The Usefulness of 18F-FDG PET to Differentiate Subtypes of Dementia: The Systematic Review and Meta-Analysis.

Background and Purpose: Dementia subtypes, including Alzheimer's dementia (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD), pose diagnostic challenges. This review examines the effectiveness of 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG PET) in differentiating these subtypes for precise treatment and management. Methods: A systematic review following Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines was conducted using databases like PubMed and Embase to identify studies on the diagnostic utility of 18F-FDG PET in dementia. The search included studies up to November 16, 2022, focusing on peer-reviewed journals and applying the gold-standard clinical diagnosis for dementia subtypes. Results: From 12,815 articles, 14 were selected for final analysis. For AD versus FTD, the sensitivity was 0.96 (95% confidence interval [CI], 0.88-0.98) and specificity was 0.84 (95% CI, 0.70-0.92). In the case of AD versus DLB, 18F-FDG PET showed a sensitivity of 0.93 (95% CI 0.88-0.98) and specificity of 0.92 (95% CI, 0.70-0.92). Lastly, when differentiating AD from non-AD dementias, the sensitivity was 0.86 (95% CI, 0.80-0.91) and the specificity was 0.88 (95% CI, 0.80-0.91). The studies mostly used case-control designs with visual and quantitative assessments. Conclusions: 18F-FDG PET exhibits high sensitivity and specificity in differentiating dementia subtypes, particularly AD, FTD, and DLB. This method, while not a standalone diagnostic tool, significantly enhances diagnostic accuracy in uncertain cases, complementing clinical assessments and structural imaging.

Relationship Between Amyloid Positivity and Sleep Characteristics in the Elderly With Subjective Cognitive Decline.

Background and Purpose: Alzheimer's disease (AD) is a neurodegenerative disease characterized by a progressive decline in cognition and performance of daily activities. Recent studies have attempted to establish the relationship between AD and sleep. It is believed that patients with AD pathology show altered sleep characteristics years before clinical symptoms appear. This study evaluated the differences in sleep characteristics between cognitively asymptomatic patients with and without some amyloid burden. Methods: Sleep characteristics of 76 subjects aged 60 years or older who were diagnosed with subjective cognitive decline (SCD) but not mild cognitive impairment (MCI) or AD were measured using Fitbit® Alta HR, a wristwatch-shaped wearable device. Amyloid deposition was evaluated using brain amyloid plaque load (BAPL) and global standardized uptake value ratio (SUVR) from fluorine-18 florbetaben positron emission tomography. Each component of measured sleep characteristics was analyzed for statistically significant differences between the amyloid-positive group and the amyloid-negative group. Results: Of the 76 subjects included in this study, 49 (64.5%) were female. The average age of the subjects was 70.72±6.09 years when the study started. 15 subjects were classified as amyloid-positive based on BAPL. The average global SUVR was 1.598±0.263 in the amyloid-positive group and 1.187±0.100 in the amyloid-negative group. Time spent in slow-wave sleep (SWS) was significantly lower in the amyloid-positive group (39.4±13.1 minutes) than in the amyloid-negative group (49.5±13.1 minutes) (p=0.009). Conclusions: This study showed that SWS is different between the elderly SCD population with and without amyloid positivity. How SWS affects AD pathology requires further research.

A Longitudinal Study on Memory Enhancement in Subjective Cognitive Decline Patients: Clinical and Neuroimaging Perspectives.

BACKGROUND: Subjective cognitive decline (SCD) refers to the self-reported persistent cognitive decline despite normal objective testing, increasing the risk of dementia compared to cognitively normal individuals. OBJECTIVE: This study aims to investigate the attributes of SCD patients who demonstrated memory function improvement. METHODS: In this prospective study of SCD, a total of 120 subjects were enrolled as part of a multicenter cohort study aimed at identifying predictors for the clinical progression to mild cognitive impairment or dementia (CoSCo study). All subjects underwent 18F-florbetaben PET and brain MRI scans at baseline and annual neuropsychological tests. At the 24-month follow-up, we classified SCD patients based on changes in memory function, the z-score of the Seoul verbal learning test delayed recall. RESULTS: Of the 120 enrolled patients, 107 successfully completed the 24-month follow-up assessment. Among these, 80 patients (74.8%) with SCD exhibited memory function improvements. SCD patients with improved memory function had a lower prevalence of coronary artery disease at baseline and performed better in the trail-making test part B compared to those without improvement. Anatomical and biomarker analysis showed a lower frequency of amyloid PET positivity and larger volumes in the left and right superior parietal lobes in subjects with improved memory function. CONCLUSIONS: Our prospective study indicates that SCD patients experiencing memory improvement over a 24-month period had a lower amyloid burden, fewer cardiovascular risk factors, and superior executive cognitive function. Identifying these key factors associated with cognitive improvement may assist clinicians in predicting future memory function improvements in SCD patients.

