Association of plasma amyloid-ß oligomerization with theta/beta ratio in older adults.

Background: Oligomeric Aß (OAß) is a promising candidate marker for Alzheimer's disease (AD) diagnosis. Electroencephalography (EEG) is a potential tool for early detection of AD. Still, whether EEG power ratios, particularly the theta/alpha ratio (TAR) and theta/beta ratio (TBR), reflect Aß burden-a primary mechanism underlying cognitive impairment and AD. This study investigated the association of TAR and TBR with amyloid burden in older adults based on MDS-OAß levels. Methods: 529 individuals (aged ≥60 years) were recruited. All participants underwent EEG (MINDD SCAN, Ybrain Inc., South Korea) and AlzOn™ test (PeopleBio Inc., Gyeonggi-do, Republic of Korea) for quantifying MDS-OAß values in the plasma. EEG variables were log-transformed to normalize the data distribution. Using the MDS-OAß cutoff value (0.78 ng/mL), all participants were classified into two groups: high MDS-OAß and low MDS-OAß. Results: Participants with high MDS-OAß levels had significantly higher TARs and TBRs than those with low MDS-OAß levels. The log-transformed TBRs in the central lobe (ß = 0.161, p = 0.0026), frontal lobe (ß = 0.145, p = 0.0044), parietal lobe (ß = 0.166, p = 0.0028), occipital lobe (ß = 0.158, p = 0.0058), and temporal lobe (beta = 0.162, p = 0.0042) were significantly and positively associated with increases in MDS-OAß levels. After adjusting for the Bonferroni correction, the TBRs in all lobe regions, except the occipital lobe, were significantly associated with increased MDS-OAß levels. Conclusion: We found a significant association of MDS-OAß with TBR in older adults. This finding indicates that an increase in amyloid burden may be associated with an increase in the low-frequency band and a decrease in the relatively high-frequency band.

Association Between the Loss of Gait Harmony and Cognitive Impairment: Cross-Sectional Study.

BACKGROUND: Functional limitations and disabilities have been associated with a decrease in cognitive function due to increasing age. Gait performance and cognitive function have been associated with gait variability in executive function, the phase domain in memory, and gait abnormalities in cognitive decline. OBJECTIVE: Our study aimed to investigate whether gait harmony was associated with cognitive function in the older adult population. Moreover, we aimed to investigate whether gait harmony was associated with cognitive function and explore each cognitive function in a specific harmonic state. METHODS: The study population included 510 adults aged ≥60 years who visited the Department of Neurology at the Veterans Health Service Medical Center, Seoul, South Korea. Gait data were collected using a 3D motion capture device with a wireless inertial measurement unit system. For cognitive function assessments, we used the Seoul Neuropsychological Screening Battery-Core test, which evaluates the level of cognitive function or impairment in 5 cognitive domains. RESULTS: In general, the association between the Seoul Neuropsychological Screening Battery-Core tests and the stance-to-swing ratio in the >1.63 ratio group yielded lower ß coefficients than those in the 1.50-1.63 ratio group. After adjustment for confounders, the odds ratio (OR) for the Digit Symbol Coding test (adjusted OR 0.42, 95% CI 0.20-0.88) and the Korean version of the Color Word Stroop Test: 60 seconds (adjusted OR 0.51, 95% CI 0.29-0.89) for frontal and executive function were significantly lower for the >1.63 ratio group than the reference group. CONCLUSIONS: Our findings suggest that the gait phase ratio is a valuable indicator of walking deficits and may also be associated with cognitive impairment in older adults.

Corrigendum: Use of electroencephalogram, gait, and their combined signals for classifying cognitive impairment and normal cognition.

[This corrects the article DOI: 10.3389/fnagi.2022.927295.].

Deep learning-based diagnosis of Alzheimer's disease using brain magnetic resonance images: an empirical study.

