Abbreviation (ISO4): Chinese Journal of Alzheimer's Disease and Related Disorders
Editor in chief: Jun WANG
Alzheimer's disease (AD) is a chronic neurodegenerative disease with an insidious onset, often occurring in old age or pre old age. The main symptoms of the disease are a decline in memory and cognitive function, accompanied by language disorders, spatial orientation disorders, and behavioral impairments. AD is a common type of irreversible dementia, and its pathophysiological processes are initiated decades before clinical symptoms appear. Therefore, exploring biomarkers that can reveal early functional changes in AD and establishing objective and accurate auxiliary diagnostic tools have become the forefront and core of current research. Resting state functional magnetic resonance imaging (rs-fMRI) provides a unique window for non-invasive, in vivo evaluation of the functional integration and separation characteristics of large-scale brain networks by capturing spontaneous fluctuations in blood oxygen level dependent signals. This article reviews the research on combining artificial intelligence technology (AI) with rs-fMRI to achieve early auxiliary diagnosis of AD. This review first systematically introduces the biomarker potential of rs-fMRI in early diagnosis of AD; Secondly, the AI methodology applied to rs-fMRI analysis was elaborated, and the evolution of these AI methodologies, as well as multimodal fusion and interpretable AI strategies, were analyzed in detail; Finally, this article discusses the current challenges of these technologies, such as model generalization, data heterogeneity, interpretability barriers, and clinical translation obstacles, and provides prospects for the future development of this field. The deep integration of AI and rs-fMRI is driving a profound transformation in the early diagnosis of AD from an experience-based paradigm toward a data-driven, quantitative, and personalized paradigm. It will assist clinical doctors to cultivate and optimize medical decision-making, improve clinical diagnosis and treatment levels, and promote precision medicine.
Objective: To explore the association between the levels of adaptor protein complex 2 (AP2) in cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) and AD pathology, brain structural changes, and cognitive function. Methods: This study enrolled 138 patients with Alzheimer's disease (AD), 403 patients with mild cognitive impairment (MCI), and 167 cognitively normal (CN) subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Levels of AP2 (α2 and β1 subunits) in the cerebrospinal fluid (CSF) were measured. Data on core AD biomarkers, including amyloid-beta 1-42 (Aβ42), total tau protein (t-Tau), and phosphorylated tau at threonine 181 (p-Tau181), brain structural measures including ventricular volume, hippocampal volume, and entorhinal cortex thickness, and cognitive scores, including the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating - Sum of Boxes (CDRSB) were collected at baseline and over a five-year follow-up period. Statistical analyses were performed using one-way analysis of covariance, multiple linear regression models, and linear mixed-effects models. Results: At baseline, there were no significant differences in CSF AP2 levels among the CN, MCI, and AD groups, but they were significantly elevated in apolipoprotein (APOE) ε4 carriers. CSF AP2 levels increased with age, consistent with AD pathology progression. Elevated CSF AP2 levels were significantly associated with increased CSF Aβ42, T-tau, and p-Tau181 concentrations and smaller ventricular volume, especially in the CN and MCI stages. CSF AP2β1 was negatively correlated with CDRSB and positively correlated with hippocampal volume and entorhinal cortex thickness. Additionally, CSF AP2 affected longitudinal changes in brain structure and cognition, particularly in the non-AD group. Conclusion: CSF AP2 may be involved in early Aβ and tau pathology and is closely related to changes in ventricular volume, hippocampal volume, entorhinal cortex thickness, and cognition, especially in the preclinical and prodromal stages of AD.
Objective: To observe values of the third generation sequencing（TGS）in detecting tandem repeats of NIID（neuronal intranuclear inclusion disease). Methods: Peripheral blood samples were collected from 10 confirmed NIID patients (confirmed group), 10 clinically suspected cases (suspected group), and 10 healthy controls (control group) between January 2017 and December 2023. The NOTCH2NLC GGC repeats were amplified by long-range PCR (LR-PCR) and repeat-primed PCR (RP-PCR). The amplification products were first screened using capillary electrophoresis (CE). Results: The ten confirmed cases were again found with clinically significant GGC repeats in all cases, but in the earlier testing lab and the current testing lab the exact sequence repeats number were not available in 2 cases when the repeats were estimated to be more than 110. In the suspected group, there were 4 cases found with significant GGC repeats, but there were also two cases where CE platform could not give exact numbers of GGC repeats when the repeat numbers were estimated to be more than 110. In contrast,TGS could give exact numbers of GGC repeats, including the four cases where CE could not give the exact numbers of GGC repeats. There were no false positive or negative result in either platforms.Conclusions: This study confirms that TGS effectively overcomes the technical limitations of CE in quantifying highly repetitive sequences in NIID, enabling precise quantification and structural resolution of sequences, thereby providing more reliable technical support for molecular subtyping and precise diagnosis and treatment of NIID.
