Special Issue: Alzheimer's disease
Alzheimer's disease (AD) is a common and irreversible neurodegenerative brain disease that severely affects the quality of life and survival of patients, while there is still a lack of effective treatments to delay or stop disease progression. Traditional Chinese medicine (TCM) and its active ingredients have important potential in the prevention and treatment of AD.
To investigate the effects of poric acid (PA) on cognitive impairment and nuclear factor E2-related factor 2 (Nrf2) /solute carrier family 7A11 (SLC7A11) /glutathione peroxidase 4 (GPX4) signaling pathway in AD rats.
Seventy-five male SPF grade SD rats aged 6 to 8 weeks were divided into the control group (Control group), AD Model group (Model group), PA treatment group (PA group) and PA+Nrf2 inhibitor group (PA+ML385 group) by random number table method to prepare AD rat model from January to September, 2022. After successful modeling 50 mg/kg PA was intraperitoneally injected into the PA group, 50 mg/kg PA and 30 mg/kg ML385 was intraperitoneally injected into the PA+ML385 group, and 0.9% sodium chloride solution was intraperitoneally injected into the Control group and Model group. The Morris water maze experiment was performed 24 h after the last dose, and the positioning navigation experiment was carried out on days 2, 4 and 6 to record the time when the rats arrived at the platform (escape latency). The platform was removed on day 7, and the duration of the rats staying on the platform and the number of times they crossed the platform within 120 s were recorded. The pathological changes of hippocampal neurons in each group were observed after Nissl staining. Iron deposition was detected by Prussian blue staining, GPX4 expression and GSH, MDA and Fe2+ contents were detected by immunofluorescence staining. The protein expression levels of Nrf2, SLC7A11 and GPX4 in rat hippocampus were detected by Western blotting.
The escape latency of the Model group was higher than that of the Control group and PA group, and escape latency of the PA+ML385 group was higher than that of the PA group at 2, 4 and 6 days after the last administration. The platform residence time and platform crossing times in the Model group were lower than those in the Control group and PA group, and those in the PA+ML385 group were lower than those in PA group, and the difference was statistically significant (P<0.05). The results of Nissl staining showed severe neuronal necrosis, nucleus shrinkage and decreased number of Nissl bodies in the Model group, decreased neuronal necrosis with tight arrangement and increased number of Nissl bodies in the PA group, significantly increased neuronal damage and decreased the number of Nissl bodies in the PA+ML385 group. The Prussian blue staining results showed that iron deposition in the Model group was higher than that in the Control group, iron deposition in the PA group was lower than that in the Model group, and iron deposition in the PA+ML385 was higher than that in the PA group. The results of immunofluorescence staining showed that green fluorescence was weakened and GPX4 positive cells were reduced in the Model group, green fluorescence was enhanced and GPX4 positive cells were increased in the PA group compared with the Model group, and GPX4 positive cells were decreased in the PA+ML385 group compared with the PA group. GSH in the Model group was lower than that in the Control group and PA group, GSH in the PA+ML385 group was lower than that in the PA group. MDA and Fe2+ in the Model group were higher than those in the Control group and PA group, and those in the PA+ML385 group were higher that the PA group, and the differences were statistically significant (P<0.05). The relative expression levels of Nrf2, SLC7A11 and GPX4 in the Model group were lower than those in the Control group and PA group, and those in the PA+ML385 group were lower than those in the PA group, and the differences were statistically significant (P<0.05) .
PA can improve the cognitive impairment of AD rats, and its mechanism may be related to the inhibition of iron death by activating Nrf2/SLC7A11/GPX4 signal pathway.
Recent studies have identified a trend toward cognitive decline and even progression to dementia in patients with metabolic syndrome (MetS), and Alzheimer's disease (AD) is the most important subtype of dementia. In reviewing the correlation between cognitive impairment due to MetS and development of AD in previous studies, this paper highlights the growing body of data that supports MetS as a whole as well as its components of hypertension and hyperglycemia as risk factors for AD, whereas insulin resistance, neurologic chronic inflammation, and adipokine disorders play important roles in the pathogenesis. Since there are now no viable treatment alternatives available to stop or reverse the degenerative progression of AD, it is expected to provide scientific evidence for a comprehensive strategy for early prevention and treatment of AD by targeting relatively curable MetS for intervention.
Mild cognitive impairment (MCI) is an important stage to intervene and delay the progression of dementia, and it has been shown closely associated with genetic factors, among which apolipoprotein E (APOE) ε4 is recognized as an important risk allele of MCI in the medical field. Due to the lack of Genome-Wide Association Study (GWAS) summary data of MCI, it is common to use the GWAS summary data of Alzheimer's disease (AD) as the base dataset to calculate the polygenic risk score (PRS) of MCI, resulting in suboptimal PRS genetic risk prediction for MCI.
To explore the and optimize the statistical modeling strategy of genetic risk in MCI from the perspective of generalized linear model and machine learning, using meta-polygenic risk score (metaPRS) and APOEε4 as important predictors.
PRS for the 12 MCI-related traits were calculated and integrated into metaPRS for MCI by elastic-net Logistic regression model. SCOREAPOE was calculated by weighting the APOEε4 effect size with age correction. XGBoost, GBM, Logistic regression and Lasso regression were used as statistical modeling methods to verify the inclusion strategies of different predictors based on metaPRS, SCOREAPOE and basic demographic information (age, gender, education level) . AUC and F-measure were used to evaluate the predictive effect of statistical modeling of genetic risk of MCI.
metaPRS and SCOREAPOE have high predictive value for the genetic risk of MCI. After including metaPRS, SCOREAPOE and basic demographic information (age, gender, education level) , the predictive effect of each statistical modeling method is XGBoost (AUC=0.69, F-measure=0.88) , GBM (AUC=0.76, F-measure=0.87) , Logistic regression (AUC=0.77, F-measure=0.89) , and Lasso regression (AUC=0.76, F-measure=0.92) .
