Alzheimer′s disease (AD) is one of the most common neurodegenerative diseases, and its diagnosis heavily relies on imaging biomarkers. This paper integrates core pathological markers, such as amyloid β (Aβ)-positron emission tomography (PET), tau-PET, structural magnetic resonance imaging, and fluorodeoxyglucose-PET, with the latest advancements in novel imaging biomarkers, including inflammation, synaptic imaging, and cerebrovascular injury-related markers, based on the Aβ proteinopathy, tau proteinopathy, neurodegeneration, inflammation, α-synuclein and vascular brain injury biomarkers (AT 1T 2NISV) framework proposed by the 2024 Alzheimer′s Association diagnostic guidelines. With the development of machine learning and artificial intelligence technologies, future research should focus on enhancing the specificity of imaging biomarkers and developing precise diagnostic models for comorbidities to better address the heterogeneity and complex pathological features of AD.

BACKGROUND: Physical activity, sedentary behavior (SB), and sleep duration are associated with brain health. Effects of those on developing Parkinson's disease (PD) are poorly investigated. This study aimed to examine the independent and joint associations of physical activity, SB, sleep with PD risk. METHODS: We analyzed data on 401,697 participants from the UK Biobank cohort, which was enrolled in 2006-2010. Physical activities were measured based on a questionnaire. Sleep and SB time were defined through self-reported total number of hours. Models fitted with restricted cubic spline were conducted to test for linear and non-linear shapes of each association. Cox proportional hazards regression models were used to estimate the association of three modifiable behaviors. RESULTS: Our analytic sample included 401,697 participants with 3030 identified cases of PD (mean age, 63 years; 62.9% male). PD risk was 18% lower in the high total physical activity group (95% CI, 0.75-0.90), 22% lower in the high leisure-time physical activity (LTPA) group (95% CI, 0.71-0.86) compared with the low level and 14% higher in the high sleep duration group (95% CI, 1.05-1.24) compared to moderate group. Total SB time was irrelevant with PD risk, while high TV viewing showed a 12% increase of PD risk compared to the low group (95% CI, 1.02-1.22). Low computer use (0 h/day) was associated with a 14% higher risk compared to 1 h/day use (95% CI, 1.04-1.26). Those associations were independent. A combination of 7 h/day sleep, moderate-to-high computer use, and moderate-to-vigorous intensity of LTPA showed lowest PD risk (HR, 0.70; 95% CI, 0.57-0.85). CONCLUSIONS Physical activity, SB, and sleep were associated with PD risks separately. Our findings emphasize the possibility for changing these three daily activities concurrently to lower the risk of PD. These findings may promote an active lifestyle for PD prevention.
Humans ; Parkinson Disease/physiopathology* ; Male ; Sedentary Behavior ; Female ; Middle Aged ; Exercise/physiology* ; Prospective Studies ; Sleep/physiology* ; Aged ; Surveys and Questionnaires ; Proportional Hazards Models ; Risk Factors

BACKGROUND: Neuroticism has been associated with numerous health outcomes. However, most research has focused on a single specific disorder and has produced controversial results, particularly regarding mortality risk. Here, we aimed to examine the association of neuroticism with morbidity and mortality and to elucidate how neuroticism affects trajectories from a healthy state, to one or more neuroticism-related disorders, and subsequent mortality risk. METHODS: We included 483,916 participants from the UK Biobank at baseline (2006-2010). Neuroticism was measured using the Eysenck Personality Questionnaire. Three clusters were constructed, including worry, depressed affect, and sensitivity to environmental stress and adversity (SESA). Cox proportional hazards regression and multistate models were used. Linear regression was used to examine the association between neuroticism and immune parameters and neuroimaging measures. RESULTS: High neuroticism was associated with 37 non-overlapping diseases, including increased risk of infectious, cardiometabolic, neuropsychiatric, digestive, and respiratory diseases, and decreased risk of cancer. After adjustment for sociodemographic variables, physical measures, healthy behaviors, and baseline diagnoses, moderate-to-high neuroticism was associated with a decreased risk of all-cause mortality. In multistate models, high neuroticism was associated with an increased risk of transitions from a healthy state to a first neuroticism-related disease (hazard ratio [HR] [95% confidence interval (CI)] = 1.09 [1.05-1.13], P  <0.001) and subsequent transitions to multimorbidity (1.08 [1.02-1.14], P  = 0.005), but was associated with a decreased risk of transitions from multimorbidity to death (0.90 [0.84-0.97], P for trend = 0.006). The leading neuroticism cluster showing a detrimental role in the health-illness transition was depressed affect, which correlated with higher amygdala volume and lower insula volume. The protective effect of neuroticism against mortality was mainly contributed by the SESA cluster, which, unlike the other two clusters, did not affect the balance between innate and adaptive immunity. CONCLUSION This study provides new insights into the differential role of neuroticism in health outcomes and into new perspectives for establishing mortality prevention programs for patients with multimorbidity.
Humans ; Neuroticism/physiology* ; Male ; Female ; Middle Aged ; Aged ; Proportional Hazards Models ; Surveys and Questionnaires ; Adult ; Risk Factors

