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Herbicide-resistant weeds pose a challenge to agriculture and food production. New herbicide tolerance traits in crops will provide farmers with more options to effectively manage weeds. Mesotrione, a selective pre- and post-emergent triketone herbicide used in corn production, controls broadleaf and some annual grass weeds via hydroxyphenylpyruvate dioxygenase (HPPD) inhibition. Recently, the rice HIS1 gene, responsible for native tolerance to the selective triketone herbicide benzobicyclon, was identified. Expression of HIS1 also confers a modest level of mesotrione resistance in rice. Here we report the use of the HIS1 gene to develop a mesotrione tolerance trait in soybean.Conventional soybean is highly sensitive to mesotrione. Ectopic expression of a codon-optimized version of the rice HIS1 gene (TDO) in soybean confers a commercial level of mesotrione tolerance. In TDO transgenic soybean plants, mesotrione is rapidly and locally oxidized into noninhibitory metabolites in leaf tissues directly exposed to the herbicide. These metabolites are further converted into compounds similar to known classes of plant secondary metabolites. This rapid metabolism prevents movement of mesotrione from treated leaves into vulnerable emerging leaves. Minimizing the accumulation of the herbicide in vulnerable emerging leaves protects the function of HPPD and carotenoid biosynthesis more generally while providing tolerance to mesotrione.Mesotrione has a favorable environmental and toxicological profile. The TDO-mediated soybean mesotrione tolerance trait described here provides farmers with a new option to effectively manage difficult-to-control weeds using familiar herbicide chemistry. This trait can also be adapted to other mesotrione-sensitive crops (e.g. cotton) for effective weed management. © 2022 Bayer Crop Science. Pest Management Science published by John WileySons Ltd on behalf of Society of Chemical Industry.

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.

Background Hormonal and menstrual factors are known to influence migraines in women. However, studies in the postmenopausal period are relatively insufficient for clinical translation. This study investigated the influence of endogenous and exogenous hormonal factors on migraines in spontaneous menopausal women. Methods We obtained and analyzed the data related to hormonal factors from the Korean Health Examination database. A migraine diagnosis was identified using the Korean National Health Insurance Service database between 2009 and 2018. We observed migraine occurrence in spontaneous postmenopausal women. Study populations were divided into two groups depending on new diagnosis of migraine during the follow up periods. We investigated the association between endogenous and exogenous hormonal factors and migraine. Results 1,114,742 spontaneous postmenopausal women were enrolled. Migraine risk tended to increase in the shorter lifetime number of years of menstruation group compared to the group with lifetime number of years of menstruation ≥40 years. All of the hormone replacement therapy (HRT) groups showed higher risk compared with the non-HRT group. Migraine risk tends to increase with greater postmenopausal years compared to the postmenopausal Conclusion Our study suggests that female hormonal factors, including endogenous and exogenous estrogen exposure, may be associated with migraine occurrence in spontaneous menopausal women.

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.

Purpose The purpose of this study was to investigate whether routine insertion of peripherally inserted central catheter (PICC) at admission to a hospice-palliative care (HPC) unit is acceptable in terms of safety and efficacy and whether it results in superior patient satisfaction compared to usual intravenous (IV) access.Materials and Methods Terminally ill cancer patients were randomly assigned to two arms: routine PICC access and usual IV access arm. The primary endpoint was IV maintenance success rate, defined as the rate of functional IV maintenance until the intended time (discharge, transfer, or death).Results A total of 66 terminally ill cancer patients were enrolled and randomized to study arms. Among them, 57 patients (routine PICC, 29; usual IV, 28) were analyzed. In the routine PICC arm, mean time to PICC was 0.84 days (range, 0 to 3 days), 27 patients maintained PICC with function until the intended time. In the usual IV arm, 11 patients maintained peripheral IV access until the intended time, and 15 patients underwent PICC insertion. The IV maintenance success rate in the routine PICC arm (27/29, 93.1%) was similar to that in the usual IV arm (26/28, 92.8%, p=0.958). Patient satisfaction at day 5 was better in the routine PICC arm (97%, ‘a little comfort’ or ‘much comfort’) compared with the usual IV arm (21%) (p

