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Introduction: Subjective cognitive decline (SCD) is a self-reported cognitive decline without objective cognitive impairment. The relationship between audiometric hearing loss (HL) and cognitive function has not been reported in SCD. The purpose of this study was to investigate whether HL affects cognition-related indexes in SCD individuals. Methods: This is a cross-sectional study that used the baseline data of a multicenter cohort study that monitors clinical progression from SCD to dementia. Individuals aged ≥60 years who reported cognitive decline but had no objective cognitive impairment on comprehensive neuropsychological tests were recruited. Participants were grouped into the normal-hearing (NH) and bilateral HL groups. The demographics, clinical characteristics, dementia biomarkers, global cognition, questionnaire scores, neuropsychological test scores, and segmental brain volumes from MRI were compared between the groups. Results: Of a total of 120 participants, one hundred and two had NH (n = 57) or bilateral HL (n = 45). There were no group differences in the demographic and clinical data except the age. The biomarkers, global cognition, and questionnaire scores were not different between the groups. The HL group performed worse (the z-score of −0.06) in the Stroop Color Word Test than the NH group (0.27) (p = 0.025). Brain volumetric analysis revealed that the HL group had reduced gray matter volumes in four brain subregions: left temporal pole, left caudal middle frontal gyrus, left hippocampus, and right isthmus of the cingulate gyrus. Conclusion: In SCD, HL exerted an adverse effect on cognitive function, primarily frontal executive function tested in the Stroop task. HL was also related to gray matter volume reductions in brain subregions, although causality needs further investigation. This study may provide evidence for a potential link between hearing and cognition in SCD, an emerging clinical entity.

Introduction: Subjective cognitive decline (SCD) can be considered as the preclinical manifestation of Alzheimer’s disease (AD). The National Institute on Aging and the Alzheimer’s Association criteria for preclinical AD proposed that subtle cognitive changes appear along with AD biomarkers in the late stage of preclinical AD. The objective of this study was to explore whether subtle cognitive impairment (SCI) in individuals with SCD is associated with brain amyloid-β (Aβ) status and SCD severity. Methods: One hundred twenty individuals with SCD (mean age: 70.87 ± 6.10 years) were included in this study. SCI was defined as performance ≤ −1.0 SD on at least two neuropsychological tests. Participants underwent an amyloid positron emission tomography, which was assessed visually and quantitatively using standardized uptake value ratio (SUVR). The severity of SCD was assessed using two self-reported questionnaires: the SCD questionnaire based on the SCD-plus features and the Korean-Everyday Cognition (K-ECog) scale. Results: SCD individuals with SCI (n = 25) had more Aβ positivity than the SCD only group (n = 95) (44% vs. 15.79%; p = 0.002). In addition, the SCI group had a higher global SUVR than the SCD only group (p = 0.048). For self-reported questionnaires, there were no differences in SCD questionnaire total scores and K-ECog global and cognitive domain-specific scores between two groups. Conclusions: In SCD individuals, SCI was associated with higher Aβ positivity, but not with the severity of self-reported cognitive decline, compared to the SCD only group. These results suggest that the recognition of objectively defined subtle cognitive deficits may contribute to the early identification of AD in SCD.

Subjective cognitive decline (SCD) refers to the self-perception of cognitive decline with normal performance on objective neuropsychological tests. SCD, which is the first help-seeking stage and the last stage before the clinical disease stage, can be considered to be the most appropriate time for prevention and treatment. This study aimed to compare characteristics between the amyloid positive and amyloid negative groups of SCD patients.A cohort study to identify predictors for the clinical progression to mild cognitive impairment (MCI) or dementia from subjective cognitive decline (CoSCo) study is a multicenter, prospective observational study conducted in the Republic of Korea. In total, 120 people aged 60 years or above who presented with a complaint of persistent cognitive decline were selected, and various risk factors were measured among these participants. Continuous variables were analyzed using the Wilcoxon rank-sum test, and categorical variables were analyzed using the χThe multivariate logistic regression model indicated that amyloid positivity on PET was related to a lack of hypertension, atrophy of the left temporal lateral and entorhinal cortex, low body mass index, low waist circumference, less body and visceral fat, fast gait speed, and the presence of the apolipoprotein E ε4 allele in amnestic SCD patients.The CoSCo study is still in progress, and the authors aim to identify the risk factors that are related to the progression of MCI or dementia in amnestic SCD patients through a two-year follow-up longitudinal study.

