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INTRODUCTION: Whether brain functional connectivity (FC) is consistently disrupted in individuals with mild cognitive impairment (MCI) with isolated language impairment (ilMCI), and its potential to differentiate between MCI subtypes remains uncertain. METHODS: Cross-sectional data from 404 participants in two cohorts (the Chinese Preclinical Alzheimer's Disease Study and the Alzheimer's Disease Neuroimaging Initiative) were analyzed, including neuropsychological tests, resting-state functional magnetic resonance imaging (fMRI), cerebral amyloid positivity, and apolipoprotein E (APOE) status. RESULTS: Temporo-frontoparietal FC, particularly between the bilateral superior temporal pole and the left inferior frontal/supramarginal gyri, was consistently decreased in ilMCI compared to amnestic MCI (aMCI) and normal controls, which was correlated with semantic impairment. Using mean temporo-frontoparietal FC as a classifier could improve accuracy in identifying ilMCI subgroups with positive cerebral amyloid deposition and APOE risk alleles. DISCUSSION: Temporal-frontoparietal hypoconnectivity was observed in individuals with ilMCI, which may reflect semantic impairment and serve as a valuable biomarker to indicate potential mechanisms of underlying neuropathology. HIGHLIGHTS: Temporo-frontoparietal hypoconnectivity was observed in impaired language mild cognitive impairment (ilMCI). Temporo-frontoparietal hypoconnectivity may reflect semantic impairment. Temporo-frontoparietal functional connectivity can classify ilMCI subtypes.
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Alkaloids have remarkable biological and pharmacological properties and have recently garnered extensive attention. Various alkaloids, including commercially available drugs such as berberine, substantially affect ferroptosis. In addition to the three main pathways of ferroptosis, iron metabolism, phospholipid metabolism, and the glutathione peroxidase 4-regulated pathway, novel mechanisms of ferroptosis are continuously being identified. Alkaloids can modulate the progression of various diseases through ferroptosis and exhibit the ability to exert varied effects depending on dosage and tissue type underscores their versatility. Therefore, this review comprehensively summarizes primary targets and the latest advancements of alkaloids in ferroptosis, as well as the dual roles of alkaloids in inhibiting and promoting ferroptosis.
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Introduction: Some evidence suggests that fruit and alcohol consumption may be related to cognitive impairment. Methods: This study conducted a cross-sectional study on the "correlation between eating habits and cognitive function of the middle-aged and elderly population in China." The purpose of this study is to explore the relationship between fruit consumption, drinking habits and cognitive impairment in Chinese people over 50 years old. Results: The results show that the protective factors of cognitive impairment are the preference for berries and the daily intake of 100-200 grams grapes in Chinese middle-aged and elderly people with objective cognitive unimpaired. The habit of drinking red wine is a protective factor for cognitive impairment in Chinese middle-aged and elderly people with mild cognitive impairment (MCI). However, this study did not find the relationship between white wine, beer, yellow rice wine, liquor and cognitive impairment. Discussion: Therefore, we believe that berries, grapes and red wine consumption can protect the cognitive function of the middle-aged and elderly people in China, and the protective function is related to the basic cognitive state.
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Semantic dementia is a kind of neurodegenerative disorder, characterized by prominent semantic impairments and anterior temporal lobe atrophy. Since 2010, more studies have devoted to this rare disorder, revealing that it is more complex than we think. Clinical advances include more specific findings of semantic impairments and other higher order cognitive deficits. Neuroimaging techniques can help revealing the different brain networks affected (both structurally and functionally) in this condition. Pathological and genetic studies have also found more complex situations of semantic dementia, which might explain the huge variance existing in semantic dementia. Moreover, the current diagnosis criteria mainly focus on semantic dementia's classical prototype. We further delineated the features of three subtypes of semantic dementia based on atrophy lateralization with three severity stages. In a broader background, as a part of the continuum of neurodegenerative disorders, semantic dementia is commonly compared with other resembling conditions. Therefore, we summarized the differential diagnosis between semantic dementia and them. Finally, we introduced the challenges and achievements of its diagnosis, treatment, care and cross cultural comparison. By providing a comprehensive picture of semantic dementia on different aspects of advances, we hope to deepen the understanding of semantic dementia and promote more inspirations on both clinical and theoretical studies about it.
