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Standard methods for determining the CSF TT response are based on the clinical impression of changes in gait after lumber puncture. iNPH patients who are unable to ambulate (e.g., the patient is wheelchair bound) may not be able to comply with the gait evaluation but still benefit from shunt placement. There were no statistically significant differences in age, sex, disease duration, iNPHGS scores, MMSE scores, MoCA scores, or 10 m walking time (all P >0.05), but there was a statistically significant difference in ADL questionnaire scores (t = 2.53, P = 0.02) [Supplementary Table 1, http://links.lww.com/CM9/B841] between the CSF TT responder and CSF TT non-responder groups. Similar patterns were found in the correlation analysis of periventricular white matter lesion DTI parameters with the 10 m walking time and the TUG time results (all P <0.05) [Supplementary Table 3, http://links.lww.com/CM9/B841]. The correlation between upper extremity motor function and gait in iNPH patients was supported by the association of GPT scores, SDMT scores, and the complex visual motor index performance improvement ratio with the walking test improvement ratio at the corresponding time point.

In the clinic, practitioners encounter many patients with an abnormal pattern of dense punctate magnetic resonance imaging (MRI) signal in the basal ganglia, a phenomenon known as \"cheese sign\". This sign is reported as common in cerebrovascular diseases, dementia, and old age. Recently, cheese sign has been speculated to consist of dense perivascular space (PVS). This study aimed to assess the lesion types of cheese sign and analyze the correlation between this sign and vascular disease risk factors. A total of 812 patients from Peking Union Medical College Hospital (PUMCH) dementia cohort were enrolled. We analyzed the relationship between cheese sign and vascular risk. For assessing cheese sign and defining its degree, the abnormal punctate signals were classified into basal ganglia hyperintensity (BGH), PVS, lacunae/infarctions and microbleeds, and counted separately. Each type of lesion was rated on a four-level scale, and then the sum was calculated; this total was defined as the cheese sign score. Fazekas and Age-Related White Matter Changes (ARWMC) scores were used to evaluate the paraventricular, deep, and subcortical gray/white matter hyperintensities. A total of 118 patients (14.5%) in this dementia cohort were found to have cheese sign. Age (odds ratio [OR]: 1.090, 95% confidence interval [CI]: 1.064-1.120, P <0.001), hypertension (OR: 1.828, 95% CI: 1.123-2.983, P = 0.014), and stroke (OR: 1.901, 95% CI: 1.092-3.259, P = 0.025) were risk factors for cheese sign. There was no significant relationship between diabetes, hyperlipidemia, and cheese sign. The main components of cheese sign were BGH, PVS, and lacunae/infarction. The proportion of PVS increased with cheese sign severity. The risk factors for cheese sign were hypertension, age, and stroke. Cheese sign consists of BGH, PVS, and lacunae/infarction.

Most studies have focused on individuals with normal cognition, subjective cognitive decline, or mild cognitive impairment, examining the predictive role of plasma biomarker levels in AD progression. [...]we assessed the accuracy of plasma Aβ40, Aβ42, pTau181, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) levels in diagnosing AD among dementia patients, expanding the use of the AT(N) system for blood-based diagnostics. Ethical approval for this study was obtained from the Ethics Committee of Peking Union Medical College Hospital (No. [...]the plasma Aβ42/40 ratio and pTau181 and GFAP levels are promising noninvasive biomarkers for detecting brain Aβ pathology in dementia patients and have the potential to increase diagnostic accuracy when these measurements are combined with clinical assessments by machine learning models. Funding This study was supported by grants from the National Key Research and Development Program of China (Nos. 2020YFA0804500 and 2020YFA0804501), CAMS Innovation fund for medical sciences (CIFMS) (Nos. 2021-I2M-1-020 and 2020-I2M-C&T-B-010), National Natural Science Foundation of China (Nos. 81550021 and 30470618), and National High Level Hospital Clinical Research Funding (Nos. 2022-PUMCH-D-007 and 2022-PUMCH-A-254).