When the sample size is 325 (less than 500) , the Lasso regression model constructed by including metaPRS, SCOREAPOE and basic demographic information (age, gender, education level) as predictors has the best effect on MCI genetic risk prediction, providing a new idea and perspective for statistical modeling of genetic risk of complex diseases such as MCI.
Handwriting synthesis techniques have been extensively studied in the detection of cognitive impairment in dementia and Parkinson's disease. But handwriting characteristics in older adults with mild cognitive impairment (MCI) still need to be studied further.
To explore the differences between the handwriting characteristics of elderly patients with MCI and normal elderly people, and to assess the value of handwriting features in MCI screening.
By use of convenience sampling, 33 older adults with MCI were recruited from Huzhou communities from January to April 2022 (observation group), and were compared to age-, sex- and education level-matched 43 community-living older adults with normal cognitive function (control group). The General Information Questionnaire, the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment-Basic (MoCA-B), the Activity of Daily Living Scale (ADL), and the 15-item Geriatric Depression Scale (GDS-15) were used to survey subjects. Subjects were invited to complete six handwriting tasks (four are Chinese characters tasks and the other two are graphical drawing tasks) using a dot matrix digital pen to collect their kinematic parameters of handwriting. The classification accuracy, sensitivity and specificity of handwriting characteristics for the diagnosis of MCI were analyzed by discriminant analysis and receiver operating characteristic (ROC) curve, and predictive values of different schemes for MCI were analyzed.
Compared with the control group, the observation group had higher average pressure in writing (Z=-2.122, P=0.034), longer time in air (Z=-4.302, P<0.001), writing time (Z=-3.663, P<0.001) and total time (t'=-5.565, P<0.001), lower average writing velocity (Z=-2.458, P=0.014), horizontal (Z=-2.950, P=0.003) and vertical (Z=-2.094, P=0.040) average writing velocity and maximum horizontal writing velocity (Z=-2.206, P=0.027), lower average acceleration of writing in horizontal direction (Z=-2.667, P=0.008) and overall score for writing correctness (Z=-3.593, P<0.001) in completing graphical drawing tasks. The observation group had relatively longer time in air (Z=-3.464, P=0.001) and total time (Z=-2.940, P=0.003) in completing Chinese characters tasks. Compared with the total time for completing Chinese characters tasks, the total time for completing graphical drawing tasks had higher specificity (93.0% vs 55.8%) in differentiating between MCI and control groups, with an area under the curve (AUC) of 0.828. The summary of handwriting characteristics for graphical drawing tasks correctly classified 80.3% (61/76) of older adults with MCI, with 87.9% sensitivity and 79.1% specificity, and had higher diagnostic efficacy for those with MCI than the MMSE scale (Z=1.993, P=0.046) and the summary of handwriting characteristics for Chinese characters tasks (Z=2.408, P=0.016) .
Handwriting characteristics of graphical drawing tasks may have potential application in screening of older adults at risk for MCI, which can be used simultaneously or prior to sets of neuropsychological tests conducted for the diagnosis of MCI in community health care facilities.
Parkinson's disease (PD) is frequently accompanied with anxiety, depression, sleep disorders, autonomic dysfunction, cognitive impairment, and other non-motor symptoms, among which autonomic dysfunction and cognitive impairment severely impair the quality of life. The relationship between autonomic dysfunction and cognitive impairment in PD is still controversial.
To analyze the characteristic of autonomic dysfunction and its correlation with cognitive impairment in PD patients.
A total of 156 patients with idiopathic PD admitted to Henan Provincial People's Hospital between September 2018 and November 2020 were enrolled. General data of patients, including age, sex, duration of disease, age of onset and years of education, were collected. According to the prevalence and duration of autonomic dysfunction, they were divided into autonomic dysfunction group (AutD group, n=107) and non-autonomic dysfunction group (NAutD group, n=49) . The part Ⅲ of the Unified Parkinson's Disease Rating Scale (UPDRS-Ⅲ) was used to assess motor symptoms. The Hoehn-Yahr (H-Y) scale was used to assess the severity of PD. The non-motor symptoms were assessed by the Non-motor Symptoms Scale (NMSS) . The Hamilton Anxiety Scale (HAMA) and Hamilton Rating Scale for Depression 24-item (HAMD-24) were used to evaluate anxiety and depression symptoms, respectively. The 39-item Parkinson's Disease Questionnaire (PDQ-39) was used to evaluate PD-specific health related quality of life. Autonomic function was evaluated by Scales for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT) . Cognitive function was evaluated by Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) . Spearman correlation analysis was used to explore the correlation between autonomic function (assessed using the SCOPA-AUT score) and cognitive function (assessed using the MMSE score and MoCA score) .