Early detection of subjective cognitive decline (SCD) due to Alzheimer's disease (AD) is important for clinical research and effective prevention and management. This study examined if quantitative electroencephalography (qEEG) could be used for early detection of AD in SCD.Participants with SCD from 6 dementia clinics in Korea were enrolled.The present study included 95 participants aged over 65 years, including 26 amyloid PET (+) and 69 amyloid PET (-). In participants with amyloid PET (+), relative power at delta band was higher in frontal (SCD participants with amyloid PET (+) showed increased delta and decreased alpha 1 activity. qEEG is a potential means for predicting amyloid pathology in SCD. Further longitudinal studies are needed to confirm these findings.

Multiple neurological complications have been associated with the coronavirus disease-19 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2. This is a narrative review to gather information on all aspects of COVID-19 in elderly patients with cognitive impairment. First, the following three mechanisms have been proposed to underlie the neurological complications associated with COVID-19: 1) direct invasion, 2) immune and inflammatory reaction, and 3) hypoxic brain damage by COVID-19. Next, because the elderly dementia patient population is particularly vulnerable to COVID-19, we discussed risk factors and difficulties associated with cognitive disorders in this vulnerable population. We also reviewed the effects of the patient living environment in COVID-19 cases that required intensive care unit (ICU) care. Furthermore, we analyzed the impact of stringent social restrictions and COVID-19 pandemic-mediated policies on dementia patients and care providers. Finally, we provided the following strategies for working with elderly dementia patients: general preventive methods; dementia care at home and nursing facilities according to the activities of daily living and dementia characteristics; ICU care after COVID-19 infection; and public health care system and government response. We propose that longitudinal follow-up studies are needed to fully examine COVID-19 associated neurological complications, such as dementia, and the efficacy of telemedicine/telehealth care programs., Graphical Abstract

Background Recently, a Korean research group suggested a consensus protocol, based on the Alzheimer's Disease Neuroimaging Initiative study protocol but with modifications for minimizing the confounding factors, for the evaluation of cerebrospinal fluid (CSF) biomarkers. Objective Here, we analyzed fluid and imaging biomarkers of Alzheimer's disease (AD) in Korean population. We used the updated protocol to propose a more accurate CSF biomarker value for the diagnosis of AD. Methods Twenty-seven patients with AD and 30 cognitively normal controls (NC) were enrolled. CSF was collected from 55 subjects (patients with AD = 26, NC = 29) following the Korea consensus protocol. CSF biomarkers were measured using the INNO-BIA AlzBio3 immunoassay, and Pittsburgh compound B (PIB) positron emission tomography (PET) scans were also performed. Results The cutoff values of CSF amyloid beta 1-42 (Aβ42), total tau (t-Tau), and phosphorylated tau (p-Tau) proteins were 357.1 pg/ml, 83.35 pg/ml, and 38.00 pg/ml, respectively. The cutoff values of CSF t-Tau/Aβ42 and p-Tau/Aβ42 ratio- were 0.210 (sensitivity 100%, specificity 86.21%) and 0.1350 (sensitivity 88.46%, specificity of 92.86%). The concordance rate with PIB-PET was higher using the CSF t-Tau/Aβ42 ratio (κ= 0.849, CI 0.71-0.99) than CSF Aβ42 alone (κ= 0.703, CI 0.51-0.89). Conclusions Here, we improved controversial factors associated with the previous CSF study protocol and suggested a new cutoff value for the diagnosis of AD. Our results showed good diagnostic performance for differentiation of AD. Thus, we expect our findings could be a cornerstone in the establishment and clinical application of biomarkers for AD diagnosis.

