Regional Comparison of Imaging Biomarkers in the Striatum between Early- and Late-onset Alzheimer’s Disease

Striatal changes in the pathogenesis of Alzheimer’s disease (AD) is not fully understood yet. We compared structural and functional image differences in the striatum between patients with early onset AD (EOAD) and late onset AD (LOAD) to investigate whether EOAD harbors autosomal dominant AD like imaging findings. The clinical, neuropsychological and neuroimaging biomarkers of 77 probable AD patients and 107 elderly subjects with normal cognition (NC) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI)-2 dataset were analyzed. Enrolled each subject completed a 3-Tesla MRI, baseline 18F-FDG-PET, and baseline 18F-AV-45 (Florbetapir) amyloid PET studies. AD patients were divided into two groups based on the onset age of clinical symptoms (EOAD <65 yrs; LOAD ≥65 yrs). A standardized uptake value ratio of the striatum and subcortical structures was obtained from both amyloid and FDG-PET scans. Structural MR imaging analysis was conducted using a parametric boundary description protocol, SPHARM-PDM. Of the 77 AD patients, 18 were EOAD and 59 were LOAD. Except for age of symptom onset, there were no statistically significant differences between the groups in demographics and detailed neuropsychological test results. 18F-AV-45 amyloid PET showed marked β-amyloid accumulation in the bilateral caudate nucleus and left pallidum in the EOAD group. Intriguingly, the caudate nucleus and putamen showed maintained glucose metabolism in the EOAD group compared to the LOAD group. Our image findings in the striatum of EOAD patients suggest that sporadic EOAD may share some pathophysiological changes noted in autosomal dominant AD.

18 FTHK-5351 PET Patterns in Patients With Alzheimer’s Disease and Negative Amyloid PET Findings

Background@#and Purpose Alzheimer’s disease (AD) does not always mean amyloid positivity. [ 18 F]THK-5351 has been shown to be able to detect reactive astrogliosis as well as tau accompanied by neurodegenerative changes. We evaluated the [ 18 F]THK-5351 retention patterns in positron-emission tomography (PET) and the clinical characteristics of patients clinically diagnosed with AD dementia who had negative amyloid PET findings. @*Methods@#We performed 3.0-T magnetic resonance imaging, [ 18 F]THK-5351 PET, and amyloid PET in 164 patients with AD dementia. Amyloid PET was visually scored as positive or negative. [ 18 F]THK-5351 PET were visually classified as having an intratemporal or extratemporal spread pattern. @*Results@#The 164 patients included 23 (14.0%) who were amyloid-negative (age 74.9±8.3 years, mean±standard deviation; 9 males, 14 females). Amyloid-negative patients were older, had a higher prevalence of diabetes mellitus, and had better visuospatial and memory functions. The frequency of the apolipoprotein E ε4 allele was higher and the hippocampal volume was smaller in amyloid-positive patients. [ 18 F]THK-5351 uptake patterns of the amyloid-negative patients were classified into intratemporal spread (n=10) and extratemporal spread (n=13).Neuropsychological test results did not differ significantly between these two groups. The standardized uptake value ratio of [ 18 F]THK-5351 was higher in the extratemporal spread group (2.01±0.26 vs. 1.61±0.15, p=0.001). After 1 year, Mini Mental State Examination (MMSE) scores decreased significantly in the extratemporal spread group (-3.5±3.2, p=0.006) but not in the intratemporal spread group (-0.5±2.8, p=0.916). The diagnosis remained as AD (n=5, 50%) or changed to other diagnoses (n=5, 50%) in the intratemporal group, whereas it remained as AD (n=8, 61.5%) or changed to frontotemporal dementia (n=4, 30.8%) and other diagnoses (n=1, 7.7%) in the extratemporal spread group. @*Conclusions@#Approximately 70% of the patients with amyloid-negative AD showed abnormal [ 18 F]THK-5351 retention. MMSE scores deteriorated rapidly in the patients with an extratemporal spread pattern.