The limited accessibility of medical specialists for Alzheimer's disease (AD) can make obtaining an accurate diagnosis in a timely manner challenging and may influence prognosis. We investigated whether VUNO Med-DeepBrain AD (DBAD) using a deep learning algorithm can be employed as a decision support service for the diagnosis of AD. This study included 98 elderly participants aged 60 years or older who visited the Seoul Asan Medical Center and the Korea Veterans Health Service. We administered a standard diagnostic assessment for diagnosing AD. DBAD and three panels of medical experts (ME) diagnosed participants with normal cognition (NC) or AD using T1-weighted magnetic resonance imaging. The accuracy (87.1% for DBAD and 84.3% for ME), sensitivity (93.3% for DBAD and 80.0% for ME), and specificity (85.5% for DBAD and 85.5% for ME) of both DBAD and ME for diagnosing AD were comparable; however, DBAD showed a higher trend in every analysis than ME diagnosis. DBAD may support the clinical decisions of physicians who are not specialized in AD; this may enhance the accessibility of AD diagnosis and treatment.

Use of electroencephalogram, gait, and their combined signals for classifying cognitive impairment and normal cognition.

Background: Early identification of people at risk for cognitive decline is an important step in delaying the occurrence of cognitive impairment. This study investigated whether multimodal signals assessed using electroencephalogram (EEG) and gait kinematic parameters could be used to identify individuals at risk of cognitive impairment. Methods: The survey was conducted at the Veterans Medical Research Institute in the Veterans Health Service Medical Center. A total of 220 individuals volunteered for this study and provided informed consent at enrollment. A cap-type wireless EEG device was used for EEG recording, with a linked-ear references based on a standard international 10/20 system. Three-dimensional motion capture equipment was used to collect kinematic gait parameters. Mild cognitive impairment (MCI) was evaluated by Seoul Neuropsychological Screening Battery-Core (SNSB-C). Results: The mean age of the study participants was 73.5 years, and 54.7% were male. We found that specific EEG and gait parameters were significantly associated with cognitive status. Individuals with decreases in high-frequency EEG activity in high beta (25-30 Hz) and gamma (30-40 Hz) bands increased the odds ratio of MCI. There was an association between the pelvic obliquity angle and cognitive status, assessed by MCI or SNSB-C scores. Results from the ROC analysis revealed that multimodal signals combining high beta or gamma and pelvic obliquity improved the ability to discriminate MCI individuals from normal controls. Conclusion: These findings support prior work on the association between cognitive status and EEG or gait, and offer new insights into the applicability of multimodal signals to distinguish cognitive impairment.

Diagnostic Performance for Differential Diagnosis of Atypical Parkinsonian Syndromes from Parkinson's Disease Using Quantitative Indices of 18F-FP-CIT PET/CT.

We are aimed to evaluate the diagnostic performances of quantitative indices obtained from dual-phase 18F-FP-CIT PET/CT for differential diagnosis of atypical parkinsonian syndromes (APS) from Parkinson's disease (PD). We analyzed 172 subjects, including 105 non-Parkinsonism, 26 PD, 8 PSP, 1 CBD, 8 MSA-P, 9 MSA-C, and 15 DLB retrospectively. Two sequential PET/CT scans were acquired at 5 min and 3 h. We compared subregional binding potentials, putamen-to-caudate nucleus ratio of the binding potential, asymmetry index, and degree of washout. To differentiate APS, all BPs in both early and late phases (except late BPbrainstem) and all factors of the percent change except for putamen in APS significantly differed from PD. When a cut-off for early BPcerebellum was set as 0.79, the sensitivity, specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy for differentiating APS 73.2%, 91.7%, 93.8%, 66.7%, and 80.0%. The early BPcerebellum showed significantly greater SP and PPV than the late quantitative indices. Combined criteria regarding both early and late indices exhibited only greater NPV. The quantitative indices showed high diagnostic performances in differentiating APS from PD. Our findings provide the dual-phase 18F-FP-CIT PET/CT would be useful for differentiating APS from PD.

Chronic Status of Serum Albumin and Cognitive Function: A Retrospective Cohort Study.

