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*For medical professionals only, early diagnosis and early treatment are the key to intervening in Alzheimer's disease!
Alzheimer's disease (AD), commonly known as "Alzheimer's disease", is a neurodegenerative disease with progressive cognitive impairment as the core clinical manifestation, and its diagnostic criteria have been continuously updated in the past three decades, and the diagnostic accuracy has been significantly improved
.
September 21, 2022 is "World Alzheimer's Day", the theme is "Know Yourself and Know Each Other Early Prevention", on the occasion of "World Alzheimer's Day", "Medical Neurology Channel" and the Department of Neurology of Huashan Hospital affiliated to Fudan University launched a series of activities, and this issue specially invited Professor Zhao Qianhua of the Department of Neurology of Huashan Hospital Affiliated to Fudan University to talk about those things
about AD diagnosis.
AD in the clinic divided into three stages of dementia is the last mentioned earlier, the core clinical manifestations of AD is progressive cognitive impairment, that is to say, there is a gradual process of cognitive impairment from occurrence to development, what is it?
Professor Zhao Qianhua explained that the pathological changes in the brain of AD patients are a long process
of gradual accumulation.
Studies have found that AD patients have begun to have pathological changes in the brain fifteen to twenty years before the appearance of clinical symptoms (such as memory impairment), and due to the long course of the disease, we currently divide AD into three stages
.
Figure 1: AD course (source Zhao Qianhua Professor PPT)
The first stage is preclinical AD, as the name suggests, at this stage, the patient's daily life is generally the same as normal people, there is no clinical manifestations such as cognitive or memory damage, and the condition does not meet the clinical criteria for
AD diagnosis.
At this stage, the use of more advanced examination methods, such as positron emission computed tomography (PET-CT), lumbar puncture, etc.
, to detect biological markers in the brain, the corresponding core biological indicators can be observed
.
The second stage is called mild cognitive impairment (MCI), at this stage the patient's memory and thinking ability has some slight changes, the patient's basic daily living ability is normal, such as dressing, eating, bathing, etc.
, but there is a financial management, shopping, visiting and other instrumental daily ability or social function mild damage, some patients may appear indifferent, depression and other emotional disorders, careful observation may
。
At this stage, not only can advanced tests be used to support evidence, but also an objective screening assessment
of cognitive function can be carried out using neuropsychological scales.
The third stage is AD dementia stage, what everyone calls "Alzheimer's disease" refers to this stage, and most patients visit the doctor
at this stage.
At this time, memory, thinking and behavioral symptoms have impaired the patient's daily life and function, patients not only have difficulty in completing complex instrumental daily activities (financial management, shopping, visits, etc.
), dressing, eating, bathing and other basic daily living abilities may also be gradually lost, some patients indifference, depression and other emotions are becoming more and more serious
.
All in all, AD onset is insidious, the course of the disease is long, and there is a progressive exacerbation process, so early diagnosis and early intervention are of great significance
.
The earlier the intervention, the better
the effect.
In this regard, Professor Zhao Qianhua also expressed the hope that more patients can come to the early stage of
the disease.
Aβ and tau proteins are key to diagnosis or can be screened 15-20 years in advance of the early 20th century, a German scientist named Alzheimer's defined and reported the first case of AD, and after the patient's death, brain slices were observed, and amyloid plaque deposition and hyperphosphorylation tau protein formation of neuronal fiber tangles
.
More than 100 years later, to this day, β-amyloid (Aβ) and tau protein are still considered to be the two most important pathological signs of AD, and are the key links to promote the pathophysiological changes of the AD waterfall cascade, and the relevant biomarkers are included in the diagnostic framework
.
Figure 2: ATN diagnostic framework (source Zhao Qianhua Professor PPT)
Professor Zhao Qianhua introduced, the current A/T/N biomarker diagnostic system in the "A" refers to Aβ, "T" refers to the tau protein, through PET-CT, you can intuitively observe whether there is Aβ deposition in the human brain, where the Aβ deposition site is, how the degree of Aβ deposition is.
.
.
For tau proteins, PET-CT can also visualize
them.
In addition to PET-CT, another major test is cerebrospinal fluid examination, which requires lumbar puncture (a test method used to pierce the lumbar intervertebral space into the spinal canal with a fine needle), which can detect important markers
such as Aβ40/42 and P-tau in the cerebrospinal fluid.
It is worth mentioning that with the advancement of science and technology, an important result has been achieved in recent years - peripheral blood detection of AD-related biomarkers
.
By collecting the peripheral blood of the patient, isolating the serum and plasma, and then analyzing it through a high-precision detection platform (such as single-molecule immune array technology, immunoprecipitation mass spectrometry analysis, etc.
), the Aβ40/42 and tau content
in the blood can be sensitively detected.
The study found that through the detection of these biomarkers, it is expected that the screening and diagnosis
of AD can be carried out in the preclinical stage (the preclinical AD stage may be up to 15-20 years, during which there may be no symptoms of cognitive impairment).
The biomarker diagnostic system has made rapid progress but still needs to be cautious about the previous AD diagnostic criteria, mainly using the method of exclusion to diagnose and differentiate
AD.