Alzheimer′s disease (AD) is one of the most common neurodegenerative diseases, and its diagnosis heavily relies on imaging biomarkers. This paper integrates core pathological markers, such as amyloid β (Aβ)-positron emission tomography (PET), tau-PET, structural magnetic resonance imaging, and fluorodeoxyglucose-PET, with the latest advancements in novel imaging biomarkers, including inflammation, synaptic imaging, and cerebrovascular injury-related markers, based on the Aβ proteinopathy, tau proteinopathy, neurodegeneration, inflammation, α-synuclein and vascular brain injury biomarkers (AT 1T 2NISV) framework proposed by the 2024 Alzheimer′s Association diagnostic guidelines. With the development of machine learning and artificial intelligence technologies, future research should focus on enhancing the specificity of imaging biomarkers and developing precise diagnostic models for comorbidities to better address the heterogeneity and complex pathological features of AD.

Vascular cognitive impairment (VCI) encompasses a wide spectrum of cognitive disorders, ranging from mild cognitive impairment to vascular dementia. Its diagnosis relies on thorough clinical evaluations and neuroimaging. VCI predominately arises from vascular risk factors (VRFs) and cerebrovascular disease, either independently or in conjunction with neurodegeneration. Growing evidence underscores the prevalence of VRFs, highlighting their potential for early prediction of cognitive impairment and dementia in later life. The precise mechanisms linking vascular pathologies to cognitive deficits remain elusive. Chronic cerebrovascular pathology is the most common neuropathological feature of VCI, often interacting synergistically with neurodegenerative processes. Current research efforts are focused on developing and validating reliable biomarkers to unravel the etiology of vascular brain changes in VCI. The collaborative integration of these biomarkers into clinical practice, alongside routine incorporation into neuropathological assessments, presents a promising strategy for predicting and stratifying VCI. The cornerstone of VCI prevention remains the control of VRFs, which includes multi-domain lifestyle modifications. Identifying appropriate pharmacological approaches is also of paramount importance. In this review, we synthesize recent advancements in the field of VCI, including its definition, determinants of vascular risk, pathophysiology, neuroimaging and fluid-correlated biomarkers, predictive methodologies, and current intervention strategies. Increasingly evident is the notion that more rigorous research for VCI, which arises from a complex interplay of physiological events, is still needed to pave the way for better clinical outcomes and enhanced quality of life for affected individuals.
Humans ; Cognitive Dysfunction/diagnosis* ; Dementia, Vascular/therapy* ; Risk Factors ; Biomarkers ; Cerebrovascular Disorders/diagnosis*

In recent years, precision medicine has made significant progress in the early diagnosis and treatment of Alzheimer′s disease (AD), bringing revolutionary changes to traditional models. In response to these innovative developments, the Chinese Society of Dementia and Cognitive Impairment, starting from the needs of China′s healthcare system and patients, has formulated and released the "Chinese expert consensus on the diagnosis and treatment of mild cognitive impairment due to Alzheimer′s disease 2024". This consensus establishes a systematic and comprehensive diagnostic and therapeutic framework, which not only provides practical guidelines for implementation but also lays a solid foundation for the new stage of precise prevention and treatment of AD. Based on this, in-depth discussions and comments were conducted on AD′s biomarkers, clinical diagnostic criteria, disease staging, and early intervention strategies, aiming to assist clinical and research professionals in constructing a comprehensive AD precision medicine system and to emphasize the importance of early precision recognition and management of the disease, thus advancing early diagnostic and therapeutic efforts for AD into a new era of precision medicine.