Previous studies have found an association between serum albumin levels and cognitive function. However, the results of this association are inconsistent, and the effect of Apolipoprotein E (APOE) on the association is less clear. Using retrospective cohort data (2008-2020), we investigated whether chronic serum albumin was associated with cognitive performance in older adults. We further assessed how the APOE genotype modifies its relevance. A total of 2396 Korean veterans and their families who were aged 65 years or older in 2008 and who had both data of serum albumin and cognitive performance (assessed by the Mini-Mental State Examination, MMSE) were included for the current study. The serum albumin levels were divided into four groups by quartiles: Group 1 (<4.0 g/dL), Group 2 (4.0-4.19 g/dL), Group 3 (4.2-4.49 g/dL), and Group 4 (≥4.5 g/dL). APOE ε4 carriers were defined as the presence of at least one ε4 allele (ε2/4, ε3/4, ε4/4). After adjusting for age, sex, and medical conditions, serum albumin levels (assessed by the median serum albumin levels during the study period) were significantly associated with increases in the median MMSE scores (beta = 3.30, p < 0.0001). Compared with the lowest median albumin category (Group 1), the beta coefficients for the median MMSE score were significantly and gradually increased in Group 2 (beta = 2.80, p < 0.0001), Group 3 (beta = 3.71, p < 0.0001), and Group 4 (beta = 4.01, p < 0.0001), respectively. In the analysis of repeated albumin measures, similar patterns were observed in cognitive function. All regression coefficients were greater in ε4 carriers than in non-carriers. Our findings suggested that sustained lower serum albumin levels were associated with lower MMSE scores. This observation may be modified by APOE polymorphisms.

Serum sodium in relation to various domains of cognitive function in the elderly US population.

BACKGROUND: Recent evidence suggests that sodium imbalances may be associated with cognitive impairment; however, the association between specific domains of cognition remains unclear. This study examines the association between serum sodium levels and immediate and delayed verbal memory as measured by the CERAD Word Learning Test (CERAD WLT), executive function as measured by the Animal Fluency test (AFT), and sustained attention, working memory, and processing speed as measured by the Digit Symbol Substitution test (DSST) in the elderly population of the US aged 60 and older who participated in the 2011-2014 National Health and Nutrition Examination Surveys (n = 2,541). METHODS: Cognitive function tests were performed by trained interviewers and sodium levels were measured using indirect ion selective electrode methodology. RESULTS: After adjusting for all covariates, quintiles of CERAD WLT scores showed significant positive associations with log-transformed sodium levels (Immediate recall (IR) ß = 4.25 (SE = 1.83, p-value 0.027); Delayed recall (DR) ß = 6.54 (SE = 1.82, p-value 0.001)). Compared to normal sodium levels, hyponatremia was significantly associated with lower CERAD WLT-IR (ß = -0.34, SE = 0.15, p-value 0.035) and CERAD WLT-DR scores (ß -0.48, SE = 0.10, p-value < 0.001) and showed borderline significance with AFT scores (ß = = -0.38, SE = 0.19, p-value 0.052). Hypernatremia did not show any significant relationships with cognitive test scores, compared to normal sodium levels. CONCLUSIONS: Our cross-sectional study showed that lower sodium levels were associated with cognitive change, especially regarding memory and executive function.

Characterization of idiopathic Parkinson's disease subgroups using quantitative gait analysis and corresponding subregional striatal uptake visualized using 18F-FP-CIT positron emission tomography.

BACKGROUND: Gait disturbance is one of the most common symptoms among patients with idiopathic Parkinson's disease (IPD). Nevertheless, Parkinson's disease subtype clustering according to gait characteristics has not been thoroughly investigated. RESEARCH QUESTION: The aim of this study was to identify subgroups according to gait pattern among patients with IPD. METHODS: This study included 88 patients with IPD who underwent 18F-fluorinated-N-3-fluoropropyl-2-ß-carboxymethoxy-3-ß-4-iodophenyl-nortropane positron emission tomography (18F-FP-CIT PET) and three-dimensional gait analysis (3DGA) between January 1, 2014 and December 31, 2016. We performed cluster analysis using temporal-spatial gait variables (gait speed, stride length, cadence, and step width) and divided patients into four subgroups. The kinematic and kinetic gait variables in 3DGA were compared among the four subgroups. Furthermore, we compared the uptake patterns of striatum among the four subgroups using 18F-FP-CIT PET. RESULTS: The patients were clustered into subgroups based on gait hypokinesia and cadence compensation. Group 1 had decreased stride length compensating with increased cadence. Group 2 had decreased stride length without cadence compensation and wider step width. Group 3 had relatively spared stride length with decreased cadence. Group 4 had spared stride length and cadence. The uptake of posterior putamen was significantly decreased in Group 3 compared with Group 4. SIGNIFICANCE: Gait hypokinesia and cadence can help to classify gait patterns in IPD patients. Our subgroups may reflect the different gait patterns in IPD patients.

