Effects of risk factors on the development and mortality of early- and late-onset dementia: an 11-year longitudinal nationwide population-based cohort study in South Korea.

BACKGROUND: Early-onset dementia (EOD, onset age < 65) and late-onset dementia (LOD, onset age ≥ 65) exhibit distinct features. Understanding the risk factors for dementia development and mortality in EOD and LOD respectively is crucial for personalized care. While risk factors are known for LOD development and mortality, their impact on EOD remains unclear. We aimed to investigate how hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, and osteoporosis influence the development and mortality of EOD and LOD, respectively. METHODS: Using the Korean National Health Insurance Service (NHIS) database, we collected 546,709 dementia-free individuals and followed up for 11 years. In the two study groups, the Younger group (< 65 years old) and the Older group (≥ 65 years old), we applied Cox proportional hazard models to assess risk factors for development of EOD and LOD, respectively. Then, we assessed risk factors for mortality among EOD and LOD. RESULTS: Diabetes mellitus and osteoporosis increased the risk of EOD and LOD development. Hypertension increased the risk of EOD, while atrial fibrillation increased the risk of LOD. Conversely, hyperlipidemia exhibited a protective effect against LOD development. Additionally, diabetes mellitus increased mortality in EOD and LOD. Hypertension and atrial fibrillation increased mortality in LOD, while hyperlipidemia decreased mortality in EOD and LOD. CONCLUSIONS: Risk factors influencing dementia development and mortality differed in EOD and LOD. Targeted public health interventions addressing age-related risk factors may reduce dementia incidence and mortality.

Hypoperfusion in Alzheimer's Disease-Prone Regions and Dementia Conversion in Parkinson's Disease.

PURPOSE OF THE REPORT: Although early detection of individuals at risk of dementia conversion is important in patients with Parkinson's disease (PD), there is still no consensus on neuroimaging biomarkers for predicting future cognitive decline. We aimed to investigate whether cerebral perfusion patterns on early-phase 18 F-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane ( 18 F-FP-CIT) PET have the potential to serve as a neuroimaging predictor for early dementia conversion in patients with PD. MATERIALS AND METHODS: In this retrospective analysis, we enrolled 187 patients with newly diagnosed PD who underwent dual-phase 18 F-FP-CIT PET at initial assessment and serial cognitive assessments during the follow-up period (>5 years). Patients with PD were classified into 2 groups: the PD with dementia (PDD)-high-risk (PDD-H; n = 47) and the PDD-low-risk (PDD-L; n = 140) groups according to dementia conversion within 5 years of PD diagnosis. We explored between-group differences in the regional uptake in the early-phase 18 F-FP-CIT PET images. We additionally performed a linear discriminant analysis to develop a prediction model for early PDD conversion. RESULTS: The PDD-H group exhibited hypoperfusion in Alzheimer's disease (AD)-prone regions (inferomedial temporal and posterior cingulate cortices, and insula) compared with the PDD-L group. A prediction model using regional uptake in the right entorhinal cortex, left amygdala, and left isthmus cingulate cortex could optimally distinguish the PDD-H group from the PDD-L group. CONCLUSIONS: Regional hypoperfusion in the AD-prone regions on early-phase 18 F-FP-CIT PET can be a useful biomarker for predicting early dementia conversion in patients with PD.

Hippocampal Perfusion Affects Motor and Cognitive Functions in Parkinson Disease: An Early Phase 18 F-FP-CIT Positron Emission Tomography Study.

