiography; Heart rate; Image quality; Multi-slice computed tomography.

The diagnostic accuracy of 256-row computed tomographic angiography compared with invasive coronary angiography in patients with suspected coronary artery disease.

AIMS: To assess the diagnostic accuracy of 256-row computed tomographic angiography (CTA) in patients with suspected coronary artery disease (CAD). Non-invasive imaging of the coronary artery by CTA has increasingly been used in recent years. The accuracy of 256-row CTA has not yet been studied. We sought to assess the accuracy of 256-row CTA compared with invasive coronary angiography (ICA) in the diagnosis and assessment of CAD. METHODS AND RESULTS: We prospectively evaluated 104 consecutive individuals who accepted CTA and then underwent ICA. The presence of stenosis > or =50% was considered obstructive. The diagnostic accuracy of CTA for detecting obstructive stenosis was compared with that of ICA. The area under the receiver-operating-characteristic curve (AUC) was used to evaluate the diagnostic accuracy of CTA relative to ICA. A total of 86 patients had obstructive CAD. The patient-based analysis of CTA for detecting stenosis > or =50% according to ICA revealed an AUC of 0.744 [95% confidence interval (CI), 0.572-0.916], with a sensitivity of 98.8%, a specificity of 50%, a positive predictive value (PPV) of 92.4%, and a negative predictive value (NPV) of 87.5%. The segment-based analysis revealed an AUC of 0.915 (95% CI, 0.847-0.982), with a sensitivity of 93.5%, a specificity of 95%, a PPV of 77.6%, and an NPV of 98.7%. The vessel-based analysis revealed an AUC of 0.887 (95% CI, 0.808-0.966), with a sensitivity of 94.3%, a specificity of 87.3%, a PPV of 82.7%, and an NPV of 95.9%. CONCLUSION: 256-Row CTA is a highly sensitive test of CAD and has a high predictive value. 256-Row CTA may be a potential alternative to detect coronary artery stenosis and rule out CAD in suspected patients.