Gait Patterns in Parkinson's Disease with or without Cognitive Impairment.

BACKGROUND AND PURPOSE: Cognitive and gait disturbance are common symptoms in Parkinson's disease (PD). Although the relationship between cognitive impairment and gait dysfunction in PD has been suggested, specific gait patterns according to cognition are not fully demonstrated yet. Therefore, the aim of this study was to investigate gait patterns in PD patients with or without cognitive impairment. METHODS: We studied 86 patients at an average of 4.8 years after diagnosis of PD. Cognitive impairment was defined as scoring 1.5 standard deviation below age- and education-specific means on the Korean version of the Mini-Mental State Examination (K-MMSE). Three-dimensional gait analysis was conducted for all patients and quantified gait parameters of temporal-spatial data were used. Relationships among cognition, demographic characteristics, clinical features, and gait pattern were evaluated. RESULTS: Cognitive impairment was observed in 41 (47.7%) patients. Compared to patients without cognitive impairment, patients with cognitive impairment displayed reduced gait speed, step length, and stride length. Among K-MMSE subcategories, "registration," "attention/calculation," and "visuospatial function" were significantly associated with speed, step length, and stride length. However, age, disease duration, Hoehn-Yahr (HY) stage, or Unified Parkinson's Disease Rating Scale (UPDRS) motor score was not significantly related to any gait analysis parameter. CONCLUSIONS: Our present study shows that cognitive impairment is associated with slow and short-stepped gait regardless of HY stage or UPDRS motor score, suggesting that cognitive impairment may serve as a surrogate marker of gait disturbance or fall in PD patients.

Efficacy and Safety of a Large Conjunctival Autograft for Recurrent Pterygium.

PURPOSE: To evaluate the efficacy and safety of pterygium excision using a large conjunctival autograft for the treatment of recurrent pterygium. METHODS: The medical records of 120 patients (126 eyes) with recurrent pterygium were reviewed. For each affected eye, pterygium excision with a large conjunctival autograft was performed. The graft was harvested from the superior bulbar area and measured more than 8 × 10 mm in size. Only patients who completed at least six months of follow-up were included. Postoperative clinical outcomes, recurrence rate, and complications were analyzed. Patients with any evidence of recurrence after surgery received a subconjunctival bevacizumab injection. RESULTS: The average patient age was 56.5 ± 10.2 years, and 45 out of 120 patients were male. The mean study follow-up period was 17.7 ± 17.6 months. Most patients were satisfied with the cosmetic outcome. Postoperative visual acuity improved from 0.69 to 0.75 (p < 0.05). Postoperative refractive astigmatism and corneal astigmatism decreased by 0.55 and 2.73 diopters, respectively (p < 0.05). The postoperative recurrence rate was 4.0%, and the average recurrence period was 7.4 ± 0.6 weeks. A subconjunctival injection of 5 mg bevacizumab was performed in cases of recurrence; no progression of the pterygium was observed following the injection. Postoperative complications included 2 cases of conjunctival graft edema in 2 eyes, 5 donor site scars in 5 eyes, 13 pyogenic granulomas in 13 eyes, and a conjunctival epithelial inclusion cyst in 7 eyes. CONCLUSIONS: Pterygium excision with a large conjunctival autograft for the treatment of recurrent pterygium produced an excellent cosmetic outcome, a low recurrence rate, and minimal complications. A subconjunctival bevacizumab injection given in cases of recurrence following surgery might be effective in preventing progression of the pterygium.

Structural and functional improvements due to robot-assisted gait training in the stroke-injured brain.