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Demencia Frontotemporal , Neuroimagen , Humanos , Neuroimagen/métodos , Demencia Frontotemporal/diagnóstico por imagen , Demencia Frontotemporal/patología , Demencia Frontotemporal/psicología , Demencia Frontotemporal/fisiopatología , Demencia Frontotemporal/diagnóstico , Neuropsicología/tendencias , Neuropsicología/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Encéfalo/fisiopatologíaRESUMEN
BACKGROUND & AIMS: It has been revealed good nutritional status and no physical frailty, which are modifiable lifestyle factors, are linked to less cognitive decline and a lower risk of Alzheimer's disease (AD). We aimed to investigate the associations between nutritional status and physical frailty and plasma AD biomarkers, especially the Tau-associated biomarkers in older cognitively unimpaired (CU) adults with higher ß-amyloid (Aß) burden. METHODS: The nutritional status and physical frailty were assessed via Mini-Nutritional Assessment Short-Form (MNA-SF) and Fried frailty index. The participants underwent the examination of plasma AD biomarkers and 18F-florbetapir PET scan as well as 18F-MK6240 PET in the validation cohort. Correlation and multiple linear regression analyses were used to investigate the associations between nutritional status and frailty and AD biomarkers. RESULTS: Two cohorts were included in our study. A total of 129 participants with Aß-PET positive were enrolled in the development cohort. Multiple linear regression analysis showed MNA-SF scores, normal nutritional status, Fried frailty index scores, frailty and some domains of frailty including weight loss, maximal grip strength and exhaustion were associated with plasma p-Tau-181. Furthermore, weight loss, Fried frailty index scores and frailty were associated with higher Aß-PET standard uptake value ratio. We further performed subgroup analyses stratified by age, sex and apolipoprotein E ε4 genotype to investigate the beneficial characteristics of nutrition and frailty in the special subgroups. Validation cohort contained 38 Aß-PET positive participants. MNA-SF scores, normal nutritional status, Fried frailty index scores and frailty were associated with Tau burden evaluated by 18F-MK6240 PET Braak-like stages. CONCLUSIONS: Our data indicates that normal nutritional status and no physical frailty may be associated with expected trend of plasma AD biomarkers, especially less Tau pathology in older CU adults with Aß deposition. Adjusting to these characteristics of nutrition and physical frailty may help reduce the risk of AD development.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Fragilidad , Estado Nutricional , Tomografía de Emisión de Positrones , Humanos , Masculino , Femenino , Anciano , Biomarcadores/sangre , Enfermedad de Alzheimer/sangre , Fragilidad/sangre , Péptidos beta-Amiloides/sangre , Tomografía de Emisión de Positrones/métodos , Proteínas tau/sangre , Anciano de 80 o más Años , Evaluación Nutricional , Estudios de Cohortes , Anciano Frágil , Cognición/fisiología , Evaluación Geriátrica/métodos , Fuerza de la Mano/fisiologíaRESUMEN
The metabolic implications in Alzheimer's disease (AD) remain poorly understood. Here, we conducted a metabolomics study on a moderately aging Chinese Han cohort (n = 1397; mean age 66 years). Conjugated bile acids, branch-chain amino acids (BCAAs), and glutamate-related features exhibited strong correlations with cognitive impairment, clinical stage, and brain amyloid-ß deposition (n = 421). These features demonstrated synergistic performances across clinical stages and subpopulations and enhanced the differentiation of AD stages beyond demographics and Apolipoprotein E ε4 allele (APOE-ε4). We validated their performances in eight data sets (total n = 7685) obtained from Alzheimer's Disease Neuroimaging Initiative (ADNI) and Religious Orders Study and Memory and Aging Project (ROSMAP). Importantly, identified features are linked to blood ammonia homeostasis. We further confirmed the elevated ammonia level through AD development (n = 1060). Our findings highlight AD as a metabolic disease and emphasize the metabolite-mediated ammonia disturbance in AD and its potential as a signature and therapeutic target for AD.