OBJECTIVE: We investigated whether hippocampal perfusion changes are associated with cognitive decline, motor deficits, and the risk of dementia conversion in patients with Parkinson disease (PD). METHODS: We recruited patients with newly diagnosed and nonmedicated PD and healthy participants who underwent dual phase 18 F-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane positron emission tomography scans. Patients were classified into 3 groups according to hippocampal perfusion measured by standard uptake value ratios (SUVRs): (1) PD hippocampal hypoperfusion group (1 standard deviation [SD] below the mean hippocampal SUVR of healthy controls; PD-hippo-hypo), (2) PD hippocampal hyperperfusion group (1 SD above the mean; PD-hippo-hyper), and (3) the remaining patients (PD-hippo-normal). We compared the baseline cognitive performance, severity of motor deficits, hippocampal volume, striatal dopamine transporter (DAT) availability, and risk of dementia conversion among the groups. RESULTS: We included 235 patients (PD-hippo-hypo, n = 21; PD-hippo-normal, n = 157; PD-hippo-hyper, n = 57) and 48 healthy participants. Patients in the PD-hippo-hypo group were older and had smaller hippocampal volumes than those in the other PD groups. The PD-hippo-hypo group showed less severely decreased DAT availability in the putamen than the other groups despite similar severities of motor deficit. The PD-hippo-hypo group had a higher risk of dementia conversion compared to the PD-hippo-normal (hazard ratio = 2.59, p = 0.013) and PD-hippo-hyper (hazard ratio = 3.73, p = 0.006) groups, despite similar cognitive performance at initial assessment between groups. INTERPRETATION: Hippocampal hypoperfusion may indicate a reduced capacity to cope with neurodegenerative processes in terms of the development of motor deficits and cognitive decline in patients with PD. ANN NEUROL 2024;95:388-399.

Emerging role of vascular burden in AT(N) classification in individuals with Alzheimer's and concomitant cerebrovascular burdens.

OBJECTIVES: Alzheimer's disease (AD) is characterised by amyloid-beta accumulation (A), tau aggregation (T) and neurodegeneration (N). Vascular (V) burden has been found concomitantly with AD pathology and has synergistic effects on cognitive decline with AD biomarkers. We determined whether cognitive trajectories of AT(N) categories differed according to vascular (V) burden. METHODS: We prospectively recruited 205 participants and classified them into groups based on the AT(N) system using neuroimaging markers. Abnormal V markers were identified based on the presence of severe white matter hyperintensities. RESULTS: In A+ category, compared with the frequency of Alzheimer's pathological change category (A+T-), the frequency of AD category (A+T+) was significantly lower in V+ group (31.8%) than in V- group (64.4%) (p=0.004). Each AT(N) biomarker was predictive of cognitive decline in the V+ group as well as in the V- group (p<0.001). Additionally, the V+ group showed more severe cognitive trajectories than the V- group in the non-Alzheimer's pathological changes (A-T+, A-N+; p=0.002) and Alzheimer's pathological changes (p<0.001) categories. CONCLUSION: The distribution and longitudinal outcomes of AT(N) system differed according to vascular burdens, suggesting the importance of incorporating a V biomarker into the AT(N) system.

Dementia incidence and population-attributable fraction for dementia risk factors in Republic of Korea: a 12-year longitudinal follow-up study of a national cohort.

Background: We aimed to investigate the incidence of dementia by age and year as well as the population-attributable fractions (PAFs) for known dementia risk factors in Republic of Korea. Methods: A 12-year, nationwide, population-based, retrospective cohort study was conducted. We used customized health information from the National Health Insurance Service (NHIS) data from 2002 to 2017. We analyzed age- and sex-adjusted incidence rates and PAF of dementia for each risk factor such as depression, diabetes, hemorrhagic stroke, ischemic stroke, hypertension, osteoporosis and physical inactivity using Levin's formula. Results: Of the 794,448 subjects in the dementia-free cohort, 49,524 (6.2%) developed dementia. Dementia incidence showed annual growth from 1.56 per 1,000 person-years in 2006 to 6.94 per 1,000 person-years in 2017. Of all dementia cases, 34,544 subjects (69.8%) were female and 2,479 subjects (5.0%) were early onset dementia. AD dementia accounted for 66.5% of the total dementia incidence. Considering relative risk and prevalence, physical inactivity attributed the greatest to dementia (PAF, 8.1%), followed by diabetes (PAF, 4.2%), and hypertension (PAF, 2.9%). Altogether, the significant risk factors increased the risk of dementia by 18.0% (overall PAF). Conclusion: We provided the incidence of dementia and PAFs for dementia risk factors in Republic of Korea using a 12-year, nationwide cohort. Encouraging lifestyle modifications and more aggressive control of risk factors may effectively prevent dementia.

Contribution of clinical information to the predictive performance of plasma ß-amyloid levels for amyloid positron emission tomography positivity.