Among the 156 patients, 83 were male and 73 were female, with a mean age of (63.9±0.7) years. AutD group had greater mean age (t=-4.391, P<0.001) and longer mean duration of PD (Z=-6.947, P<0.001) than NAutD group. AutD group also had higher mean UPDRS-Ⅲscore (t=-8.967) , higher prevalence of moderate-to-severe PD graded by the H-Y scale (χ2=44.350) , higher mean NMSS score (t=-13.707) , HAMA score (t=-3.665) , HAMD-24 score (t=-4.808) , and PDQ-39 score (t=-11.893) (P<0.001) . Digestive symptoms were the most prevalent symptoms (91.7%) , followed by urinary symptoms (91.0%) , dysregulation of body temperature (59.6%) and cardiovascular symptoms (50.0%) , while pupillary dysregulation (12.2%) and sexual dysfunction (5.1%) were less common. Compared to NAutD group, AutD group had lower mean total score of MMSE (Z=-3.826, P<0.001) , total score of MoCA (Z=-2.921, P=0.003) and the mean score of the naming item (Z=-2.868, P=0.004) , mean domain scores of attention (Z=-2.968, P=0.003) , language (Z=-3.546, P<0.001) , and delayed recall (Z=-2.804, P=0.005) . Spearman correlation analysis showed that, the score of SCOPA-AUT (rs=-0.214, -0.181) , the score of urinary domain (rs=-0.245, -0.191) and the score of thermoregulatory domain (rs=-0.215, -0.225) were negatively correlated with the scores of MMSE and MoCA (P<0.05) .
PD patients with autonomic dysfunction have more severe non-motor symptoms such as anxiety, depression, and cognitive impairment, and lower quality of life. The incidence of autonomic dysfunction in PD is high, involving multiple systems. And the increase in the severity of autonomic dysfunction is associated with increased severity of cognitive impairment.
A common complication of stroke patients is post-stroke cognitive impairment (PSCI) , which significantly reduces their quality of life. There are no effective targeted treatment measures currently available for PSCI in clinical practice. A large number of studies have already indicated that the activation of NLRP3 inflammasome plays a crucial role in PSCI, and many inhibitory treatments have been shown to improve cognitive impairment. The purpose of this study was to summarized the activation and modulating factors of NLRP3 inflammatory bodies and the relationship with PSCI. Some studies have been demonstrated that inhibiting NLRP3 or its associated inflammatory body components reduces the inflammatory response, promoting cognitive function recovery in cell and animal models of PSCI. Consequently, targeting NLRP3 inflammatory bodies may be a new trends of dealing with PSCI treatment. Despite the fact that numerous drugs and therapeutic measures have been proved to suppress the activation of NLRP3 inflammatory bodies, their clinical efficacy and safety have not yet been confirmed.
The prevalence of age-related cognitive impairment, including dementia, has significantly increased with population aging. It has been shown that cognitive function is associated with gait status. Previously, researchers used statistical analysis methods instead of machine learning methods to study the gait of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) .
To develop a model to identify aMCI and AD based on gait status using machine learning methods, explore gait markers differentiating between aMCI and AD, and to assess their possible values as aided tools in diagnosing aMCI and AD.
We recruited 102 cases from the Rehabilitation Hospital Affiliated to National Research Center for Rehabilitation Technical Aids, the First People's Hospital of Foshan, and Affiliated Zhongshan Hospital of Dalian University from December 2018 to December 2020, and included 98 of them according to the screening criteria, including 55 patients with aMCI, 10 patients with AD, and 33 healthy controls (HC) . The gait parameters of the participants were collected during performing single-task (free walking) , dual-task (counting backwards in sevens) and another dual-task (counting backwards from 100) using a wearable device. Random forest (RF) algorithm and gradient boosting decision tree (GBDT) algorithm were separately used to establish a model to compare the effect of two algorithms in recognizing three groups, with 10 gait parameters as predictive variables and the physical status (healthy, aMCI, AD) as response variables. Then important features were chosen using a machine learning algorithm combined with recursive feature elimination (RFE) .
No statistically significant differences were found among the three groups in terms of sex ratio, average age, height, body weight or shoe size (P>0.05) , while the differences in terms of average MMSE score and MoCA score were statistically significant (P<0.05) . In the free walking test, aMCI group and AD group had shorter average stride length and smaller average heel-to-ground angle (HtA) than HC group (P<0.05) . AD group had slower average gait speed and smaller average toe-off angle (ToA) than both HC group and aMCI group (P<0.05) . In performing the dual-task of counting backwards in sevens, compared with HC group, aMCI group and AD group had slower average gait speed and smaller average ToA and HtA (P<0.05) . AD group had longer average stance phase than HC group (P<0.05) . AD group had average smaller ToA than aMCI group (P<0.05) .In performing the dual-task of counting backwards from 100, AD group had slower average gait speed and smaller average HtA and ToA than both HC group and aMCI group (P<0.05) . Moreover, AD group had shorter average stride length than HC group (P<0.05) . The average HtA in aMCI group was smaller than that in HC group (P<0.05) . Using the GBDT-RFE method, we found important gait features in distinguishing between aMCI and AD to be the stride length, ToA and HtA, and the model using the RF algorithm performed better in identifying aMCI and AD, with an accuracy as high as 87.69%.
Stride length, ToA and HtA are important gait markers to identify aMCI and AD. These findings could help clinicians diagnose aMCI and AD in the future.
Cognitive impairment prevalence is increasing as aging population grows in China, which greatly affects the quality of life of the sufferers. Currently, the screening forcognitive-linguistic impairment still relies on traditional neuropsychological scales, which are technically demanding, time-consuming, and poorly tolerant.
To explore the feasibility of the Computer-aided Language Assessment System (CLAS) in the measurement of cognitive-linguistic impairment.