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Enfermedad de Alzheimer , Amoníaco , Metabolómica , Fenotipo , Humanos , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/genética , Amoníaco/metabolismo , Anciano , Femenino , Masculino , Persona de Mediana Edad , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/genética , Péptidos beta-Amiloides/metabolismo , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Ácidos y Sales Biliares/metabolismo , Anciano de 80 o más Años , Estudios de CohortesRESUMEN
INTRODUCTION: Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer's disease (AD). METHODS: Ten cognitively impaired (CI) individuals and 10 healthy controls (HCs) underwent [18F]SynVesT-1 and [18F]PSS232 positron emission tomography (PET)/magnetic resonance to assess synaptic density and mGluR5 availability. The associations between mGluR5 availability and synaptic density were examined. A mediation analysis was performed to investigate the possible mediating effects of mGluR5 availability and synaptic loss on the relationship between amyloid deposition and cognition. RESULTS: CI patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and cognition. CONCLUSIONS: Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD and are closely linked. HIGHLIGHTS: Cognitively impaired patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and global cognition. With further research, modulating mGluR5 availability might be a potential therapeutic strategy for improving synaptic function in AD.
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Disfunción Cognitiva , Tomografía de Emisión de Positrones , Receptor del Glutamato Metabotropico 5 , Humanos , Receptor del Glutamato Metabotropico 5/metabolismo , Masculino , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Femenino , Anciano , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Imagen por Resonancia Magnética , Sinapsis/metabolismo , Sinapsis/patología , Persona de Mediana Edad , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/patologíaRESUMEN
The associations of synaptic loss with amyloid-ß (Aß) and tau pathology measured by positron emission tomography (PET) and plasma analysis in Alzheimer's disease (AD) patients are unknown. Seventy-five participants, including 26 AD patients, 19 mild cognitive impairment (MCI) patients, and 30 normal controls (NCs), underwent [18F]SynVesT-1 PET/MR scans to assess synaptic density and [18F]florbetapir and [18F]MK6240 PET/CT scans to evaluate Aß plaques and tau tangles. Among them, 19 AD patients, 12 MCI patients, and 29 NCs had plasma Aß42/40 and p-tau181 levels measured by the Simoa platform. Twenty-three individuals, 6 AD patients, 4 MCI patients, and 13 NCs, underwent [18F]SynVesT-1 PET/MRI and [18F]MK6240 PET/CT scans during a one-year follow-up assessment. The associations of Aß and tau pathology with cross-sectional and longitudinal synaptic loss were investigated using Pearson correlation analyses, generalized linear models and mediation analyses. AD patients exhibited lower synaptic density than NCs and MCI patients. In the whole cohort, global Aß deposition was associated with synaptic loss in the medial (r = -0.431, p < 0.001) and lateral (r = -0.406, p < 0.001) temporal lobes. Synaptic density in almost all regions was related to the corresponding regional tau tangles independent of global Aß deposition in the whole cohort and stratified groups. Synaptic density in the medial and lateral temporal lobes was correlated with plasma Aß42/40 (r = 0.300, p = 0.020/r = 0.289, p = 0.025) and plasma p-tau 181 (r = -0.412, p = 0.001/r = -0.529, p < 0.001) levels in the whole cohort. Mediation analyses revealed that tau tangles mediated the relationship between Aß plaques and synaptic density in the whole cohort. Baseline tau pathology was positively associated with longitudinal synaptic loss. This study suggested that tau burden is strongly linked to synaptic density independent of Aß plaques, and also can predict longitudinal synaptic loss.
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INTRODUCTION: We aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants. METHODS: One hundred ten CI participants underwent amyloid positron emission tomography (PET) with 18F-florbetapir and synaptic density PET with 18F-SynVesT-1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype on the associations of synaptic density with Alzheimer's disease (AD) biomarkers. The mediation effects of AD biomarkers on ε4-associated synaptic density loss were analyzed. RESULTS: Compared with non-carriers, APOE ε4 allele carriers exhibited significant synaptic loss in the medial temporal lobe. Amyloid beta (Aß) and tau pathology mediated the effects of APOE ε4 on synaptic density to different extents. The associations between synaptic density and tau pathology were regulated by the APOE ε4 genotype. DISCUSSION: The APOE ε4 allele was associated with decreased synaptic density in CI individuals and may be driven by AD biomarkers.