That is, after a series of laboratory tests to rule out other diseases that may cause cognitive impairment, considering that the diagnosis is likely to be AD, there is inevitably a certain proportion of misdiagnosis and omission
.
Professor Zhao Qianhua said that although the progress in the field of AD treatment has been relatively slow in the past few decades, the rapid development of biomarker detection technology has promoted the continuous updating and iteration
of AD diagnostic standards.
Table 1: The evolution of AD diagnostic criteria/frameworks Note:
Compared with the previous exclusion method, the current biomarker diagnostic system has significant advantages, one is to improve the sensitivity and specificity of diagnosis, and the other is to make the early diagnosis of AD possible
.
However, the transition in the diagnosis of AD from clinical to biological criteria requires caution
.
Reliance solely on biomarkers and neglect of clinical manifestations should be avoided
.
Professor Zhao Qianhua pointed out that in clinical practice, some patients meet AD standards in terms of biomarkers, but do not have AD symptoms
throughout their lives.
Therefore, Professor Zhao Qianhua said: "For the biomarker diagnostic system that is still being continuously updated and improved, we must clearly see its advantages while maintaining a cautious attitude
.
Comprehensive diagnosis should be made on the basis of objective analysis of clinical manifestations combined with laboratory tests
.
"The difficulty of the popularization of the current biomarker detection technology is mentioned in the three main AD biomarker detection methods
: PET-CT, cerebrospinal fluid examination, and peripheral blood detection.
PET-CT technology threshold is high, the cost is high, and there are certain difficulties in popularization; CSF examination requires lumbar puncture, which is aggressive and difficult to accept
by most people.
When talking about the non-invasive examination method with application prospects, Professor Zhao Qianhua replied that this is a problem that needs to be solved in the clinic, and peripheral blood detection has more application prospects
than PET-CT and cerebrospinal fluid examination.
As research progresses, the boundaries of peripheral blood demarcation become clearer and more clearly defined, which will have better diagnostic value
.
In addition to peripheral blood testing, other non-invasive tests, such as: gait, eye movements, retinal imaging, electrophysiological examination, etc.
, multi-dimensional collection of human body information, is expected to form an AD comprehensive diagnostic model, with good application prospects
.
What are the conditions for an ideal biological marker? idealProfessor Zhao Qianhua pointed out: 1.
Early diagnosis:
can be identified at the beginning of AD pathological progression, that is, it should be closely related to the pathological changes of AD core or directly reflect the pathological changes
of the core of the disease.
2.
Dynamic disease surveillance: AD disease course is long, the ideal detection index should be able to be used for disease dynamic monitoring, can stratify the severity of the disease, and can reflect the treatment effect
in real time.
3.
Helps with accurate diagnosis: the sensitivity of detecting AD > 80%, and the specificity of distinguishing AD from other dementia > 80%.
4.
Predict clinical outcome: predict the disease development trend
of patients in the next 5 to 10 years.
5.
Easy to mass popularization: simple operation, low cost, suitable for large-scale community screening and routine clinical practice
.
Expert profile
Zhao Qianhua
Come to the "Doctor's Station" and take a look 👇
Copyright noticeThis
article is original, reproduced please contact the authorization-End-submitted/reprinted/business cooperation, please contact: yxjsjbx@yxj.
org.
cn*The medical community strives to be accurate and reliable when the published content is approved, but does not make any commitment and guarantee for the timeliness of the published content, as well as the accuracy and completeness of the cited information (if any), etc.
, and does not assume that the content is outdated, Any liability arising from the possible inaccuracy or incompleteness of the referenced materials
.
Relevant parties are invited to verify separately when adopting or using this as a basis for decision-making
.
Alzheimer's disease (AD), commonly known as "Alzheimer's disease", is a neurodegenerative disease with progressive cognitive impairment as the core clinical manifestation, and its diagnostic criteria have been continuously updated in the past three decades, and the diagnostic accuracy has been significantly improved
.
September 21, 2022 is "World Alzheimer's Day", the theme is "Know Yourself and Know Each Other Early Prevention", on the occasion of "World Alzheimer's Day", "Medical Neurology Channel" and the Department of Neurology of Huashan Hospital affiliated to Fudan University launched a series of activities, and this issue specially invited Professor Zhao Qianhua of the Department of Neurology of Huashan Hospital Affiliated to Fudan University to talk about those things
about AD diagnosis.
AD in the clinic divided into three stages of dementia is the last mentioned earlier, the core clinical manifestations of AD is progressive cognitive impairment, that is to say, there is a gradual process of cognitive impairment from occurrence to development, what is it?
Professor Zhao Qianhua explained that the pathological changes in the brain of AD patients are a long process
of gradual accumulation.
Studies have found that AD patients have begun to have pathological changes in the brain fifteen to twenty years before the appearance of clinical symptoms (such as memory impairment), and due to the long course of the disease, we currently divide AD into three stages
.