Background: Early detection of ß-amyloid (Aß) accumulation, a major biomarker for Alzheimer's disease (AD), has become important. As fluid biomarkers, the accuracy of cerebrospinal fluid (CSF) Aß for predicting Aß deposition on positron emission tomography (PET) has been extensively studied, and the development of plasma Aß is beginning to receive increased attention recently. In the present study, we aimed to determine whether APOE genotypes, age, and cognitive status increase the predictive performance of plasma Aß and CSF Aß levels for Aß PET positivity. Methods: We recruited 488 participants who underwent both plasma Aß and Aß PET studies (Cohort 1) and 217 participants who underwent both cerebrospinal fluid (CSF) Aß and Aß PET studies (Cohort 2). Plasma and CSF samples were analyzed using ABtest-MS, an antibody-free liquid chromatography-differential mobility spectrometry-triple quadrupole mass spectrometry method and INNOTEST enzyme-linked immunosorbent assay kits, respectively. To evaluate the predictive performance of plasma Aß and CSF Aß, respectively, logistic regression and receiver operating characteristic analyses were performed. Results: When predicting Aß PET status, both plasma Aß42/40 ratio and CSF Aß42 showed high accuracy (plasma Aß area under the curve (AUC) 0.814; CSF Aß AUC 0.848). In the plasma Aß models, the AUC values were higher than plasma Aß alone model, when the models were combined with either cognitive stage (p < 0.001) or APOE genotype (p = 0.011). On the other hand, there was no difference between the CSF Aß models, when these variables were added. Conclusion: Plasma Aß might be a useful predictor of Aß deposition on PET status as much as CSF Aß, particularly when considered with clinical information such as APOE genotype and cognitive stage.

Case report: Cerebrotendinous xanthomatosis with a novel mutation in the CYP27A1 gene mimicking behavioral variant frontotemporal dementia.

Background: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive lipid storage disease caused by a mutation in the CYP27A1 gene. Due to the disruption of bile acid synthesis leading to cholesterol and cholestanol accumulation, CTX manifests as premature cataracts, chronic diarrhea, and intellectual disability in childhood and adolescence. This report presents a case of CTX with an unusual phenotype of behavioral variant frontotemporal dementia (bvFTD) in middle age. Case presentation: A 60-year-old woman presented with behavioral and personality changes. She showed disinhibition, such as hoarding and becoming aggressive over trifles; compulsive behavior, such as closing doors; apathy; and dietary change. The patient showed a progressive cognitive decline and relatively sparing memory and visuospatial function. She had hyperlipidemia but no family history of neurodegenerative disorders. Initial fluid-attenuated inversion recovery (FLAIR) images showed a high signal in the periventricular area, and brain spectroscopy showed hypoperfusion in the frontal and temporal lobes, mimicking bvFTD. However, on physical examination, xanthomas were found on both the dorsum of the hands and the Achilles tendons. Hyperactive deep tendon reflexes in the bilateral biceps, brachioradialis, and knee and positive Chaddock signs on both sides were observed. Four years later, FLAIR images showed symmetrical high signals in the bilateral dentate nuclei of the cerebellum. Her serum cholestanol (12.4 mg/L; normal value ≤6.0) and 7α,12α-dihydroxycholest-4-en-3-one (0.485 nmol/mL; normal value ≤0.100) levels were elevated. A novel likely pathogenic variant (c.1001T>A, p.Met334Lys) and a known pathogenic variant (c.1420C>T, p.Arg474Trp) of the CYP27A1 gene were found in trans-location. The patient was diagnosed with CTX and prescribed chenodeoxycholic acid (750 mg/day). Conclusions: This report discusses the case of a middle-aged CTX patient with an unusual phenotype of bvFTD. A novel likely pathogenic variant (c.1001T>A, p.Met334Lys) was identified in the CYP27A1 gene. Early diagnosis is important because supplying chenodeoxycholic acid can prevent CTX progression.

The effects of imaging markers on clinical trajectory in cerebral amyloid angiopathy: a longitudinal study in a memory clinic.