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Péptidos beta-Amiloides , Apolipoproteína E4 , Disfunción Cognitiva , Tomografía de Emisión de Positrones , Sinapsis , Humanos , Masculino , Femenino , Apolipoproteína E4/genética , Anciano , Disfunción Cognitiva/genética , Disfunción Cognitiva/patología , Sinapsis/patología , Sinapsis/metabolismo , Péptidos beta-Amiloides/metabolismo , Proteínas tau/genética , Proteínas tau/metabolismo , Genotipo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Biomarcadores , Persona de Mediana Edad , Alelos , Anciano de 80 o más Años , Encéfalo/patología , Encéfalo/diagnóstico por imagenRESUMEN
Alzheimer's disease (AD) is a common cause of dementia, characterised by cerebral amyloid-ß deposition, pathological tau and neurodegeneration. The prodromal stage of AD (pAD) refers to patients with mild cognitive impairment (MCI) and evidence of AD's pathology. At this stage, disease-modifying interventions should be used to prevent the progression to dementia. Given the inherent heterogeneity of MCI, more specific biomarkers are needed to elucidate the underlying AD's pathology. Although the uses of cerebrospinal fluid and positron emission tomography are widely accepted methods for detecting AD's pathology, their clinical applications are limited by their high costs and invasiveness, particularly in low-income areas in China. Therefore, to improve the early detection of Alzheimer's disease (AD) pathology through cost-effective screening methods, a panel of 45 neurologists, psychiatrists and gerontologists was invited to establish a formal consensus on the screening of pAD in China. The supportive evidence and grades of recommendations are based on a systematic literature review and focus group discussion. National meetings were held to allow participants to review, vote and provide their expert opinions to reach a consensus. A majority (two-thirds) decision was used for questions for which consensus could not be reached. Recommended screening methods are presented in this publication, including neuropsychological assessment, peripheral biomarkers and brain imaging. In addition, a general workflow for screening pAD in China is established, which will help clinicians identify individuals at high risk and determine therapeutic targets.
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Subjective cognitive decline is potentially the earliest symptom of Alzheimer's disease, whose objective neurological basis remains elusive. To explore the potential biomarkers for subjective cognitive decline, we developed a novel deep learning method based on multiscale dynamical brain functional networks to identify subjective cognitive declines. We retrospectively constructed an internal data set (with 112 subjective cognitive decline and 64 healthy control subjects) to develop and internally validate the deep learning model. Conventional deep learning methods based on static and dynamic brain functional networks are compared. After the model is established, we prospectively collect an external data set (26 subjective cognitive decline and 12 healthy control subjects) for testing. Meanwhile, our method provides monitoring of the transitions between normal and abnormal (subjective cognitive decline-related) dynamical functional network states. The features of abnormal dynamical functional network states are quantified by network and variability metrics and associated with individual cognitions. Our method achieves an area under the receiver operating characteristic curve of 0.807 ± 0.046 in the internal validation data set and of 0.707 (P = 0.007) in the external testing data set, which shows improvements compared to conventional methods. The method further suggests that, at the local level, the abnormal dynamical functional network states are characterized by decreased connectivity strength and increased connectivity variability at different spatial scales. At the network level, the abnormal states are featured by scale-specifically altered modularity and all-scale decreased efficiency. Low tendencies to stay in abnormal states and high state transition variabilities are significantly associated with high general, language and executive functions. Overall, our work supports the deficits in multiscale brain dynamical functional networks detected by the deep learning method as reliable and meaningful neural alternation underpinning subjective cognitive decline.