Patterns of Cerebrospinal Fluid Biomarkers and Amyloid Positron Emission Tomography in a Patient with Cerebral Amyloid Angiopathy-Related Inflammation

Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a distinct subset of cerebral amyloid angiopathy characterized by the auto-inflammatory response to amyloid-laden small arteries of cerebral cortex and leptomeninges. Clinical features include cognitive-behavioral change, headache, focal neurologic deficits and seizure. Because anti-inflammatory treatments can rapidly relieve neurologic symptoms, early diagnosis is critical. Herein, we report a CAA-RI case with distinct laboratory findings of a decreased cerebrospinal fluid amyloid beta 1-42 level and relatively reduced florbetaben uptake in the focal inflammatory lesion during the acute phase of CAA-RI.

Patterns of Cerebrospinal Fluid Biomarkers and Amyloid Positron Emission Tomography in a Patient with Cerebral Amyloid Angiopathy-Related Inflammation

Cerebral amyloid angiopathy-related inflammation (CAA-RI) is a distinct subset of cerebral amyloid angiopathy characterized by the auto-inflammatory response to amyloid-laden small arteries of cerebral cortex and leptomeninges. Clinical features include cognitive-behavioral change, headache, focal neurologic deficits and seizure. Because anti-inflammatory treatments can rapidly relieve neurologic symptoms, early diagnosis is critical. Herein, we report a CAA-RI case with distinct laboratory findings of a decreased cerebrospinal fluid amyloid beta 1-42 level and relatively reduced florbetaben uptake in the focal inflammatory lesion during the acute phase of CAA-RI.

Degradation Properties of a Bi-layered Crosslinked Collagen Membrane for Localized Bone Regeneration: In Vitro and In Vivo Study

Purpose@#(i) To evaluate the biologic properties of a bi-layered 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride-cross-linked collagen membrane (CCM) In Vitro. (ii) To assess the efficacy of CCM for localized bone regeneration In Vivo. @*Materials and Methods@#Biodegradation of CCM compared to a native collagen membrane (NCM) was assessed In Vitro. In Vivo, twelve male New Zealand White rabbits were used. Four calvarial, circular defects (diameter 8 mm) were created in each animal. The sites were randomly allocated to i) CCM+biphasic calcium phosphate (BCP) (CCM-BCP group), ii) CCM alone (CCM), iii) BCP alone (BCP) and, iv) negative control (control). Animals were sacrificed at 2 (n=6) and 8 weeks (n=6). Outcome measures included: micro-computed tomography (μCT) analysis (total augmented volume [TAV], new bone volume) and histomorphometry (total augmented area [TAA], newly formed bone, remaining membrane thickness [RMT]).Result: CCM was more resistant to degradation than NCM. μCT analysis showed CCM-BCP (196.43±25.30 mm 3 ) and BCP (206.23±39.13 mm 3 ) groups had significantly (P<0.01) larger TAV than the control (149.72±12.28 mm 3 ) after 8 weeks. Histomorphometrically, CCM-BCP group (17.75±5.97 mm 2 ) had significantly (P<0.01) greater TAA compared to the CCM group (7.74±2.25 mm 2 ) and the control (8.13±1.81 mm 2 ) after 8 weeks. After 8 weeks, RMT was reduced by 67%. @*Conclusion@#CCM can be a favorable choice of barrier membrane when performing guided bone regeneration (GBR) in localized bone defects. CCM has better resistance to degradation than the natural collagen membrane, In Vitro. In Vivo, CCM provides an advantageous integration of prolonged barrier function and biocompatibility for GBR.

Severe periodontitis with tooth loss as a modifiable risk factor for the development of Alzheimer, vascular, and mixed dementia: National Health Insurance Service-National Health Screening Retrospective Cohort 2002–2015