Impacts of baseline biomarkers on cognitive trajectories in subjective cognitive decline: the CoSCo prospective cohort study.

BACKGROUND: Subjective cognitive decline (SCD) is a risk factor for Alzheimer's disease (AD); however, the rates of cognitive decline are variable according to underlying pathologies and biomarker status. We conducted an observational study and aimed to investigate baseline characteristics and biomarkers related with cognitive declines in SCD. Our study also assessed whether SCD participants showed different cognitive and biomarker trajectories according to baseline amyloid deposition. METHODS: This study is a part of a longitudinal cohort study conducted in multi-centers in South Korea between 2018 and 2021. Individuals (≥ 60 years old) with persistent cognitive complaint despite of normal cognitive functions were eligible for the study. All participants underwent neuropsychological tests, florbetaben PET scans, plasma amyloid markers, and brain MRI scans. Annual follow-up evaluations included neuropsychological tests and assessments for clinical progressions. Regional brain volumetry and amyloid burden represented by PET-based standardized uptake value ratio (SUVR) were measured. We compared cognitive and brain atrophic changes over 24 months between amyloid positive-SCD (Aß + SCD) and amyloid negative-SCD (Aß-SCD) groups. Baseline factors associated with cognitive outcomes were investigated. RESULTS: A total of 120 participants with SCD were enrolled and 107 completed follow-up evaluations. Aß + SCD participants (n = 20, 18.5%) were older and more frequently APOE4 carriers compared with Aß-SCD participants (n = 87). Baseline cognitive scores were not different between the two groups, except the Seoul Verbal Learning Test (SVLT) scores showing lower scores in the Aß + SCD group. After 24 months, plasma amyloid markers were higher, and regional volumes (entorhinal, hippocampal, and pallidum) were smaller in the Aß + SCD participants compared with Aß-SCD participants adjusted by age, sex, and baseline volumes. SVLT delayed recall and controlled oral word association test (COWAT) scores indicated more declines in Aß + SCD participants. Baseline left entorhinal volumes were related to verbal memory decline, while baseline frontal volumes and global SUVR values were related to frontal functional decline. CONCLUSION: Aß + SCD participants showed more cognitive decline and medial temporal atrophic changes during 24 months. Baseline neurodegeneration and amyloid burden were related with future cognitive trajectories in SCD. TRIAL REGISTRATION: This study was registered at CRIS (KCT0003397).

Effects of the APOEɛ4 Allele on the Relationship Between Tau and Amyloid-ß in Early- and Late-Onset Alzheimer's Disease.

BACKGROUND: Little is known regarding the differential effects of the apolipoprotein E (APOE) ɛ4 on the regional topography of amyloid and tau in patients with both early-onset (EOAD) and late-onset Alzheimer's disease (LOAD). OBJECTIVE: To compare the distribution and association of tau, amyloid, and cortical thickness among groups classified by the presence of APOEɛ4 allele and onset age. METHODS: A total of 165 participants including 54 EOAD patients (29 ɛ4-; 25 ɛ4+), 45 LOAD patients (21 ɛ4-; 24 ɛ4+), and 66 age-matched controls underwent 3T MRI, 18F-THK5351 (THK) and 18F-flutemetamol (FLUTE) PET scans, APOE genotyping, and neuropsychological tests. Data for voxel-wise and standardized uptake values from PET scans were analyzed in the context of APOE and age at onset. RESULTS: EOAD ɛ4- patients showed greater THK retention in the association cortices, whereas their EOAD ɛ4+ counterparts had more retention in medial temporal areas. THK topography of LOAD ɛ4+ was similar to EOAD ɛ4 + . THK correlated positively with FLUTE and conversely with mean cortical thickness, being lowest in EOAD ɛ4-, highest in LOAD ɛ4-, and modest in ɛ4+ groups. Even in the APOEɛ4+ groups, THK tended to correlate with FLUTE and mean cortical thickness in the inferior parietal region in EOAD and in the medial temporal region in LOAD. LOAD ɛ4- manifested with prevalent small vessel disease markers and the lowest correlation between THK retention and cognition. CONCLUSION: Our observations suggest the differential effects of the APOEɛ4 on the relationship between tau and amyloid in EOAD and LOAD.

