Non-linear relationship between serum cholesterol levels and cognitive change among older people in the preclinical and prodromal stages of dementia: a retrospective longitudinal study in Taiwan.

BACKGROUND: Adverse effects of rigorously lowering low-density lipoprotein cholesterol on cognition have been reported; therefore, we aimed to study the contribution of serum cholesterol in cognitive decline in older people with or without dementia. METHODS: Cognitive function was assessed by the Cognitive Abilities Screening Instrument (CASI). We investigated associations between serum cholesterol with cognitive decline using multiple regressions controlling for the effects of demographics, vascular risk factors, and treatments. RESULTS: Most associations between cholesterol and CASI scores could be explained by non-linear and inverted U-shaped relationships (R2 = 0.003-0.006, p < 0.016, Sidákcorrection). The relationships were most evident between changes in cholesterol and CASI scores in older people at the preclinical or prodromal stages of dementia (R2 = 0.02-0.064, p values < 0.016). There were no differences in level of changes in CASI scores between individuals in 1st decile and 10th decile groups of changes in cholesterol (p = 0.266-0.972). However, individuals in the 1st decile of triglyceride changes and with stable and normal cognitive functions showed significant improvement in CASI scores compared to those in the 10th decile (t(202) = 2.275, p values < 0.05). CONCLUSION: These findings could implicate that rigorously lowering cholesterol may not be suitable for the prevention of cognitive decline among older people, especially among individuals in preclinical or prodromal stages of dementia.

Determining optimal cutoff scores of Cognitive Abilities Screening Instrument to identify dementia and mild cognitive impairment in Taiwan.

BACKGROUND: The early detection of dementia depends on efficient methods for the assessment of cognitive capacity. Existing cognitive screening tools are ill-suited to the differentiation of cognitive status, particularly when dealing with early-stage impairment. METHODS: The study included 8,979 individuals (> 50 years) with unimpaired cognitive functions, mild cognitive impairment (MCI), or dementia. This study sought to determine optimal cutoffs values for the Cognitive Abilities Screening Instrument (CASI) aimed at differentiating between individuals with or without dementia as well as between individuals with or without mild cognitive impairment. Cox proportional hazards models were used to evaluate the value of CASI tasks in predicting conversion from MCI to all-cause dementia, dementia of Alzheimer's type (DAT), or to vascular dementia (VaD). RESULTS: Our optimized cutoff scores achieved high accuracy in differentiating between individuals with or without dementia (AUC = 0.87-0.93) and moderate accuracy in differentiating between CU and MCI individuals (AUC = 0.67 - 0.74). Among individuals without cognitive impairment, scores that were at least 1.5 × the standard deviation below the mean scores on CASI memory tasks were predictive of conversion to dementia within roughly 2 years after the first assessment (all-cause dementia: hazard ratio [HR] = 2.81 - 3.53; DAT: 1.28 - 1.49; VaD: 1.58). Note that the cutoff scores derived in this study were lower than those reported in previous studies. CONCLUSION: Our results in this study underline the importance of establishing optimal cutoff scores for individuals with specific demographic characteristics and establishing profiles by which to guide CASI analysis.

Function-based dementia severity assessment for vascular cognitive impairment.

BACKGROUND/PURPOSES: Unimpaired activities of daily living (ADL) is essential for the diagnosis of normal cognition and mild cognitive impairment. However, diagnosis according to this concept is difficult to apply to patients comorbid with motor dysfunction. We aim to use a novel ADL questionnaire for operationally diagnosing unimpaired ADL in vascular cognitive impairment with no dementia (VCIND). METHODS AND PARTICIPANTS: This was a retrospective cohort study with both cross-sectional and long-term follow-up analysis. Patients with cerebrovascular disease with normal cognition (CVDNC), VCIND, and vascular dementia (VaD) were analyzed. Cutoff scores for differentiating different stages of cognitive impairment were compared between the new History-based Artificial Intelligent ADL questionnaire (HAI-ADL) and other tools. RESULTS: A total of 596 individuals were analyzed, including 40 CVDNC, 167 VCIND, 218 mild, 119 moderate, and 52 severe-dementia patients. The cutoff scores for determining unimpaired ADL in VCIND were 8.5, 3.5, 5, 100, and 60 in HAI-ADL, CDR-SB, IADL, BI, and CASI, respectively. HAI-ADL had the highest correlations with CDR-SB and the CDR staging system compared to other tools. Four models of progression rates from CVDNC/VCIND to VaD revealed it was much higher in the group with HAI-ADL > 8.5 compared to those with HAI-ADL≦8.5 with odds ratios of 3.75, 3.66, 3.31, and 2.77, respectively. CONCLUSION: Our study showed that HAI-ADL provides an operational determinates unimpaired ADL which is necessary for the diagnosis of VCIND. The predictive value for progression to dementia was proved by a long-term follow-up analysis of the research cohort.