Background Sex hormones significantly impact the risk and pattern of migraine in women. Women experience various hormonal changes associated with pregnancy, childbirth, breastfeeding, and contraception. This study investigated the influence of reproductive factors on migraine in women. Methods We used the linked Korean National Health Insurance Service (KNHIS) and Korean Health Examination (KHE) databases. Reproductive factors were defined as parity, breastfeeding, and oral contraceptive use and were obtained from the KHE database. A migraine diagnosis was identified using the KNHIS database. We investigated migraine occurrence in premenopausal women between the ages of 40 and 60 years. The study population was divided into two groups depending on whether the patient was newly diagnosed with migraines during the follow-up period (2009–2018). We investigated the association between reproductive factors and migraine risk in premenopausal women. Results This study enrolled 1,059,579 premenopausal women. The risk of migraine tended to increase in the primiparous (HR: 1.175; 95% CI: 1.136–1.215) and multiparous groups (HR: 1.197; 95% CI: 1.161–1.235) compared to the nulliparous group. Breastfeeding (6–12 months, HR: 1.047; 95% CI: 1.029–1.066, and ≥ 12 months, HR: 1.104; 95% CI: 1.085–1.123) significantly increased migraine risk compared with not breastfeeding. All women in the oral contraceptive groups (

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.

Background: Subjective cognitive decline (SCD) is a self-perceived cognitive worsening without objective cognitive impairment. Due to its heterogeneity and potential risk of Alzheimer’s disease (AD), baseline biomarkers to predict progression are clinically important. In the present study, cognitive trajectories during a 24-month period were compared between amyloid-positive SCD (A+SCD) and amyloid-negative SCD (A−SCD) subjects, and biomarkers associated with memory decline were investigated. Methods: Data from a prospective cohort study in Korea between 2016 and 2019 were analyzed. SCD subjects ≥50 years of age were eligible. All participants underwent neuropsychological tests, brain magnetic resonance imaging, and florbetaben positron emission tomography scans. Amyloid burden and regional volumes were measured. Cognitive changes corrected for age were compared between A+SCD and A−SCD groups. Biomarkers associated with memory decline were assessed. Results: Forty-seven SCD subjects (69.9 ± 6.7 years, mini-mental state examination (MMSE) score 27.5) were enrolled, and 31 completed at least 1 annual follow-up (mean follow-up: 24.7 months). Baseline characteristics except age, hippocampal atrophy, and white matter hyperintensities were similar between A+SCDs (n = 12, 25.6%) and A−SCDs (n = 35). A+SCD subjects showed greater decline in the verbal memory function compared with the A−SCD subjects after adjustment for age. MMSE scores decreased more in the A+SCD (1.1 in the A+SCD; 0.55 in the A−SCD), although it was not statistically significant. Amyloid burden and baseline memory score were associated with memory decline. Conclusions: Within SCD, A+SCD subjects showed faster memory decline compared with the A−SCD subjects and amyloid burden might be associated with future memory decline in SCD.

A quantitative analysis of brain volume can assist in diagnosis of Alzheimer’s disease (AD) ususally accompannied by brain atrophy. With an automated analysis program Quick Brain Volumetry (QBraVo) developed for volumetric measurements, we measured regional volumes and ratios to evaluate their performance in discriminating AD dementia (ADD) and mild cognitive impairment (MCI) patients from normal controls (NC). Validation of QBraVo was based on intra-rater and inter-rater reliability with a manual measurement. The regional volumes and ratios to total intracranial volume (TIV) and to total brain volume (TBV) or total cerebrospinal fluid volume (TCV) were compared among subjects. The regional volume to total cerebellar volume ratio named Standardized Atrophy Volume Ratio (SAVR) was calculated to compare brain atrophy. Diagnostic performances to distinguish among NC, MCI, and ADD were compared between MMSE, SAVR, and the predictive model. In total, 56 NCs, 44 MCI, and 45 ADD patients were enrolled. The average run time of QBraVo was 5 minutes 36 seconds. Intra-rater reliability was 0.999. Inter-rater reliability were high for TBV, TCV, and TIV (R = 0.97, 0.89 and 0.93, respectively). The medial temporal SAVR showed the highest performance for discriminating ADD from NC (AUC = 0.808, diagnostic accuracy = 80.2%). The predictive model using both MMSE and medial temporal SAVR improved the diagnostic performance for MCI in NC (AUC = 0.844, diagnostic accuracy = 79%). Our results demonstrated QBraVo as a fast and accurate method to measure brain volume. The regional volume calculated as SAVR could help to diagnose ADD and MCI and increase diagnostic accuracy for MCI.