Clinical Significance of Physical Frailty in Subjects With Subjective Cognitive Decline: A Prospective Study With Amyloid PET Data.

BACKGROUND AND PURPOSE: Physical frailty is known to be closely associated with cognitive impairment and to be an early sign of Alzheimer's disease. We aimed to understand the characteristics of physical frailty and define factors associated with physical frailty in subjects with subjective cognitive decline (SCD) by analyzing amyloid data. METHODS: We prospectively enrolled subjects with SCD from a cohort study to identify predictors for the clinical progression to mild cognitive impairment or dementia from SCD (CoSCo). All of the subjects underwent brain magnetic resonance imaging, and brain amyloid positron-emission tomography (PET) to detect amyloid beta plaques. Self-reported exhaustion, handgrip strength, and gait speed were used to measure physical frailty. RESULTS: Of 120 subjects with SCD, 26 (21.7%) were amyloid-positive in PET. Female (odds ratio [OR]=3.79, p=0.002) and amyloid-PET-positive (OR=3.80, p=0.008) subjects with SCD were at high risks of self-reported exhaustion. Amyloid PET positivity (OR=3.22, p=0.047) and high burden from periventricular white-matter hyperintensity (OR=3.34, 95% confidence interval=1.18-9.46, p=0.023) were significantly associated with a weaker handgrip. The subjects with SCD with self-reported exhaustion and weaker handgrip presented with lower cognitive performance in neuropsychological tests, especially for information processing speed and executive function. Subjects with a slower gait performed worse in visual memory function tests. CONCLUSIONS: Amyloid PET positivity was associated with a higher risk of self-reported exhaustion and weaker handgrip in subjects with SCD. The subjects with SCD and physical frailty also performed worse in neuropsychological tests.

A Multicentre, Randomised, Open-Label, Prospective Study to Estimate the Add-On Effects Of Memantine as Ebixa® Oral Pump (Solution) on Language in Patients with Moderate to Severe Alzheimer's Disease Already Receiving Donepezil (ROMEO-AD).

INTRODUCTION: This multicentre, randomised, open-label, and prospective study aimed to evaluate the effectiveness of memantine (memantine solution) on speech function in patients with moderate to severe Alzheimer's disease (AD) who were already on donepezil therapy. METHODS: Participants were divided into two groups: the drug trial group was administered donepezil + memantine (memantine solution), while the control group was administered only donepezil. Patients in the test group were required to increase the dose of memantine by 5 mg/day per week for the first 4 weeks and were maintained at 20 mg/day until the end of the trial. RESULTS: Of the 188 participants, 24 dropped out, and 164 completed the final research process. As the primary outcome, K-WAB showed an increase in scores in both groups compared to baseline scores; however, the difference was not statistically significant (P = 0.678). After 12 weeks, the donepezil treatment group had higher K-MMSE and lower CDR-SB scores than the donepezil and memantine combination group, indicating better cognitive and functional status. However, this effect was not sustained for 24 weeks. Patients who were assigned to receive only donepezil had Relevant Outcome Scale for AD (ROSA) scores that were higher by an average of 4.6 points compared to the donepezil and memantine combination group. The NPI-Q index improved compared to baseline values in both groups. CONCLUSIONS: Although several clinical studies have reported significant improvements in speech function after the administration of memantine, clinical studies on speech function improvement in patients with Alzheimer's disease are still insignificant. There are no studies on the effect of donepezil and memantine in combination treatment on language function in the moderate and severe stages of AD. Therefore, we investigated the effect of memantine (memantine solution) on speech function in patients with moderate to severe AD who were administered donepezil at a stable dose. Although the efficacy of the combination therapy was not superior to that of donepezil monotherapy alone, memantine was effective in improving behavioural symptoms in patients with moderate or severe AD.

Genetic Screening in Korean Patients with Frontotemporal Dementia Syndrome.