Plasma Total α-Synuclein and Neurofilament Light Chain: Clinical Validation for Discriminating Parkinson's Disease from Normal Control.

BACKGROUND: A previously published paper (referred to as the original cohort) showed that using a cutoff value of 116.1 fg/mL for the plasma total α-synuclein concentrations could discriminate Parkinson's disease (PD) patients from normal controls (NCs). In this study, another independent cohort (referred to as the validation cohort) was recruited to validate the agreement between the clinical diagnosis and the use of plasma total α-synuclein to identify PD patients. In addition to total α-synuclein, plasma neurofilament light chain (NfL) in the validation cohort was detected. METHODS: Seventy PD patients and 33 NCs were enrolled in the validation cohort. A clinical diagnosis and the immunomagnetic reduction (IMR) assay for plasma total α-synuclein were performed for each participant. Thirty-three of 70 PD patients and 23 of 33 NCs were subjected to the plasma NfL assay via IMR. RESULTS: The positive, negative, and overall percentages of agreement between the clinical diagnosis and plasma total α-synuclein diagnosis determined based on 116.1 fg/mL as the cutoff value were found to be 0.943, 0.818, and 0.903, respectively. The PD patients and NCs showed plasma NfL levels of 8.38 ± 4.19 pg/mL and 17.6 ± 7.95 pg/mL (p < 0.001), respectively. The cutoff value of the plasma NfL level used to differentiate PD patients from NCs was 12.8 pg/mL, with sensitivity and specificity values of 0.788 and 0.870, respectively. CONCLUSION: The results demonstrate the usefulness of the plasma total α-synuclein concentration to discriminate PD patients from NCs and reveal the elevation of the plasma NfL level in PD patients.

An Informant-Based Simple Questionnaire for Language Assessment in Neurodegenerative Disorders.

BACKGROUND/AIMS: Language dysfunction is a crucial feature of brain disorders. This study investigated language dysfunction in patients with dementia with or without parkinsonism by using an informant-based simple questionnaire. METHODS: Language dysfunction in normal controls (NCs), and patients with Parkinson disease (PD), Parkinson disease dementia (PDD), dementia with Lewy bodies (DLB), or Alzheimer disease (AD) were analyzed and compared. RESULTS: A total of 1,662 individuals were studied: 285 NCs, 157 PD patients, 161 PDD patients, 248 DLB patients, and 811 AD patients. Patients with PD displayed higher frequency of language dysfunction in several language domains than NC. Patients with PDD and DLB showed higher frequency of language dysfunction in most of the language domains than those with AD. A composite score of our simple questionnaire was comparable with the score for the language domain of the Cognitive Abilities Screening Instrument (CASI) in different stages of dementia due to Lewy body diseases or not. CONCLUSION: Our study showed that the informant-based simple questionnaire is a practical screening tool and is comparable with the language subscale of CASI. This tool can be applied in clinical practice and in the registration platform for rapid language dysfunction screening.

Gender difference in the association and presentation of visual hallucinations in dementia with Lewy bodies: a cross-sectional study.

OBJECTIVE: Visual hallucinations (VHs) are among the most striking features of dementia with Lewy bodies (DLB). We investigated gender differences in the association and presentation of VHs in DLB. METHODS: A cross-sectional analysis of baseline data from a prospective, longitudinal study on dementia was performed. Cumulative frequency, 1-month frequency, and phenomenology of VHs were summarized and compared between female and male patients with DLB. Gender differences in the factors associated with VHs were investigated in patients with and without hallucinations. RESULTS: A total of 152 patients including 65 (42.8%) women and 87 (57.2%) men were analyzed. The cumulative and 1-month frequencies of VHs were 60% and 55.4%, respectively, in women and 44.8% and 41.4%, respectively, in men. Adjusting for age and disease severity resulted in the inclusion of more women in the VH group [odds ratio (OR) = 2.33, p = 0.028)] than in the non-VH group. In female participants, older age (OR = 9.16, p = 0.003) and higher neuropsychiatric inventory score (OR = 4.89, p = 0.009) were associated with VHs, whereas in male participants, more severe dementia stage (clinical dementia rating 2-3 versus clinical dementia rating 0.5, OR = 6.22, p = 0.008) and higher rates of using antipsychotics (OR = 9.64, p = 0.047) were associated with VHs. CONCLUSION: The frequencies of 1-month and cumulative VHs were high in DLB, which indicated a high prevalence as well as a high persistency of VHs in DLB. The patterns of factors associated with VHs differed between female and male patients. Copyright © 2017 John Wiley & Sons, Ltd.