Background and purpose Subjective cognitive decline (SCD) may be the first stage corresponding to subtle cognitive changes in patients with Alzheimer's disease (AD) spectrum disorders. We evaluated the differences in cortical thinning patterns among patients with SCD who progressed to mild cognitive impairment or dementia (pSCD), those who remained stable (sSCD), and healthy normal controls (NCs). Methods We retrospectively recruited SCD subjects (14 pSCD and 21 sSCD cases) and 29 NCs. Structural 3-dimensional-T1-weighted magnetic resonance imaging was performed using a single 1.5 Tesla scanner. Freesurfer software was used to map cortical thickness for group comparisons. Results Compared with NC group, the sSCD group showed diffuse cortical atrophy associated with bilateral fronto-parieto-temporal area. The pSCD group showed further characteristic cortical atrophy in AD-vulnerable regions including the inferior parieto-temporal and middle temporal areas. Cortical thinning in the bilateral medial frontal areas was observed in patients with sSCD and involved the right inferior temporal and left precentral areas in those with pSCD. Conclusions Our study showed that SCD subjects exhibit different cortical thinning patterns depending on their prognosis.

Background and purpose A 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.

A simple fluorescence-based cell-free DNA (CFD) assay has been previously developed that can directly measure nucleic acids without prior DNA extraction and amplification. However, studies on fluorescence-based CFD are lacking. In particular, there is no known information regarding the stability with regard to pre-analytical storage conditions in relation to time and temperature, or on the influence of freeze-thawing. Plasma was directly assayed to measure CFD using PicoGreen™ reagent. Standard linearity and accuracy were confirmed using salmon sperm DNA. Whole blood was left at room temperature (RT) and at 4˚C, and then plasma was separated. The CFD was also measured using thawed plasma after 1 week of freezing. As a correlation with a sperm DNA concentration, CFD demonstrated linearity over a wide range of concentrations, with a 0.998 correlation coefficient. The CFD level showed a change of up to 2.5 µg/ml according to pre-analytical storage time, and the changes were not consistent over time. The CFD values at RT after 1 h were similar to the baseline values, and the relative standard deviation was lowest under this condition. The CFD values between 4˚C and RT were similar over all time periods assessed. After freeze-thawing, the change in CFD value was reduced compared to that before freezing. The present study showed that CFD measurements using plasma processed within 1 h were optimal. Additionally, the effects of substantial changes according to storage conditions were reduced after freeze-thawing, and thus studies using stored samples is viable and relevant.

Background: Donepezil 23 mg is considered for Alzheimer’s disease (AD) to optimize cognitive benefits; however, increased adverse events (AEs) can negatively influence drug adherence. We investigated whether body weight (BW) differs based on the presence of AEs, and which baseline factors were relevant to the safety of high-dose donepezil. Methods: This study was a post hoc analysis of a multicenter randomized trial between 2014 and 2016. We included patients with moderate to severe AD treated with 10 mg/day of donepezil, and the daily dose was escalated to 23 mg with/without dose titration. Dose titration indicates 15 mg/day of donepezil before escalation or 10 mg and 23 mg/day on alternate days before escalation during the first 4 weeks. The patients were divided into 2 groups based on occurrence of AEs of special interest (AESIs) to compare baseline characteristics. We also assessed relationships between BW and AESIs. Results: Among the 160 participants in the safety population, the baseline BWs differed between the AESI (+) (n = 67) and AESI (−) (n = 93) groups. Baseline BW was inversely correlated with the occurrence of AESIs (p = 0.020), and this relationship was prominent in the no-dose titration group (p = 0.009) but absent in the dose-titration groups (p > 0.05). Conclusions: BW is the most important factor that correlated with cholinergic AEs. Hence, stepwise dose titration should be considered, particularly in patients with low BW, to minimize the inverse relationship between BW and the occurrence of AEs (“Clinicaltrials.gov” No. NCT02550665 registered on September 15, 2015).