Random sampling method was used to recruit 73 participants, among them 55 (75.3%) were stroke/brain injury patients〔with a baseline score of 10-20 on the Mini-Mental State Examination (MMSE) 〕hospitalized in Department of Rehabilitation Medicine, the First Hospital of Jinan University from March 2018 to March 2020, and the other 18 (24.7%) were healthy volunteers (consisting of undergraduate medicalinterns from Jinan University, family members and accompanying caregivers of the patients) . The CLAS, Montreal Cognitive Assessment Scale (MoCA) , MMSE and Aphasia Battery of Chinese (ABC) were used to evaluate the linguistic and cognition functions of the participants. The Spearman correlation was used to assess the correlation of the score of CLAS with that of MoCA and MMSE. A receiver operating characteristic curve (ROC) of CLAS was plotted to estimate its diagnostic value for cognitive-linguistic impairment, with sensitivity, specificity and accuracy being calculated as well. A satisfaction survey was conducted in 18 healthy volunteers to understand their satisfaction with the use of the CLAS.
The total CLAS score was positively correlated with that of MMSE, and MoCA (rs=0.910, 0.884, P<0.05) .Compared with MoCA (total MoCA score <26) in combination with ABC in diagnosing cognitive impairment, the CLAS had an AUC of 0.733〔95%CI (0.632, 0.834) , P<0.001〕in identifying cognitive-linguistic impairment when the optimal cut-off value was set as 85 points, and the maximum Youden index was obtained, with 1.000 sensitivity, 0.703 specificity, and 0.931 (68/73) accuracy. The average satisfaction score of 18 healthy volunteers was (4.07±0.48) , indicating an overall satisfaction level of "satisfactory".
High participant satisfaction with the CLAS was obtained in this study. And as the CLAS has proven to have good validity and diagnostic accuracy, as well as good performance in identifying cognitive-linguistic impairment, it could be applied to the screening and identification of cognitive-linguistic impairment.
Both frailty and potentially inappropriate medication (PIM) are relatively highly prevalent in adults with mild cognitive impairment (MCI) in the community, but the association of PIM with frailty in MCI population remains to be further explored.
To examine the association between PIM and frailty in older adults with MCI in the community.
This study was conducted between March to July 2021. By use of multistage sampling, older adults with MCI (n=230) were recruited from Baohe District, Hefei City. Sociodemographics, lifestyle indicators and physical functions of the subjects were collected by using the General Information Questionnaire developed by our research team. Frailty was assessed by the Comprehensive Frailty Assessment Instrument. PIM was assessed by the 2017 Criteria of Potentially Inappropriate Medications for Older Adults in China. Logistic regression analysis was applied to analyze the association of the number and types of PIM with frailty.
The prevalence of frailty and PIM in these older adults with MCI was 59.1% (136/230) and 59.1% (136/230) , respectively. The prevalence of PIM in the frailty group was much higher than that of non-frailty group〔80.9% (110/136) vs 27.7% (26/94) 〕 (P<0.05) . Multivariate Logistic regression analysis demonstrated that compared with MCI older adults without PIM, the risk of frailty was 4.591 times higher in those with only one PIM〔95%CI (1.903, 11.076) 〕, and 8.859 times higher in those with two or more PIMs〔95%CI (2.589, 30.321) 〕. Compared with MCI older adults with neurological disease but without PIM, the risk of frailty was 5.310 times higher in those with PIM〔95%CI (1.011, 27.877) 〕. The risk of frailty was 3.108 times higher in those with cardiovascular disease and PIM than that in those without PIM〔95%CI (1.173, 8.241) 〕.
The prevalence of frailty and PIM was higher in older adults with MCI in the community, and PIM was significantly associated with frailty. To decrease the prevalence of frailty and delay the progression of dementia in this population via reducing the prevalence of PIM, community-based health efforts should be made to strengthen the screening for frailty, enhance the identification of frailty related to medication use, and promote medication review and management.
Dementia is a major public health challenge associated with population aging. This paper introduces the background of the development of WHO "Global Action Plan on the Public Health Response to Dementia 2017—2025", with a focus on targets set across seven areas: dementia as a public health priority, dementia awareness and friendliness, dementia risk reduction, dementia diagnosis, treatment, care and support, support for dementia carers, information systems for dementia, and dementia research and innovation. We found 25 countries (regions) who have developed policies, strategies, plans or action frameworks on dementia since 2009, with targets involving areas of prevention, intervention, research, support, implementation, legislation and evaluation. As China still lacks a national dementia action plan, we put forward the following recommendations on the development of a China's national action plan on dementia: referring to the action priorities and specific measures for containing dementia of the WHO and 25 countries (regions) ; appropriately drawing lessons from successful experiences of WHO Member States in early screening for dementia in high-risk groups, reducing dementia risk factors, developing long-term dementia care insurance, creating a dementia friendly social environment, and building a national dementia monitoring system.
With the deepening and acceleration of the aging process, an increasing prevalence of mild cognitive impairment (MCI) is found in China's elderly population. To reduce MCI prevalence in this group, early screening and diagnosis are approaches having great social significance. To provide support for the choice of appropriate tools for early screening and identifying MCI in community-dwelling Chinese older adults, we comprehensively reviewed the commonly used scales in clinical MCI screening and assessment〔Informant Questionnaire on Cognitive Decline in the Elderly Individuals (IQCODE) , Cambridge Neuropsychological Test Automated Battery, Montreal Cognitive Assessment, Clock Drawing Test, Clock Reading Test, Clock Setting Test, Consortium to Establish a Registry for Alzheimer's Disease, Ascertain Dementia 8 (AD8) , Addenbrooke's Cognitive Examination-Revised (ACE) , and General Practitioner Assessment of Cognition〕, and put forward a strategy after analyzing the advantages and disadvantages of each of the above-mentioned scales, namely, combined use of the quick and highly effective AD8, IQCODE, and the sensitive and comprehensive ACE, for these three scales may make up for each other's shortcomings when they are used together.