Impact of Alzheimer's Disease in Nine Asian Countries.

BACKGROUND: Asia will soon have the majority of demented patients in the world. OBJECTIVE: To assess dementia using a uniform data system to update the current status of dementia in Asia. METHODS: A uniformed data set was administered in Taiwan, China, Hong Kong, Korea, Japan, Philippines, Thailand, Singapore, and Indonesia to gather data with regard to Alzheimer's disease (AD) and its related issues for these countries. RESULTS: In total, 2,370 AD patients and their caregivers were recruited from 2011 to 2014. The demographic characteristics of these patients and the relationships between patients and caregivers were different among individuals in these countries (p < 0.001). Of note, the family history for having dementia was 8.2% for females in contrast to 3.2% for males. CONCLUSION: Our study highlighted the differences in dementia assessment and care in developing versus developed countries. Greater effort with regard to studying dementia, especially in developing countries, is necessary.

Development of a Revised Version of Subjective Memory Complaints Questionnaire in Taiwan: A Preliminary Study.

OBJECTIVES: Research has suggested that subjective memory complaints (SMC) are predictive of cognitive decline in cases of Alzheimer's disease; however, multidimensional characteristics of SMC make it difficult to formulate causal links. The Subjective Memory Complaints Questionnaire (SMCQ) has proven effective in capturing the nature of SMC. In this study, we developed a revised version of SMCQ (SMCQ-R) with corresponding normative data for application in Taiwan. METHODS: This study recruited 100 cognitively normal participants (> 45 years) stratified according to demographic characteristics. Assessments were performed to evaluate test-retest reliability, criterion-related validity, and construct validity of SMCQ-R. SMCQ-R scores of 20 matched patients with mild cognitive impairment (MCI) were also compared with those of normal participants to test construct validity. RESULTS: Reliability of SMCQ-R was satisfactory (0.81-0.95). Factor analysis revealed a three-factor structure: everyday memory problems (EMP), recent severe memory problems (RSMP), and long-term memory problems (LTMP). EMP and RSMP scores were negatively associated with objective cognitive function (r = -.20 to .39). Depressive symptoms were positively associated with all factors (r = .23-.33). Age was positively associated with total (b = 0.09, p < .05) and EMP scores (b = 0.06, p < .01). MCI patients obtained higher scores (p < .05) on all subscales. SMCQ-R scores discriminated between normal and MCI individuals (area under the curve = 0.77). This study established a norm based on scores adjusted to control for effects of age. CONCLUSIONS: SMCQ-R has sound psychometric properties and could potentially be used as a tool to assess SMC in clinical settings.

Classification Prediction of Alzheimer's Disease and Vascular Dementia Using Physiological Data and ECD SPECT Images.

Alzheimer's disease (AD) and vascular dementia (VaD) are the two most common forms of dementia. However, their neuropsychological and pathological features often overlap, making it difficult to distinguish between AD and VaD. In addition to clinical consultation and laboratory examinations, clinical dementia diagnosis in Taiwan will also include Tc-99m-ECD SPECT imaging examination. Through machine learning and deep learning technology, we explored the feasibility of using the above clinical practice data to distinguish AD and VaD. We used the physiological data (33 features) and Tc-99m-ECD SPECT images of 112 AD patients and 85 VaD patients in the Taiwanese Nuclear Medicine Brain Image Database to train the classification model. The results, after filtering by the number of SVM RFE 5-fold features, show that the average accuracy of physiological data in distinguishing AD/VaD is 81.22% and the AUC is 0.836; the average accuracy of training images using the Inception V3 model is 85% and the AUC is 0.95. Finally, Grad-CAM heatmap was used to visualize the areas of concern of the model and compared with the SPM analysis method to further understand the differences. This research method can quickly use machine learning and deep learning models to automatically extract image features based on a small amount of general clinical data to objectively distinguish AD and VaD.