We conducted this meta-analysis about the effects of Souvenaid on cognition and functional abilities, with the hypothesis that Souvenaid may have beneficial effects in certain groups and the goal of finding the outcome measures, disease states, and so on, applicable for further clinical trials.We searched Medline, Embase, Web of Science, CINAHL, and the Cochrane Library. Only double- blind randomized controlled trials were included. Outcome measurements were cognition, clinical global change, functional ability, and adverse events. The duration of treatment was not restricted, but trials performed in patients who did not have Alzheimer's disease (AD) were excluded.This review using meta-analyses of 4 clinical trials showed that Souvenaid had no significant effects on cognition as measured by ADAS-Cog (MD=0.08, 95% CI=-0.71-0.88) and the neuropsychological test battery total scores (MD=0.05, 95% CI=-0,02- 0.12), on global clinical function as measured by CDR-SB (MD=-0.21, 95% CI=-0.47-0.06), or on functional ability as measured by ADCS-ADL (MD=0.36, 95% CI=-0.54-1.25). There were no differences in any adverse events (OR=0.84, 95% CI=0.63-1.12) or in serious adverse events (OR=0.95, 95% CI=0.66-1.36). However, Souvenaid may benefit the domains of cognition that are affected by AD (attention, memory, and executive function), and it may have greater potential for benefits earlier rather than later in the disease.The results of current clinical trials do not suggest that Souvenaid has any beneficial effects on cognition, functional ability, or global clinical change. Further studies with outcome measures suitable in patients with early stages of AD will be needed.

Background: Donepezil 23mg is considered for Alzheimer’s disease (AD) to optimize cognitive benefits; however, this increases adverse events (AEs), which can negatively influence drug adherence. We investigated whether baseline body weight (BW) differs based on the presence of AEs, and which factors were relevant to the safety of high-dose donepezil. Methods: This study was a post-hoc analysis of a multicenter randomized trial between 2014 and 2016. We included patients with moderate to severe AD treated with donepezil 10mg/day and the daily dose was escalated to 23mg with/without dose titration. Dose titration indicates 15mg/day of donepezil before the escalation or 10mg and 23mg/day on alternate days before the escalation during the first 4 weeks. The patients were divided into two groups according to the occurrence of AEs of special interest (AESIs) to compare baseline characteristics. We also assessed relationships between BW and AESIs.Results: Among 160 safety set population, baseline BWs were different between the AESI (+) (n=67) and AESI (-) (n=93) groups. Baseline BW was inversely correlated with the occurrence of AESIs (p=0.020), and this relationship was more prominent in the no-dose titration group (p=0.009) and disappeared in the dose titration groups (p>0.05).Conclusions: BW was the most important factor which correlated with cholinergic AEs. Hence, stepwise dose-titration should be considered, particularly in patients with low BW, to minimize the inverse relationship between BW and AEs occurrence. (‘Clinicaltrials.gov’ number NCT02550665 registered on Sep. 15, 2015)

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.

This study aimed to detect different patterns of cerebral hypoperfusion in DLB according to clinical staging. Thirty-three patients with DLB were recruited by clinical dementia rating (CDR) stage. Compared with control, cerebral hypoperfusion was mainly observed in the lingual gyrus, the cuneus, the occipital gyrus in CDR 0.5 group; the fusiform gyrus, the middle temporal gyrus, and the posterior cingulate in CDR 1; and the lingual gyrus, the cuneus, the hippocampus, the fusiform gyrus, and the inferior frontal gyrus in CDR 2. Our findings suggest that cerebral hypoperfusion spreads to the frontal cortex and temporal lobes as disease progresses.

