Deep learning-based binary classification of beta-amyloid plaques using 18 F florapronol PET.

PURPOSE: This study aimed to investigate a deep learning model to classify amyloid plaque deposition in the brain PET images of patients suspected of Alzheimer's disease. METHODS: A retrospective study was conducted on patients who were suspected of having a mild cognitive impairment or dementia, and brain amyloid 18 F florapronol PET/computed tomography images were obtained from 2019 to 2022. Brain PET images were visually assessed by two nuclear medicine specialists, who classified them as either positive or negative. Image rotation was applied for data augmentation. The dataset was split into training and testing sets at a ratio of 8 : 2. For the convolutional neural network (CNN) analysis, stratified k-fold ( k  = 5) cross-validation was applied using training set. Trained model was evaluated using testing set. RESULTS: A total of 175 patients were included in this study. The average age at the time of PET imaging was 70.4 ±â€…9.3 years and included 77 men and 98 women (44.0% and 56.0%, respectively). The visual assessment revealed positivity in 62 patients (35.4%) and negativity in 113 patients (64.6%). After stratified k-fold cross-validation, the CNN model showed an average accuracy of 0.917 ±â€…0.027. The model exhibited an accuracy of 0.914 and an area under the curve of 0.958 in the testing set. These findings affirm the model's high reliability in distinguishing between positive and negative cases. CONCLUSION: The study verifies the potential of the CNN model to classify amyloid positive and negative cases using brain PET images. This model may serve as a supplementary tool to enhance the accuracy of clinical diagnoses.

Task-specific facial dystonia following COVID-19 infection: A case report.

RATIONALE: During the coronavirus disease of 2019 (COVID-19) pandemic, various movement disorders associated with COVID-19 infection have been reported. However, the incidence of dystonia specifically associated with COVID-19 infection has been particularly rare. PATIENT CONCERNS: A 43-year-old male patient presented to the movement disorders clinic with complaints of facial grimacing while chewing and experiencing spasms during nasal breathing. These symptoms appeared 2 weeks after he tested positive for COVID-19. DIAGNOSES: Based on normal diagnostic test results, including brain imaging and blood tests, it was concluded that task-specific facial dystonia following COVID-19 infection. INTERVENTIONS: Despite treatment with clonazepam, trihexyphenidyl, and carbamazepine, his condition did not improve. Subsequently, botulinum toxin injections were administered to the affected facial muscles identified through video analysis. OUTCOMES: Botulinum toxin injections led to a significant improvement in the patient's symptoms. LESSONS: Task-specific dystonia affecting the facial muscles, particularly induced by specific actions such as chewing and nasal breathing, is rare and may represent an atypical post-infectious manifestation of COVID-19.

Potential Novel Genes for Late-Onset Alzheimer's Disease in East-Asian Descent Identified by APOE-Stratified Genome-Wide Association Study.

The present study reports two novel genome-wide significant loci for late-onset Alzheimer's disease (LOAD) identified from APOE ε4 non-carrier subjects of East Asian origin. A genome-wide association study of Alzheimer's disease was performed in 2,291 Korean seniors in the discovery phase, from the Gwangju Alzheimer' and Related Dementias (GARD) cohort study. The study was replicated in a Japanese cohort of 1,956 subjects that suggested two novel susceptible SNPs in two genes: LRIG1 and CACNA1A. This study demonstrates that the discovery of AD-associated variants is feasible in non-European ethnic groups using samples comprising fewer subjects from the more homogeneous genetic background.

Human Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Therapy for Cerebellar Ataxia: A Case Report.

To date, there is no curable treatment option for non-hereditary degenerative cerebellar ataxia. Here we report the case of a patient with sporadic adult-onset ataxia (SAOA) who underwent allogeneic bone marrow-derived mesenchymal stem cell (MSC) therapy via the intrathecal route. A 60-year-old male patient visited our clinic complaining of progressive gait disturbance that commenced two years ago. Upon neurologic examination, the patient exhibited limb dysmetria and gait ataxia. Brain magnetic resonance imaging (MRI) revealed cerebellar atrophy whereas the autonomic function test was normal. The patient was diagnosed with SAOA. The medications that were initially prescribed had no significant effects on the course of this disease and the symptoms deteriorated progressively. At the age of 64, the patient was treated with allogeneic bone marrow-derived MSC therapy. The subsequent K-SARA (Korean version of the Scale for the Assessment and Rating of Ataxia) scores demonstrated a distinct improvement up until 10 months post-administration. No adverse events were reported. The improved post-treatment K-SARA scores may suggest that the MSC therapy can have a neuroprotective effect and that stem cell therapy may serve as a potential therapeutic option for degenerative cerebellar ataxia.