Onset headache predicts good outcome in patients with first-ever ischemic stroke.

BACKGROUND AND PURPOSE: The study aimed to assess whether onset headache is an ominous sign in patients with first-ever ischemic stroke. METHODS: A large population of ischemic stroke patients was obtained from the Taiwan Stroke Registry. Stroke subtypes were classified by the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria. On the basis of the International Classification of Headache Disorders, second version, onset headache was defined as a new headache that developed at the onset of ischemic stroke. Clinical features and impact on stroke outcomes, including in-hospital stroke in evolution, changes in National Institutes of Health Stroke Scale on discharge, and Barthel index and modified Rankin scale ≤6 months after stroke were compared between those with and without onset headache. RESULTS: Among 11 523 patients with first-ever ischemic stroke, 848 had onset headache (7.4%). Patients with specific cause, large-artery atherosclerosis, or cardioembolism were more likely to have onset headache. Patients with onset headache were younger, predominantly female, and more likely to have posterior circulation ischemic lesions. Compared with patients without onset headache, those with onset headache had a lower frequency of stroke in evolution (4.5% versus 6.7%; adjusted relative risk, 0.64; 95% confidence interval, 0.52-0.79), greater improvement in National Institutes of Health Stroke Scale score on discharge (0.08 versus -0.20; P=0.02), higher mean Barthel index scores (86.5±20.0 versus 83.9±23.3; adjusted difference, 1.43; 95% confidence interval, 0.28-2.89), and a lower frequency of modified Rankin scale higher than 2 (27.6% versus 31.5%; adjusted relative risk, 0.85; 95% confidence interval, 0.72-0.95) at 1-month follow-up. There was also a trend for better functional outcome in 3- and 6-month follow-ups. CONCLUSIONS: By adopting standard classification criteria, this large-scale study demonstrated that onset headache was associated with modest but significantly better outcomes after ischemic stroke.

Development of a simple screening tool for determining cognitive status in Alzheimer's disease.

Cognitive screening is often a first step to document cognitive status of patients suspected having Alzheimer's disease (AD). Unfortunately, screening neuropsychological tests are often insensitivity in the detection. The goal of this study was to develop a simple and sensitive screening neuropsychological test to facilitate early detection of AD. This study recruited 761 elderly individuals suspected of having AD and presenting various cognitive statuses (mean age: 77.69 ± 8.45 years; proportion of females: 65%; cognitively unimpaired, CU, n = 133; mild cognitive impairment, MCI, n = 231; dementia of Alzheimer's type, DAT, n = 397). This study developed a novel screening neuropsychological test incorporating assessments of the core memory deficits typical of early AD and an interview on memory function with an informant. The proposed History-based Artificial Intelligence-Show Chwan Assessment of Cognition (HAI-SAC) was assessed in terms of psychometric properties, test time, and discriminative ability. The results were compared with those obtained using other common screening tests, including Cognitive Abilities Screening Instrument (CASI), Montreal Cognitive Assessment (MoCA), and an extracted Mini-Mental State Examination score from CASI. HAI-SAC demonstrated acceptable internal consistency. Factor analysis revealed two factors: memory (semantic and contextual) and cognition-related information from informants. The assessment performance of HAI-SAC was strongly correlated with that of the common screening neuropsychological tests addressed in this study. HAI-SAC outperformed the other tests in differentiating CU individuals from patients with MCI (sensitivity: 0.87; specificity: 0.58; area under the curve [AUC]: 0.78) or DAT (sensitivity: 0.99; specificity: 0.89; AUC: 0.98). Performance of HAI-SAC on differentiating MCI from DAT was on par with performances of other tests (sensitivity: 0.78; specificity: 0.84; AUC: 0.87), while the test time was less than one quarter that of CASI and half that of MoCA. HAI-SAC is psychometrically sound, cost-effective, and sensitive in discriminating the cognitive status of AD.

Minimal amount of exercise prevents incident dementia in cognitively normal older adults with osteoarthritis: a retrospective longitudinal follow-up study.