Purpose@#The purpose of this study was to evaluate severe periodontitis with tooth loss as a modifiable risk factor for Alzheimer dementia (AD), vascular dementia (VaD), and mixed dementia (MD) using the National Health Insurance Service-National Health Screening Retrospective Cohort database with long-term follow-up over 14 years. @*Methods@#Multivariate Cox hazards regression analysis was applied to a longitudinal retrospective database, which was updated in 2018, to evaluate the association between severe periodontitis with few remaining teeth and dementia after adjusting for potential risk factors, including sociodemographic factors and comorbid diseases. @*Results@#Among 514,866 individuals in South Korea, 237,940 (46.2%) participants satisfying the inclusion criteria were selected. A total of 10,115 age- and sex-matched participants with severe periodontitis and 10,115 periodontally healthy participants were randomly selected and evenly assigned. The results showed that the risks of AD (hazard ratio [HR], 1.08), VaD (HR, 1.24), and MD (HR, 1.16) were significantly higher in patients with severe periodontitis with 1–9 remaining teeth after adjustment for sociodemographic factors, anthropomorphic measurements, lifestyle factors, and comorbidities. @*Conclusions@#Severe periodontitis with few remaining teeth (1–9) may be considered a modifiable risk factor for the development of AD, VaD, and MD in Korean adults.

Severe periodontitis with tooth loss as a modifiable risk factor for the development of Alzheimer, vascular, and mixed dementia: National Health Insurance Service-National Health Screening Retrospective Cohort 2002–2015

Purpose@#The purpose of this study was to evaluate severe periodontitis with tooth loss as a modifiable risk factor for Alzheimer dementia (AD), vascular dementia (VaD), and mixed dementia (MD) using the National Health Insurance Service-National Health Screening Retrospective Cohort database with long-term follow-up over 14 years. @*Methods@#Multivariate Cox hazards regression analysis was applied to a longitudinal retrospective database, which was updated in 2018, to evaluate the association between severe periodontitis with few remaining teeth and dementia after adjusting for potential risk factors, including sociodemographic factors and comorbid diseases. @*Results@#Among 514,866 individuals in South Korea, 237,940 (46.2%) participants satisfying the inclusion criteria were selected. A total of 10,115 age- and sex-matched participants with severe periodontitis and 10,115 periodontally healthy participants were randomly selected and evenly assigned. The results showed that the risks of AD (hazard ratio [HR], 1.08), VaD (HR, 1.24), and MD (HR, 1.16) were significantly higher in patients with severe periodontitis with 1–9 remaining teeth after adjustment for sociodemographic factors, anthropomorphic measurements, lifestyle factors, and comorbidities. @*Conclusions@#Severe periodontitis with few remaining teeth (1–9) may be considered a modifiable risk factor for the development of AD, VaD, and MD in Korean adults.

Erratum to: A Multicenter, Randomized Clinical Trial to Assess the Efficacy of a Therapeutic Intervention Program for Caregivers of People with Dementia

Efficacies of Cognitive Interventions in the Elderly with Subjective Cognitive Decline: A Prospective, Three-Arm, Controlled Trial

Background@#and PurposeA cognitive intervention (CI) is thought to improve cognition and delay cognitive decline via neuronal plasticity and cognitive resilience. Subjective cognitive decline (SCD) might be the first symptomatic stage of Alzheimer's disease, but few studies have examined the beneficial effect of CIs in SCD. We aimed to determine the efficacy of a 12-week, small-group-based, multidomain CI in elderly patients with SCD. @*Methods@#Participants diagnosed with SCD (aged 55–75 years) were consecutively allocated to three groups: group 1, which received group-based CI implementation with lifestyle modifications; group 2, which received home-based lifestyle modifications without CI; and group 3, in which no action was taken. The primary outcome variables were the scores on computerized tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB). The secondary outcomes included scores on tests evaluating general cognition, memory, visuospatial, and executive functions, as well as scores for the quality of life (QoL), anxiety, depression, and degree of subjective complaints. Changes in scores during the study period were compared between groups. @*Results@#The study was completed by 56 SCD participants. The baseline characteristics did not differ among the groups. The primary outcomes (CANTAB scores) did not differ among the groups. However, the outcomes for phonemic word fluency, verbal memory, QoL, and mood were better for group 1 than for the other two groups. Improvements in verbal memory function and executive function were related to the baseline cognitive scores and group differences. @*Conclusions@#CI in SCD seems to be partially beneficial for executive function, memory, QoL, and mood, suggesting that CI is a useful nonpharmacological treatment option in this population.

