Alzheimer's disease (AD) is the most common cause of age-associated dementia and will exponentially rise in prevalence in the coming decades, supporting the parallel development of the early stage detection and disease-modifying strategies. While primarily considered as a cognitive disorder, AD also features motor symptoms, primarily gait dysfunction. Such gait abnormalities can be phenotyped across classic clinical syndromes as well as by quantitative kinematic assessments to address subtle dysfunction at preclinical and prodromal stages. As such, certain measures of gait can predict the future cognitive and functional decline. Moreover, cross-sectional and longitudinal studies have associated gait abnormalities with imaging, biofluid, and genetic markers of AD across all stages. This suggests that gait assessment is an important tool in the clinical assessment of patients across the AD spectrum, especially to help identify at-risk individuals.Copyright © 2023 Elsevier B.V. All rights reserved.

为更好地应对我国阿尔茨海默病（Alzheimer's disease，AD）防控的严峻挑战，国家发布了《应对老年期痴呆国家行动计划（2024-2030年）》。为早日实现其中的核心目标，整合多学科专家意见与循证依据，采用德尔菲法结合GRADE证据分级，特制定《阿尔茨海默病多元康复干预中国专家共识》（2025）。本共识强调“医院-社区-家庭”三级联动的协同管理模式，促进AD多维度防治、康复和照护的系统化和规范化，为医疗机构、基层社区及家庭照护提供科学指导，助力健康老龄化目标的实现。在预防层面，将AD危险因素进行量化分级，分为低危、中危和高危，以便制定个性化防控干预方案。治疗方面，根据AD严重程度分别推荐西药、中医药和神经调控等。康复需要根据功能障碍评估结果，结合患者的个人爱好和家庭支持，制定个体化、针对性的康复干预方案，早、中期AD患者以主动康复为主，晚期以被动康复为主。康复措施主要包括认知疗法（认知训练、认知刺激和认知康复）、生活方式干预（营养干预，运动疗法包括有氧运动、力量和心身训练）、人工干预（怀旧和沉浸式技术）、艺术疗法（音乐、舞蹈和美术）、自然疗法（园艺和动物辅助）及感官刺激疗法（光照和芳香）。中、晚期照护策略聚焦伴随精神行为异常或严重失智失能的AD患者，应遵循以人为本的理念，增强自我认同，提供安宁疗护，防治并发症等。

Despite being available for more than three decades, quantitative gait analysis remains largely associated with research institutions and not well leveraged in clinical settings. This is mostly due to the high cost/cumbersome equipment and complex protocols and data management/analysis associated with traditional gait labs, as well as the diverse training/experience and preference of clinical teams. Observational gait and qualitative scales continue to be predominantly used in clinics despite evidence of less efficacy of quantifying gait.

Gait disturbance results in an increase in the risk of falls in patients with Alzheimer’s disease (AD). The falls are events that might be related to an increase in the number of fractures, loss of mobility, being bedridden, early institutionalization, and increased use of medication. Therefore, the reduction in the number of falls is important for the maintenance of the functional independence of the patients as well as for the prevention of sequelae resulting from those events. Alterations in the gait occur very frequently in AD, and the gait disturbance occurs relatively early in the course of the disease. This study has important implications for public health and clinical practice. This study and previous studies have reported that abnormal gait predicts greater risk of falls, dementia, institutionalization, and death. The high prevalence and incidence of abnormal gait and its association with multiple adverse outcomes in older adults require urgent attention. Our results allow us to identify the risk factors.

\n Gait and key-tapping are individually associated with mild cognitive impairment (MCI) and dementia. However, it is unclear if these motor functions are correlated, or whether combining them improves classification of objective (dementia, MCI) and subjective cognitive impairment (SCI). We recruited 73 participants with dementia, 106 MCI, 57 SCI, and 83 cognitively healthy controls (HC). Consensus diagnosis was made after gold-standard interdisciplinary assessment. Fast-paced gait was assessed on an electronic walkway and fast-paced key-tapping on a computer keyboard. Correlations between gait and key-tapping measures (speed, frequency, variability and contact) were tested using Pearson’s correlation. Classification accuracy was calculated using area under receiver-operating-characteristic curves (AUC) and compared to the null model comprising age, sex and education. Gait and key-tapping measures correlated moderately. Combined gait and key-tapping speed improved classification accuracy of dementia (.97), and MCI (.91), from HC, but not SCI, compared to gait (dementia:.94, MCI:.87) or the null model (dementia:.89, MCI:.79). Gait and key-tapping measures were associated with Alzheimer’s disease and vascular dementia, but the effect size for key-tapping variability was larger in vascular dementia (\n β\n : 225.71) compared to Alzheimer’s disease (\n β\n : 38.30). Gait and key-tapping variability was associated with non-amnestic MCI. Measures of gait were correlated with corresponding key-tapping measures, but their association with cognitive impairment was not the same. Combining gait and key-tapping motor measures improved classification accuracy of MCI and dementia. This suggests gait and key-tapping measures provide information about different aspects of motor-cognitive association worth further investigation.\n