Robust evidence suggests that regular exercise, including walking more than 6000 steps, is effective for preventing dementia; however, such activity is less feasible in older people with osteoarthritis (OA) or other motor disabilities. Therefore, we aimed to test whether the minimal amount of exercise (MAE) could help prevent dementia in older adults with OA. A retrospective longitudinal study was performed and a non-demented cohort (≥ 50-years-old) of 242 people (155 [64.0%] non-converters and 87 [36.0%] converters) from three centers in Taiwan was analyzed with a mean follow-up of 3.1 (range 0.3-5.9) and 2.9 (range 0.5-6.0) years, respectively. MAE was defined as walking for approximately 15-30 min or 1500-3000 steps. Rate of MAE (0, 1-2, or ≥ 3) within one week were defined as MAE-no, MAE-weekly, or MAE-daily, respectively. The incidence rates of dementia were compared between groups. Multivariate logistic regression and Cox proportional hazards analyses were used to study the influence of MAE on dementia occurrence. Age, education, sex, activities of daily living, neuropsychiatric symptoms, cognition, multiple vascular risk factors, and related medications were adjusted. Compared to the MAE-no group, the odds ratios for the incidents of dementia were 0.48 and 0.19 in the MAE-weekly and MAE-daily groups, respectively. In addition, older age, poorer cognition, poorer ADL performance, and congestive heart failure increased the incidence of dementia. Daily and weekly MAE prevented dementia in older adults with OA. As such, an informative public health policy may help promote adequate exercise in at-risk groups.

Cholesterol Levels, Hormone Replacement Therapy, and Incident Dementia among Older Adult Women.

Previous studies revealed that hormone replacement therapy (HRT) probably has a protective effect for preventing dementia in post-menopausal women. However, the results were still controversial. The association between cholesterol levels and incident dementia in older women is not fully understood either. We conducted a retrospective analysis on a cohort of non-demented women aged older than 50 years, which was registered in the History-based Artificial Intelligence Clinical Dementia Diagnostic System database from September 2015 to August 2021. We followed this cohort longitudinally to examine the rates of conversion to dementia. Using a Cox regression model, we investigated the impact of the quartile of total cholesterol (TC) levels on incident dementia, adjusting for age, sex, education, neuropsychiatric symptoms, neuropsychological assessments, HRT, as well as various vascular risk factors and medications. We examined a cohort of 787 participants, comprising 539 (68.5%) individuals who did not develop dementia (non-converters). Among these non-converters, 68 individuals (12.6%) were treated with HRT. By contrast, there were 248 (31.5%) who did develop dementia (converters). Among the converters, 28 individuals (11.3%) were treated with HRT. The average follow-up durations were 2.9 ± 1.5 and 3.3 ± 1.6 years for non-converters and converters, respectively. Compared to the lowest quartile of TC levels (<153), the hazard ratios (HR) for converting to dementia were 0.61, 0.58, and 0.58 for the second (153-176), third (177-201), and highest (>201) quartiles, respectively (all p < 0.05). However, the low-density lipoprotein cholesterol (LDL-C) level and HRT did not alter the rate of conversion to dementia. In conclusion, the lowest quartile of TC increased incident dementia in post-menopausal women without dementia; however, HRT did not contribute to conversion to dementia. Some studies suggest that post-menopausal women who have reduced estrogen levels might have an increased risk of Alzheimer's disease if they also have high cholesterol. Nonetheless, the evidence is inconclusive, as not all studies support this finding. The "Lower LDL-C is better" strategy for preventing cardiac vascular disease should be re-examined for the possible serial adverse effects of new onset dementia due to very low cholesterol levels.

Predictive value of hypercholesterolemia, vegetarian diet, and hypertension for incident dementia among elderly Taiwanese individuals with low educational levels.