Management of peri-implantitis associated with tear-like implant fracture: case reports

Implant fracture is rare, but one of the most serious problem in implantation. Treatment of implant fracture can be different according to the extent of the fracture and on the state of the surrounding prosthetic restoration. Maintaining or submerging implant after treatment of peri-implantitis can be useful options for cases of tear-like fracture on the coronal area of an implant.

A Case of a Patient Who Presented with Rapidly Progressive Dementia and Capricious RT-QuIC Results

No abstract available.

Three-dimensional observations of the incisive foramen on cone-beam computed tomography image analysis

PURPOSE: The purpose of this study was to utilize cone-beam computed tomography (CBCT) image analysis to obtain anatomical information related to the morphology of the incisive foramen to provide useful data regarding implant placement and clinical procedures such as anesthesia.METHODS: The study included 167 patients who underwent CBCT scans over 20 years. Three components were measured: 1) the anteroposterior and mediolateral diameter of the incisive foramen, 2) the horizontal bone thickness anterior to the incisive foramen, and 3) the vertical bone height coronal to the incisive foramen. All measurements were expressed as mean±standard deviation and were analyzed by a single examiner.RESULTS: The anteroposterior diameter of the incisive foramen was wider than the mediolateral diameter (P<0.001). The diameter of the incisive foramen in patients in whom the central incisors were present was smaller than that in those in whom at least one central incisor was absent, but no statistically significant difference between the groups was observed. The horizontal bone thickness in the patients with central incisors was statistically significantly larger than that in the patients without at least one central incisor (P<0.001). The same pattern was observed with regard to vertical height, but that difference was not statistically significant.CONCLUSIONS: The buccal bone thickness anterior to the incisive foramen was significantly decreased after central incisor loss. It is necessary to identify the morphology of the bone and the location of the incisive foramen via CBCT to avoid invasion of the incisive foramen and nasopalatine canal.

Risk Factors of Behavioral and Psychological Symptoms in Patients with Alzheimer Disease: The Clinical Research of Dementia of South Korea Study / 가정의학회지

BACKGROUND: Few studies have evaluated risk factors for behavioral and psychological symptoms of dementia at the initial assessment for Alzheimer disease in large patient samples. In this study, the factors influencing Alzheimer disease were examined using the Clinical Research of Dementia of South Korea data. METHODS: This cross-sectional study was conducted using data of 1,128 patients with Alzheimer disease. The behavioral and psychological symptoms of dementia were examined using the Korean version of the Neuropsychiatric Inventory. Demographic characteristics, health-related behavior, neuropsychological tests, comorbidities, blood test results, and caregiver characteristics were assessed. Median logistic regression analysis with adjustment for covariates was conducted. RESULTS: The behavioral and psychological symptoms of dementia were negatively associated with memory (P=0.022) and frontal/executive (P < 0.001) function in the Seoul Neuropsychological Screening Battery-dementia, Barthel Index for Activities of Daily Living (P < 0.001), Korean version of the Mini-Mental State Examination score (P=0.003), and caregiver age (P=0.005) after adjustment for confounding factors, and positively associated with the Seoul-Instrumental Activities of Daily Living score (P < 0.001), Clinical Dementia Rating Sum of Box (P < 0.001), Global Deterioration Scale score (P < 0.001), abnormality of free T4 level (P < 0.001), anemia (P < 0.001), and family history of stroke (P=0.001). Patients with female caregivers exhibited more severe behavioral and psychological symptoms of dementia than those with male caregivers. CONCLUSION: Behavioral and psychological symptoms of dementia in Alzheimer disease patients were associated with various risk factors including the inability to live independently and Alzheimer disease severity. These findings suggest that prevention and treatment strategies for the behavioral and psychological symptoms of dementia should be comprehensive.