背景 随着老龄化社会的到来，与年龄密切相关的认知障碍(包括痴呆)的患病率明显增加。先前的研究表明，具有不同认知能力的人群所表现的步态状态也不一样。过去研究者们在研究遗忘型轻度认知障碍（aMCI）和阿尔茨海默病（AD）的步态时，使用了统计分析方法，对机器学习方法的使用较少。 目的 构建基于步态的机器学习模型识别aMCI和AD，探索aMCI和AD之间的步态标志物，以便将其用作帮助诊断aMCI患者和AD患者的可能工具。 方法 于2018年12月至2020年12月，从国家康复辅具研究中心附属康复医院、佛山市第一人民医院、大连大学附属中山医院招募了102例受试者，按照筛选标准最终纳入98例受试者，其中55例为aMCI患者，10例为AD患者，33例为健康对照（HC）者。使用可穿戴设备采集参与者在单任务（自由行走）、双任务（倍数7）和双任务（倒数100）时的步态参数。使用随机森林算法（RF）和梯度提升决策树算法（GBDT）建立模型，10个步态参数作为预测变量，疾病状态（HC、aMCI、AD）作为响应变量，比较两种机器学习算法对3个疾病组的识别效果。然后使用机器学习算法结合递归特征消除法（RFE）进行重要特征选择。 结果 三组年龄、性别、身高、体质量、鞋码比较，差异无统计学意义（P>0.05）；MMSE评分、MoCA评分比较，差异有统计学意义（P<0.05）。自由行走测试时，aMCI组和AD组受试者步幅较HC组短，足跟着地角度较HC组小；AD组步速较HC组和aMCI组受试者慢，足趾离地角度较HC组小（P<0.05）。双任务倍数7测试时，aMCI组和AD组受试者步速较HC组慢，足趾离地角度和足跟着地角度较HC组小；AD组支撑时间较HC组长，足趾离地角度较aMCI组小（P<0.05）。双任务倒数100测试时，AD组步速较HC组和aMCI组受试者慢，足趾离地角度和足跟着地角度较HC组和aMCI组小，步幅较HC组短；aMCI组足跟着地角度较HC组小（P<0.05）。GBDT-RFE方法发现aMCI和AD之间的重要步态特征是步幅、足趾离地角度和足跟着地角度，并在RF模型中实现了识别aMCI和AD的最佳性能，最高准确率为87.69%。 结论 步幅、足趾离地角度和足跟着地角度是识别aMCI患者和AD患者的重要步态标志物，未来临床医生可依据重要步态标志物诊断和治疗aMCI患者和AD患者。

We aimed to extend our knowledge on the relationship between physical fitness (PF) and both white matter microstructure and cognition through in-depth investigation of various cognitive domains while accounting for potentially relevant nuisance covariates in a well-powered sample. To this end, associations between walking endurance, diffusion-tensor-imaging (DTI) based measures of fractional anisotropy (FA) within brain white matter and cognitive measures included in the NIH Toolbox Cognition Battery were investigated in a sample of n = 1206 healthy, young adults (mean age = 28.8; 45.5% male) as part of the human connectome project. Higher levels of endurance were associated with widespread higher FA (p< 0.05) as well as with enhanced global cognitive function (p < 0.001). Significant positive relationships between endurance and cognitive performance were similarly found for almost all cognitive domains. Higher FA was significantly associated with enhanced global cognitive function (p < 0.001) and FA was shown to significantly mediate the association between walking endurance and cognitive performance. Inclusion of potentially relevant nuisance covariates including gender, age, education, BMI, HBA1c, and arterial blood pressure did not change the overall pattern of results. These findings support the notion of a beneficial and potentially protective effect of PF on brain structure and cognition.

In vivo Alzheimer's disease diagnosis and staging is traditionally based on clinical features. However, the agreement between clinical and pathological Alzheimer's disease diagnosis, whose diagnosis assessment includes amyloid and Braak histopathological tau staging, is not completely convergent. The development of positron emission tomography (PET) tracers targeting neurofibrillary tangles offers prospects for advancing the staging of Alzheimer's disease from both biological and clinical perspectives. Recent advances in radiochemistry made it possible to apply the postmortem Braak staging framework to tau-PET images obtained in vivo. Here, our aim is to provide a narrative review of the current literature on the relationship between Alzheimer's disease clinical features and the PET-based Braak staging framework. Overall, the available studies support the stepwise increase in disease severity following the advance of PET-based Braak stages, with later stages being associated with worse cognitive and clinical symptoms. In line with this, there is a trend for unimpaired cognition, mild cognitive impairment, and Alzheimer's disease dementia to be compatible with early, intermediate, and late patterns of tau deposition based on PET-based Braak stages. Moreover, neuropsychiatric symptom severity seems to be linked to the extent of tau-PET signal across Braak areas. In sum, this framework seems to correspond well with the clinical progression of Alzheimer's disease, which is an indication of its potential utility in research and clinical practice, especially for detecting preclinical tau levels in individuals without symptoms. However, further research is needed to improve the generalizability of these findings and to better understand the applications of this staging framework.

