Parkinson’s disease (PD) is a neurodegenerative disease that occurs due to loss of nerve cells that produce dopamine in the brain, affecting approximately 4 million people worldwide. PD patients often feel an increas...Parkinson’s disease (PD) is a neurodegenerative disease that occurs due to loss of nerve cells that produce dopamine in the brain, affecting approximately 4 million people worldwide. PD patients often feel an increase in anxiety levels daily. While there are medications/exercises to help relieve anxiety, there are limited methods to reduce anxiety without the help of a caretaker. As a result, MEDIC Foundation, a non-profit organization in British Columbia, Canada, is designing an automated system that consists of a wristband and an application which uses vi-bration therapy to help reduce anxiety of PD patients. Literature reviews were conducted to document the project’s needs. Phase I of the project focused on de-veloping a prototype for the application and phase II on developing the wrist-band. The team developed prototypes of a wristband that automatically applies vibration near the median nerve as the heart rate variability (HRV) deviates away from the normal threshold of the user, and an application that displays real-time heart rate variability signals as well as provides for relaxation. The development of the prototype is still in early progress. By creating this automated system, we aim to provide a solution to senior PD patients to relieve anxiety independently. .展开更多
Objective： To study the significance of dementia rating scales in the diagnosis of Alzheimer＇ s disease（AD）. Methods： Probable AD patients（118 cases） diagnosed according to NINCDS-ADRDA criteria and the normal ...Objective： To study the significance of dementia rating scales in the diagnosis of Alzheimer＇ s disease（AD）. Methods： Probable AD patients（118 cases） diagnosed according to NINCDS-ADRDA criteria and the normal controls（100 cases） were examined with a battery of neuropsychological tests and the dementia severity of AD patients was determined with clinical dementia rating （CDR）. Changed neuropsychological characteristics of different AD dementia severities were analyzed. The discriminant analysis and ROC curve analysis were perfomed to analyze the specificity, the sensitivity, and the general accuracy of various dementia rating scales in the diagnosis of AD, and the area under the ROC curve. Results： The total cognition function in mild （CDR = 1 ）, moderate（CDR = 2） and severe stages（CDR=3） of AD had an obvious trend of continuous decline, with the MMSE values 17.44±2.64, 13.90±4.32, and 5.50 ± 3.90 respectively. The trend of decline of the verbal fluency function in AD was same as that of total cognition function. The visuospatial function was reduced in early stage of AD （CDR = 1 ） and completely lost in moderate and severe AD. Delay memory function began to show decline in the early stage of AD, and the decline turned apparent in moderate and severe AD. Immediate memory function showed unchanged in early stage of AD, while showed decline in moderate AD, and the decline became very quick in severe AD. The impairment of daily living ability and social activity function developed with the severity degree of AD. But the decline of social activity function was very quick in moderate stage of AD. In general, the leading scale to diagnose AD was FOM, followed by RVR, POD, MMSE, BD,ADL and DS. When MMSE was combined with one or more of FOM, RVR, BD, DS, the general accuracy in distinguishing AD from the normal controls was improved. Conclusion： Neuropsychological test is useful in the diagnosis of AD, especially in the early stage. The validity is improved when dementia rating scales are combined correctly.展开更多
Parkinson＇s disease has a negative impact on health-related quality of life in Parkinson＇s disease patients. Depression, cognitive impairment, coping strategies, dyskinesia, gait disorders and complications of dopam...Parkinson＇s disease has a negative impact on health-related quality of life in Parkinson＇s disease patients. Depression, cognitive impairment, coping strategies, dyskinesia, gait disorders and complications of dopaminergic drugs are the variables that most affect health-related quality of life. The ecological model of human development focuses attention on both individual and social environmental factors as targets for health interventions. From this perspective, the aim of this cross-sectional survey was to evaluate the influence of gender, family size and perceived autonomy on health-related quality of life in Parkinson＇s disease patients in nOrtheastern Sicily, Italy. Ninety Parkinson＇s disease patients, attending the Movement Disorders Clinic at IRCCS Centro Neurolesi ＂Bonino-Pulejo＂ （Messina）, were consecutively enrolled. The Unified Parkinson Disease Rating Scale motor subscale （UPDRS-Ⅲ） scores, the Parkinson Disease Questionnaire-39 Item scores （as a disease-specific measure of health-related quality of life）, scores on the Short Form （36） Health Survey Questionnaire （as a generic measure）, and answers to a brief checklist were recorded. A total of 85 Parkinson＇s disease patients （49% males and 51% females; mean age 70.8 ± 8.6 years mean UPDRS-Ⅲ 24.15 ± 6.55; mean disease duration 5.52 ± 4.65 years） completed the booklet of questionnaires. In the multivariate regression analysis, we included clinical and social variables as independent predictors of health-related quality of life. Our results suggest a potential compounding effect of ecological intrapersonal and interpersonal levels on health-related quality of life outcomes. Gender, self-evaluated autonomy and family size significantly impacted health-related quality of life. If quality of life is used as an indicator of treatment outcomes, an ecological perspective of the case history will be important to disclose relevant prognostic information and trigger personalized health care interventions.展开更多