Although driving by adults with cognitive impairment is an important public health concern, little is known about the indicators of driving cessation in patients with mild cognitive impairment (MCI). We aimed to investigate the prevalence of driving cessation in patients with MCI and the predictive value of cognitive performances for driving cessation. Patients with MCI were recruited in the Seoul National University Bundang Hospital; they met following inclusion criteria. Age range of 51–80 years, Clinical Dementia Rating scale score of 0.5, and ever car drivers including former and current drivers. All participants underwent comprehensive standardized cognitive assessments and information on driving status was obtained via an interview using a systematic questionnaire. The median age of the 135 participants was 72 years, and 54 participants (40%) were women; 93 patients (68.9%) were current drivers and 42 (31.1%) were former drivers. In univariate analysis, former drivers showed poorer performances in digit span backward and categorical fluency tests than current drivers. In multivariate logistic regression analysis, a poor digit span backward test score was significantly related with driving cessation (odds ratio: 0.493, 95% confidence interval: 0.258–0.939). In patients with MCI, poor performance in the digit span backward test, which represents impaired working memory capacity, was associated with a higher probability of driving cessation.

Mutations in presenilin 1 (PSEN1) are the most common cause of autosomal dominant Alzheimer's disease. Here, we report a 37-year-old male Korean patient carrying a PSEN1 p.Gly417Ala mutation with exceptionally early and severe presentations, including a wide range of atypical symptoms of rapid cognitive decline with a stooped posture, rigidity, and bradykinesia. Targeted next-generation sequencing of proband revealed a novel nucleotide substitution (c.1250G>C) in exon 12 of PSEN1 gene, altering glycine to alanine at 417 position. Three-dimensional protein structure prediction revealed that the variant may cause perturbations in the 8th transmembrane region, perturbing its functions from the increased hydrophobicity and size of alanine with decreased flexibility. Since several glycine>alanine substitutions in other PSEN1 transmembrane helices revealed aggressive Alzheimer's disease phenotypes, PSEN1 Gly417Ala may share a common pathogenic mechanism.

Background: Clinical diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) is currently based on changes occurring in the late disease stages, which limits early-stage detection. Therefore, we investigated the disease course from the vague symptomatic to the terminal phase. Methods: We retrospectively reviewed 36 sCJD patient records, classifying the disease progression into 4 stages based on clinical manifestations: vague symptomatic, possible CJD, probable CJD and chronic vegetative state. We analyzed findings from diffusion-weighted imaging (DWI), electroencephalography (EEG) and cerebrospinal fluid (CSF) 14-3-3 protein testing performed at each stage. Results: In stage 1, the most distinctive feature was DWI hyperintensities in the neocortex, even with negative CSF 14-3-3 protein and EEG results. In stage 2, DWI hyperintensities in the limbic cortex were more remarkable. CSF 14-3-3 protein testing yielded positive results in >80% of patients; EEG showed sensitivity in Conclusions: Understanding disease stage-dependent differences in clinical symptoms and laboratory test results will facilitate early and accurate diagnosis.

Background Cognitive impairment impedes stroke rehabilitation. However, it is unclear whether cognitive impairment of specific domains or the degree of severity is more critical to functional recovery in patients with poststroke disability. Methods We identified 182 patients who were disabled at 3 months after acute stroke, as defined by a modified Rankin Scale score of 2-5. At a single time point between 3 months and 1 year after onset, the following 4 cognitive domains were assessed: executive function, visuospatial ability, language, and memory. With respect to the severity of cognitive impairment, the patients were classified as having vascular dementia (VD), vascular cognitive impairment no dementia (VCIND), or normal cognition. The primary outcome was functional recovery between 3 months and 1 year after onset. To examine the association between cognitive status and functional recovery, multiple logistic regression with backward stepwise analysis was performed. Results A total of 74 (40.7% of 182) patients demonstrated functional improvement at 1 year compared with 3 months. Patients with executive impairment demonstrated significantly less improvement in functional outcomes, with an adjusted odds ratio (OR) of .472 (95% confidence interval [CI], .245-.910). Patients with VD also demonstrated less functional recovery, with an adjusted OR of .289 (95% CI, .120-.700). The remaining 3 cognitive domains and VCIND were not significantly associated with functional recovery. Conclusions Executive function is a strong predictor of recovery from disability in patients with acute stroke. In addition, functional recovery is significantly hampered by cognitive impairment due to VD, but not VCIND.