Qualitative Comparison of Semantic Memory Impairment in Patients with Amnestic Mild Cognitive Impairment Based on β-Amyloid Status

BACKGROUND AND PURPOSE: Semantic memory remains more stable than episodic memory across the lifespan, which makes it potentially useful as a marker for distinguishing pathological aging from normal senescence. To obtain a better understanding of the transitional stage evolving into Alzheimer's dementia (AD), we focused on the amnestic mild cognitive impairment (aMCI) stage stratified based on β-amyloid (Aβ) pathology. METHODS: We analyzed the raw data from Korean version of the Boston Naming Test (K-BNT) and the Controlled Oral Word Association Test (COWAT). For K-BNT, the frequencies of six error types and accuracy rates were evaluated. For a qualitative assessment of the COWAT, we computed the number of switching, number of clusters, and mean cluster size. RESULTS: The data from 217 participants were analyzed (53 normal controls, 66 with Aβ− aMCI, 56 with Aβ+ aMCI, and 42 disease controls). There were fewer semantically related errors and more semantically unrelated errors on the K-BNT in Aβ+ aMCI than in Aβ− aMCI, without a gross difference in the z score. We also found that Aβ+ aMCI showed a more prominent deficit in the number of clusters in the semantic fluency task [especially for animal names (living items)] than Aβ− aMCI. CONCLUSIONS: In spite of similar clinical manifestations, Aβ+ aMCI was more similar to AD than Aβ− aMCI in terms of semantic memory disruption. Semantic memory may serve as an early indicator of brain Aβ pathology. Therefore, semantic memory dysfunction deserves more consideration in clinical practice. Longitudinal research with the follow-up data is needed.

A Comparison Study of Cilostazol and Aspirin on Changes in Volume of Cerebral Small Vessel Disease White Matter Changes: Protocol of a Multicenter, Randomized Controlled Trial

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is the most common cause of vascular dementia and a major contributor to mixed dementia. CSVD is characterized by progressive cerebral white matter changes (WMC) due to chronic low perfusion and loss of autoregulation. In addition to its antiplatelet effect, cilostazol exerts a vasodilating effect and improves endothelial function. This study aims to compare the effects of cilostazol and aspirin on changes in WMC volume in CSVD.METHODS: The comparison study of Cilostazol and aspirin on cHAnges in volume of cerebral smaLL vEssel disease white matter chaNGEs (CHALLENGE) is a double blind, randomized trial involving 19 hospitals across South Korea. Patients with moderate or severe WMC and ≥ 1 lacunar infarction detected on brain magnetic resonance imaging (MRI) are eligible; the projected sample size is 254. Participants are randomly assigned to a cilostazol or aspirin group at a 1:1 ratio. Cilostazol slow release 200 mg or aspirin 100 mg are taken once daily for 2 years. The primary outcome measure is the change in WMC volume on MRI from baseline to 104 weeks. Secondary imaging outcomes include changes in the number of lacunes and cerebral microbleeds, fractional anisotropy and mean diffusivity on diffusion tensor imaging, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability.CONCLUSIONS: CHALLENGE will provide evidence to support the selection of long-term antiplatelet therapy in CSVD.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01932203

Association between health status and tooth loss in Korean adults: longitudinal results from the National Health Insurance Service-Health Examinee Cohort, 2002–2015

PURPOSE: This study investigated the association between health status and tooth loss based on data from the National Health Insurance Service-Health Examinee Cohort in 2002–2015. METHODS: Multivariate Cox proportional hazards regression analyses were applied to a longitudinal retrospective database, which was updated and newly released in 2018, to assess the association between health status and tooth loss while adjusting for potential confounders among sociodemographic and economic factors (sex, age, household income, insurance, and presence of disability), general and oral health status (body mass index [BMI], smoking and drinking status, periodic dental visits and scaling, and brushing before sleep), and comorbid disease (hypertension, diabetes mellitus [DM], and Charlson comorbidity index [CCI]). RESULTS: Among 514,866 participants from a South Korean population, 234,247 (45.5%) participants satisfying the inclusion criteria were analyzed. In the adjusted multivariate analysis, sex, age, household income, insurance, presence of disability, BMI, smoking and drinking status, periodic scaling, tooth brushing before sleep, DM, and CCI showed statistically significant associations with the loss of at least 1 tooth. The risk of experiencing a loss of ≥4 teeth was associated with an increase in age (in those 50–59 years of age: hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.93–2.03; in those 60–69 years of age: HR, 2.93; 95% CI, 2.85–3.02; and in those 70–79 years of age: HR, 2.93; 95%, CI 2.81–3.05), smoking (HR, 1.69; 95% CI, 1.65–1.73), and DM (HR, 1.43; 95% CI, 1.38–1.48). CONCLUSIONS: The results of this study showed that the risk of experiencing tooth loss was related to multiple determinants. DM and smoking were especially significantly associated with tooth loss.