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A newly developed SV2A radiotracer, 18F-SynVesT-1, was used in this study to investigate synaptic density and its association with Alzheimer's disease (AD) "A/T/N" biomarkers. The study included a cohort of 97 subjects, consisting of 64 patients with cognitive impairment (CI) and 33 individuals with normal cognition (CU). All subjects underwent 18F-SynVesT-1 PET/MR and 18F-florbetapir PET/CT scans. Additionally, a subgroup of individuals also underwent 18F-MK-6240, 18F-FDG PET/CT, plasma Aß42/Aß40 and p-tau181 tests. The differences in synaptic density between the groups and the correlations between synaptic density and AD "A/T/N" biomarkers were analyzed. The results showed that compared to the CU group, the CI with Aß+ (CI+) group exhibited the most pronounced synapse loss in the hippocampus, with some loss also observed in the neocortex. Furthermore, synaptic density in the hippocampus and parahippocampal gyrus showed associations with AD biomarkers detected by both imaging and plasma tests in the CI group. The associations between synaptic density and FDG uptake and hippocampal volume were also observed in the CI+ group. In conclusion, the study demonstrated significant synaptic density loss, as measured by the promising tracer 18F-SynVesT-1, and its close correlation with "A/T/N" biomarkers in patients with both Alzheimer's clinical syndrome and pathological changes.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Biomarcadores , Sinapsis , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Masculino , Femenino , Anciano , Sinapsis/metabolismo , Sinapsis/patología , Péptidos beta-Amiloides/metabolismo , Persona de Mediana Edad , Proteínas tau/metabolismo , Imagen por Resonancia Magnética/métodos , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/diagnóstico por imagen , Glicoproteínas de Membrana/metabolismo , Radioisótopos de Flúor , Proteínas del Tejido Nervioso/metabolismo , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the initial pathophysiological mechanism of Alzheimer's disease (AD). The study aims to investigate the association between mGluR5 availability and AD's biomarkers and cognitive function. METHODS: We examined 35 individuals with mGluR5 tracer [18F]PSS232 to assess mGluR5 availability, and with [18F]Florbetapir PET to assess global amyloid deposition, and [18F]FDG PET to assess glucose metabolism. The plasma neurofilament light (NfL) and p-tau181 levels in a subset of individuals were measured (n = 27). The difference in mGluR5 availability between the AD and normal control (NC) groups was explored. The associations of mGluR5 availability with amyloid deposition, glucose metabolism, gray matter volume (GMV), neuropsychological assessment scores, and plasma biomarkers were analyzed. RESULTS: The mGluR5 availability was significantly reduced in AD patients' hippocampus and parahippocampal gyrus compared to NCs. Global amyloid deposition was positively associated with mGluR5 availability in the AD group and reversely associated in the NC group. The mGluR5 availability was positively correlated with regional glucose metabolism in the overall and stratified analyses. The availability of mGluR5 in the hippocampus and parahippocampal gyrus demonstrated a strong relationship with the GMV of the medial temporal lobe, plasma p-tau181 or NfL levels, and global cognitive performance. CONCLUSIONS: [18F]PSS232 PET can quantify the changes of mGluR5 availability in the progression of AD. mGluR5 availability correlated not only with neuropathological biomarkers of AD but also with neurodegenerative biomarkers and cognitive performance. mGluR5 may be a novel neurodegenerative biomarker, and whether mGluR5 could be a potential therapeutic target for AD needs to be further studied.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Oximas , Piridinas , Humanos , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Biomarcadores/metabolismo , Encéfalo/metabolismo , Disfunción Cognitiva/metabolismo , Glucosa/metabolismo , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Receptor del Glutamato Metabotropico 5/metabolismoRESUMEN
The Category Switching Test (CaST) is a verbal fluency test with active semantic category switching. This study aimed to explore the association between CaST performance and brain amyloid-ß (Aß) burden in patients with mild cognitive impairment (MCI) and the neurofunctional mechanisms. A total of 112 participants with MCI underwent Florbetapir positron emission tomography, resting-state functional magnetic resonance imaging, and a neuropsychological test battery. The high Aß burden group had worse CaST performance than the low-burden group. CaST score and left middle temporal gyrus fractional amplitude of low-frequency fluctuations (fALFF) related inversely to the global Florbetapir standardized uptake value rate. Functional connectivity between the left middle temporal gyrus and frontal lobe decreased widely and correlated with CaST score in the high Aß burden group. Thus, CaST score and left middle temporal gyrus fALFF were valuable in discriminating high Aß burden. CaST might be useful in screening for MCI with high Aß burden.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Glicoles de Etileno , Humanos , Enfermedad de Alzheimer/diagnóstico , Disfunción Cognitiva/diagnóstico por imagen , Péptidos beta-Amiloides , Compuestos de AnilinaRESUMEN