Background: Frontotemporal dementia (FTD) syndrome is a genetically heterogeneous group of diseases. Pathogenic variants in the chromosome 9 open reading frame 72 (C9orf72), microtubule-associated protein tau (MAPT), and progranulin (GRN) genes are mainly associated with genetic FTD in Caucasian populations. Objective: To understand the genetic background of Korean patients with FTD syndrome. Methods: We searched for pathogenic variants of 52 genes related to FTD, amyotrophic lateral sclerosis, familial Alzheimer's disease, and other dementias, and hexanucleotide repeats of the C9orf72 gene in 72 Korean patients with FTD using whole exome sequencing and the repeat-primed polymerase chain reaction, respectively. Results: One likely pathogenic variant, p.G706R of MAPT, in a patient with behavioral variant FTD (bvFTD) and 13 variants of uncertain significance (VUSs) in nine patients with FTD were identified. Of these VUSs, M232R of the PRNP gene, whose role in pathogenicity is controversial, was also found in two patients with bvFTD. Conclusions: These results indicate that known pathogenic variants of the three main FTD genes (MAPT, GRN, and C9orf72) in Western countries are rare in Korean FTD patients.

Study Design and Baseline Results in a Cohort Study to Identify Predictors for the Clinical Progression to Mild Cognitive Impairment or Dementia From Subjective Cognitive Decline (CoSCo) Study.

Background and Purpose: 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. Methods: 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 χ2 test or Fisher's exact test. Logistic regression models were used to assess the predictors of amyloid positivity. Results: The 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. Conclusions: 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.

Electroencephalography for Early Detection of Alzheimer's Disease in Subjective Cognitive Decline.

Background and Purpose: 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. Methods: Participants with SCD from 6 dementia clinics in Korea were enrolled. 18F-florbetaben brain amyloid positron emission tomography (PET) was conducted for all the participants. qEEG was performed to measure power spectrum and source cortical activity. Results: 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 (p=0.025), parietal (p=0.005), and occipital (p=0.022) areas even after adjusting for age, sex, and education. Source activities of alpha 1 band were significantly decreased in the bilateral fusiform and inferior temporal areas, whereas those of delta band were increased in the bilateral cuneus, pericalcarine, lingual, lateral occipital, precuneus, posterior cingulate, and isthmus areas. There were increased connections between bilateral precuneus areas but decreased connections between left rostral middle frontal area and bilateral frontal poles at delta band in participants with amyloid PET (+) showed. At alpha 1 band, there were decreased connections between bilateral entorhinal areas after adjusting for covariates. Conclusions: 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.

The Effect of Hearing Loss on Cognitive Function in Subjective Cognitive Decline.

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.

A Multinational, Multicenter, Randomized, Double-Blind, Active Comparator, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Donepezil Transdermal Patch in Patients With Alzheimer's Disease.

BACKGROUND AND PURPOSE: Oral administration of cholinesterase inhibitors is often associated with adverse gastrointestinal effects, and so developing an alternative administration route, such as transdermal, is urgently needed. The primary objective of this study was to determine the efficacy and safety of the IPI-301 donepezil transdermal patch compared with donepezil tablets (control) in mild-to-moderate probable Alzheimer's disease (AD). METHODS: This prospective, randomized, double-blind, double-dummy, two-arm parallel, multicenter trial included 399 patients, among whom 303 completed the trial. For randomization, the patients were stratified based on previous treatment and donepezil dose; patients in each stratum were randomized to the test and control groups at a 1:1 ratio. RESULTS: The difference between the control group and the IPI-301 group, quantified as the Hodges-Lehmann estimate of location shift, was 0.00 (95% confidence interval: -1.00 to 1.33), with an upper limit of less than 2.02. The change in Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) score differed significantly between the IPI-301 and control groups (p=0.02). However, the changes in the full-itemized ADCS-ADL scores at week 24 did not differ significantly between the two groups. There were no differences between the two groups regarding the scores for the Clinician Interview-Based Impression of Change (p=0.9097), Mini-Mental State Examination (p=0.7018), Neuropsychiatric Inventory (p=0.7656), or Clinical Dementia Rating (p=0.9990). Adverse events, vital signs, and laboratory test results were comparable between the two groups. CONCLUSIONS: IPI-301 was safe and efficacious in improving cognitive function in patients with mild-to-moderate AD.

Executive Summary of the 2021 International Conference of Korean Dementia Association: A Report From the Academic Committee of the Korean Dementia Association.