Objective: To evaluate the clinical efficacy of low-frequency transcranial magnetic stimulation (TMS) combined with mirror therapy (MT) in patients with hemiplegia and cognitive impairment following hemorrhagic stroke.Methods: Between February 2022 and February 2025, 92 patients with hemiplegia and cognitive impairment following hemorrhagic stroke admitted to our hospital were enrolled. They were randomly assigned to either the TMS group or the combined group, each comprising 46 subjects. The TMS group received conventional therapy plus low-frequency TMS, while the combined group added mirror therapy to the TMS regimen. Upper limb motor function, balance function, neurophysiological indicators, cognitive function, and activities of daily living were compared between the two groups. Results: Baseline upper limb FMA, BBS, MMSE, MBI scores, MEP amplitude, and CMCT were comparable between the TMS and combined groups, with no statistically significant differences (P > 0.05). After 4 weeks of treatment and 1 month post-treatment, both groups showed significant improvements in upper limb FMA, BBS, MMSE, and MBI scores compared to baseline (P < 0.05). Post-treatment scores in the combined group were significantly higher than those in the TMS group (P < 0.05). Additionally, at 4 weeks and 1 month post-treatment, the combined group showed greater improvements in MEP amplitude and CMCT (P < 0.05). Conclusion: Combined TMS and MT therapy promotes upper limb motor function and balance recovery in patients with hemiplegia and cognitive impairment following hemorrhagic stroke. It improves neuroelectrophysiological indicators, enhances cognitive function, and increases activities of daily living capabilities.
Objective: To retrospectively investigate the correlation between the monocyte to high-density lipoprotein cholesterol ratio（MHR）, tumor necrosis factor（TNF-α）, and brain-derived neurotrophic factor （BDNF） levels in the serum of early stroke patients and post-stroke cognitive impairment（PSCI）, and to explore the role of early serum MHR, TNF-α, and BDNF levels in predicting and evaluating PSCI. Methods: Stroke patients who were hospitalized in the Department of Neurology of the Fourth People's Hospital of Wujiang District, Suzhou City from January 2022 to June 2025 and returned to our hospital for follow-up within 6 months were selected. The cognitive function of all patients was evaluated using the Mini-Mental State Examination（MMSE）. According to the MMSE results and educational background, the patients were divided into the PSCI group and the non-PSCI group. All patients had detailed blood tests. The differences in MHR, TNF-α, and BDNF levels between the two groups were statistically analyzed. Results: A total of 60 patients were collected, with 30 patients in each group. Statistical analysis showed no significant differences in gender, age, and MHR between the two groups. There were significant differences in TNF-α and BDNF levels between the two groups（P<0.05）. Pearson correlation analysis showed that TNF-α level was negatively correlated with MMSE score （rs = -0.256, P = 0.048）, while BDNF level was not correlated with MMSE score （rs=0.198,P=0.129）. Logistic regression analysis showed that TNF-α （P<0.05, OR=0.903, 95% CI: 0.854 - 0.956） was an independent risk factor for PSCI. The area under the ROC curve for TNF-α level in predicting PSCI was 0.819 （0.711 - 0.928）, and the critical value was 36.965 ng/L when the Youden index was at its maximum value of 0.600. Conclusions: The TNF-α level in early stroke patients is significantly negatively correlated with the occurrence of PSCI. A higher TNF-α level is an independent risk factor for PSCI. The TNF-α level has certain predictive and diagnostic value for the occurrence of PSCI. A serum TNF-α level higher than 36.965 ng/L may increase the risk of PSCI.
Objective: To study the effect of pramipexole hydrochloride in the treatment of Parkinson's disease and its influence on neurological function and adverse reactions. Methods: A total of 80 patients with Parkinson's disease in our hospital from February 2021 to May 2025 were selected and randomly divided into control group and pramipexole hydrochloride group, 40 cases in each group. The pramipexole hydrochloride group was treated with pramipexole hydrochloride tablets, and the control group was treated with placebo. The neurological function of the patients was evaluated by the Parkinson's disease autonomic nervous symptoms scale (SCOPA-AUT), and the clinical efficacy and quality of life were evaluated by the Unified Parkinson's Disease Rating Scale (UPDRS) and quality of life score. The levels of dopamine, norepinephrine (NA), serotonin (5-HT) and epinephrine were detected by high performance liquid chromatography. The level of superoxide dismutase (SOD) was detected by xanthine oxidase method, the level of glutathione (GSH) was detected by colorimetric quantitative analysis, and the level of malondialdehyde was detected by thiobarbituric acid colorimetric analysis. The incidence of adverse reactions was counted. Results: After treatment, the scores of SCOPA-AUT and UPDRS in pramipexole group were significantly lower than those in the control group, and the quality of life score was significantly improved (P<0.05). In pramipexole group, the levels of serum polyamine, Na, 5-HT, GSH and SOD increased, while the levels of epinephrine and MDA decreased (P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (P>0.05). Conclusion: Pramipexole hydrochloride can improve the neurological function and antioxidant stress state of patients with Parkinson's disease, with good safety.
Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder characterized by progressive memory loss and cognitive decline. Sleep disorders, recognized both as an early clinical manifestation and as an important risk factor for AD, have attracted increasing attention in recent years. A growing body of evidence indicates that impaired sleep quality and reduced sleep duration are closely associated with the accumulation of amyloid-β (Aβ) and tau protein in the brains of AD patients. Microglia, the resident immune cells of the central nervous system, play pivotal roles in maintaining neural homeostasis, clearing Aβ, and regulating neuroinflammation. Sleep disturbances can activate microglia by disrupting circadian rhythms and inducing inflammatory responses, driving them toward a pro-inflammatory phenotype while impairing their phagocytic and clearance capacities. These alterations exacerbate Aβ deposition, promote tau pathology, and thereby accelerate AD progression. This review systematically summarizes current findings on the interplay among sleep disorders, microglial dysfunction, and AD pathogenesis, with a particular focus on mechanistic links and bidirectional regulation. In addition, we highlight recent advances in non-pharmacological interventions, pharmacotherapies, and related emerging regulatory strategies targeting sleep disorders and AD. A deeper understanding of these mechanisms may provide early clues for AD onset and offer novel targets for its prevention and treatment.
Senile dementia has attracted much attention due to its complex pathogenesis and the increasing incidence rate along with the aging population. Currently, modern medicine is confronted with problems such as low early recognition rate, limited treatment methods and high costs. In contrast, traditional Chinese medicine (TCM) has advantages in emphasizing syndrome differentiation and treatment, as well as treating different diseases with the same therapy. In recent years, many studies on the treatment of different syndrome types of senile dementia with Chinese patent medicines have been published. Based on the core pathogenesis theory of "deficiency at the root and excess at the surface" in TCM, this article screens the existing research literature on clear syndrome types of this disease, aiming to provide evidence-based support for the clinical application of Chinese patent medicines.
Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder. Its pathogenic framework has evolved beyond the conventional amyloid-β (Aβ) cascade hypothesis toward a multifactorial interactive network model. Aβ, tau, neuroinflammation, synaptic dysfunction, the microbiota-gut-brain axis, and epigenetic regulation collectively form a complex pathological loop that drives progressive cognitive decline. In addition to cerebrospinal fluid and molecular imaging biomarkers, emerging blood-based biomarkers show considerable promise for clinical application. Therapeutic strategies targeting Aβ clearance have demonstrated disease-modifying effects, yet amyloid-related imaging abnormalities demand improved risk prediction and management. Concurrently, novel approaches including anti-tau antibodies, TREM2 agonists, and multi-target agents are advancing rapidly. Evidence also supports multimodal lifestyle interventions in delaying disease onset. Moving forward, elucidating the intricate interactions within AD pathological pathways using cutting-edge technologies, integrating and expanding the clinical implementation of multimodal biomarkers, and addressing therapeutic bottlenecks arising from pathological heterogeneity will be pivotal to achieving effective risk prediction, early detection and interception, and personalized treatment in AD.
Objective: To evaluate the predictive performance of biomarkers for the conversion of mild cognitive impairment（MCI） to Alzheimer's disease（AD）. Methods: A literature review summarized the predictive accuracy of individual and combined biomarkers for MCI-to-AD progression.Results: CSF amyloid-beta 42（Aβ42） showed 81% sensitivity at 64% specificity, while Aβ-PET sensitivity ranged 83%-100% and specificity 46%-88%. Phosphorylated Tau217 （P-tau217） had an accuracy of 0.88. Medial temporal lobe MRI demonstrated 0.65-0.7 sensitivity and 0.64-0.68 specificity. CSF total tau（T-tau） showed 75% sensitivity at 72% specificity, and FDG-PET 76% sensitivity at 82% specificity. Plasma neurofilament light chain（NfL） had high sensitivity （98.1%） but low specificity（16.1%）, accuracy 0.631; plasma GFAP accuracy was 0.77-0.84. Multi-biomarker models achieved accuracy 0.72-0.96, sensitivity 0.56-0.85, and specificity 0.56-0.91. Conclusions: Aβ biomarkers showed higher sensitivity than FDG-PET, while FDG-PET had higher specificity. Multi-biomarker combinations, particularly cognitive scales with MRI, provided superior prediction for MCI-to-AD conversion.
Alzheimer's disease is a common neurodegenerative disease with pathological features including amyloid beta deposits and neurofibrillary tangles. Microglia-mediated neuroinflammation plays an important role in the occurrence and development of AD, mainly manifested by microglial activation and release of pro-inflammatory factors. Recent studies have found that microglia activate and differentiate into a variety of phenotypes and interact with Aβ and Tau, jointly affecting the pathology of AD. The expression of various inflammatory molecules in activated microglia is up-regulated, and NF-kB and NLRP3 are involved in the regulation. Recent treatments targeting microglia activation, phenotypic transformation, and inflammatory signals have been fruitful: new drug formulations such as LNP have enhanced the ability to penetrate the blood-brain barrier, and many natural ingredients derived from Chinese herbal medicines have also been effective. In this review, we will introduce the pathogenesis and treatment of AD from two aspects: activation and phenotypes of microglia, and activation of microglia-related inflammatory molecules(mainly NF-kB and NLRP3).
ISSN 2096-5516 (Print)
Started from 2018
Published by: China Association for Alzheimer’s Disease