Acrylamide (ACR) is an axonal toxicant that produces peripheral neuropathy in laboratory animals and humans. Epidemiological study found that diet ACR exposure was associated with a mild cognitive decline in men. However, limited information is available as regards its potential and underlying mechanism to cause memory alterations. Curcumin is a polyphenol with neuroprotective and cognitive-enhancing properties. In this study, we aimed to investigate the mechanism of ACR-induced spatial memory impairment and the beneficial effect of curcumin. ACR exposure at 10 mg/kg/d for 7 weeks caused slight gait abnormality and spatial memory deficits, which was associated with an activation of glial cells, a reduction of phosphorylated cAMP response elements binding protein (P-CREB) and an aggregation of hyperphosphorylated tau including p-tau (Ser), AT8 (p-tau Ser/Thr) and PHF1 (p-tau Ser) in the hippocampus and cortex. ACR markedly regulate the expression of glycogen synthase kinase-3β (GSK-3β) and cyclin-dependent kinase-5 (cdk5) to accelerate tau hyperphosphorylation. ACR inhibited the protein phosphatase 2A (PP2A) and lysosomal protease cathepsin D to decrease the p-tau dephosphorylation and degradation. The P-CREB and brain derived neurotrophic factor (BDNF) were significantly decreased by ACR. The upstream signalings of P-CREB, extracellular signal-related kinase (ERK) and Akt were markedly inhibited. The protein kinase RNA-like endoplasmic reticulum kinase (PERK) -eukaryotic initiation factor-2α (eIF2α) - activating transcription factor 4 (ATF4) signaling which negatively regulate memory processes by suppressing CREB was activated by ACR. Curcumin alleviated ACR-induced spatial memory impairment through reversing tau abnormalities and P-CREB reduction in the hippocampus. These results offered deeper insight into the mechanisms of and presented a potential new treatment for ACR-induced neurotoxicity.Copyright © 2018 Elsevier Inc. All rights reserved.

人类的嗅觉与认知、情感存在着密切的联系，三者的功能障碍几乎同时出现并伴随着阿尔茨海默病（Alzheimer disease, AD）整个疾病过程，嗅觉障碍在AD病理机制中的作用及其对认知和情感障碍的影响迄今尚未清楚阐明。拟从嗅觉的解剖与生理机制出发，结合近年来AD领域嗅觉相关研究进展，阐述嗅觉病理在AD病理机制中的作用，探讨嗅觉障碍识别技术和嗅觉疗法在AD防治中的应用前景。

NIHSS for stroke is widely used in clinical, but it is complex and subjective. The purpose of the study is to present a quantitative evaluation method of stroke association based on multi-dimensional gait parameters by using machine learning.

In this longitudinal study, we aimed to examine if slowing gait speed preceded cognitive decline and correlated with brain amyloidosis.The sample (n = 287) was derived from the Gothenburg H70 Birth Cohort Studies, with follow-ups between 2000 and 2015. Gait speed was measured by indoor walk, and cognition using the Clinical Dementia Rating (CDR) score. All participants had CDR = 0 at baseline. Some participants had data on cerebrospinal fluid (CSF) amyloid beta (Aβ) concentrations at the 2009 examination.Gait speed for participants who worsened in CDR score during follow-up was slower at most examinations. Baseline gait speed could significantly predict CDR change from baseline to follow-up. Subjects with pathological CSF Aβ concentrations at the 2009 visit had lost more gait speed compared to previous examinations.Our results indicate that gait speed decline precedes cognitive decline, is linked to Alzheimer's pathology, and might be used for early detection of increased risk for dementia development.© 2021 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Gait analysis with accelerometers is a relatively inexpensive and easy to use method to potentially support clinical diagnoses of Alzheimer's disease and other dementias. It is not clear, however, which gait features are most informative and how these measures relate to Alzheimer's disease pathology.In this study, we tested if calculated features of gait 1) differ between cognitively normal subjects (CN), mild cognitive impairment (MCI) patients, and dementia patients, 2) are correlated with cerebrospinal fluid (CSF) biomarkers related to Alzheimer's disease, and 3) predict cognitive decline.Gait was measured using tri-axial accelerometers attached to the fifth lumbar vertebra (L5) in 58 CN, 58 MCI, and 26 dementia participants, while performing a walk and dual task. Ten gait features were calculated from the vertical L5 accelerations, following principal component analysis clustered in four domains, namely pace, rhythm, time variability, and length variability. Cognitive decline over time was measured using MMSE, and CSF biomarkers were available in a sub-group.Linear mixed models showed that dementia patients had lower pace scores than MCI patients and CN subjects (p < 0.05). In addition, we found associations between the rhythm domain and CSF-tau, especially in the dual task. Gait was not associated with CSF Aβ42 levels and cognitive decline over time as measured with the MMSE.These findings suggest that gait - particularly measures related to pace and rhythm - are altered in dementia and have a direct link with measures of neurodegeneration.

To evaluate the effectiveness of multimodal features based on gait analysis and eye tracking for elderly people screening with subjective cognitive decline in the community.