Objective:To summarize the current clinical evidence related to the therapeutic effects and safety of adjuvant scalp electro-acupuncture (SEA) treatment for Parkinson's disease in China.Methods:Following the PRISM...Objective:To summarize the current clinical evidence related to the therapeutic effects and safety of adjuvant scalp electro-acupuncture (SEA) treatment for Parkinson's disease in China.Methods:Following the PRISMA statement,seven electronic databases were searched to retrieve randomized controlled clinical trials that used SEA combined with medication as the treatment intervention,and medication as the control.RevMan 5.3 was used to analyze outcomes,including the Unified Parkinson's Disease Rating Scale (UPDRS),Webster scale,effectiveness rate,and UPDRS III.Results:Nine randomized controlled trials,with certain methodological flaws and risks of bias,were included that involved 474 participants.SEA combined with medication was more effective than medication alone in overall therapeutic effects,as evidenced by total UPDRS scores (mean difference (MD):7.15,95% confidence interval [CI] 0.24 to 14.07,P =.04),Webster scores (MD:1.60,95% CI 0.20 to 2.99,P =.03),and effectiveness rate (risk ratio:1.35,95% CI 1.19 to 1.54,P <.001).In addition,there was significant improvement in pooled motor function results after adjuvant SEA treatment compared with medication alone (MD:5.75,95% Cl 4.18 to 7.32,P <.001).Conclusion:The combination of SEA and medication may be a promising intervention for patients with Parkinson's disease,especially to improve motor function.However,results were inconclusive,and additional studies with rigorous experimental design and larger sample sizes are needed to verify these results.展开更多
After Alzheimer’s disease, Parkinson’s disease (PD) is the most common neurodegenerative disease. According to WHO data, about 1% of the world’s population over 60 years of age is affected by PD, and its incidence ...After Alzheimer’s disease, Parkinson’s disease (PD) is the most common neurodegenerative disease. According to WHO data, about 1% of the world’s population over 60 years of age is affected by PD, and its incidence increases with age. Information about mortality plays a relevant role in the planning and distribution of financial resources in the areas of public health, social assistance and the like. Thus, this article aims to describe the evolution of PD mortality in the Brazilian state capitals, in the period from 2010 to 2019. A descriptive and retrospective study was conducted, based on data collection (number of deaths and estimated resident population), by sex and age group, available in the DATASUS SIM. Mortality rates were calculated per 100 thousand inhabitants;and statistical tests of linear regression, the t-test, ANOVA and the Tukey test, using the R program, were performed to evaluate the significance of the data. The number of deaths and mortality rates were higher in males compared to females and the incidence of mortality was higher in the over 80s. Notably, the southeastern region presented the highest mortality rates, which is to be expected because it concentrates the highest proportion of elderly people. It is hoped that such data will aid the implementation of public health policies and adequate social assistance for those affected by PD, in order to improve their quality of life.展开更多
Parkinson’s disease is a neurodegenerative disorder characterized by motor, autonomic, and neuropsychiatric symptoms, among the latter, apathy has been found to be present in up to 70% of patients. The main objective...Parkinson’s disease is a neurodegenerative disorder characterized by motor, autonomic, and neuropsychiatric symptoms, among the latter, apathy has been found to be present in up to 70% of patients. The main objective of the present study was to assess the psychometric properties of the Apathy Scale for evaluation of Ecuadorian patients with Parkinson’s. This was a cross sectional study, with re-test. There were 73 women (34.5%) in the final sample of 211 patients. Mean age was 67.5 ± 10.2 years, mean length of illness was 7.1 ± 5.5 years, and the mean ldopa dose was 656.1 ± 292.7 mg/day. The mean Apathy Scale score was 12.7 ± 7.1. Reliability: The Guttman’s λ obtained was 0.89. The SEM was 2.34 for the AS. The ICC using an absolute agreement definition was: ICC = 0.78 [(95% IC 0.73?- 0.82) f = 4.96;p ≤ 0.000]. Discriminative validity, analyzed with the Kruskal-Wallis statistic and using H&Y stages as segmentation variable registered an X(2) value of p 0.0001. In conclusion the Apathy Scale proved to have suitable metric attributes in this specific PD patient sample: internal consistency, reliability, stability, and convergent and known-groups validity.展开更多