•The novel Aβ-targeted PET radioligand [18F]-Florbetazine had distinct binding profiles in AD patients and healthy controls in the dynamic PET study.•[18F]-Florbetazine PET show high gray-to-white contrast in AD patients that are favorable in visual read.•SUVR of a static [18F]-Florbetazine PET scan can be used to differentiated HCs and AD patients. [18F]-Florbetazine ([18F]-92) is a selective PET tracer for β-amyloid (Aβ) depositions with a novel diaryl-azine scaffold to reduce lipophilicity and to achieve higher gray-to-white matter contrast. We aimed to assess its diagnostic value in Alzheimer's disease (AD) and pharmacokinetics characteristics in human subjects. Six healthy controls (HCs) and nine AD patients underwent dynamic PET examination with [18F]-Florbetazine and a structural MRI scan. The time-activity-curves (TACs) for volumes of interest (VOIs) in cerebral cortex, cerebellar cortex and cerebral white matter was depicted and their standardized uptake value ratios (SUVRs) with cerebellar cortex as reference were compared between HCs and AD patients. The cerebral gray-to-white matter SUV ratio (GWR) was also calculated. In HCs, radioactivities in the cerebral cortex VOIs were homogeneously low and at the same level as in cerebellar cortex, while in AD patients, cortical VOIs expected to contain Aβ exhibited high radioactivity. Cerebral cortex SUVRs remain relatively low in HCs while keep increasing along with time in AD patients. After 15 min, the cerebral cortex SUVRs became significant higher in AD patients compared to HCs with 100 % discrimination accuracy. In AD patients, GWR remained over 1.3 for all time intervals and visual inspection showed lower uptake in cerebral white matter compared to cerebral cortex. [18F]-Florbetazine PET showed high uptake on Aβ plaques and high gray-to-white contrast in AD patients that are favorable in visual read. [18F]-Florbetazine can be potentially used for detection and quantification of Aβ depositions in the living human brain. [Display omitted]

Machine learning (ML) has been extensively involved in assistant disease diagnosis and prediction systems to emancipate the serious dependence on medical resources and improve healthcare quality. Moreover, with the booming of pre-training language models (PLMs), the application prospect and promotion potential of machine learning methods in the relevant field have been further inspired. PLMs have recently achieved tremendous success in diverse text processing tasks, whereas limited by the significant semantic gap between the pre-training corpus and the structured electronic health records (EHRs), PLMs cannot converge to anticipated disease diagnosis and prediction results. Unfortunately, establishing connections between PLMs and EHRs typically requires the extraction of curated predictor variables from structured EHR resources, which is tedious and labor-intensive, and even discards vast implicit information.In this work, we propose an Input Prompting and Discriminative language model with the Mixture-of-experts framework (IPDM) by promoting the model’s capabilities to learn knowledge from heterogeneous information and facilitating the feature-aware ability of the model. Furthermore, leveraging the prompt-tuning mechanism, IPDM can inherit the impacts of the pre-training in downstream tasks exclusively through minor modifications. IPDM remarkably outperforms existing models, proved by experiments on one disease diagnosis task and two disease prediction tasks. Finally, experiments with few-feature and few-sample demonstrate that IPDM achieves significant stability and impressive performance in predicting chronic diseases with unclear early-onset characteristics or sudden diseases with insufficient data, which verifies the superiority of IPDM over existing mainstream methods, and reveals the IPDM can powerfully address the aforementioned challenges via establishing a stable and low-resource medical diagnostic system for various clinical scenarios.