Background Although medial temporal atrophy (MTA) is a useful imaging marker of the progression to dementia in mild cognitive impairment (MCI), substantial numbers of MCI patients without MTA still progress to dementia. Objective We investigated whether visual ratings of posterior atrophy (PA) on magnetic resonance imaging show independent predictive value for the progression to dementia in MCI patients. Methods This was a retrospective cohort study of elderly patients who visited Seoul National University Bundang Hospital between 2004 and 2012. A total of 148 patients who were initially diagnosed with MCI were followed for up to 3 years (median 22 months) to determine whether they progressed to dementia. We used 4-point and 5-point visual rating scales to assess PA and MTA, respectively. PA and MTA scores were dichotomized into normal (no atrophy) or abnormal (atrophy) in each patient. We performed a Cox regression analysis to examine the hazard ratios (HRs) of PA and MTA for the progression to dementia with adjustment for age, APOEɛ4 allele status, and baseline Mini-Mental State Examination score. Results Among the study population, 47 patients progressed to dementia. Visual assessment of the MRI scans revealed that 67 patients (45.3%) showed PA, whereas 85 patients (57.3%) showed MTA. The HRs with 95% confidence intervals for PA and MTA were 2.516 (1.244-5.091) and 4.238 (1.680-10.687), respectively. The predictive values of visually assessed PA and MTA remained significant, independent of the covariates. Conclusion Visual assessment of PA has independent predictive value for progression to dementia in MCI patients.

of cognition. Methods: Phone monitors were installed in the homes of 26 independent elderly individuals from the ORCATECH Life Laboratory cohort (age 86 6 4.5, 88% female) and used to monitor the total daily number of incoming phone calls for an average of 174 days. General cognitive status was assessed using a composite score composed of five Z-normalized cognitive domain tests. Because the daily number of incoming calls is a count variable, we used a mixed effects Poisson regression to model the effect of cognition on phone use controlling for age, sex, education, loneliness and pain. Results: Individuals with higher cognitive function receive significantly more phone calls (b 1⁄40.41, p

Dear Editor, The ongoing and rapid increase in the number of elderly people in Korea has led to an increasing number of cognitive problems among this population.1 A nationwide survey has estimated the prevalence rates of mild cognitive impairment (MCI) and dementia among Koreans aged at least 65 years to be 24.1% and 8.1%, respectively.2 The number of dementia patients is expected to double every 20 years until 2050.2 Alzheimer's disease (AD) is the most common cause of MCI and dementia.1,2 Since medial temporal atrophy (MTA) occurs early and prominently in patients with AD,3 a 5-point scoring system has been developed to rate the severity of the condition, from grade 0 (no MTA) to grade 4 (severe MTA).4 This scoring system is applied to oblique coronal T1-weighted images that are obtained parallel to the brainstem axis (Fig. 1).4 It is known that the medial temporal anatomy is visualized better in coronal images than in axial images.5 Visual rating of MTA based on coronal images has been used as a reliable marker for AD since its introduction more than 20 years ago.6 Although a visual rating system for MTA using T1-weighted axial images was developed recently,7 it has not been used in other studies. The Neuroimaging Work Group of the Alzheimer's Association also recommended the use of coronal T1-weighted images for assessing MTA.8 Fig. 1 Medial temporal atrophy (MTA) on oblique coronal T1-weighted images. Examples of oblique coronal T1-weighted images demonstrating MTA from grade 0 (no MTA) to 4 (severe MTA). All the examples are from the left hemisphere, as shown in the white box. Oblique coronal scans are often not included in the routine MRI protocol in Korea, and as a consequence many elderly patients who are referred to our center only have brain MRI scans in the axial or sagittal plane (i.e., not in the oblique coronal plane). We have reviewed a consecutive series of 759 MRI examinations of patients aged at least 65 years who visited the Neurocognitive Behavioral Center of Seoul National University Bundang Hospital (SNUBH) between July 2013 and March 2014 due to neurodegenerative disorders. Among them, 667 examinations were performed using MRI scanners at SNUBH, and 92 examinations were performed using MRI scanners at other hospitals. A total of 193 examinations did not include the oblique coronal images: 158 out of 667 examinations (23.7%) at SNUBH and 35 out of 92 examinations (38.0%) at other hospitals. Visual rating of MTA obtained from oblique coronal images is a valuable tool for diagnosing and predicting cognitive impairment. The authors suggest that oblique coronal scans should be obtained when brain MRI is being performed to investigate cognitive impairment. Given the growing prevalence of cognitive impairment among elderly Koreans, when brain MRI is requested for elderly patients aged at least 65 years it is prudent to take a history pertaining to cognitive decline and to consider obtaining oblique coronal images even if cognitive impairment is not the main reason for performing the procedure.