Introduction: The research focuses on the clinical study of cerebral angioarchitectonics and microcirculation disorders in the development of Alzheimer’s disease (AD) in comparison with other neurodegenerative and is...Introduction: The research focuses on the clinical study of cerebral angioarchitectonics and microcirculation disorders in the development of Alzheimer’s disease (AD) in comparison with other neurodegenerative and ischemic lesions. Materials and methods: 1117 patients with different types and stages of neurodegenerative and ischemic lesions were examined, 93 of whom (8.33%) had different stages of AD—Test Group;1024 (91.67%) had cerebral atherosclerosis, Binswanger disease (BD), vascular Parkinsonism (VP)—Control Group. The examination included definition of CDR, MMSE, cerebral CT, MRI, cerebral sciagraphy (SG), rheoencephalography (REG), morphometric detection of AD stages with TDR, and cerebral multi-gated angiography (MUGA). Results: In all patients with AD, regardless of the disease stage, specific сerebral small vessel disease (CSVD), manifested by dyscirculatory angiopathy of Alzheimer’s type (DAAT), was detected in the temporal and fronto-parietal areas. Conclusions: DAAT is an AD-specific lesion of cerebral microvessels that changes hemodynamics, causes cerebral hypoxia, and contributes to impaired amyloid beta metabolism. The combination of deposition of amyloid beta in the cerebral tissue and vascular wall, as well as specific disorders of microcirculation, cause neurodegeneration and AD development. Patients with other neurodegenerative and ischemic lesions had no DAAT manifestations.展开更多
Background The clinical utility and safety of sargramostim has previously been reported in cancer,acute radiation syndrome,autoimmune disease,inflammatory conditions,and Alzheimer’s disease.The safety,tolerability,an...Background The clinical utility and safety of sargramostim has previously been reported in cancer,acute radiation syndrome,autoimmune disease,inflammatory conditions,and Alzheimer’s disease.The safety,tolerability,and mecha-nisms of action in Parkinson’s disease(PD)during extended use has not been evaluated.Methods As a primary goal,safety and tolerability was assessed in five PD patients treated with sargramostim(Leukine®,granulocyte-macrophage colony-stimulating factor)for 33 months.Secondary goals included numbers of CD4+T cells and monocytes and motor functions.Hematologic,metabolic,immune,and neurological evaluations were assessed during a 5-day on,2-day off therapeutic regimen given at 3μg/kg.After 2 years,drug use was discon-tinued for 3 months.This was then followed by an additional 6 months of treatment.Results Sargramostim-associated adverse events included injection-site reactions,elevated total white cell counts,and bone pain.On drug,blood analyses and metabolic panels revealed no untoward side effects linked to long-term treatment.Unified Parkinson’s Disease Rating Scale scores remained stable throughout the study while regulatory T cell number and function were increased.In the initial 6 months of treatment,transcriptomic and proteomic mono-cyte tests demonstrated autophagy and sirtuin signaling.This finding paralleled anti-inflammatory and antioxidant activities within both the adaptive and innate immune profile arms.Conclusions Taken together,the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim treatment.Confirmation in larger patient populations is planned in a future phase II evaluation.展开更多
Despite decades of research, at present there is no curative therapy for Alzheimer＇s disease. Changes in the way new drugs are tested appear to be necessary. Three changes are presented here and will be discussed. Th...Despite decades of research, at present there is no curative therapy for Alzheimer＇s disease. Changes in the way new drugs are tested appear to be necessary. Three changes are presented here and will be discussed. The first change is that Alzheimer＇s disease must be considered a disease of four major pathological processes, not one. The four processes are： 1） vascular hy- poperfusion of the brain with associated mitochondrial dysfunction, 2） destructive protein inclusions, 3） uncontrolled oxidative stress, and 4） proinflammatory immune processes second- ary to microglial and astrocytic dysfunction in the brain. The second change recommended is to alter the standard cognitive measurement tools used to quantify mental decline in test patients. Specifically the Dementia Severity Rating Scale （DSRS） should supersede Mini-Mental State Examination （MMSE） and other popular tests, and a measurement scale developed in research should be used to produce a linear and non-irregular baseline. Finally, accepting the concept that four etiologies cause Alzheimer＇s disease leads to the last necessary change, that new thera- pies must be employed directed against all four causes, likely as a combination. There are drugs ready to be employed in such a combinations which are available and used clinically for other purposes so can be used ＂offlabel＂ and one such combination is suggested.展开更多