Sex disparities in serum bile acid (BA) levels and Alzheimer's disease (AD) prevalence have been established. However, the precise link between changes in serum BAs and AD development remains elusive. Here, authors quantitatively determined 33 serum BAs and 58 BA features in 4 219 samples collected from 1 180 participants from the Alzheimer's Disease Neuroimaging Initiative. The findings revealed that these BA features exhibited significant correlations with clinical stages, encompassing cognitively normal (CN), early and late mild cognitive impairment, and AD, as well as cognitive performance. Importantly, these associations are more pronounced in men than women. Among participants with progressive disease stages (n = 660), BAs underwent early changes in men, occurring before AD. By incorporating BA features into diagnostic and predictive models, positive enhancements are achieved for all models. The area under the receiver operating characteristic curve improved from 0.78 to 0.91 for men and from 0.76 to 0.83 for women for the differentiation of CN and AD. Additionally, the key findings are validated in a subset of participants (n = 578) with cerebrospinal fluid amyloid-beta and tau levels. These findings underscore the role of BAs in AD progression, offering potential improvements in the accuracy of AD prediction.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Masculino , Humanos , Femenino , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides/líquido cefalorraquídeo , Ácidos y Sales BiliaresRESUMEN
BACKGROUND: Little is known about association between neuropsychiatric symptoms and plasma biomarkers across the entire Alzheimer's continuum. METHODS: A total of 305 individuals with amyloid-ß (Aß) deposition (determined by 18F-florbetapir PET) participated in this study, including cognitively normal controls (n = 53), subjective cognitive decline (SCD, n = 75), mild cognitive impairment (MCI, n = 74), and dementia (n = 103). Plasma biomarkers (Aß1-42, Aß1-40, total tau [t-tau], phosphorylated tau 181 [p-tau181], and neurofilament light [NfL]), apolipoprotein E (APOE) genotyping and Neuropsychiatric Inventory Questionnaire (NPI-Q) were completed. Neuropsychiatric symptoms were classified into four subsymdromes (hyperactivity, psychosis, affective, and apathy). Logistic regression analysis was conducted to investigate relationships between neuropsychiatric symptoms and plasma biomarkers. RESULTS: About one-third of cognitively unimpaired individuals (normal controls: 34.0 %, SCD: 28.0 %) reported one or more neuropsychiatric symptoms, and more in symptomatic stages such as MCI (40.5 %) and dementia (81.0 %). Plasma NfL significantly increased in dementia group compared to SCD and healthy controls, relating to a higher risk of aberrant motor behavior, anxiety, sleep disturbance, disinhibition, and euphoria. Older age (odds ratio [OR] = 1.079, 95 % confidence interval [CI] = 1.022-1.140, p = 0.006), lower cognitive score (OR = 0.846, 95%CI = 0.791-0.905, p < 0.001) and increased plasma NfL (OR = 1.021, 95%CI = 1.00-1.042, p = 0.041) could predict psychosis. No significant differences were found in plasma Aß1-42/Aß1-40, t-tau or p-tau181 across all groups, and none correlated with neuropsychiatric symptoms. LIMITATIONS: The cross-sectional design, small sample size and use of NPI-Q. CONCLUSIONS: This study supported neuropsychiatric symptoms as early manifestations of preclinical Alzheimer's disease, and suggested plasma NfL to be a potential biomarker for detecting neuropsychiatric symptoms in Alzheimer's continuum.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Estudios Transversales , Péptidos beta-Amiloides , Disfunción Cognitiva/psicología , BiomarcadoresRESUMEN
Brain disorders in the early and late life of humans potentially share pathological alterations in brain functions. However, the key neuroimaging evidence remains unrevealed for elucidating such commonness and the relationships among these disorders. To explore this puzzle, we build a restricted single-branch deep learning model, using multi-site functional magnetic resonance imaging data (N = 4,410, 6 sites), for classifying 5 different early- and late-life brain disorders from healthy controls (cognitively unimpaired). Our model achieves 62.6 ± 1.9% overall classification accuracy and thus supports us in detecting a set of commonly affected functional subnetworks, including default mode, executive control, visual, and limbic networks. In the deep-layer representation of data, we observe young and aging patients with disorders are continuously distributed, which is in line with the clinical concept of the "spectrum of disorders." The relationships among brain disorders from the revealed spectrum promote the understanding of disorder comorbidities and time associations in the lifespan.