Robot-assisted gait training (RAGT) can improve walking ability after stroke. Because the underlying mechanisms are still unknown, we analyzed changes in post-stroke injured brains after RAGT. Ten non-ambulatory patients receiving inpatient rehabilitation were examined within 3 months of stroke onset. RAGT consisted of 45min of training, 3days per week. We acquired diffusion tensor imaging (DTI) data before and after 20 sessions of RAGT. Fractional anisotropy (FA) maps were then used to determine neural changes after RAGT. Fugl-Meyer motor assessment of the lower extremity, motricity index of the lower extremity, functional ambulation category, and trunk control tests were also conducted before training, after 10 and 20 RAGT sessions, and at the 1-month follow-up. After RAGT, the supplementary motor area of the unaffected hemisphere showed increased FA, but the internal capsule, substantia nigra, and pedunculopontine nucleus of the affected hemisphere showed decreased FA. All clinical outcome measures improved after 20 sessions of RAGT. Our findings indicate that RAGT can facilitate plasticity in the intact supplementary motor area, but not the injured motor-related areas, in the affected hemisphere.

Unusual FDG-PET Findings in Traumatic Brain Injury; Did Traumatic Brain Injury Provoke Rapid Progression of Alzheimer's Disease?

Traumatic brain injury (TBI) is common, and is often the leading cause of disability and death. Complications after TBI include increased risk for chronic central nervous system disease, such as Alzheimer's disease (AD). However, the pathophysiology relating acute injury to neurodegeneration is unclear. Here we present a case of a patient whose cognition declined after TBI, and whose 18F fluorodeoxyglucose positron emission tomography scan showed an AD pattern.

Hypertension and Neuropsychiatric Symptoms in Patients with Drug-Naïve Alzheimer's Disease.

BACKGROUND AND PURPOSE: Neuropsychiatric symptoms (NPS) such as anxiety, depression, and delusions affect up to 90% of all patients with Alzheimer's disease (AD). NPS is associated with significant caregiver burden and patient distress. Given the severe burden of NPS in AD, it is critical to know potential modifiable risk factors of NPS in AD. This study explores the association between hypertension and NPS in patients with drug-naïve AD. METHODS: We reviewed medical records of 149 patients with AD with (n=80) and without (n=69) hypertension. NPS were assessed using the Korean version of Neuropsychiatric Inventory (K-NPI). Affective, psychotic, and behavior symptom clusters were assessed separately. RESULTS: The total score of K-NPI was not significantly different between patients with AD with and without hypertension. Among K-NPI domains, scores of depression/dysphoria (p=0.045), anxiety (p=0.022), and apathy/indifference (p=0.037) were significantly higher in patients with AD with hypertension. Systolic blood pressure (BP) was associated with higher total K-NPI and affective symptom cluster scores. Diastolic BP was associated with affective symptom cluster scores. CONCLUSIONS: Results suggest that hypertension increases risk of specific NPS in patients with AD. Among NPS, hypertension was associated with affective symptom cluster.

Autologous Platelet-rich Plasma Eye Drops in the Treatment of Recurrent Corneal Erosions.

PURPOSE: To evaluate the effect of platelet-rich plasma (PRP) eye drops in the treatment of recurrent corneal erosions (RCE). METHODS: A total of 47 eyes were included in this retrospective study. Clinical records of 20 consecutive patients with RCE who had been treated with conventional lubricant eye drops (conventional treatment group) from June 2006 to December 2008 and 27 consecutive patients treated with autologous PRP eye drops in addition to lubricant eye drops (PRP eye drops treated group) from January 2009 to September 2014 were reviewed. Major and minor recurrences were recorded and compared between two groups. RESULTS: This study included 31 men and 16 women. The mean age was 44.5 ± 14.5 years (range, 19 to 86 years), and the mean follow-up duration was 14.9 ± 14.4 months (range, 6 to 64 months). Of the 27 cases in the PRP eye drops treated group, there were seven major recurrences in six eyes (22.2%) and ten minor recurrences in seven eyes (25.9%). In contrast, 16 eyes (80.0%) from the 20 patients in the conventional lubricant eye drops treated group had major recurrences, and all patients in this group reported minor recurrences. The mean frequency of recurrence was 0.06 ± 0.08 per month in the PRP eye drops treated group and 0.39 ± 0.24 per month in the conventional treatment group (p = 0.003). No side effects were noted in any of the patients over the follow-up period. CONCLUSIONS: The use of PRP eye drops for the treatment of RCE was shown to be effective in reducing the recurrence rate without any significant complications.

Hydrocephalus in Patient with Multiple System Atrophy: Innocent Bystander or Guilty Party?