BACKGROUND: We investigated the relevance of various imaging markers for the clinical trajectory of cerebral amyloid angiopathy (CAA) patients in a memory clinic. METHODS: A total of 226 patients with probable CAA were included in this study with a mean follow-up period of 3.5 ± 2.7 years. Although all had more than one follow-up visit, 173 underwent follow-up Mini-Mental Status Examination (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR-SB) ranging from 2 to 15 time points. Among 226, 122 patients underwent amyloid-ß (Aß) PET imaging. The prevalence of intracerebral hemorrhage (ICH) and its imaging predictors was investigated. The effects of CAA imaging markers and Aß PET positivity on longitudinal cognition based on the MMSE and CDR-SB were evaluated using mixed effects models. RESULTS: During the follow-up, 10 (4.4%) patients developed ICH: cortical superficial siderosis (cSS; hazard ratio [HR], 6.45) and previous lobar ICH (HR, 4.9), but lobar cerebral microbleeds (CMBs) were not predictors of ICH development. The presence of CMIs (p = 0.045) and Aß positivity (p = 0.002) were associated with worse MMSE trajectory in CAA patients. Regarding CDR-SB trajectory, only Aß positivity was marginally associated with worse longitudinal change (p = 0.050). CONCLUSION: The results of the present study indicated that various imaging markers in CAA patients have different clinical relevance and predictive values for further clinical courses.

Transferability of Alzheimer Disease Polygenic Risk Score Across Populations and Its Association With Alzheimer Disease-Related Phenotypes.

Importance: Polygenic risk scores (PRSs), which aggregate the genetic effects of single-nucleotide variants identified in genome-wide association studies (GWASs), can help distinguish individuals at a high genetic risk for Alzheimer disease (AD). However, genetic studies have predominantly focused on populations of European ancestry. Objective: To evaluate the transferability of a PRS for AD in the Korean population using summary statistics from a prior GWAS of European populations. Design, Setting, and Participants: This cohort study developed a PRS based on the summary statistics of a large-scale GWAS of a European population (the International Genomics of Alzheimer Project; 21 982 AD cases and 41 944 controls). This PRS was tested for an association with AD dementia and its related phenotypes in 1634 Korean individuals, who were recruited from 2013 to 2019. The association of a PRS based on a GWAS of a Japanese population (the National Center for Geriatrics and Gerontology; 3962 AD cases and 4074 controls) and a transancestry meta-analysis of European and Japanese GWASs was also evaluated. Data were analyzed from December 2020 to June 2021. Main Outcomes and Measures: Risk of AD dementia, amnestic mild cognitive impairment (aMCI), earlier symptom onset, and amyloid ß deposition (Aß). Results: A total of 1634 Korean patients (969 women [59.3%]), including 716 individuals (43.6%) with AD dementia, 222 (13.6%) with aMCI, and 699 (42.8%) cognitively unimpaired controls, were analyzed in this study. The mean (SD) age of the participants was 71.6 (9.0) years. Higher PRS was associated with a higher risk of AD dementia independent of APOE ɛ4 status in the Korean population (OR, 1.95; 95% CI, 1.40-2.72; P < .001). Furthermore, PRS was associated with aMCI, earlier symptom onset, and Aß deposition independent of APOE ɛ4 status. The PRS based on a transancestry meta-analysis of data sets comprising 2 distinct ancestries showed a slightly improved accuracy. Conclusions and Relevance: In this cohort study, a PRS derived from a European GWAS identified individuals at a high risk for AD dementia in the Korean population. These findings emphasize the transancestry transferability and clinical value of PRSs and suggest the importance of enriching diversity in genetic studies of AD.

Prediction of conversion to dementia using interpretable machine learning in patients with amnestic mild cognitive impairment.