Oro-Pharyngeal Dysphagia in Parkinson's Disease and Related Movement Disorders

Oro-pharyngeal dysphagia is a common symptom in patients with Parkinson's disease (PD) and related disorders, even in their early stage of diseases. Dysphagia in these patients has been underdiagnosed, probably due to poor the self-awareness of the conditions and the underuse of validated tools and objective instruments for assessment. The early detection and intervention of dysphagia are closely related to improving the quality of life and decreasing the mortality rate in these patients. The purpose of this paper is to give an overview of the characteristics of dysphagia, including the epidemiology, pathophysiology, and clinical symptomatology, in patients with PD compared with other parkinsonian disorders and movement disorders. The management of dysphagia and future research directions related to these disorders are also discussed.

Erratum to: A Multicenter, Randomized Clinical Trial to Assess the Efficacy of a Therapeutic Intervention Program for Caregivers of People with Dementia

Unfortunately, the original version of this article had errors in the data displayed in flow diagram.

Prediction of Alzheimer's Pathological Changes in Subjective Cognitive Decline Using the Self-report Questionnaire and Neuroimaging Biomarkers

BACKGROUND AND PURPOSE: Subjective cognitive decline (SCD) may be the first symptomatic stage of Alzheimer's disease (AD). Hence, a screening tool to characterize the patients' complaints and assess the risk of AD is required. We investigated the SCD neuroimaging biomarker distributions and the relevance between the self-report questionnaire and Alzheimer's pathologic changes. METHODS: Individuals aged 50 and above with consistent cognitive complaints without any objective cognitive impairments were eligible for the study. The newly developed questionnaire consisted of 2 parts; 10 questions translated from the ‘SCD-plus criteria’ and a Korean version of the cognitive failure questionnaire by Broadbent. All the subjects underwent physical examinations such as blood work, detailed neuropsychological tests, the self-report questionnaire, brain magnetic resonance imagings, and florbetaben positron emission tomography (PET) scans. Amyloid PET findings were interpreted using both visual rating and quantitative analysis. Group comparisons and association analysis were performed using SPSS (version 18.0). RESULTS: A total of 31 participants with SCD completed the study and 25.8% showed positive amyloid depositions. The degree of periventricular white matter hyperintensities (WMH) and hippocampal atrophy were more severe in amyloid-positive SCDs compared to the amyloid-negative group. In the self-reported questionnaire, the ‘informant's report a decline’ and ‘symptom's onset after 65 years of age’ were associated with more Alzheimer's pathologic changes. CONCLUSIONS: Amyloid-positive SCDs differed from amyloid-negative SCDs on WMH, hippocampal atrophy, and a few self-reported clinical features, which gave clues on the prediction of AD pathology.

National dementia research and development project

The Ministry of Science and ICT and the Ministry of Health and Welfare of the Republic of Korea have organized the first National Committee for Dementia Research, to which all domestic experts in the field have been invited as they endeavor to achieve ‘national dementia liability’, which is one of the core national agenda items of the current Korean government. To make this initiative sustainable and bring dementia under control, we should not focus only on providing care and economic support to the family of patients with dementia. Instead, a large-scale, long-term research and development (R&D) strategy for dementia prevention, diagnosis, and therapy is warranted. This R&D project comprises several parts: 1) elucidation of the etiology and prevention of dementia, 2) innovative diagnostics for dementia, 3) tailored therapies for dementia, and 4) tangible and effective care for dementia. Given the fact that dementia is a very heterogeneous condition involving multiple pathogenic factors and typically having a chronic disease course, comprehensive and integrated approaches across various disciplines should be explored for primary, secondary, and tertiary prevention of this disease. With the success of this R&D project, the national dementia liability system will gain momentum and come into its own. Integrated efforts in terms of both policyrelated and scientific initiatives would allow us to take a step closer to realizing our shared goal of living in a world of dementia carefree.