Objective: Early management of modifiable dementia-related factors is seen as a novel approach to preventing dementia onset; however, these efforts are often hindered by the complexity of interactions among these factors. In addition, different modifiable dementia-related factors may contribute to different etiologies of dementia. Design: The current study investigated the effects of common modifiable dementia-related factors on prediction of incident dementia, dementia of the Alzheimer's type (DAT), and vascular dementia (VaD). Methods: Vascular- and lifestyle-related factors were used as predictors of incident dementia, DAT, and VaD among 1,285 elderly individuals without obvious signs of dementia or mild cognitive impairment. Cox proportional hazard models were used to evaluate the risks associated with each modifiable factor. Results: After controlling for factors other than stroke-related factors, hypercholesterolemia was correlated with a relatively low risk of all-cause incident dementia and DAT, whereas a vegetarian diet was correlated with an elevated risk of all-cause incident dementia and VaD. Hypertension was correlated with incident VaD. After controlling for stroke-related factors, a vegetarian diet was correlated with an elevated risk of all-cause dementia. A history of myocardiac infarction and the use of anti-platelet medication were, respectively, associated with a reduced risk of DAT and elevated risk of VaD. The use of anti-hypertensives was associated with a reduced risk of all-cause dementia, whereas the use of anti-lipid agents was associated with slow progression DAT (i.e. exceeding the average conversion time). Hypercholesterolemia was associated with an elevated risk for slow progression DAT. Conclusion: These findings could perhaps be used as clinical markers in predicting and preventing incident dementia, DAT, and VaD.

Cholesterol Paradox in Older People with Type 2 Diabetes Mellitus Regardless of Lipid-Lowering Drug Use: A Cross-Sectional Cohort Study.

Lipid-lowering drugs (LLDs) have protective effects against coronary artery disease (CAD) and cerebrovascular disease (CVD); however, a paradoxical association with cholesterol has been identified in several diseases, such as diabetes, dementia, and atrial fibrillation. We aimed to analyze the association between LLDs and cholesterol levels in older adults with type 2 diabetes mellitus (T2DM). This cross-sectional study enrolled consecutive patients aged ≥50 years from three centers in Taiwan. A multiple logistic regression model was used, and odds ratios (ORs) for different levels of total cholesterol (TC) or low-density-lipoprotein cholesterol (LDL-C) compared with the highest level were adjusted for age, triglyceride level, sex, comorbidities, and medications. Among the 3688 participants, 572 with and 676 without T2DM used LLDs. After adjusting for age and sex, the non-T2DM group demonstrated better medical conditions, cognition, and daily function than the T2DM group, regardless of LLD use. Compared to the highest TC level (≥240 mg/dL), ORs were significantly increased as TC levels decreased. A similar pattern of T2DM prevalence was observed in LDL-C levels. Older people with T2DM demonstrated low cognitive and daily functions. Significantly reduced TC and LDL levels were associated with a higher T2DM prevalence in older adults regardless of LLD use. T2DM was associated with impaired cognitive and daily functioning. A higher prevalence of T2DM in older people with low cholesterol levels raises doubt surrounding cognition and daily function being jeopardized when the "lower is better" strategy is applied for the secondary prevention of CAD or CVD.

Generative adversarial network-based attenuation correction for 99mTc-TRODAT-1 brain SPECT.

Background: Attenuation correction (AC) is an important correction method to improve the quantification accuracy of dopamine transporter (DAT) single photon emission computed tomography (SPECT). Chang's method was developed for AC (Chang-AC) when CT-based AC was not available, assuming uniform attenuation coefficients inside the body contour. This study aims to evaluate Chang-AC and different deep learning (DL)-based AC approaches on 99mTc-TRODAT-1 brain SPECT using clinical patient data on two different scanners. Methods: Two hundred and sixty patients who underwent 99mTc-TRODAT-1 SPECT/CT scans from two different scanners (scanner A and scanner B) were retrospectively recruited. The ordered-subset expectation-maximization (OS-EM) method reconstructed 120 projections with dual-energy scatter correction, with or without CT-AC. We implemented a 3D conditional generative adversarial network (cGAN) for the indirect deep learning-based attenuation correction (DL-ACµ) and direct deep learning-based attenuation correction (DL-AC) methods, estimating attenuation maps (µ-maps) and attenuation-corrected SPECT images from non-attenuation-corrected (NAC) SPECT, respectively. We further applied cross-scanner training (cross-scanner indirect deep learning-based attenuation correction [cull-ACµ] and cross-scanner direct deep learning-based attenuation correction [call-AC]) and merged the datasets from two scanners for ensemble training (ensemble indirect deep learning-based attenuation correction [eDL-ACµ] and ensemble direct deep learning-based attenuation correction [eDL-AC]). The estimated µ-maps from (c/e)DL-ACµ were then used in reconstruction for AC purposes. Chang's method was also implemented for comparison. Normalized mean square error (NMSE), structural similarity index (SSIM), specific uptake ratio (SUR), and asymmetry index (%ASI) of the striatum were calculated for different AC methods. Results: The NMSE for Chang's method, DL-ACµ, DL-AC, cDL-ACµ, cDL-AC, eDL-ACµ, and eDL-AC is 0.0406 ± 0.0445, 0.0059 ± 0.0035, 0.0099 ± 0.0066, 0.0253 ± 0.0102, 0.0369 ± 0.0124, 0.0098 ± 0.0035, and 0.0162 ± 0.0118 for scanner A and 0.0579 ± 0.0146, 0.0055 ± 0.0034, 0.0063 ± 0.0028, 0.0235 ± 0.0085, 0.0349 ± 0.0086, 0.0115 ± 0.0062, and 0.0117 ± 0.0038 for scanner B, respectively. The SUR and %ASI results for DL-ACµ are closer to CT-AC, Followed by DL-AC, eDL-ACµ, cDL-ACµ, cDL-AC, eDL-AC, Chang's method, and NAC. Conclusion: All DL-based AC methods are superior to Chang-AC. DL-ACµ is superior to DL-AC. Scanner-specific training is superior to cross-scanner and ensemble training. DL-based AC methods are feasible and robust for 99mTc-TRODAT-1 brain SPECT.