Purpose: Amnestic mild cognitive impairment (aMCI) is a transitional state between normal aging and Alzheimer's disease (AD). However, not all aMCI patients are observed to convert to AD dementia. Therefore, developing a predictive algorithm for the conversion of aMCI to AD dementia is important. Parametric methods, such as logistic regression, have been developed; however, it is difficult to reflect complex patterns, such as non-linear relationships and interactions between variables. Therefore, this study aimed to improve the predictive power of aMCI patients' conversion to dementia by using an interpretable machine learning (IML) algorithm and to identify the factors that increase the risk of individual conversion to dementia in each patient. Methods: We prospectively recruited 705 patients with aMCI who had been followed-up for at least 3 years after undergoing baseline neuropsychological tests at the Samsung Medical Center between 2007 and 2019. We used neuropsychological tests and apolipoprotein E (APOE) genotype data to develop a predictive algorithm. The model-building and validation datasets were composed of data of 565 and 140 patients, respectively. For global interpretation, four algorithms (logistic regression, random forest, support vector machine, and extreme gradient boosting) were compared. For local interpretation, individual conditional expectations (ICE) and SHapley Additive exPlanations (SHAP) were used to analyze individual patients. Results: Among the four algorithms, the extreme gradient boost model showed the best performance, with an area under the receiver operating characteristic curve of 0.852 and an accuracy of 0.807. Variables, such as age, education, the scores of visuospatial and memory domains, the sum of boxes of the Clinical Dementia Rating scale, Mini-Mental State Examination, and APOE genotype were important features for creating the algorithm. Through ICE and SHAP analyses, it was also possible to interpret which variables acted as strong factors for each patient. Conclusion: We were able to propose a predictive algorithm for each aMCI individual's conversion to dementia using the IML technique. This algorithm is expected to be useful in clinical practice and the research field, as it can suggest conversion with high accuracy and identify the degree of influence of risk factors for each patient.

Predictive Scale for Amyloid PET Positivity Based on Clinical and MRI Variables in Patients with Amnestic Mild Cognitive Impairment.

The presence of amyloid-ß (Aß) deposition is considered important in patients with amnestic mild cognitive impairment (aMCI), since they can progress to Alzheimer's disease dementia. Amyloid positron emission tomography (PET) has been used for detecting Aß deposition, but its high cost is a significant barrier for clinical usage. Therefore, we aimed to develop a new predictive scale for amyloid PET positivity using easily accessible tools. Overall, 161 aMCI patients were recruited from six memory clinics and underwent neuropsychological tests, brain magnetic resonance imaging (MRI), apolipoprotein E (APOE) genotype testing, and amyloid PET. Among the potential predictors, verbal and visual memory tests, medial temporal lobe atrophy, APOE genotype, and age showed significant differences between the Aß-positive and Aß-negative groups and were combined to make a model for predicting amyloid PET positivity with the area under the curve (AUC) of 0.856. Based on the best model, we developed the new predictive scale comprising integers, which had an optimal cutoff score ≥ 3. The new predictive scale was validated in another cohort of 98 participants and showed a good performance with AUC of 0.835. This new predictive scale with accessible variables may be useful for predicting Aß positivity in aMCI patients in clinical practice.

18F-THK5351 PET Positivity and Longitudinal Changes in Cognitive Function in ß-Amyloid-Negative Amnestic Mild Cognitive Impairment.

PURPOSE: Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. 18F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer's disease-type tau aggregates. ß-amyloid (Aß)-negative (Aß-) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer's disease pathophysiology. Accordingly, we investigated associations between 18F-THK5351 PET positivity and cognitive decline among Aß- aMCI patients. MATERIALS AND METHODS: The present study included 25 amyloid PET negative aMCI patients who underwent a minimum of two follow-up neuropsychological evaluations, including clinical dementia rating-sum of boxes (CDR-SOB). The patients were classified into two groups: 18F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of 18F-THK5351 PET positivity on cognitive prognosis among Aß- aMCI patients. RESULTS: Among the 25 Aß- aMCI patients, 10 (40.0%) were 18F-THK5351 positive. The patients in the 18F-THK5351-positive group were older than those in the 18F-THK5351-negative group (77.4±2.2 years vs. 70.0±5.5 years; p<0.001). There was no difference between the two groups with regard to the proportion of apolipoprotein E ε4 carriers. Interestingly, however, the CDR-SOB scores of the 18F-THK5351-positive group deteriorated at a faster rate than those of the 18F-THK5351-negative group (B=0.003, p=0.033). CONCLUSION: The results of the present study suggest that increased 18F-THK5351 uptake might be a useful predictor of poor prognosis among Aß- aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498).

Distinctive Temporal Trajectories of Alzheimer's Disease Biomarkers According to Sex and APOE Genotype: Importance of Striatal Amyloid.