文摘Parkinson’s disease (PD) is a neurodegenerative disease that occurs due to loss of nerve cells that produce dopamine in the brain, affecting approximately 4 million people worldwide. PD patients often feel an increase in anxiety levels daily. While there are medications/exercises to help relieve anxiety, there are limited methods to reduce anxiety without the help of a caretaker. As a result, MEDIC Foundation, a non-profit organization in British Columbia, Canada, is designing an automated system that consists of a wristband and an application which uses vi-bration therapy to help reduce anxiety of PD patients. Literature reviews were conducted to document the project’s needs. Phase I of the project focused on de-veloping a prototype for the application and phase II on developing the wrist-band. The team developed prototypes of a wristband that automatically applies vibration near the median nerve as the heart rate variability (HRV) deviates away from the normal threshold of the user, and an application that displays real-time heart rate variability signals as well as provides for relaxation. The development of the prototype is still in early progress. By creating this automated system, we aim to provide a solution to senior PD patients to relieve anxiety independently. .
文摘Objective： To study the significance of dementia rating scales in the diagnosis of Alzheimer＇ s disease（AD）. Methods： Probable AD patients（118 cases） diagnosed according to NINCDS-ADRDA criteria and the normal controls（100 cases） were examined with a battery of neuropsychological tests and the dementia severity of AD patients was determined with clinical dementia rating （CDR）. Changed neuropsychological characteristics of different AD dementia severities were analyzed. The discriminant analysis and ROC curve analysis were perfomed to analyze the specificity, the sensitivity, and the general accuracy of various dementia rating scales in the diagnosis of AD, and the area under the ROC curve. Results： The total cognition function in mild （CDR = 1 ）, moderate（CDR = 2） and severe stages（CDR=3） of AD had an obvious trend of continuous decline, with the MMSE values 17.44±2.64, 13.90±4.32, and 5.50 ± 3.90 respectively. The trend of decline of the verbal fluency function in AD was same as that of total cognition function. The visuospatial function was reduced in early stage of AD （CDR = 1 ） and completely lost in moderate and severe AD. Delay memory function began to show decline in the early stage of AD, and the decline turned apparent in moderate and severe AD. Immediate memory function showed unchanged in early stage of AD, while showed decline in moderate AD, and the decline became very quick in severe AD. The impairment of daily living ability and social activity function developed with the severity degree of AD. But the decline of social activity function was very quick in moderate stage of AD. In general, the leading scale to diagnose AD was FOM, followed by RVR, POD, MMSE, BD,ADL and DS. When MMSE was combined with one or more of FOM, RVR, BD, DS, the general accuracy in distinguishing AD from the normal controls was improved. Conclusion： Neuropsychological test is useful in the diagnosis of AD, especially in the early stage. The validity is improved when dementia rating scales are combined correctly.
基金supported by a grant from the Ministry of Health (Research for the Strategic Program 2007)
文摘Parkinson＇s disease has a negative impact on health-related quality of life in Parkinson＇s disease patients. Depression, cognitive impairment, coping strategies, dyskinesia, gait disorders and complications of dopaminergic drugs are the variables that most affect health-related quality of life. The ecological model of human development focuses attention on both individual and social environmental factors as targets for health interventions. From this perspective, the aim of this cross-sectional survey was to evaluate the influence of gender, family size and perceived autonomy on health-related quality of life in Parkinson＇s disease patients in nOrtheastern Sicily, Italy. Ninety Parkinson＇s disease patients, attending the Movement Disorders Clinic at IRCCS Centro Neurolesi ＂Bonino-Pulejo＂ （Messina）, were consecutively enrolled. The Unified Parkinson Disease Rating Scale motor subscale （UPDRS-Ⅲ） scores, the Parkinson Disease Questionnaire-39 Item scores （as a disease-specific measure of health-related quality of life）, scores on the Short Form （36） Health Survey Questionnaire （as a generic measure）, and answers to a brief checklist were recorded. A total of 85 Parkinson＇s disease patients （49% males and 51% females; mean age 70.8 ± 8.6 years mean UPDRS-Ⅲ 24.15 ± 6.55; mean disease duration 5.52 ± 4.65 years） completed the booklet of questionnaires. In the multivariate regression analysis, we included clinical and social variables as independent predictors of health-related quality of life. Our results suggest a potential compounding effect of ecological intrapersonal and interpersonal levels on health-related quality of life outcomes. Gender, self-evaluated autonomy and family size significantly impacted health-related quality of life. If quality of life is used as an indicator of treatment outcomes, an ecological perspective of the case history will be important to disclose relevant prognostic information and trigger personalized health care interventions.