Recently, aducanumab, a beta amyloid targeted immunotherapy, has been approved by the US Food and Drug Administration for the treatment of Alzheimer's dementia (AD). Although many questions need to be answered, this approval provides a promising hope for the development of AD drugs that could be supported by new biomarkers such as blood-based ones and composite neuropsychological tests that can confirm pathologic changes in early stages of AD. It is important to elucidate the complexity of AD which is known to be associated with other factors such as vascular etiologies and neuro-inflammation. Through the second international conference of the Korean Dementia Association (KDA), researchers from all over the world have participated in the exchange of opinions with KDA members on the most up-to-date topics. The Academic Committee of the KDA summarizes lectures to provide the depth of the conference as well as discussions. This will be an important milestone to widen the latest knowledge in the research of AD's diagnosis, therapeutics, pathogenesis that can lead to the establishment of future directions.

Subtle Cognitive Deficits Are Associated with Amyloid-ß Positivity, but Not Severity of Self-Reported Decline: Results from the CoSCo Study.

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-ß (Aß) 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 Aß 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 Aß 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.

Survival in Korean Patients with Frontotemporal Dementia Syndrome: Association with Behavioral Features and Parkinsonism.

We investigated the survival time of each clinical syndrome of frontotemporal dementia (FTD) and the impacts of behavioral and motor features on survival of FTD. A total of 216 patients with FTD [82 behavioral variant FTD (bvFTD), 78 semantic variant primary progressive aphasia (svPPA), 43 non-fluent/agrammatic variant PPA (nfvPPA), 13 FTD-motor neuron disease (MND)] were enrolled from 16 centers across Korea. Behaviors and parkinsonism were assessed using the Frontal Behavioral Inventory and Unified Parkinson's Disease Rating Scale Part III, respectively. The Kaplan-Meier method was used for the survival analysis and the Cox proportional hazards model was applied for analysis of the effect of behavioral and motor symptoms on survival, after controlling vascular risk factors and cancer. An overall median survival of FTD was 12.1 years. The survival time from onset was shortest for FTD-MND and longest for svPPA. The median survival time of patients with bvFTD was unavailable but likely comparable to that of patients with nfvPPA. In the bvFTD group, negative behavioral symptoms and akinetic rigidity were significantly associated with survival. In the nfvPPA group, the presence of dysarthria had a negative impact on survival. These findings provide useful information to clinicians planning for care.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase IIb Clinical Study to Evaluate the Safety and Efficacy of DHP1401 in Patients with Mild to Moderate Alzheimer's Disease Treated with Donepezil: DHP1401 Randomized Trial in Mild to Moderate Alzheimer's Disease (DRAMA).

BACKGROUND: Preclinical studies in transgenic models of Alzheimer's disease (AD) suggest that DHP1401 has neuroprotective and memory-enhancing effects. OBJECTIVE: To evaluate the efficacy and safety of DHP1401 in AD patients treated with donepezilMethods:Methods: In a double-blind study, patients with mild-to-moderate AD were randomized (1:1:1) to receive a twice daily total dose of 500 mg or 1000 mg DHP1401 or placebo for 24 weeks. Tolerability and safety were monitored at baseline and weeks 12 and 24. RESULTS: total of 180 patients were randomized to Active 1 (500 mg: n = 62), Active 2 (1000 mg: n = 53), and control groups (n = 65) in 16 sites in Korea. There was no significant difference in the Alzheimer's Disease Assessment Scale (ADAS-cog) score, the primary efficacy endpoint, from baseline. However, in the subgroup with mild AD patients (MMSE, 20-26) who received the high dose of DHP1401 and the group that received donepezil 5 mg, the ADAS-cog scores improved. MMSE and K-TMT-e type B were significant in both active groups at week 24. The most frequently observed symptom was dizziness (2.78%), and the most commonly observed reactions were related to metabolism and nutrition disorders (5.00%). No remarkable adverse events were observed for 24 weeks. CONCLUSION: Although the effectiveness of DHP1401 was not proved to be superior as the primary efficacy endpoint, the secondary endpoints, MMSE and K-TMT-e type B, showed significant beneficial effects. Also, the subgroups showed that ADAS-cog scores significantly were improved. DHP1401 could be proven beneficial for the AD treatment by further clinical trials.

Annual Incidence of Dementia from 2003 to 2018 in Metropolitan Seoul, Korea: A Population-Based Study.