PURPOSE: Previously, sex and apolipoprotein E (APOE) genotype had distinct effects on the cognitive trajectory across the Alzheimer's disease (AD) continuum. We therefore aimed to investigate whether these trajectory curves including ß-amyloid (Aß) accumulation in the cortex and striatum, and tau accumulation would differ according to sex and APOE genotype. METHODS: We obtained 534 subjects for 18F-florbetapir (AV45) PET analysis and 163 subjects for 18F-flortaucipir (AV1451) PET analysis from the Alzheimer's Disease Neuroimaging Initiative database. For cortical Aß, striatal Aß, and tau SUVR, we fitted penalized splines to model the slopes of SUVR value as a non-linear function of baseline SUVR value. By integrating the fitted splines, we obtained the predicted SUVR curves as a function of time. RESULTS: The time from initial SUVR to the cutoff values were 14.9 years for cortical Aß, 18.2 years for striatal Aß, and 22.7 years for tau. Although there was no difference in cortical Aß accumulation rate between women and men, striatal Aß accumulation was found to be faster in women than in men, and this temporal difference according to sex was more pronounced in tau accumulation. However, APOE ε4 carriers showed faster progression than non-carriers regardless of kinds of AD biomarkers' trajectories. CONCLUSION: Our temporal trajectory models illustrate that there is a distinct progression pattern of AD biomarkers depending on sex and APOE genotype. In this regard, our models will be able to contribute to designing personalized treatment and prevention strategies for AD in clinical practice.

Association Between Body Mass Index and Cognitive Function in Mild Cognitive Impairment Regardless of APOE ε4 Status.

BACKGROUND AND PURPOSE: In this study we aimed to find the association between neuropsychological performance and body mass index (BMI) in patients with mild cognitive impairment (MCI). In addition, we investigated the effects of the apolipoprotein E (APOE) genotype in the relationship between the BMI and cognition in MCI. METHODS: We enrolled a cohort of 3,038 subjects with MCI aged 65-90 from the Clinical Research Center for Dementia of South Korea and a dementia cohort of the Ewha Womans University Mokdong Hospital. MCI patients were classified into three subgroups according to the Asian standard of BMI. We compared cognitive performances between groups by one-way analysis of variance. To investigate the effects of the APOE genotype, we used multivariate linear regression models after adjusting for possible confounders. RESULTS: Even though normal BMI groups were younger, had more females, and had less comorbidities, the higher BMI groups had better cognitive functions. Among subjects with APOE ε4 carriers, there was a positive relationship between the BMI and the memory task alone. CONCLUSIONS: Our findings suggested that higher BMI in patients with MCI were associated with better cognitive performance. The effects of the APOE ε4 genotype in the associations between BMI and cognition were distinguishing. Therefore, according to physical status, APOE ε4 genotype-specific strategies in the assessments and treatments may be necessary in elderly patients with MCI.

Aberrantly higher functional connectivity in the salience network is associated with transient global amnesia.

Triple intrinsic brain networks including the salience network (SN), default mode network (DMN), and central executive network (CEN), are known to be important in human cognition. Therefore, investigating those intrinsic brain networks in transient global amnesia (TGA) may offer novel insight useful for the pathophysiology of TGA. Fifty TGA patients underwent the resting state functional magnetic resonance imaging (rsfMRI) within 24 h, at 72 h, and 3 months after TGA onset. Twenty-five age, gender matched controls also underwent rsfMRI. Within 24 h of TGA onset, TGA patients showed greater functional connectivity in the SN and lower functional connectivity in the DMN, while relatively preserved functional connectivity was observed in the CEN. Interestingly, TGA patients continued to show decreased connectivity in the DMN, while no alterations were shown in the SN 72 h after illness onset. Three months after TGA onset, alterations of functional connectivity in the SN or the DMN were normalized. Our findings suggest that TGA is associated with transient greater functional connectivity in the SN and lower connectivity in the DMN.

Dual-phase 18F-florbetaben PET provides cerebral perfusion proxy along with beta-amyloid burden in Alzheimer's disease.