Objective:To investigate the neuropsychological and imaging features of patients with posterior cortical atrophy (PCA).Methods:Patients of PCA, dementia with Lewy bodies (DLB), typical Alzheimer′s disease (t-AD) who were diagnosed in the Department of Neurology, Huashan Hospital, Fudan University from September 27, 2019, to September 24, 2021 were enrolled, and the normal controls who visited the Outpatient and Physical Examination Centers of Huashan Hospital, Fudan University and Rizhao People′s Hospital at the same time were enrolled, too. Neuropsychological assessments, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT data of the 4-group subjects were collected. Variance analysis was used to compare the differences in neuropsychological performance among the 4 groups, and the imaging features of PCA patients were summarized.Results:Eleven PCA patients, 17 DLB patients, 31 t-AD patients, and 11 normal controls were included in the study. The cognitive function of patients in the PCA group [Mini-Mental State Examination (MMSE) score 13.52±1.81; Montreal Cognitive Assessment (MoCA) score 7.06±1.72] was significantly impaired compared to the normal control group (MMSE score 27.85±1.75, t=-6.561, P<0.001; MoCA score 23.60±1.59, t=-7.968, P<0.001]. However, there was no statistically significant difference compared to the DLB group and the t-AD group. Patients in the PCA group exhibited more severe impairments in attention, executive function, and language compared to the DLB group (Trail Making Test A score: 298.86±16.16 vs 110.07±18.62, t=9.980, P<0.001; Trail Making Test B score: 305.51±18.89 vs 230.34±23.59, t=2.865, P=0.024; Boston Naming Test score: 8.67±1.53 vs 15.66±1.56, t=-2.682, P=0.013) and the t-AD group (148.91±12.77, t=7.071, P<0.001; 200.78±19.34, t=3.789, P=0.004; 15.15±1.05, t=-2.544, P=0.016). Scores for visuospatial function [PCA group: 1(0, 1), normal control group: 3(3, 3), Z=-4.023, P<0.001] and visual perception [PCA group: 0(0, 1), normal control group: 35(34, 36), Z=-3.704, P<0.001] were significantly lower in the PCA group compared to the normal control group. The cranial MRI findings of PCA patients showed atrophy of the parietal and occipital lobes, with less obvious atrophy of the medial temporal lobe, which can be distinguished from t-AD. 18F-fluorodeoxyglucose PET/CT of the PCA patients showed a relative reduced glucose metabolism in the bilateral parietal lobe, occipital lobe and posterior cingulate gyrus, while the 18F-florbetapir PET/CT showed deposition of amyloid protein in the bilateral frontal lobe, parietal lobe, temporal lobe, and cingulate gyrus. Conclusions:PCA patients exhibit neuropsychological characteristics of visuospatial dysfunction, along with impairments in various cognitive domains such as memory, attention, and executive functions. The typical MRI feature is parietal occipital lobe atrophy, and the PET/CT findings are consistent with metabolic changes in AD.

We report a case of spinocerebellar ataxia type 8(SCA8)presenting with multisystem atrophic phenotype.The patient was a 57-year-old male with a 4-year course of illness with dizziness and ataxia as the first symptoms,followed by autonomic dysfunction and rapid eye movement sleep disorder.Neurological examination reveals autonomic dysfunction,nystagmus,dysarthria,ataxia,brain stem and cerebellar symmetrical atrophy and"hot cross bun"sign on MRI.The diagnosis of SCA8 was confirmed by the genetic testing which showed an abnormally high number of CTA/CTG repeats in the two alleles of the ATXN8OS.The patient responded well to symptomatic treatment such as ataxia and autonomic dysfunction.SCA8 is a rare movement disorder with high clinical heterogeneity.This report suggests that SCA8 can also present with autonomic dysfunction,ataxia,pontine"hot cross bun"sign and other characteristics similar to multisystem atrophy phenotype.Thus,it is necessary for clinicians to avoid misdiagnosis or missing the diagnosis of SCA8 presenting with multiple system atrophy cerebral type in clinical work.

Alzheimer′s disease (AD) is the most common neurodegenerative disease. Its etiology and pathogenesis remain unclear. Since its inception, the amyloid-β (Aβ) cascade hypothesis has dominated the field of AD research and has provided the intellectual framework for disease-modifying therapies. Nowadays, many Aβ-targeted therapies have been accelerated approval or received Food and Drug Administration′s breakthrough therapy designation which offers a new dawn for disease-modifying treating AD. This article reviews the research progress of clinical trials of Aβ-targeting modification therapies, and summarizes the lessons learned from the clinical failure with several classes of anti-Aβ drugs. Although many challenges remain, anti-Aβ therapies have become a promising treatment strategy for AD.