Increased plasma levels of chitinase 3-like 1 (CHI3L1) protein in patients with idiopathic normal-pressure hydrocephalus.

Idiopathic normal-pressure hydrocephalus (iNPH) is an uncommon neurological disorder with no known pathological hallmarks. INPH may share common degenerative pathways with other neurological diseases, such as Alzheimer's disease (AD). However, the reversible properties of iNPH may share differing pathophysiological mechanisms with other diseases. This study aimed at assessing the diagnostic value of plasma chitinase 3-like 1 (CHI3L1) protein levels as a disease-specific biomarker for iNPH. We selected both iNPH and AD patients as well as normal and disease control subjects from an enrolled dementia registry. A total of 121 AD, 80 iNPH, 13 idiopathic Parkinson's disease, and 23 mild cognitive impairment patients with 83 healthy controls were included in the final analysis. The Aß42, total tau, and phosphorylated tau levels within the cerebrospinal fluid, as well as plasma levels of CHI3L1, were measured using commercially available enzyme-linked immunosorbent assay kits. CHI3L1 levels for iNPH patients were higher than those of the other groups. Analysis of covariance adjusting for age showed significantly increased plasma CHI3L1 levels in iNPH patients than in the controls (p < 0.001). CHI3L1 plasma levels may be useful in differentiating iNPH patients from healthy individuals.

Lipopolysaccharide administration for a mouse model of cerebellar ataxia with neuroinflammation.

Most cerebellar ataxias (CAs) are incurable neurological disorders, resulting in a lack of voluntary control by inflamed or damaged cerebellum. Although CA can be either directly or indirectly related to cerebellar inflammation, there is no suitable animal model of CA with neuroinflammation. In this study, we evaluated the utility of an intracerebellar injection of lipopolysaccharide (LPS) to generate an animal model of inflammatory CA. We observed that LPS administration induced the expression of pro-inflammatory molecules following activation of glial cells. In addition, the administration of LPS resulted in apoptotic Purkinje cell death and induced abnormal locomotor activities, such as impaired motor coordination and abnormal hindlimb clasping posture. Our results suggest that intracerebellar LPS administration in experimental animals may be useful for studying the inflammatory component of CA.

Gliome database: a comprehensive web-based tool to access and analyze glia secretome data.

Glial cells are phenotypically heterogeneous non-neuronal components of the central and peripheral nervous systems. These cells are endowed with diverse functions and molecular machineries to detect and regulate neuronal or their own activities by various secreted mediators, such as proteinaceous factors. In particular, glia-secreted proteins form a basis of a complex network of glia-neuron or glia-glia interactions in health and diseases. In recent years, the analysis and profiling of glial secretomes have raised new expectations for the diagnosis and treatment of neurological disorders due to the vital role of glia in numerous physiological or pathological processes of the nervous system. However, there is no online database of glia-secreted proteins available to facilitate glial research. Here, we developed a user-friendly 'Gliome' database (available at www.gliome.org), a web-based tool to access and analyze glia-secreted proteins. The database provides a vast collection of information on 3293 proteins that are released from glia of multiple species and have been reported to have differential functions under diverse experimental conditions. It contains a web-based interface with the following four key features regarding glia-secreted proteins: (i) fundamental information, such as signal peptide, SecretomeP value, functions and Gene Ontology category; (ii) differential expression patterns under distinct experimental conditions; (iii) disease association; and (iv) interacting proteins. In conclusion, the Gliome database is a comprehensive web-based tool to access and analyze glia-secretome data obtained from diverse experimental settings, whereby it may facilitate the integration of bioinformatics into glial research.

CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimer's disease as an indicator of tau phosphorylation.