基金the National Natural Science Foundation of China(81573773 and 81774110)Self-determined Project of Beijing University of Chinese Medicine(2017-JYB-JS-004).
文摘Objective:To summarize the current clinical evidence related to the therapeutic effects and safety of adjuvant scalp electro-acupuncture (SEA) treatment for Parkinson's disease in China.Methods:Following the PRISMA statement,seven electronic databases were searched to retrieve randomized controlled clinical trials that used SEA combined with medication as the treatment intervention,and medication as the control.RevMan 5.3 was used to analyze outcomes,including the Unified Parkinson's Disease Rating Scale (UPDRS),Webster scale,effectiveness rate,and UPDRS III.Results:Nine randomized controlled trials,with certain methodological flaws and risks of bias,were included that involved 474 participants.SEA combined with medication was more effective than medication alone in overall therapeutic effects,as evidenced by total UPDRS scores (mean difference (MD):7.15,95% confidence interval [CI] 0.24 to 14.07,P =.04),Webster scores (MD:1.60,95% CI 0.20 to 2.99,P =.03),and effectiveness rate (risk ratio:1.35,95% CI 1.19 to 1.54,P <.001).In addition,there was significant improvement in pooled motor function results after adjuvant SEA treatment compared with medication alone (MD:5.75,95% Cl 4.18 to 7.32,P <.001).Conclusion:The combination of SEA and medication may be a promising intervention for patients with Parkinson's disease,especially to improve motor function.However,results were inconclusive,and additional studies with rigorous experimental design and larger sample sizes are needed to verify these results.
文摘After Alzheimer’s disease, Parkinson’s disease (PD) is the most common neurodegenerative disease. According to WHO data, about 1% of the world’s population over 60 years of age is affected by PD, and its incidence increases with age. Information about mortality plays a relevant role in the planning and distribution of financial resources in the areas of public health, social assistance and the like. Thus, this article aims to describe the evolution of PD mortality in the Brazilian state capitals, in the period from 2010 to 2019. A descriptive and retrospective study was conducted, based on data collection (number of deaths and estimated resident population), by sex and age group, available in the DATASUS SIM. Mortality rates were calculated per 100 thousand inhabitants;and statistical tests of linear regression, the t-test, ANOVA and the Tukey test, using the R program, were performed to evaluate the significance of the data. The number of deaths and mortality rates were higher in males compared to females and the incidence of mortality was higher in the over 80s. Notably, the southeastern region presented the highest mortality rates, which is to be expected because it concentrates the highest proportion of elderly people. It is hoped that such data will aid the implementation of public health policies and adequate social assistance for those affected by PD, in order to improve their quality of life.
文摘Parkinson’s disease is a neurodegenerative disorder characterized by motor, autonomic, and neuropsychiatric symptoms, among the latter, apathy has been found to be present in up to 70% of patients. The main objective of the present study was to assess the psychometric properties of the Apathy Scale for evaluation of Ecuadorian patients with Parkinson’s. This was a cross sectional study, with re-test. There were 73 women (34.5%) in the final sample of 211 patients. Mean age was 67.5 ± 10.2 years, mean length of illness was 7.1 ± 5.5 years, and the mean ldopa dose was 656.1 ± 292.7 mg/day. The mean Apathy Scale score was 12.7 ± 7.1. Reliability: The Guttman’s λ obtained was 0.89. The SEM was 2.34 for the AS. The ICC using an absolute agreement definition was: ICC = 0.78 [(95% IC 0.73?- 0.82) f = 4.96;p ≤ 0.000]. Discriminative validity, analyzed with the Kruskal-Wallis statistic and using H&Y stages as segmentation variable registered an X(2) value of p 0.0001. In conclusion the Apathy Scale proved to have suitable metric attributes in this specific PD patient sample: internal consistency, reliability, stability, and convergent and known-groups validity.