Alzheimer's disease (AD) prevalence is increasing as aging advances worldwide, but its diagnosis is difficult due to atypical early clinical symptoms. Therefore, exploring new and reliable imaging techniques to improve early diagnosis rate of AD has become an important challenge in medical research.
To assess the correlation of amide proton content in brain with clinical symptoms of AD.
41 AD patients over 55 years old in Affiliated Psychological Hospital of Anhui Medical University were enrolled from November 2019 to August 2021, and 37 healthy volunteers were recruited at the same time. The Mini-Mental State Examination (MMSE) and the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) were used to evaluate the cognitive function, and behavioral symptoms, respectively. APTw MRI was used to take cephalograms. Spearman rank correlation analysis was used to explore the relationship between content of brain amide protons and psychiatric symptom factors in AD patients.
(1) The results showed that the MMSE and BEHAVE-AD scores were significantly different between AD patients and healthy controls (P<0.05) . AD patients had significantly increased contents of amide protons in the right, left, and total hippocampus under 2 ut, and in the right, left and total hippocampus under 4 ut, than did healthy controls (P<0.05) . But the contents of amide protons in the left and total hippocampus under 3 ut in AD patients were lower than those in healthy controls (P<0.05) . (2) Spearman rank correlation analysis showed that the content of amide protons in the right hippocampus under 2 ut was positively correlated with the scores of delusional ideation factor (rs=0.574, P=0.040) and hallucinations factor (rs=0.595, P=0.032) and diurnal rhythm disturbances factor (rs=0.591, P=0.033) . Under 3 ut, the content of amide protons in the right hippocampus was positively correlated with the scores of delusional ideation factor (rs=0.588, P=0.034) and hallucinations factor (rs=0.572, P=0.041) and diurnal rhythm disturbances factor (rs=0.650, P=0.016) , whereas content of amide protons in the left hippocampus was negatively correlated with the score of spatial orientation (rs=-0.590, P=0.034) . The amide proton content in the total hippocampus under 3 ut was positively correlated with scores of delusional ideation factor (rs=0.625, P=0.022) and hallucinations factor (rs=0.606, P=0.028) and diurnal rhythm disturbances factor (rs=0.611, P=0.026) . Under 4 ut, the content of amide protons in the right hippocampus was positively correlated with the score of emotion factor (rs=0.615, P=0.025) , whereas content of amide proton in the left hippocampus was negatively correlated with scores of temporal orientation (rs=-0.570, P=0.042) , attention (rs=-0.570, P=0.042) , and remote memory (rs=-0.732, P=0.004) . The amide proton content in the total hippocampus under 4 ut was positively correlated with score of emotion factor (rs=0.580, P=0.038) .
We found that there were abnormal changes in the content of amide protons in the hippocampus of AD patients, which may be related to the patients' cognitive fuction and psychotic symptoms. This study may provide a new idea for clinical diagnosis of AD.
Expert Consensus on the Management of Cognitive Impairment after Stroke 2021 has made it clear that, post-stroke cognitive impairment (PSCI) prevalence needs to be assessed by cognitive assessment 3-6 months after stroke, but the influencing factors found by existing studies are still controversial and need the support of EBM evidence.
To investigate the influencing factors of cognitive impairment 3 to 6 months after ischemic stroke, to provide an evidence-based reference for the prevention and intervention of PSCI.
We searched databases of the Cochrane Library, PubMed, EMBase, CINAHL, Web of Science, CNKI, SinoMed, VIP and Wanfang Data for cohort studies or case-control studies about influencing factors of cognitive impairment 3 to 6 months after ischemic stroke from inception to December 2020. RevMan5.3 software was used to conduct the Meta-analysis.
A total of 27 studies were finally included, involving 8 677 patients (4 322 with PSCI and the other 4 355 without) . Meta-analysis results demonstrated that, age〔OR=1.10, 95%CI (1.06, 1.14) , P<0.000 01〕, educational level〔OR=0.82, 95%CI (0.78, 0.85) , P<0.000 01〕, hypertension〔OR=2.69, 95%CI (1.90, 3.81) , P<0.000 01〕, diabetes〔OR=1.95, 95%CI (1.58, 2.39) , P<0.000 01〕, atrial fibrillation〔OR=2.92, 95%CI (1.92, 4.45) , P<0.000 01〕, history of stroke〔OR=2.68, 95%CI (1.95, 3.68) , P<0.000 01〕, Fazakas score〔OR=1.86, 95%CI (1.57, 2.21) , P<0.000 01〕, NIHSS score at admission〔OR=1.44, 95%CI (1.17, 1.77) , P=0.000 6〕, hyperhomocysteinemia〔OR=1.08, 95%CI (1.02, 1.14) , P=0.006〕and drinking〔OR=2.85, 95%CI (2.00, 4.04) , P<0.000 01〕 were associated with cognitive impairment 3 to 6 months after ischemic stroke.
Available evidence suggests that, age, educational level, hypertension, diabetes, atrial fibrillation, history of prior stroke, Fazakas score, NIHSS score at admission, hyperhomocysteinemia and drinking may be associated factors of cognitive impairment 3 to 6 months after ischemic stroke. To reduce the incidence of PSCI, individualized rehabilitation program is suggested to made according to the above-mentioned associated factors for PSCI in combination with the patient's details.
Cognitive impairment (CI) is highly prevalent in patients with end-stage renal disease (ESRD) , which seriously affects the prognosis of patients. Early identification of its associated factors is of great significance, but there is no agreement as to existing relevant research conclusions, and no relevant systematic reviews conducted with Chinese patients with ESRD.