BACKGROUND: Recently, several studies suggested potential involvements of α-synuclein in Alzheimer's disease (AD) pathophysiology. Higher concentrations of α-synuclein were reported in cerebrospinal fluid (CSF) of AD patients with a positive correlation towards CSF tau, indicating its possible role in AD. We analyzed the CSF biomarkers to verify whether α-synuclein could be an additional supported biomarker in AD diagnosis. METHODS: In this cross-sectional study, CSF samples of 71 early-onset AD, 34 late-onset AD, 11 mild cognitive impairment, 17 subjective cognitive decline, 45 Parkinson's disease, and 32 healthy control (HC) were collected. CSF amyloid-ß1-42 (A), total tau (N), and phosphorylated tau181 (T) were measured by commercial ELISA kits, and in-house ELISA kit was developed to quantify α-synuclein. The cognitive assessments and amyloid-PET imaging were also performed. RESULTS: CSF α-synuclein manifested a tendency to increase in AD and to decreased in Parkinson's disease compared to HC. The equilibrium states of total tau and α-synuclein concentrations were changed significantly in AD, and the ratio of total tau/α-synuclein (N/αS) was dramatically increased in AD than HC. Remarkably, N/αS revealed a strong positive correlation with tau phosphorylation rate. Also, the combination of N/αS with amyloid-ß1-42/phosphorylated tau181 ratio had the best diagnosis performance (AUC = 0.956, sensitivity = 96%, specificity = 87%). In concordance analysis, N/αS showed the higher diagnostic agreement with amyloid-ß1-42 and amyloid-PET. Analysis of biomarker profiling with N/αS had distinctive characteristics and clustering of each group. Especially, among the group of suspected non-Alzheimer's disease pathophysiology, all A-T+N+ patients with N/αS+ were reintegrated into AD. CONCLUSIONS: The high correlation of α-synuclein with tau and the elevated N/αS in AD supported the involvement of α-synuclein in AD pathophysiology. Importantly, N/αS improved the diagnostic performance, confirming the needs of incorporating α-synuclein as a biomarker for neurodegenerative disorders. The incorporation of a biomarker group [N/αS] could contribute to provide better understanding and diagnosis of neurodegenerative disorders.

Lower Glucose Level Associated With Increased Risk for Post-Dural Puncture Headache.

OBJECTIVE AND BACKGROUND: Post-dural puncture headache is the most common significant adverse event following lumbar puncture. In this study, we investigated the possible systemic factors associated with risk for post-dural puncture headache (PDPH). METHODS: We performed a retrospective cohort study in 969 patients who underwent diagnostic lumbar puncture following a standardized protocol. We compared the clinical and laboratory profiles of the post-dural puncture headache group and non-headache group. We also identified independent factors associated with the incidence of post-dural puncture headache. RESULTS: A total of 48 patients (5%) reported headache; 12 of these patients (25%) received a therapeutic epidural blood patch and the remaining 36 patients improved with conservative treatment. After adjusting for other variables that could be related to PDPH, we found that the development of post lumbar puncture headache was independently associated with age (OR: 0.97, 95% CI: 0.95-0.99, P = .001) and serum glucose levels (OR: 0.98, 95% CI: 0.97-0.99, P = .008).When the patients were classified by age, serum glucose levels were persistently lower in patients with PDPH vs those patients without PDPH in all age groups, with more clearly significant differences observed in the elderly (age <30 years, 103.4 mg/dL vs 106.3 mg/dL, P = .716; >60 years, 111.8 mg/dL vs 137.3 mg/dL, P = .023). CONCLUSIONS: Low glucose levels were inversely associated with risk for post-dural puncture headache. Patients with low serum glucose should be carefully monitored for headache after lumbar puncture.

Characterization of Mesenchymal Stem Cells Derived from Patients with Cerebellar Ataxia: Downregulation of the Anti-Inflammatory Secretome Profile.