Background and purpose: Poststroke cognitive impairment (PSCI) is common, but the impact of β-amyloid (Aβ) on PSCI is uncertain. The proposed study will investigate amyloid pathology in participants with PSCI and how differently their cognition progress according to the amyloid pathology. Methods: This multicenter study was designed to be prospective and observational based on a projected cohort size of 196 participants with either newly developed cognitive impairment, or rapidly aggravated CI, within 3 months after acute cerebral infarction. They will undergo 18F-flutemetamol positron emission tomography at baseline and will be categorized as either amyloid-positive (A+) or amyloid-negative (A−) by visual rating. The primary outcome measures will be based on Korean Mini-Mental State Examination changes (baseline to 12 months) between the A+ and A− groups. The secondary outcome measures will be the dementia-conversion rate and changes in the Korean version of the Montreal Cognitive Assessment (baseline to 12 months) between the A+ and A− groups. Conclusions: This study will provide a broadened perspective on the impact of Aβ on the cause and outcomes of PSCI in clinical practice. Identifying amyloid pathology in patients with PSCI will help select patients who need more focused treatments such as acetylcholinesterase inhibitors Trial registration: Clinical Research Information Service identifier: KCT0005086

We investigated the amyloid and vascular burden in Pittsburgh compound B (PiB)-negative subcortical vascular mild cognitive impairment (svMCI) and PiB-negative subcortical ischemic vascular dementia (SIVD) to elucidate the potential roles of amyloid deposition and small vessel disease (SVD). Thirty-eight svMCI patients and 42 SIVD patients were enrolled. The regional PiB uptake values and SVD markers were obtained and compared between groups. Additionally, correlations among amyloid burden, SVD, and cognition were made. Patients with PiB-negative SIVD showed more amyloid deposition than those with PiB-negative svMCI, particularly in the cuneus, lingual gyrus, supramarginal, and angular gyri. Despite subthreshold levels for amyloid deposition, our findings showed a marked regional difference in amyloid uptake between svMCI and SIVD, particularly in posteriorly located brain areas. However, lacune, a proxy for vascular burden, showed a broader association with cognition and had more impacts on developing dementia than amyloid burden. The topographical pattern of amyloid deposition and its impact on clinical status in pure subcortical vascular cognitive impairment were different from those in Alzheimer's disease.

Subjective cognitive decline (SCD) represents subjective complaints about cognitive decline in the absence of objective impairment in neuropsychological tests. Recently, growing evidence has suggested that SCD might be the first symptomatic stage of Alzheimer's disease (AD) spectrum disorders. However, SCD is a heterogeneous condition mixed with AD and non-AD related conditions. Hence, refinement of evidence from previous reports and standardization of the concept about SCD are needed to define appropriate target population with AD pathology. In this article, we review previous studies involving subjects with SCD, the new proposed research criteria, and characteristics of SCD in the aspect of preclinical AD. Biomarker status of SCD is also addressed. Future researches on SCD require a longitudinal follow-up with sufficient biomarker studies and proper outcome measures.

BACKGROUND & OBJECTIVE Depression frequently combines with dementia, including early-onset Alzheimer's disease (EOAD). We investigated differences in prevalence and characteristics of depressive symptoms according to dementia severity in EOAD patients. METHODS The 15-item Korean version of the Geriatric Depression Scale (GDS-15) was administered to 412 EOAD patients. Factor analysis was used to assess GDS-15 factor structure. We subdivided participants into three groups by disease severity, then compared the frequencies and scores of individual GDS-15 items and performed logistic regression analysis to assess associations between depressive symptoms and EOAD stage. RESULTS Factor analysis yielded three factor categories: 1) "hopelessness and ominousness" (symptoms no. 6, 8, 12, 14, 15); 2) "unhappiness and dissatisfaction" (no. 1, 3, 5, 7, 11); and 3) "monotony and lack of energy" (no. 2, 4, 9, 10, 13). Factor 2 depressive symptoms (no. 1, 5, 11) were less common in moderate EOAD. The risk of Factor 1 symptoms: no. 12 (OR, 2.04; 95% CI, 1.19-3.50; p = 0.010) and 14 (OR, 1.84; 95% CI, 1.07-3.16; p = 0.028) was higher in mild than very mild EOAD. The risk of Factor 2 symptoms: no. 9 (OR, 2.69; 95% CI, 1.08-6.71; p = 0.033) and 13 (OR, 2.12; 95% CI, 1.02-4.40; p = 0.043) was higher in moderate than mild EOAD. CONCLUSION We confirmed that depressive symptoms differ according to EOAD severity. When assessing depressive symptoms related to dementia progression, we recommend focusing on "hopelessness and ominousness" in very mild EOAD and "unhappiness and dissatisfaction" in mild EOAD.