To systematically evaluate the factors associated with CI in Chinese patients with ESRD.
Databases of PubMed, Web of Science, EMBase, CNKI, WanFangData, CQVIP and CBM were searched from inception to October 2021 for studies (including cross-sectional studies, cohort studies and case-control studies) about associated factors of CI in Chinese ESRD patients (with stage CKD5 defined in the 2002 Kidney Disease Outcomes Quality Initiative, or treatment with peritoneal dialysis or hemodialysis) using subject words in combination with free words as search terms with adjustment by the database feature when necessary. Two researchers independently performed literature screening, data extraction, and methodological quality assessment. Stata 15.0 was employed for Meta-analysis.
In total, 44 studies were included, including 42 172 patients, among which, the cohort studies and case-control studies were rated as high-quality evidence, and the cross-sectional studies as moderate or high-quality evidence. Meta-analysis revealed that older age〔OR=1.17, 95%CI (1.13, 1.22) , P<0.001〕, long duration of dialysis〔OR=1.02, 95%CI (1.00, 1.03) , P=0.008〕, hypertension〔OR=2.02, 95%CI (1.06, 3.86) , P=0.032〕, stroke〔OR=1.93, 95%CI (1.33, 2.80) , P=0.001〕, diabetes〔OR=1.99, 95%CI (1.62, 2.44) , P<0.001〕, high Charlson Comorbidity Index (CCI) 〔OR=5.28, 95%CI (1.48, 18.82) , P=0.010〕, depression〔OR=2.46, 95%CI (1.61, 3.77) , P<0.001〕, high parathyroid hormone (PTH) 〔OR=1.02, 95%CI (1.00, 1.04) , P=0.034〕, high C-reactive protein (CRP) 〔OR=1.20, 95%CI (1.01, 1.42) , P=0.040〕and high Hcy 〔OR=3.34, 95%CI (2.06, 5.42) , P<0.001〕 were associated with increased risk of CI, while male〔OR=0.55, 95%CI (0.37, 0.82) , P=0.003〕, high education level〔OR=0.45, 95%CI (0.37, 0.55) , P<0.001〕, high Hb〔OR=0.91, 95%CI (0.86, 0.95) , P<0.001〕, high serum ALB〔OR=0.77, 95%CI (0.63, 0.94) , P=0.009〕 and high serum creatinine〔OR=0.997, 95%CI (0.995, 0.999) , P=0.003〕were associated with decreased risk of CI.
The current evidence proves that the risk of CI in Chinese patients with ESRD may be increased with older age, long duration of dialysis, hypertension, stroke, diabetes, high CCI, depression, high PTH, high CRP and high Hcy, and decreased with male, high education level, and high Hb, ALB and Cr. However, the conclusion needs to be verified by more high-quality studies due to limited number and quality of included studies.
Research Progress on the Relationship between Osteoporosis and Cognitive Impairment
In recent years, studies have shown that among elderly comorbidities, the incidence of comorbidity between osteoporosis and cognitive impairment is increasing year by year, which is manifested as a high incidence of falls and an increased risk of fractures, which leads to disability, increased mortality, and serious harm to health and quality of life of patients with comorbidities also bring a heavy economic burden to the family and society, which has become a more difficult problem in the management of chronic diseases in the community. This article reviews the progress of the relationship between osteoporosis and cognitive impairment. The focus is on the co-morbidity mechanism, clinical risk factors and clinical features of co-morbidity between osteoporosis and cognitive impairment. It is found that osteoporosis is closely related to cognitive impairment and seriously endangers the health of the elderly. It is hoped that this article can provide ideas for exploring new risk factors for comorbidity of osteoporosis and cognitive impairment, and provide help for the effective prevention and management of patients with comorbidity of osteoporosis and cognitive impairment.
Chronic cerebral hypoperfusion-induced cognitive impairment (CCHCI) is a cognitive deficit caused by cerebral cortex or subcortical infarction, white matter degeneration, blood-cerebrospinal fluid barrier, and hippocampal injury due to long-term hypoperfusion of the brain. Clinical evidence shows that there is still no effective pharmacological treatment for CCHCI. But numerous animal studies have demonstrated that enriched environment can alleviate brain tissue damage caused by chronic hypoperfusion and promote nerve growth and functional recovery in ischemic brain areas. We reviewed the latest advances in the use of enriched environment as a non-drug intervention for CCHCI in animal models via regulating autophagy and epigenetic mechanisms to inhibit oxidative stress, protect the blood-cerebrospinal fluid barrier, promote neurovascular reconstruction and stimulate synaptic plasticity. We hope the review could provide new ideas for the treatment and clinical research of CCHCI to reverse CCHCI-induced neurological impairment and improve cognitive impairment.
Post-stroke mild cognitive impairment (PSMCI) is a common complication after stroke, which negatively affects patients' full recovery from stroke and imposes financial and emotional pressure on their families.
To observe the clinical efficacy of moxibustion on Governor vessel on the cognitive function and TCM syndromes in PSMCI due to deficiency of kidney essence.
Eligible patients with PSMCI (n=60) who were treated in Rehabilitation Center, the First Affiliated Hospital of Henan University of CM from July 2020 to July 2021 were selected, and evenly randomized to a control group (routine basic treatment plus routine cognitive rehabilitation training) and a moxibustion group 〔routine basic treatment plus routine cognitive rehabilitation training and moxibustion on the Governor vessel acupoints (once daily, five times per week) 〕, received four consecutive weeks of treatment. The Mini-Mental State Examination (MMSE) , and Montreal Cognitive Assessment (MoCA) were used to assess the cognitive function. Symptoms of kidney essence deficiency was assessed by the Scale for the Differentiation of Syndromes of Vascular Dementia (SDSVD) . And quality of life was measured by the Specifications for Stroke-Quality of Life (SS-QOL) . The overall clinical efficacy and safety of the two treatments were evaluated.