Mesenchymal stem cell (MSC) therapy is a promising alternative approach for the treatment of neurodegenerative diseases, according to its neuroprotective and immunomodulatory potential. Despite numerous clinical trials involving autologous MSCs, their outcomes have often been unsuccessful. Several reports have indicated that MSCs from patients have low capacities in terms of the secretion of neurotrophic or anti-inflammatory factors, which might be associated with cell senescence or disease severity. Therefore, a new strategy to improve their capacities is required for optimal efficacy of autologous MSC therapy. In this study, we compared the secretory potential of MSCs among cerebellar ataxia patients (CA-MSCs) and healthy individuals (H-MSCs). Our results, including secretome analysis findings, revealed that CA-MSCs have lower capacities in terms of proliferation, oxidative stress response, motility, and immunomodulatory functions when compared with H-MSCs. The functional differences were validated in a scratch wound healing assay and neuron-glia co-cultures. In addition, the neuroprotective and immunoregulatory protein follistatin-like 1 (FSTL1) was identified as one of the downregulated proteins in the CA-MSC secretome, with suppressive effects on proinflammatory microglial activation. Our study findings suggest that targeting aspects of the downregulated anti-inflammatory secretome, such as FSTL1, might improve the efficacy of autologous MSC therapy for CA.

Early-Phase 18F-Florbetaben PET as an Alternative Modality for 18F-FDG PET.

PURPOSE: Based on the possibility that early-phase florbetaben (E-FBB) brain PET can be a surrogate for brain perfusion imaging, we conducted this study to investigate the clinical utility of E-FBB PET instead of F-FDG brain PET. MATERIALS AND METHODS: This prospective study included 35 patients with clinical suspicion of cognitive decline or dementia and 5 healthy controls. Brain MRI, E-FBB PET, late-phase FBB PET, and FDG PET were acquired. The regional SUV ratios (SUVRs) were calculated by cortical surface region of interest analysis using individual MRI, and relationship between E-FBB and FDG PET was analyzed. All PET scans were scored and analyzed as per visual scoring system, which represent tracer uptake abnormality. Moreover, uptake patterns were analyzed to determine the disease. RESULTS: Among the 40 subjects, 19 were amyloid-positive and 21 were amyloid-negative on late-phase FBB PET. Cortical surface region of interest analysis conducted for comparing between E-FBB and FDG PET revealed significant correlations (P < 0.0001) for regional SUVR among all brain regions; however, the SUVR values of FDG PET were statistically higher than those of E-FBB PET. Similarly, although the visually rated scores for E-FBB and FDG PET showed significant correlation (P < 0.0001), it was considered that the tracer uptake was more severely decreased for FDG PET. The disease types, specified by E-FBB and FDG PET, were statistically correlated. CONCLUSIONS: E-FBB PET could potentially be a useful biomarker for the diagnosis of dementia in place of FDG PET. Nevertheless, the severity of the disease was more accurately determined by FDG PET.

Quantitative Gait Analysis and Cerebrospinal Fluid Tap Test for Idiopathic Normal-pressure Hydrocephalus.

We investigated gait performance utilizing a quantitative gait analysis for 2 groups: (1) idiopathic normal-pressure hydrocephalus (INPH) patients who had a positive response to the cerebrospinal fluid tap test (CSFTT) and (2) healthy controls. The aims of the study were (1) to analyze the characteristics of gait features, (2) to characterize changes in gait parameters before and after the CSFTT, and (3) to determine whether there was any relationship between stride time and stride length variability and Frontal Assessment Battery (FAB) scores in INPH patients. Twenty-three INPH patients and 17 healthy controls were included in this study. Compared with healthy controls, the gait of INPH patients was characterized by lower velocity, shorter stride length, and more broad-based gait. Patients with INPH had a longer stance phase with increased double-limb support. Variability in stride time and stride length was increased in INPH patients. Stride time and stride length variability were correlated with FAB score. After the CSFTT, gait velocity, stride length, and step width significantly improved. There were significant decreases in stride time and stride length variability. These results suggest that the CSFTT for INPH patients might improve the so-called balance-related gait parameter (ie, step width) as well. Stride time and stride length variability also responded to the CSFTT. Association between FAB scores and both stride time and stride length variability suggests involvement of similar circuits producing gait variability and frontal lobe functions in INPH patients.

APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE ε4 on Alzheimer's Disease Risk in a Multiracial Sample.

Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10-94; GT: OR = 15.87, p = 2.62 × 10-9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10-108; GT: OR = 12.63, p = 3.44 × 10-64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.