Apolipoprotein-E ( ) ε4 is a major genetic risk factor for Alzheimer's disease (AD). Current studies, which were mainly based on the clinical diagnosis rather than biomarkers, come to inconsistent conclusions regarding the associations of homozygotes ( ) and cerebrospinal fluid (CSF) biomarkers of AD. In addition, few studies have explored the associations of with plasma biomarkers. Therefore, we aimed to investigate the associations of with fluid biomarkers in dementia and biomarker-diagnosed AD. A total of 297 patients were enrolled. They were classified into Alzheimer's continuum, AD, and non-AD, according to CSF biomarkers and/or β amyloid PET results. AD was a subgroup of the AD continuum. Plasma Amyloid β (Aβ) 40, Aβ42, glial fibrillary acidic protein (GFAP), neurofilament light chain (NFL), and phosphorylated tau (P-tau)181 were quantified in 144 of the total population using an ultra-sensitive Simoa technology. We analyzed the associations of on CSF and plasma biomarkers in dementia and biomarker diagnosed AD. Based on the biomarker diagnostic criteria, 169 participants were diagnosed with Alzheimer's continuum and 128 individuals with non-AD, and among the former, 120 patients with AD. The frequencies were 11.8% (20/169), 14.2% (17/120), and 0.8% (1/128) in Alzheimer's continuum, AD and non-AD, respectively. Only CSF Aβ42 was shown to be decreased in carriers than in non-carriers for patients with AD (  = 0.024). Furthermore, we did not find any associations of with plasma biomarkers of AD and non-AD. Interestingly, we found that in non-AD patients, carriers had lower CSF Aβ42 (  = 0.018) and higher T-tau/Aβ42 ratios (  < 0.001) and P-tau181/Aβ42 ratios (  = 0.002) than non-carriers. Our data confirmed that of the three groups (AD continuum, AD, and non-AD), those with AD had the highest frequency of genotypes. The was associated with CSF levels of Aβ42 but not tau for AD and non-AD, suggesting that affected the Aβ metabolism of both. No associations between and plasma biomarkers of AD and non-AD were found.

Frontotemporal dementia (FTD) is a heterogeneous disease both clinically and pathologically. Genetic mutation in microtubule-associated protein tau (MAPT) is the most common cause of FTD, and the phenotype is related to the mutation location. However, the phenotype and genotype correlation varies somewhat among different cohorts and ethnicities. Whole-genome next-generation sequencing (NGS) was carried out for 1351 patients with dementia at Peking Union Medical College Hospital. MAPT variations classified as pathogenic and of uncertain significance were identified. Demographic information, clinical presentations, and neuroimaging were collected, and the phenotype-genotype correlation was analyzed with a concurrent literature review. Twenty-four patients were enrolled; 8 patients carrying the D177V mutation are discussed separately. The average onset age was young, and most of them had a positive family history. Cognitive dysfunction, behavior, and personality changes as well as aphasia were the most common presentations. Most structural MRIs showed asymmetrical atrophy of the temporal lobe, with/without similar changes in the frontal lobe. L266V carriers presented with youngest onset typical behavior variant FTD or aphasia; P301L carriers presented with behavior variant FTD or aphasia. Functional MRI and molecular imaging also showed that the involved areas were similar to those with structural atrophy. D296N carriers presented atypical parkinsonism and cognitive dysfunction at older ages. Eight D177V carriers had extraordinarily different manifestations. The clinical phenotype of most of them was not FTD, though cerebral vascular lesions were obvious in some of them. MAPT mutation is rare in Chinese dementia patients. The phenotype and genotype correlation is specific and overlaps. The D177V mutation is possibly not directly pathogenic in our cohort. Some of the variants might increase the genetic risk of neurodegenerative diseases.