Pre- and post-treatment comparisons of scores of MMSE and MoCA, SDSVD, and SS-QOL revealed that moxibustion group patients group had greater improvements in cognitive function, symptoms of kidney essence deficiency, and quality of life than control group patients (P<0.05) . Moreover, moxibustion group patients had better clinical outcomes (P<0.05) . The safety of treatment showed no significant intergroup differences (P>0.05) .
Moxibustion of the Governor vessel helps to better improve the cognitive function and TCM symptoms of PSMCI patients due to deficiency of kidney essence with good clinical efficacy and safety.
Quality Assessment of Guidelines forVascular Cognitive Impairment Using the AGREEⅡ
As the second primary type of cognitive impairment worldwide, vascular cognitive impairment (VCI) is closely associated with cerebrovascular risks, which imposes a heavy burden on the society and families. Early diagnosis and treatment are important for intervening and reversing VCI. And formulating high-quality clinical guidelines is an effective way to improve diagnosis and treatment levels of VCI.
To assess the quality of guidelines for VCI, aiming at offering support for making clinical decisions for VCI.
From August to November 2021, we searched literature databases and websites in China and abroad to identify guidelines for VCI, and assessed them using the Appraisal of Guidelines for Research & Evaluation (AGREE) Ⅱ.
A total of 18 guidelines were enrolled, 12 of which are Chinese guidelines and 6 are foreign guidelines; 9 of which are evidence-based guidelines, and the other 9 are not. The intraclass correlation coefficient was 0.935, indicating a high degree of agreement between raters. The overall quality of these guidelines was relatively low, since in the six domains, only the average score of Clarity of Presentation was greater than 60% (64.04%) , and the average scores of Scope and Purpose (52.31%) and Editorial Independence (42.01%) were between 30% and 60%, and those for other three domains, Stakeholder Involvement (27.24%) , Rigor of Development (20.05%) and Applicability (13.83%) , were all less than 30%. The grade of recommendation for 6 guidelines was B, and that for other 12 guidelines was C.
The overall quality of the included guidelines was rated relatively low, especially their average score for each of the three domains, Stakeholder Involvement, Rigor of Development, and Applicability, was below the average level. It is suggested to enhance the quality of VCI guidelines via improving the details of guidelines strictly under the evidence-based principle.
Progression and Reversion of Mild Cognitive Impairment：a Study Using Data from the Uniform Data Set
Mild cognitive impairment (MCI) has highly variable cognitive trajectories. Approximately 10% to 15% of MCI patients progress to dementia, and nearly 24% revert to normal cognition each year. There are few studies on the progression and reversion of MCI, especially there version of MCI to normal cognition.
To construct a multi-class classification model of MCI outcomes (reversion, stabilization and progression) and to explore the possible associated factors of these outcomes.
Data were collected from the National Alzheimer's Disease Coordinating Center Unified Data Set, involving 397 patients who were initially diagnosed with MCI during 2005—2019 with at least two follow-ups and complete clinical and follow-up data. Patients' demographic information, physical examination, disease history, and measurement results by assessment scales in MCI were selected for analysis. Boruta was used for feature selection. Random forest was used for supporting the classification of MCI outcomes. A stepwise multinomial logistic regression was used to explore the associated factors of different MCI outcomes.
Of the 397 cases, 124 (31.23%) reverted to normal cognition, 77 (44.58%) were in stable condition, and 96 (24.18%) progressed to dementia. In the multi-classification task, the accuracy of direct three-class classification was 67.58%. In multiple binary classifications, the accuracies of reversion and stabilization, and reversion and progression were above 90%. Among the hierarchical three-class classification, the accuracy based on stabilization→ reversion → progression was 84.38%. Stepwise multinomial Logistic regression analysis showed that age ≥80 years 〔OR=0.260, 95%CI (0.117, 0.574) 〕, self-reported cognitive impairment 〔OR=0.295, 95%CI (0.139, 0.623) 〕, and decreased Clinical Dementia Rating (CDR) scores〔OR=0.220, 95%CI (0.092, 0.525) 〕 were associated with decreased risk of MCI progressing to dementia, while history of stroke 〔OR=2.896, 95%CI (1.370, 6.122) 〕, fecal incontinence 〔OR=6.556, 95%CI (1.787, 24.047) 〕, and higher Functional Activities Questionnaire score〔OR=1.048, 95%CI (1.003, 1.095) 〕were associated with increased risk of MCI progressing to dementia. Decreased probability of reversion from MCI to normal cognition was related to age ≥80 years 〔OR=0.289, 95%CI (0.091, 0.914) 〕, obesity 〔OR=0.236, 95%CI (0.075, 0.740) 〕, self-reported cognitive impairment 〔OR=0.289, 95%CI (0.111, 0.757) 〕, and higher CDR scores 〔OR=0.015, 95%CI (0.003, 0.089) 〕, while increased probability of reversion from MCI to normal cognition was related to higher MMSE score 〔OR=1.708, 95%CI (1.428, 2.043) 〕 and higher numbers of correct naming of animals 〔OR=1.139, 95%CI (1.046, 1.240) 〕.
The outcome of MCI patients is affected by multiple factors. Advanced age, obesity, history of stroke, fecal incontinence, self-reported cognitive impairment and reduced functional activity were important factors influencing MCI progression and reversion.