National dementia plans were applied in dementia support centers established in Seoul, Korea between 2007 and 2009. However, the annual incidence rates of dementia in Seoul have not been reported. We investigated this annual incidence and the characteristics of incident cases from 2003 to 2018. The customized research database of the Korean National Health Insurance Services was used. The annual crude and age-standardized incidence of dementia patients and their characteristics were analyzed. This study analyzed 108,596 incident dementia cases aged ≥60 years. The incidence rate increased from 2003 to 2011, including a rapid increment from 2007 to 2011. From 2011 to 2018, the crude (age-standardized) incidence per 105 person-years decreased from 641.51 (577.12) to 448.26 (361.23). The proportion of incident dementia cases was highest in the highest income group every year. However, the proportion of incident dementia cases in the lowest income group increased from 10.4% in 2003 to 25.8% in 2011. The annual incidence rate of dementia showed a sharp increase immediately after 2007, the year dementia support centers began to be introduced, and then stabilized after 2011. The characteristics of incident dementia cases have changed, including the proportion in the low-income group.

Cilostazol Versus Aspirin on White Matter Changes in Cerebral Small Vessel Disease: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Cerebral small vessel disease is characterized by progressive cerebral white matter changes (WMCs). This study aimed to compare the effects of cilostazol and aspirin on changes in WMC volume in patients with cerebral small vessel disease. METHODS: In a multicenter, double-blind, randomized controlled trial, participants with moderate or severe WMCs and at least one lacunar infarction detected on brain magnetic resonance imaging were randomly assigned to the cilostazol and aspirin groups in a 1:1 ratio. Cilostazol slow release (200 mg) or aspirin (100 mg) capsules were administered once daily for 2 years. The primary outcome was the change in WMC volume on magnetic resonance images from baseline to 2 years. Secondary imaging outcomes include changes in the number of lacunes or cerebral microbleeds, fractional anisotropy, and mean diffusivity on diffusion tensor images, and brain atrophy. Secondary clinical outcomes include all ischemic strokes, all ischemic vascular events, and changes in cognition, motor function, mood, urinary symptoms, and disability. RESULTS: Between July 2013 and August 2016, 256 participants were randomly assigned to the cilostazol (n=127) and aspirin (n=129) groups. Over 2 years, the percentage of WMC volume to total WM volume and the percentage of WMC volume to intracranial volume increased in both groups, but neither analysis showed significant differences between the groups. The peak height of the mean diffusivity histogram in normal-appearing WMs was significantly reduced in the aspirin group compared with the cilostazol group. Cilostazol significantly reduced the risk of ischemic vascular event compared with aspirin (0.5 versus 4.5 cases per 100 person-years; hazard ratio, 0.11 [95% CI, 0.02-0.89]). CONCLUSIONS: There was no significant difference between the effects of cilostazol and aspirin on WMC progression in patients with cerebral small vessel disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01932203.

Relationship between the Spectral Power Density of Sleep Electroencephalography and Psychiatric Symptoms in Patients with Breathing-related Sleep Disorder.

OBJECTIVE: Patients with breathing-related sleep disorder (BRSD) often complain of psychiatric symptoms such as depression in addition to snoring, excessive sleepiness, and disturbed sleep. However, the relationship between psychiatric symptoms and severity of sleep apnea in BRSD is controversial. We conducted this study to investigate the relationship between psychiatric symptoms and sleep electroencephalography (EEG) findings in BRSD patients using spectral analysis. METHODS: All participants underwent polysomnography and evaluation using Symptom Checklist-90-Revised (SCL-90-R) scale. We analyzed the absolute spectral power density values of standard EEG frequency bands in the participants (n = 169) with BRSD during the non-rapid eye movement (NREM) sleep period. We performed correlation analysis between the domain scores of SCL-90-R scale and the absolute values of the EEG frequency bands. RESULTS: Significant positive correlation was observed between the absolute spectral power density values in the slow oscillation band and the degree of paranoid ideation (r = 0.226, p = 0.028) and depression (r = 0.216, p = 0.044) in SCL-90-R. The multiple linear regression model showed that higher paranoid ideation domain score (B = 0.007, p = 0.020), younger age (B = -0.011, p < 0.001), and female sex (B = 0.213, p = 0.004) were associated with higher slow oscillation power during NREM sleep. CONCLUSION: The results of the present study suggested a relationship between sleep EEG and psychiatric symptoms in patients with BRSD. This relationship needs to be validated with further studies.