BACKGROUND: This study investigated changes in brain perfusion and Aß burden according to the progression of Alzheimer's disease (AD) by using a dual-phase 18F-florbetaben (FBB) PET protocol. METHODS: Sixty subjects, including 12 with Aß-negative normal cognition (Aß-NC), 32 with Aß-positive mild cognitive impairment (Aß+MCI), and 16 with Aß-positive AD (Aß+AD), were enrolled. A dynamic PET scan was obtained in the early phase (0-10 min, eFBB) and delayed phase (90-110 min, dFBB), which were then averaged into a single frame, respectively. In addition to the averaged eFBB, an R1 parametric map was calculated from the eFBB scan based on a simplified reference tissue model (SRTM). Between-group regional and voxel-wise analyses of the images were performed. The associations between cognitive profiles and PET-derived parameters were investigated. RESULTS: Both the R1 and eFBB perfusion reductions in the cortical regions were not significantly different between the Aß-NC and Aß+MCI groups, while they were significantly reduced from the Aß+MCI to Aß+AD groups in regional and voxel-wise analyses. However, cortical Aß depositions on dFBB were not significantly different between the Aß+MCI and Aß+AD groups. There were strong positive correlations between the R1 and eFBB images in regional and voxel-wise analyses. Both perfusion components showed significant correlations with general and specific cognitive profiles. CONCLUSION: The results of this study demonstrated the feasibility of dual-phase 18F-FBB PET to evaluate different trajectories of dual biomarkers for neurodegeneration and Aß burden over the course of AD. In addition, both eFBB and SRTM-based R1 can provide robust indices of brain perfusion.

Asymmetric Amyloid Deposition as an Early Sign of Progression in Mild Cognitive Impairment Due to Alzheimer Disease.

PURPOSE: In typical Alzheimer disease with dementia (ADD), amyloid pathologies affect both cerebral hemispheres symmetrically. However, the spatial distribution of amyloid-ß (Aß) in the early stage of ADD or over the course of disease has not been investigated. Therefore, we explored asymmetric pattern of Aß deposition in both hemispheres according to the ADD continuum using 18F-florbetaben PET. METHODS: Sixty-eight subjects, including 15 Aß-negative normal controls, 28 Aß-positive mild cognitive impairment (Aß+ MCI), and 25 Aß-positive ADD (Aß+ ADD) subjects, were enrolled. Differences in the asymmetry index and SUV ratio in each of the 6 target regions (4 cortical lobes, cingulate, precuneus) plus composite region between groups were explored. RESULTS: The composite and target regional asymmetry indices were significantly different between groups and was highest in Aß+ MCI (composite, occipital, and temporal, P < 0.001; frontal, P = 0.004). The composite and target regional SUV ratios were significantly different according to 3 groups with gradual increase and were highest in Aß+ ADD (composite and all target regions, P < 0.001). CONCLUSIONS: The asymmetric pattern of amyloid deposition was distinct between Aß-negative normal controls and Aß+ MCI. This pattern disappeared as the disease progressed. These data indicate that asymmetric amyloid deposition may be an early sign of MCI over the course of ADD.

Relationship between Self-Reported Sleep Duration and Risk of Anemia: Data from the Korea National Health and Nutrition Examination Survey 2016-2017.

The importance of sleep has been gaining more and more attention nowadays. It has been widely studied that some major health issues, such as cardiovascular diseases or mortality, are closely related to the extreme ends of sleep durations. Anemia is one of the health problems in modern society. In this study, we aimed to find a relationship between anemia occurrence and sleep duration. Data of 11,131 Korean adults aged 19 years or older were recruited from the 2016-2017 Korea National Health and Nutrition Examination Survey and analyzed in this cross-sectional study. 'Anemia' was defined in this study by hemoglobin level of <13 g/dL in men and <12 g/dL in women. Selected data were sorted into five groups by sleep duration: <5 h, 5 h ~ <6 h, 6 h ~ <8 h, 8 h ~ <9 h, and ≥9 h per day. We performed multivariate logistic regression analysis to assess the relationship between sleep duration and risk of anemia after adjusting for covariates including age, gender, family income level, education level, physical activity, cigarette smoking, and alcohol usage. Other factors were assessed in the analysis, such as depression, hypertension, diabetes, dyslipidemia, stroke, coronary artery disease, malignancy, stress level, and body mass index (BMI). We found that sleep duration of <5 h was related to high risk of anemia (odds ratio = 1.87; 95% confidence interval = 1.01-3.49, sleep duration of 6 h ~ <8 h as the reference group). Also, sleep duration of ≥9 h was related to lower risk of anemia in most premenopausal women after adjusting for covariates (odds ratio = 0.61; 95% confidence interval = 0.38-0.96, sleep duration of 6 h ~ < 8 h as the reference group). Male individuals with sleep durations of <5 h (odds ratio = 2.01; 95% confidence interval =1.05-3.84) and of ≥9 h (odds ratio = 2.48; 95% confidence interval =1.63-3.81) had a significantly higher risk of anemia without covariate adjustment. Postmenopausal women with sleep durations of ≥9 h had a significantly higher risk of anemia (odds ratio =2.02; 95% confidence interval =1.33-3.08) without adjusting for covariates. However, the associations became statistically insignificant after adjusting for age and covariates in both men and postmenopausal women. In conclusion, we found significant associations between extreme ends of sleep duration and risk of anemia in premenopausal Korean women. However, we did not observe strong associations between self-reported sleep duration and anemia risk in men or postmenopausal women.