Levodopa-induced respiratory dysfunction confirmed by levodopa challenge test: A case report.

INTRODUCTION: Parkinson disease is associated with various nonmotor symptoms, including rare respiratory dysfunction events. However, patients with Parkinson disease often have comorbid medical problems, such as respiratory distress, and differentiating nonmotor symptoms can be difficult. CASE PRESENTATION: A 78-year-old male presented with repetitive shortness of breath. He was diagnosed with Parkinson disease and chronic obstructive pulmonary disease (COPD) several years prior. His symptoms were ambiguous between acute COPD exacerbation and levodopa-related nonmotor symptoms of Parkinson disease. To clarify the underlying cause, we performed the levodopa challenge test. After the patient complained of dyspnea following levodopa administration, levodopa-induced respiratory dysfunction was diagnosed. After adjusting antiparkinson medication, the patient's respiratory symptoms gradually improved. CONCLUSION: Respiratory dysfunction as a nonmotor symptom of Parkinson disease can be caused by levodopa medication. To determine whether the symptoms are induced by levodopa, the levodopa challenge test may be useful in clarifying symptoms related to antiparkinson medication.

Amyloid Deposits and Idiopathic Normal-Pressure Hydrocephalus: An 18F-Florbetaben Study.

BACKGROUND: The first aim of our study was to determine whether cortical 18F-florbetaben retention was different between healthy controls and idiopathic normal-pressure hydrocephalus (INPH) patients. Our second aim was to investigate whether there were any relationships between 18F-florbetaben retention and either hippocampal volume or clinical symptoms in INPH patients. METHODS: Seventeen patients diagnosed with INPH and 8 healthy controls underwent studies with magnetic resonance imaging and 18F-florbetaben positron emission tomography imaging. RESULTS: Automated region-of-interest analysis showed significant increases in 18F-florbetaben uptake in several brain regions in INPH patients compared to control subjects, with especially remarkable increases in the frontal (bilateral), parietal (bilateral), and occipital (bilateral) cortices. In the INPH group, right hippocampal volume was found to be negatively correlated with right frontal 18F-florbetaben retention. Korean-Mini Mental State Examination scores negatively correlated with right occipital 18F-florbetaben retention. Higher 18F-florbetaben retention correlated significantly with a higher Clinical Dementia Rating Scale score in the right occipital cortex. CONCLUSIONS: Our results indicate that INPH might be a disease exhibiting a characteristic pattern of cortical 18F-florbetaben retention. 18F-florbetaben retention in the frontal cortex may be related to hippocampal neuronal degeneration. Our findings may also help us understand the potential pathophysiology of cognitive impairments associated with INPH.

Serum methylmalonic acid correlates with neuropathic pain in idiopathic Parkinson's disease.

Recent studies have shown a relatively higher prevalence of peripheral neuropathy in idiopathic Parkinson's disease (IPD). The hypothesis is that prolonged levodopa exposure causes vitamin B12 deficiency, which leads to peripheral neuropathy. The aim of our study was to find the relationship between vitamin B12 and its precursor methylmalonic acid (MMA) in IPD patients with neuropathic pain. We performed a cross-sectional study by enrolling consecutive 43 patients who were clinically tested positive for F-18 FP-CIT PET and 15 patients were diagnosed with peripheral neuropathy according to the Toronto clinical scoring system (TCSS). The severity of neuropathic pain was evaluated using total neuropathy scale, revised (TNSr), and Korean Neuropathic Pain Questionnaire (KNPQ). The correlations between age, IPD duration, levodopa equivalent dose (LED), UPDRS III, vitamin B12, MMA, and homocysteine levels were assessed. The prevalence rate of peripheral neuropathy in IPD patients was 35%. Among the serums assessed, MMA levels showed a positive correlation to TNSr and KNPQ in the IPD patients with peripheral neuropathy (TNSr r = 0.882, p < 0.001, KNPQ r = 0.710, p = 0.004), while Vitamin B12 and homocysteine showed no statistically significant correlation. Our study showed a prevalence of peripheral neuropathy in 35% of Korean IPD patients. The serum MMA positively correlated with the severity of neuropathic pain and this can be used as a useful marker in assessment of peripheral neuropathy in Parkinson's disease.