Frontotemporal dementia (FTD) is the second most common early onset neurodegenerative disorder with an average age of onset of 50–60 years. It is clinically characterized by progressive behavioral changes and frontal executive deficits and/or selective language difficulties.1 As a neuropathologically heterogeneous disorder, it encompasses a range of different clinical syndromes, including the behavioral variant of FTD, the language variants, the semantic variant primary progressive aphasia, and nonfluent/agrammatic primary progressive aphasia (nfvPPA).1,2 The nfvPPA is clinically characterized by profoundly slowed and effortful non-fluent speech resulting from several different pathologies.3 Previous studies have reported that nfvPPA associated with taupathy has overlapping clinical features such as corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) that may represent different points of a single disease spectrum.4-7 To the best of our knowledge, there are only a few case reports on tau spectrum disorder including nfvPPA, CBD, and PSP that have described detailed changes of the clinical and laboratory changes based on longitudinal follow-ups. Herein, we report a patient with clinical course of nfvPPA, CBD, and PSP with initial clinical presentation of a progressive speech disorder.

Background and Purpose In memory clinics, the lumbar puncture (LP) is increasingly being used to evaluate cerebrospinal fluid for bio markers of Alzheimer’s disease (AD). Post-lumbar puncture headache (PLPH) is the most frequent complication of LP, and can prove to be a barrier for the performance of LP. Methods We retrospectively collected data from 59 subjects (patients with AD and cognitively healthy controls) who were enrolled in a study aimed to identify AD biomarkers via LP. In order to determine whether subjects experienced PLPH, we assessed recorded follow-up telephone interviews. To analyze the association between the occurrence of PLPH and several demographic- and procedure-related factors, a multiple logistic regression analysis with backward stepwise method was performed. Results The overall frequency of PLPH was 49.15%. PLPH was more frequent in younger subjects and clinical diagnosis was associated with PLPH. The use of cutting-edge needles was also suggested as a statistically significant factor in the development of PLPH, and was determined to be the only factor that could be modified in order to lower the frequency of PLPH. Conclusions Age, clinical diagnosis, and needle type were all determined to be predictive factors of PLPH.

Background: There is increasing evidence about inflammatory processes in the development of demen tia. Therefore, inflammation has been believed to play a pivot role in cognitive decline, Alzheimer’s dis ease (AD), and vascular dementia. High-sensitivity C-reactive protein (hs-CRP) is a sensitive systemic marker of inflammation, and increased levels of hs-CRP are associated with inflammatory reactions. It is important to identify modifiable risk factors, which could be used in preventing or delaying the onset of dementia. Therefore, we studied to clarify a clinical role of hs-CRP in AD and VaD. Methods: This study population consisted of a sample of 102 patients with dementia (54 patients of AD and 48 patients of VaD) and 91 controls. We have investigated hs-CRP levels and cognitive function of each group. Cognitive function was evaluated with Mini-Mental State Examination (MMSE), Global Deterioration Scale (GDS), Clinical Dementia Rating (CDR) with Sum of Box and Activities of Daily Living (ADL). Results: All subjects with dementia showed higher hs-CRP levels than subjects without dementia. But, there was no significant difference of hs-CRP levels between patients with AD and those with VaD. The odds ratio of patients with AD and VaD by hs-CRP is 2.250 (95% Cl 1.670-3.032) for Alzheimer’s disease and 4.0 (95% Cl 2.451-6.529) for vascular dementia. Conclusions: The result of our study suggests the presence of inflammatory activity is related with dementia, not only AD known to degenerative disease but also VaD associated with cerebrovascular disease. However, we could suggest that dementia with cerebrovascular lesions is more related with inflammatory activity than AD.