Depression in Taiwanese patients with Alzheimer's disease determined by the National Institutes of Mental Health Provisional Criteria.

BACKGROUND: Depression is a common behavioral and psychological symptom of Alzheimer's disease (AD). The aims of the present study were to determine the rate of depression in Taiwanese patients with AD using the National Institutes of Mental Health Provisional Criteria for Depression in AD (NIMH-dAD criteria) and to investigate the association of depression with other behavioral and psychological symptoms. METHODS: A consecutive series of 302 AD patients registered in a dementia clinic were investigated in this study. All patients met the criteria of the National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association for probable AD. The rates of depression were determined according to the criteria of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders for major depression (DSM-IV), the International Classification of Diseases-9-Clinical Modification (ICD-9-CM) for neurotic depression, the depression subscale of the Neuropsychiatric Inventory (NPI), and the NIMH-dAD criteria. Depression severity was assessed using the 17-item Hamilton Depression Rating Scale. The rates of depression determined by the NIMH-dAD criteria were compared with the rates derived from each of the other instruments. Other behavioral and psychological symptoms were assessed using NPI. A behavioral neurologist or a geriatric psychiatrist interviewed all the patients. RESULTS: Using the NIMH-dAD criteria, it was found that 90 (29.8%) of the AD patients had depression, and all depressive symptoms in NIMH-dAD were significantly higher among depressed patients. Among other depression instruments, the frequency of depression was lowest using the DSM-IV major depression criteria (9.3%) and highest with the NPI depression subscale (54%). Behavioral and psychological symptoms determined with NPI were significantly higher among depressed patients in all domains except euphoria. CONCLUSIONS: This is the first study of depression in Taiwanese patients with AD using the NIMH-dAD criteria. Our findings suggest that comorbid depression is high in Taiwanese patients with AD. It is clinically important to note the high frequency of most behavioral and psychological symptoms among depressed AD patients.

Sum of boxes of the clinical dementia rating scale highly predicts conversion or reversion in predementia stages.

Background: The clinical dementia rating (CDR) scale is commonly used to diagnose dementia due to Alzheimer's disease (AD). The sum of boxes of the CDR (CDR-SB) has recently been emphasized and applied to interventional trials for tracing the progression of cognitive impairment (CI) in the early stages of AD. We aimed to study the influence of baseline CDR-SB on disease progression to dementia or reversion to normal cognition (NC). Materials and methods: The baseline CDR < 1 cohort registered from September 2015 to August 2020 with longitudinal follow-up in the History-based Artificial Intelligence Clinical Dementia Diagnostic System (HAICDDS) database was retrospectively analyzed for the rates of conversion to CDR ≥ 1. A Cox regression model was applied to study the influence of CDR-SB levels on progression, adjusting for age, education, sex, neuropsychological tests, neuropsychiatric symptoms, parkinsonism, and multiple vascular risk factors. Results: A total of 1,827 participants were analyzed, including 1,258 (68.9%) non-converters, and 569 (31.1%) converters with mean follow-up of 2.1 (range 0.4-5.5) and 1.8 (range 0.3-5.0) years, respectively. Conversion rates increased with increasing CDR-SB scores. Compared to a CDR-SB score of 0, the hazard ratios (HR) for conversion to dementia were 1.51, 1.91, 2.58, 2.13, 3.46, 3.85, 3.19, 5.12, and 5.22 for CDR-SB scores of 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, and ≥4.5, respectively (all p < 0.05 except for CDR-SB score = 0.5). In addition, older age, lower education, lower cognitive performance, and a history of diabetes also increased conversion rates. Furthermore, reversions to NC were 12.5, 5.6, 0.9, and 0% for CDR-SB scores of 0.5, 1.0-2.0, 2.5-3.5 and ≥4.0, respectively (p < 0.001). Conclusion: CDR-SB in predementia or very mild dementia (VMD) stages highly predicts progression to dementia or reversion to NC. Therefore, CDR-SB could be a good candidate for tracing the effectiveness of pharmacological and non-pharmacological interventions in populations without dementia.