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OBJECTIVES: Amyloid deposition is considered the initial pathology in Alzheimer's disease (AD). Personalized management requires investigation of amyloid pathology and the risk factors for both amyloid pathology and cognitive decline in the Chinese population. We aimed to investigate amyloid positivity and deposition in AD patients, as well as factors related to amyloid pathology in Chinese cities. METHODS: This cross-sectional multicenter study was conducted in Shanghai and Zhengzhou, China. All participants were recruited from urban communities and memory clinics. Amyloid positivity and deposition were analyzed based on amyloid positron emission tomography (PET). We used partial least squares (PLS) models to investigate how related factors contributed to amyloid deposition and cognitive decline. RESULTS: In total, 1026 participants were included: 768 participants from the community-based cohort (COMC) and 258 participants from the clinic-based cohort (CLIC). The overall amyloid-positive rates in individuals with clinically diagnosed AD, mild cognitive impairment (MCI), and normal cognition (NC) were 85.8%, 44.5%, and 26.9%, respectively. The global amyloid deposition standardized uptake value ratios (SUVr) (reference: cerebellar crus) were 1.44 ± 0.24, 1.30 ± 0.22, and 1.24 ± 0.14, respectively. CLIC status, apolipoprotein E (ApoE) ε4, and older age were strongly associated with amyloid pathology by PLS modeling. CONCLUSION: The overall amyloid-positive rates accompanying AD, MCI, and NC in the Chinese population were similar to those in published cohorts of other populations. ApoE ε4 and CLIC status were risk factors for amyloid pathology across the AD continuum. Education was a risk factor for amyloid pathology in MCI. Female sex and age were risk factors for amyloid pathology in NC. CLINICAL RELEVANCE STATEMENT: This study provides new details about amyloid pathology in the Chinese population. Factors related to amyloid deposition and cognitive decline can help to assess patients' AD risk. KEY POINTS: ⢠We studied amyloid pathology and related risk factors in the Chinese population. ⢷The overall amyloid-positive rates in individuals with clinically diagnosed AD, MCI, and NC were 85.8%, 44.5%, and 26.9%, respectively. ⢠These overall amyloid-positive rates were in close agreement with the corresponding prevalence for other populations.
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CONTEXT: Previous research evaluating the effects in B-vitamins on the prevention and treatment of cardiovascular disease (CVD) has substantial limitations and lacks recently published large prospective studies; hence, conducting an updated meta-analysis is needed. OBJECTIVE: We investigated the association between vitamin B status and human CVD development in order to provide more specific advice about vitamin B intake for those at risk of CVD. DATA SOURCES: Relevant articles were identified by JSTOR, PubMed, and ProQuest databases. DATA EXTRACTION: Key words used to identify the studies included the different combinations of B-vitamins, folate, folic acid, vitamin B6, vitamin B12, homocysteine, cardiovascular disease, stroke, coronary disease, myocardial infarction, and cerebrovascular and transient ischemic attack. The database search was supplemented by hand-searching of reference lists of selected articles. DATA ANALYSIS: Pooled estimates were calculated from the mean differences using a random-effects model. RESULTS: Supplementation with folic acid was reported to have a clinical benefit of significantly reducing carotid intima-media thickness. Higher intakes of folic acid, vitamin B6, and vitamin B12 were generally associated with a lower risk of CVD in the general population, except in those without normal renal function and those with unstable angina or past non-ST-elevation myocardial infarction. CONCLUSION: Vitamin B supplementation resulted in the greatest cardiovascular benefit in those with normal renal function and without unstable angina or non-ST-elevation myocardial infarction recently. Factors such as age, gender, and genetic polymorphisms contribute to varying effects.