Prevalence and Distribution Trends of Mild Cognitive Impairment among Chinese Older Adults：a Meta-analysis
Mild cognitive impairment (MCI) has become a major disorder affecting the quality of life of Chinese older adults, a rapidly increasing population. Understanding MCI prevalence in this population is important for promoting healthy ageing, but there is a lack of comprehensive reports on MCI prevalence in a large national sample of older adults in the past decade.
To examine the trends of MCI prevalence and geographical distribution in Chinese older adults in the past 10 years, providing data support for further research on public service policies for the elderly.
In January 2021, we searched for studies about MCI prevalence in Chinese older adults published from January 2010 to December 2020 from databases of SinoMed, CQVIP, Wanfang Data, CNKI, PubMed, Ovid, SpringerLink, and EmBase, and extracted data regarding MCI prevalence from the eligible ones, then chose effects models with indicators based on the within-study heterogeneity.
A total of 47 studies were included, involving 137 599 samples. The overall prevalence of MCI in Chinese older adults in the last decade was 19%〔95%CI (17%, 21%) 〕. Demographic analysis showed the following results: the MCI prevalence was 17%〔95%CI (15%, 19%) 〕 and 19%〔95%CI (17%, 21%) 〕 for men and women, respectively, 16%〔95%CI (11%, 22%) 〕 and 23%〔95%CI (16%, 30%) 〕 for urban and rural areas, respectively, 16%〔95%CI (14%, 19%) 〕 and 24%〔95%CI (20%, 28%) 〕for those living with a spouse and without, respectively, and 13%〔95%CI (9%, 17%) 〕, 12%〔95%CI (9%, 15%) 〕, 17%〔95%CI (13%, 20%) 〕, 26%〔95%CI (20%, 31%) 〕, 33%〔95%CI (24%, 42%) 〕and 42%〔95%CI (22%, 62%) 〕 for those at 60-64 years, 65-69 years, 70-74 years, 75-79 years, 80-84 years, 85 and above, respectively. Besides this, MCI prevalence showed a trend of decrease with the increase of education level: 30%〔95%CI (25%, 35%) 〕 in those with little education (<1 year of education) , while 10%〔95%CI (7%, 13%) 〕 in those with university education (>12 years of education) . Spatial distribution trend: prevalence varied significantly between provinces (autonomous regions/municipalities) (15%-37%) and between northern, northwestern, eastern, south-central, southwestern parts of China (17%-22%) . Temporal distribution trend: the prevalence showed an increasing trend in the last decade (11%-28%) .
The prevalence of MCI in Chinese elderly population showed an increasing trend from January 2010 to December 2020, with differences across provinces (autonomous regions/ municipalities) and 5 geographical regions. In addition, the prevalence was higher in the female, less educated, older, rural, and spouseless groups.
Developments in the Role of Iron Imbalance in the Pathogenesis of Alzheimer's Disease
Iron load is closely associated with the initiation and progression of Alzheimer's disease (AD) . Although age-dependent deposition of β-amyloid (A β) in senile plaques (SPs) , and neurofibrillary tangles (NFTs) formed by accumulation of hyperphosphorylated tau proteins are two major pathological features of AD, there are still many different views on the inducing factors of SPs and NFTs. We reviewed the new developments in the relationship between imbalance of brain iron homeostasis and the pathogenesis of AD, with a summary presented as follows: (1) Age-related iron deposits in different brain regions may damage normal cognitive function and behavior. (2) Iron imbalance and oxidative stress may together or independently promote Aβ overproduction by activating β- or γ-secretases and inhibiting α-secretase, and also cause tau hyperphosphorylation by activating protein kinases, such as glycogen synthase kinase-3β, cyclin-dependent protein kinase-5, and inhibiting protein phosphatase 2A. Iron imbalance-induced changes will in turn aggravate brain iron deposition and distribution. The vicious circle between iron imbalance and Aβ/tau anomalies may eventually lead to AD. (3) Iron overload may also directly or indirectly injure organelles, causing endoplasmic reticulum stress, mitochondrial and autophagy dysfunction, and damaging synaptic function via inducing or aggravating the aggregation or accumulation of A βand tau. At the same time, hydroxyl radicals produced via the Fenton reaction associated with abnormal iron metabolism, may trigger oxidative stress, destroy the structure and function of cell lipids, protein and DNA, eventually leading to cell death. (4) Given the limitations and side effects of long-term application of traditional iron chelators, alpha-lipoic acid and lactoferrin as self-synthesized naturally small molecules, are expected to be applied to clinical practice, for they have shown very intriguing biological activities in blocking Aβ-aggregation, tau hyperphosphorylation and neuronal damage. We believe that iron-targeted therapies are a promising direction for the treatment of AD.
Latest Research on the Neuroprotective Mechanism of Short-chain Fatty Acids in Stroke and Its Relation with Post-stroke Cognitive Impairment
Post-stroke cognitive impairment is one of the common complications of stroke, seriously affecting patients' ability to perform activities of daily living. Recent studies about microbiota-gut-brain axis have found that gut microbiota and their metabolites play an important role in the development of neurological diseases. Short-chain fatty acids, the main metabolites of gut microbiota, are key transmitters of gut-brain communication, which have a neuroprotective effect in stroke, yet the mechanism of action is not fully clear. This paper presents a review of the neuroprotective mechanism of short-chain fatty acids in stroke, and its relation with post-stroke cognitive impairment, providing evidence for studying the pathogenesis and treatment of stroke.
Special Issue: Alzheimer's disease