White matter hyperintensities in dementia with Lewy bodies are associated with poorer cognitive function and higher dementia stages.

Purpose: White matter hyperintensities (WMHs) are frequently found in elderly individuals with or without dementia. However, the association between WMHs and clinical presentations of dementia with Lewy bodies (DLB) has rarely been studied. Methods: We conducted a retrospective analysis of patients with DLB registered in a dementia database. WMHs were rated visually using the Fazekas scale, and its associated factors including dementia severity, cognitive functions, neuropsychiatric symptoms, and core clinical features were compared among different Fazekas scores. Domains in the Clinical Dementia Rating (CDR), Cognitive abilities Screening Instruments (CASI), and Neuropsychiatric Inventory (NPI) were compared among different Fazekas groups after adjusting for age, sex, education, and disease duration. Results: Among the 449 patients, 76, 207, 110, and 56 had Fazekas score of 0, 1, 2, and 3, respectively. There was a positive association between dementia severity and WMHs severity, and the mean sums of boxes of the Clinical Dementia Rating (CDR-SB) were 5.9, 7.8, 9.5, and 11.2 (f = 16.84, p < 0.001) for the Fazekas scale scores 0, 1, 2, and 3, respectively. There was a negative association between cognitive performance and WMHs severity, and the mean CASI were 57.7, 45.4, 4.06, and 33.4 (f = 14.22, p < 0.001) for the Fazekas scale scores 0, 1, 2, and 3, respectively. However, WMHs were not associated with the core clinical features of DLB. After adjustment, all cognitive domains in CDR increased as the Fazekas score increased. In addition, performance on all cognitive domains in CASI decreased as the Fazekas score increased (all p < 0.001). Among neuropsychiatric symptoms, delusions, euphoria, apathy, aberrant motor behavior, and sleep disorders were significantly worse in the higher Fazekas groups compared to those in the group with Fazekas score of 0 after adjustment. Conclusion: WMHs in DLB might contribute to deterioration of cognitive function, neuropsychiatric symptoms, and dementia stages. However, core clinical features were not significantly influenced by WMHs in DLB.

Arrhythmia and other modifiable risk factors in incident dementia and MCI among elderly individuals with low educational levels in Taiwan.

Introduction: There is increasing evidence that arrhythmia is a risk factor for dementia; however, it appears that arrhythmia affects the cognitive function of individuals differentially across age groups, races, and educational levels. Demographic differences including educational level have also been found to moderate the effects of modifiable risk factors for cognitive decline. Methods: This study recruited 1,361 individuals including a group of cognitively unimpaired (CU) individuals, a group of patients with mild cognitive impairment (MCI), and a group of patients with dementia with low education levels. The participants were evaluated in terms of modifiable risk factors for dementia, including arrhythmia and neuropsychiatric symptoms. Results: Cox proportional hazard regression models revealed that among older MCI patients (>75 years), those with arrhythmia faced an elevated risk of dementia. Among younger MCI patients, those taking anti-hypertensive drugs faced a relatively low risk of dementia. Among younger MCI patients, male sex and higher educational level were associated with an elevated risk of dementia. Among CU individuals, those with coronary heart disease and taking anti-lipid compounds faced an elevated risk of MCI and those with symptoms of depression faced an elevated risk of dementia. Discussion: The risk and protective factors mentioned above could potentially be used as markers in predicting the onset of dementia in clinical settings, especially for individuals with low educational levels.