ObjectiveThe objective of this study is to describe the typical and atypical clinical and neuroimaging features of ALD in Chinese patients, which will help early diagnosis and intervention to improve prognosis of ALD.MethodsForty-one patients in the Leukoencephalopathy Clinic of Neurology Department, Peking Union Medical College Hospital were enrolled. Detailed clinical manifestations and MRI features were analyzed. The relationship between phenotype and genotype as well as biochemical analysis was observed.ResultsThe patients were classified according to phenotype and onset age, including 14 childhood cerebral ALD (CCALD), 8 adolescent cerebral ALD (adoCALD), 3 adult cerebral ALD (ACALD), 14 adrenomyeloneuropathy (AMN), and 2 ALD in women. AMN was the main presentation in adults. Visual impairment was usual onset symptom in CCALD and cognitive decline and psychiatric symptoms were found in adoCALD and ACALD. Typical MRI feature of CALD was symmetrical peri-ventricular “butterfly wings” like lesions in frontal and/or occipital lobe with peripheral DWI hyperintensities and Gd enhancement. Corpus callosum and internal capsule were always involved. Unilateral lesions were also possible. Cerebral AMN presented with centrum semiovale diffuse involvement. Spinocerebellar variant was a special subtype of AMN with obvious cerebellar and brainstem lesions. No relationships between phenotype and genotype as well as biochemical VLCFAs analysis were found.ConclusionsWe emphasize that corpus callosum and internal capsule are always involved in ALD. A unilateral lesion is also possible. Neuroimaging of cerebral AMN is different from typical CALD with more centrum semiovale involvement. We support spinocerebellar variant was a rare subtype of AMN.

Background and Objectives: Identifying carriers of Pathogenic/Likely Pathogenic Variants in patients with dementia is crucial for risk stratification, particularly in individuals with a family history. This study developed and validated a clinical prediction model using whole-exome sequencing-confirmed cohorts. Methods: A total of 601 Chinese patients with dementia and a family history were enrolled at Peking Union Medical College Hospital, with 476 in a retrospective derivation cohort and 125 in a temporal validation cohort. Predictive factors included age at onset, APOE ε4 status, and family history characteristics. Model performance was assessed using discrimination and calibration metrics. Results: In the derivation cohort (median age at onset 66 years), 10.3% carried Pathogenic/Likely Pathogenic Variants. Among patients with dementia, those with age at onset < 55 years (OR 2.56, p = 0.0098), more than two affected relatives (OR 3.32, p = 0.0039), parental disease history (OR 4.72, p = 0.015), and early-onset cases in the family (OR 2.61, p = 0.0096) were positively associated with Pathogenic/Likely Pathogenic Variant carriage, whereas APOE ε4 carriage was inversely associated (OR 0.36, p = 0.0041). The model achieved an area under the curve of 0.776 (95% CI, 0.701–0.853) in the derivation cohort and 0.781 (95% CI, 0.647–0.914) in the validation cohort (median age at onset 58 years), with adequate calibration. Conclusions: This model demonstrated strong predictive performance for Pathogenic/Likely Pathogenic Variant carriage, supporting its clinical utility in guiding genetic testing. Further research is needed to refine the model.

Background The pediatric genetic white matter disorders are characterized by a broad disease spectrum. Genetic testing is valuable in the diagnosis. However, there are few studies on the clinical and genetic spectrum of Chinese pediatric genetic white matter disorders. Methods The participants were enrolled from the cohort of Peking Union Medical College Hospital. They all received history collection, brain MRI and gene sequencing. Their neurologic complaints which were related to white matter disorders occurred before 18. Brain MRI indicated periventricular and/or deep white matter lesions, fazekas grade 2–3. Results Among the 13 subjects, there were 11 males and two females. The average age of onset was 10.0 ± 5.5 years old. The potential genetic variants were found in 84.6% (11/13) subjects. The ABCD1 showed the greatest mutation frequency (30.8%, 4/13). The EIF2B3 A151fs, EIF2B4 c.885 + 2T > G, EIF2B5 R129X and MPV17 Q142X were novel pathogenic/likely pathogenic variants. 100% (4/4) ABCD1 carriers were accompanied by visual impairment, whereas 100% (3/3) EIF2B carriers developed dysuria. 100% (4/4) ABCD1 carriers exhibited diffuse white matter hyperintensities mainly in the posterior cortical regions, while the EIF2B4 and EIF2B5 carriers were accompanied by cystic degeneration. Conclusion There is genotypic and phenotypic heterogeneity among Chinese subjects with pediatric genetic white matter disorders. The knowledge of these clinical and genetic characteristics facilitates an accurate diagnosis of these diseases.