The Effect of Seoul Dementia Healing Design Project on Cognition and Social Engagement.

BACKGROUND AND PURPOSE: Rapid population aging and an increase in the demented elderly became major social concerns in South Korea. Environmental design is increasingly recognized as an important aid for long-term care of patients with dementia as well as pharmacotherapy. We did a pilot study to investigate the effect of the Seoul Dementia Healing Design Project In-House Design (S-DHDP-IHD) in improving the quality of life of the cognitively impaired patients and of the S-DHDP Environmental Design (S-DHDP-ED) in increasing daily outdoor activities for cognitively impaired individuals and not cognitively impaired (NCI) elderly residents. METHODS: We applied the S-DHDP-IHD to 2 households of patients with mild cognitive impairment (MCI) and early-stage vascular dementia (VD). We assessed the effectiveness of intervention by surveys and video recordings of daily tasks. Additionally, we applied the S-DHDP-ED to 5 community facilities and randomly selected 287 residents over 65 years old (32 dementia caregivers and 255 NCI elderly) to participate in surveys. RESULTS: S-DHDP-IHD intervention showed improved instrumental activities in MCI patient and early-stage VD patient. Also, the satisfaction with an intervened home environment was increased. Following S-DHDP-ED intervention, non-demented residents engaged in more outdoor and social activities. They were also satisfied with the function and design of the installed facilities. CONCLUSIONS: S-DHDP encompassing both home and environmental improvements was effective in readapting cognitively impaired individuals and could achieve a customized, holistic approach to dementia caregiving by means of the improved design.

White Matter Integrity Is Associated With the Amount of Physical Activity in Older Adults With Super-aging.

Previous studies have introduced the concept of "SuperAgers," defined as older adults with youthful memory performance associated with the increased cortical thickness of the anterior cingulate cortex. Given that age-related structural brain changes are observed earlier in the white matter (WM) than in the cortical areas, we investigated whether WM integrity is different between the SuperAgers (SA) and typical agers (TA) and whether it is associated with superior memory performance as well as a healthy lifestyle. A total of 35 SA and 55 TA were recruited for this study. Further, 3.0-T magnetic resonance imaging (MRI), neuropsychological tests, and lifestyle factors related to cognitive function, such as physical activity and duration of sleep, were evaluated in all participants. SA was defined as individuals demonstrating the youthful performance of verbal and visual memory, as measured by the Seoul Verbal Learning Test (SVLT) and the Rey-Osterrieth Complex Figure Test (RCFT), respectively. Tract-based spatial statistics (TBSS) analysis was used to compare the diffusion values such as fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) between the SA and TA. SA exhibited better performance in memory, attention, visuospatial, and frontal executive functions than the TA did. SA also exhibited greater amounts of physical activity than the TA did. As compared to TA, SA demonstrated higher FA with lower MD, RD, and AD in the corpus callosum and higher FA and lower RD in the right superior longitudinal fasciculus (SLF), which is significantly associated with memory function. Interestingly, FA values of the body of corpus callosum were correlated with the amount of physical activity. Our findings suggest that WM integrity of the corpus callosum is associated with superior memory function and a higher level of physical activities in SA compared to TA.