BACKGROUND/OBJECTIVE There is insufficient evidence to guide decisions concerning how long anti-dementia drug (ADD) regimens should be maintained in severe Alzheimer's disease (AD). We investigated whether patients with extremely severe AD who were already receiving donepezil or memantine benefited from continuing treatment. METHODS In this randomized and rater-blinded trial, 65 AD patients with a Mini-Mental State Examination score from 0 to 5 and a score of 6c or worse on Functional Assessment Staging were randomly assigned to an ADD-continuation group (N = 30) or an ADD-discontinuation group (N = 35). The current use of donepezil or memantine was maintained for 12 weeks in the ADD-continuation group and was discontinued after baseline in the ADD-discontinuation group. Efficacy measures were obtained at baseline and 12 weeks. The primary efficacy variable was the change from baseline to the end of the study in Baylor Profound Mental State Examination (BPMSE) scores. RESULTS The change in the BPMSE from baseline to the end of the study in the ADD-continuation group (a 0.4-point improvement) was not equivalent to that in the ADD-discontinuation group (a 0.5-point decline), as determined by two one-sided tests of equivalence. Study withdrawals due to adverse events (11.4% versus 6.7%) were more frequent in the ADD-discontinuation group than in the ADD-continuation group. CONCLUSION Continued treatment with donepezil or memantine seems unequal and might be superior to withdrawal of the drugs in terms of the effects on global cognition in patients with extremely severe AD. Current Controlled Trials number: KCT0000874 (CRIS).

IntroductionRecent studies have shown that pathologically defined subtypes of Alzheimer's disease (AD) represent distinctive atrophy patterns and clinical characteristics. We investigated whether a cortical thickness–based clustering method can reflect such findings.MethodsA total of 77 AD subjects from the Alzheimer's Disease Neuroimaging Initiative 2 data set who underwent 3-T magnetic resonance imaging, [18F]-fluorodeoxyglucose-positron emission tomography (PET), [18F]-Florbetapir PET, and cerebrospinal fluid (CSF) tests were enrolled. After clustering based on cortical thickness, diverse imaging and biofluid biomarkers were compared between these groups.ResultsThree cortical thinning patterns were noted: medial temporal (MT; 19.5%), diffuse (55.8%), and parietal dominant (P; 24.7%) atrophy subtypes. The P subtype was the youngest and represented more glucose hypometabolism in the parietal and occipital cortices and marked amyloid-beta accumulation in most brain regions. The MT subtype revealed more glucose hypometabolism in the left hippocampus and bilateral frontal cortices and less performance in memory tests. CSF test results did not differ between the groups.DiscussionCortical thickness patterns can reflect pathophysiological and clinical changes in AD.

KEY MESSAGE : virG mutant strains of a nopaline type of Agrobacterium tumefaciens increase the transformation frequency in cotton meristem transformation. Constitutive cytokinin expression from the tzs gene in the virG mutant strains is responsible for the improvement. Strains of Agrobacterium tumefaciens were tested for their ability to improve cotton meristem transformation frequency. Two disarmed A. tumefaciens nopaline strains with either a virGN54D constitutively active mutation or virGI77V hypersensitive induction mutation significantly increased the transformation frequency in a cotton meristem transformation system. The virG mutant strains resulted in greener explants after three days of co-culture in the presence of light, which could be attributed to a cytokinin effect of the mutants. A tzs knockout strain of virGI77V mutant showed more elongated, less green explants and decreased cotton transformation frequency, as compared to a wild type parental strain, suggesting that expression of the tzs gene is required for transformation frequency improvement in cotton meristem transformation. In vitro cytokinin levels in culture media were tenfold higher in the virGN54D strain, and approximately 30-fold higher in the virGI77V strain, in the absence of acetosyringone induction, compared to the wild type strain. The cytokinin level in the virGN54D strain is further increased upon acetosyringone induction, while the cytokinin level in the virGI77V mutant is decreased by induction, suggesting that different tzs gene expression regulation mechanisms are present in the two virG mutant strains. Based on these data, we suggest that the increased cytokinin levels play a major role in increasing Agrobacterium attachment and stimulating localized division of the attached plant cells.