文摘Introduction: The research focuses on the clinical study of cerebral angioarchitectonics and microcirculation disorders in the development of Alzheimer’s disease (AD) in comparison with other neurodegenerative and ischemic lesions. Materials and methods: 1117 patients with different types and stages of neurodegenerative and ischemic lesions were examined, 93 of whom (8.33%) had different stages of AD—Test Group;1024 (91.67%) had cerebral atherosclerosis, Binswanger disease (BD), vascular Parkinsonism (VP)—Control Group. The examination included definition of CDR, MMSE, cerebral CT, MRI, cerebral sciagraphy (SG), rheoencephalography (REG), morphometric detection of AD stages with TDR, and cerebral multi-gated angiography (MUGA). Results: In all patients with AD, regardless of the disease stage, specific сerebral small vessel disease (CSVD), manifested by dyscirculatory angiopathy of Alzheimer’s type (DAAT), was detected in the temporal and fronto-parietal areas. Conclusions: DAAT is an AD-specific lesion of cerebral microvessels that changes hemodynamics, causes cerebral hypoxia, and contributes to impaired amyloid beta metabolism. The combination of deposition of amyloid beta in the cerebral tissue and vascular wall, as well as specific disorders of microcirculation, cause neurodegeneration and AD development. Patients with other neurodegenerative and ischemic lesions had no DAAT manifestations.
基金supported by National Institute of Neurological Disorders and Stroke Grant 5 R01NS034239-25 and private donations provided through the University of Nebraska Foundation.
文摘Background The clinical utility and safety of sargramostim has previously been reported in cancer,acute radiation syndrome,autoimmune disease,inflammatory conditions,and Alzheimer’s disease.The safety,tolerability,and mecha-nisms of action in Parkinson’s disease(PD)during extended use has not been evaluated.Methods As a primary goal,safety and tolerability was assessed in five PD patients treated with sargramostim(Leukine®,granulocyte-macrophage colony-stimulating factor)for 33 months.Secondary goals included numbers of CD4+T cells and monocytes and motor functions.Hematologic,metabolic,immune,and neurological evaluations were assessed during a 5-day on,2-day off therapeutic regimen given at 3μg/kg.After 2 years,drug use was discon-tinued for 3 months.This was then followed by an additional 6 months of treatment.Results Sargramostim-associated adverse events included injection-site reactions,elevated total white cell counts,and bone pain.On drug,blood analyses and metabolic panels revealed no untoward side effects linked to long-term treatment.Unified Parkinson’s Disease Rating Scale scores remained stable throughout the study while regulatory T cell number and function were increased.In the initial 6 months of treatment,transcriptomic and proteomic mono-cyte tests demonstrated autophagy and sirtuin signaling.This finding paralleled anti-inflammatory and antioxidant activities within both the adaptive and innate immune profile arms.Conclusions Taken together,the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim treatment.Confirmation in larger patient populations is planned in a future phase II evaluation.
文摘Despite decades of research, at present there is no curative therapy for Alzheimer＇s disease. Changes in the way new drugs are tested appear to be necessary. Three changes are presented here and will be discussed. The first change is that Alzheimer＇s disease must be considered a disease of four major pathological processes, not one. The four processes are： 1） vascular hy- poperfusion of the brain with associated mitochondrial dysfunction, 2） destructive protein inclusions, 3） uncontrolled oxidative stress, and 4） proinflammatory immune processes second- ary to microglial and astrocytic dysfunction in the brain. The second change recommended is to alter the standard cognitive measurement tools used to quantify mental decline in test patients. Specifically the Dementia Severity Rating Scale （DSRS） should supersede Mini-Mental State Examination （MMSE） and other popular tests, and a measurement scale developed in research should be used to produce a linear and non-irregular baseline. Finally, accepting the concept that four etiologies cause Alzheimer＇s disease leads to the last necessary change, that new thera- pies must be employed directed against all four causes, likely as a combination. There are drugs ready to be employed in such a combinations which are available and used clinically for other purposes so can be used ＂offlabel＂ and one such combination is suggested.