Astrocyte-derived lipocalin-2 mediates hippocampal damage and cognitive deficits in experimental models of vascular dementia.

Lipocalin-2 (LCN2) has diverse functions in multiple pathophysiological conditions; however, its pathogenic role in vascular dementia (VaD) is unknown. Here, we investigated the role of LCN2 in VaD using rodent models of global cerebral ischemia and hypoperfusion with cognitive impairment and neuroinflammation. Mice subjected to transient bilateral common carotid artery occlusion (tBCCAo) for 50 min showed neuronal death and gliosis in the hippocampus at 7 days post-tBCCAo. LCN2 expression was observed predominantly in the hippocampal astrocytes, whereas its receptor was mainly detected in neurons, microglia, and astrocytes. Furthermore, Lcn2-deficient mice, compared with wild-type animals, showed significantly weaker CA1 neuronal loss, cognitive decline, white matter damage, blood-brain barrier permeability, glial activation, and proinflammatory cytokine production in the hippocampus after tBCCAo. Lcn2 deficiency also attenuated hippocampal neuronal death and cognitive decline at 30 days after unilateral common carotid artery occlusion (UCCAo). Furthermore, intracerebroventricular (i.c.v) injection of recombinant LCN2 protein elicited CA1-neuronal death and a cognitive deficit. Our studies using cultured glia and hippocampal neurons supported the decisive role of LCN2 in hippocampal neurotoxicity and microglial activation, and the role of the HIF-1α-LCN2-VEGFA axis of astrocytes in vascular injury. Additionally, plasma levels of LCN2 were significantly higher in patients with VaD than in the healthy control subjects. These results indicate that hippocampal damage and cognitive impairment are mediated by LCN2 secreted from reactive astrocytes in VaD.

Frontal Assessment Battery and Cerebrospinal Fluid Tap Test in Idiopathic Normal-Pressure Hydrocephalus.

BACKGROUND AND PURPOSE: Our aim in this study was to assess whether the frontal assessment battery (FAB) could contribute to the differential diagnosis of cerebrospinal fluid tap test (CSFTT) responders and nonresponders with the hypothesis that CSFTT nonresponders had greater frontal lobe dysfunction. We also explored whether a relationship exists between FAB scores and gait disturbance in idiopathic normal-pressure hydrocephalus (INPH) patients. METHODS: INPH subjects were selected in a consecutive order from a prospectively enrolled INPH registry. Fifty-one INPH patients constituted the final sample for analysis. RESULTS: Logistic regression analysis using the FAB score as independent variable showed a significant influence of the FAB on the differential diagnosis of CSFTT responders and nonresponders (p = 0.025; OR 1.186; 95% CI 1.022-1.377). The FAB scores were negatively correlated with the Timed Up and Go test score (r = -0.382; p = 0.007), 10-meter walking test score (r = -0.351; p = 0.014), Gait Status Scale score (r = -0.382; p = 0.007), and INPH Grading Scale gait score (r = -0.370; p = 0.009). CONCLUSIONS: Our findings may indicate a possibility for considering FAB scores in patients with ventriculomegaly as potential cognitive markers for the prediction of CSFTT response. Association between gait function and FAB scores suggests the involvement of similar circuits producing gait symptom and frontal lobe functions in INPH.

Smart Gait-Aid Glasses for Parkinson's Disease Patients.

Parkinson's disease (PD) is a chronic progressive disease caused by loss of dopaminergic neurons in the substantia nigra, degenerating the nervous system of a patient over time. Freezing of gait (FOG), which is a form of akinesia, is a symptom of PD. Meanwhile, recent studies show that the gait of PD patients experiencing FOG can be significantly improved by providing the regular visual or auditory patterns for the patients. In this paper, we propose a gait-aid system built upon smart glasses. Our system continuously monitors the gait and so on of a PD patient to detect FOG, and upon detection of FOG it projects visual patterns on the glasses as if the patterns were actually on the floor. Conducting experiments involving ten PD patients, we demonstrate that our system achieves the accuracy of 92.86 % in detecting FOG episodes and that it improves the gait speed and stride length of PD patients by 15.3  âˆ¼  37.2% and 18.7   âˆ¼  31.7%, respectively.