Background: Patients with mild cognitive impairment (MCI) are at an increased risk for developing dementia, especially Alzheimer disease; and pharmacological therapy for MCI is limited. As a result, nonpharmacological mediums have been considered to complement standard drug therapy. In this study, we evaluated the effects of nonpharmacological therapies, occupational therapy and music therapy, on cognitive functions and depressive mood in MCI patients. Methods: We enrolled patients with MCI from the Mapo Dementia Center and divided them into two groups, group A (n=14) who participated in a cognitive program for 12 months and group B (n=15) who did not participate in a cog- nitive program. We compared the baseline and followed-up scores of the Korean-version of Mini-Mental State Exami- nation (K-MMSE), the Seoul Neuropsychological Screening Battery (SNSB), and the short version of geriatric depres- sion scale (sGDS) between the two groups. Results: Group A showed improvements in total and language scores in the K-MMSE and digit span backward scores in the SNSB and sGDS. In contrast, group B showed a decline in the Seoul Verbal Learning Test recognition score in the SNSB. Additionally, there were significant intergroup differences in the total and language scores in K-MMSE, the digit span backward score, and the Rey Complex Figure Test-delayed recall scores and depression scores. Conclusion: Occupational therapy and music therapy may help to improve cognitive functions and depressive mood in patients with MCI.

Objective As the fiberoptic gastroscopy using midazolam is being in widespread use, the exact nature of midazolam on memory should be clarified. We intended to examine whether midazolam causes selective anterograde amnesia and what impact it has on other aspects of memory and general cognitive function. Methods We recruited healthy subjects undergoing fiberoptic gastroscopy under conscious sedation. At baseline, history taking for retrograde amnesia and the Korean version of the Montreal Cognitive Assessment were performed. A man's name and address were given immediately after intravenous midazolam administration. After gastroscopy, the subjects were asked to recall those items. By the time they had fully recovered consciousness, the same test was repeated along with the Korean version of the Montreal Cognitive Assessment and a test for retrograde amnesia. Results A total of 30 subjects were enrolled in this study. Subjects with high-dose midazolam showed lower scores in the immediate and delayed recall of "a man's name and address" compared with those with low-dose midazolam. The midazolam dose was inversely correlated with the delayed recall scores of "a man's name and address." On full recovery of consciousness, the subjects did not exhibit any of anterograde or retrograde amnesia. Conclusions These findings suggest that midazolam causes transient selective anterograde amnesia in a dose-dependent manner.

Background/Aims: The aims of this study were to determine baseline factors related to the progression of subjective memory impairment (SMI) in elderly subjects and to develop a new modeling scale to predict progression. Methods: Elderly subjects with SMI were recruited from the nationwide Clinical Research Centers for Dementia of South Korea (CREDOS) multicenter cohort and divided into two groups: (1) progressed to mild cognitive impairment or Alzheimer's disease or (2) stable without progression. Baseline clinical characteristics were compared between the groups, and the most relevant predictors of progression were assessed. A new modeling scale combining the predictors was developed. Results: In total, 129 subjects with SMI were analyzed. The follow-up duration was 0.5-4.7 years, and the median time to event was 3.64 years. The progressing group (n = 29) differed from the stable group (n = 100) in terms of baseline age, apolipoprotein E4 (APOE4) status, and some cognitive domains. Older age, a lower Mini-Mental State Examination recall score, APOE4 carrier, and a lower verbal delayed recall score were the most relevant predictors of progression, and a new modeling scale with these 4 predictors provided a better explanation of progression. Conclusion: SMI subjects with a higher risk of progression can be identified using a new modeling scale and might need further evaluations and more frequent follow-up.