BACKGROUND: Normal pressure hydrocephalus (NPH) is a poorly understood condition, which typically presents with the triad of gait disturbance, urinary incontinence and cognitive decline. Diagnosis of NPH is often challenging due to its varied presentation and overlap with other neurodegenerative diseases including multiple system atrophy (MSA). CASE REPORT: A 68-year-old male developed rapidly progressive gait difficulty, urinary incontinence and memory impairment. Neurologic examination showed parkinsonism affecting the right side and impaired postural reflexes. Brain MRI showed enlargement of the ventricles and narrowing of the high convexity cerebrospinal fluid (CSF) spaces with relative dilated Sylvian fissure, the supporting features of NPH. 18F-fluorinated-N-3-fluoropropyl-2-b-carboxymethoxy-3-b-(4-iodophenyl) nortropane (18F-FP-CIT) PET showed decreased FP-CIT binding in the left posterior putamen and 18F-fluorodeoxyglucose PET showed decreased metabolism in the left basal ganglia, consistent with findings of MSA. CSF removal was performed and the symptoms were improved. The patient underwent ventriculo-peritoneal shunt and his gait and cognition improved. CONCLUSIONS: NPH is a potentially treatable neurological disorder. Therefore, it is necessary to consider the possibility of accompanying NPH when hydrocephalus is present in other neurodegenerative diseases.

Differences in Regional Glucose Metabolism of the Brain Measured with F-18-FDG-PET in Patients with Essential Tremor According to Their Response to Beta-Blockers.

OBJECTIVE: In this study, there was an investigation as to whether there is a functional difference in essential tremor (ET), according to responses to beta-blockers, by evaluating regional changes in cerebral glucose metabolism. MATERIALS AND METHODS: Seventeen male patients with ET were recruited and categorized into two groups: 8 that responded to medical therapy (group A); and 9 that did not respond to medical therapy (group B). Eleven age-sex matched healthy control male subjects were also included in this study. All subjects underwent F-18 fluorodeoxyglucose (FDG)-PET, and evaluated for their severity of tremor symptoms, which were measured as a score on the Fahn-Tolosa-Marin tremor rating scale (FTM). The FDG-PET images were analyzed using a statistical parametric mapping program. RESULTS: The mean FTM score 6 months after the initiation of propranolol therapy was significantly lower in group A (18.13 > 8.13), compared with group B (14.67 = 14.67). The glucose metabolism in group A in the left basal ganglia was seen to be decreased, compared with group B. The ET showed a more significantly decreased glucose metabolism in both the fronto-temporo-occipital lobes, precuneus of right parietal lobe, and both cerebellums compared with the healthy controls. CONCLUSION: Essential tremor is caused by electrophysiological disturbances within the cortical-cerebellar networks and degenerative process of the cerebellum. Furthermore, ET may have different pathophysiologies in terms of the origin of disease according to the response to first-line therapy.

Clinical analysis of risk factors contributing to recurrence of pterygium after excision and graft surgery.

AIM: To find the risk factors related to the reproliferation of the pterygial tissue after excision and graft surgery. METHODS: Charts of 130 eyes of 130 patients who had pterygial excision from March 2006 to April 2011 were reviewed. Preoperative pterygium morphology, surgical methods, and adjunctive treatments were statistically analyzed for their relationship with recurrence. RESULTS: During the follow-up period, recurrence was observed in 20 eyes (15.4%). None of the preoperative morphologic features were affected the rate of the recurrence. However, an age < 40y [P =0.085, odds ratio (OR) 3.609, 95% confidence interval (CI) 0.838-15.540] and amniotic membrane graft instead of conjunctival autograft (P =0.002, OR 9.093, 95% CI 2.316-35.698) were statistically significant risk factors for recurrence. Multivariate analysis revealed that intraoperative mitomycin C (MMC) (P=0.072, OR 0.298, 95% CI 0.080-1.115) decreased the rate of recurrence. CONCLUSION: Younger age is a risk factor for reproliferation of pterygial tissue after excision and amniotic membrane transplantation (AMT) are less effective in preventing recurrence of pterygium after excision based on the comparison between conjunctival autograft and AMT. Intraoperative MMC application and conjunctival autograft reduce recurrence.