Figure 1: AD course (source Zhao Qianhua Professor PPT)
The first stage is preclinical AD, as the name suggests, at this stage, the patient's daily life is generally the same as normal people, there is no clinical manifestations such as cognitive or memory damage, and the condition does not meet the clinical criteria for
AD diagnosis.
At this stage, the use of more advanced examination methods, such as positron emission computed tomography (PET-CT), lumbar puncture, etc.
, to detect biological markers in the brain, the corresponding core biological indicators can be observed
.
The second stage is called mild cognitive impairment (MCI), at this stage the patient's memory and thinking ability has some slight changes, the patient's basic daily living ability is normal, such as dressing, eating, bathing, etc.
, but there is a financial management, shopping, visiting and other instrumental daily ability or social function mild damage, some patients may appear indifferent, depression and other emotional disorders, careful observation may
。
At this stage, not only can advanced tests be used to support evidence, but also an objective screening assessment
of cognitive function can be carried out using neuropsychological scales.
The third stage is AD dementia stage, what everyone calls "Alzheimer's disease" refers to this stage, and most patients visit the doctor
at this stage.
At this time, memory, thinking and behavioral symptoms have impaired the patient's daily life and function, patients not only have difficulty in completing complex instrumental daily activities (financial management, shopping, visits, etc.
), dressing, eating, bathing and other basic daily living abilities may also be gradually lost, some patients indifference, depression and other emotions are becoming more and more serious
.
All in all, AD onset is insidious, the course of the disease is long, and there is a progressive exacerbation process, so early diagnosis and early intervention are of great significance
.
The earlier the intervention, the better
the effect.
In this regard, Professor Zhao Qianhua also expressed the hope that more patients can come to the early stage of
the disease.
Aβ and tau proteins are key to diagnosis or can be screened 15-20 years in advance of the early 20th century, a German scientist named Alzheimer's defined and reported the first case of AD, and after the patient's death, brain slices were observed, and amyloid plaque deposition and hyperphosphorylation tau protein formation of neuronal fiber tangles
.
More than 100 years later, to this day, β-amyloid (Aβ) and tau protein are still considered to be the two most important pathological signs of AD, and are the key links to promote the pathophysiological changes of the AD waterfall cascade, and the relevant biomarkers are included in the diagnostic framework
.
Figure 2: ATN diagnostic framework (source Zhao Qianhua Professor PPT)
Professor Zhao Qianhua introduced, the current A/T/N biomarker diagnostic system in the "A" refers to Aβ, "T" refers to the tau protein, through PET-CT, you can intuitively observe whether there is Aβ deposition in the human brain, where the Aβ deposition site is, how the degree of Aβ deposition is.
.
.
For tau proteins, PET-CT can also visualize
them.
In addition to PET-CT, another major test is cerebrospinal fluid examination, which requires lumbar puncture (a test method used to pierce the lumbar intervertebral space into the spinal canal with a fine needle), which can detect important markers
such as Aβ40/42 and P-tau in the cerebrospinal fluid.
It is worth mentioning that with the advancement of science and technology, an important result has been achieved in recent years - peripheral blood detection of AD-related biomarkers
.
By collecting the peripheral blood of the patient, isolating the serum and plasma, and then analyzing it through a high-precision detection platform (such as single-molecule immune array technology, immunoprecipitation mass spectrometry analysis, etc.
), the Aβ40/42 and tau content
in the blood can be sensitively detected.
The study found that through the detection of these biomarkers, it is expected that the screening and diagnosis
of AD can be carried out in the preclinical stage (the preclinical AD stage may be up to 15-20 years, during which there may be no symptoms of cognitive impairment).
The biomarker diagnostic system has made rapid progress but still needs to be cautious about the previous AD diagnostic criteria, mainly using the method of exclusion to diagnose and differentiate
AD.
That is, after a series of laboratory tests to rule out other diseases that may cause cognitive impairment, considering that the diagnosis is likely to be AD, there is inevitably a certain proportion of misdiagnosis and omission
.
Professor Zhao Qianhua said that although the progress in the field of AD treatment has been relatively slow in the past few decades, the rapid development of biomarker detection technology has promoted the continuous updating and iteration
of AD diagnostic standards.
Table 1: The evolution of AD diagnostic criteria/frameworks Note:
Compared with the previous exclusion method, the current biomarker diagnostic system has significant advantages, one is to improve the sensitivity and specificity of diagnosis, and the other is to make the early diagnosis of AD possible
.
However, the transition in the diagnosis of AD from clinical to biological criteria requires caution
.
Reliance solely on biomarkers and neglect of clinical manifestations should be avoided
.
Professor Zhao Qianhua pointed out that in clinical practice, some patients meet AD standards in terms of biomarkers, but do not have AD symptoms
throughout their lives.
Therefore, Professor Zhao Qianhua said: "For the biomarker diagnostic system that is still being continuously updated and improved, we must clearly see its advantages while maintaining a cautious attitude
.
Comprehensive diagnosis should be made on the basis of objective analysis of clinical manifestations combined with laboratory tests
.
"The difficulty of the popularization of the current biomarker detection technology is mentioned in the three main AD biomarker detection methods
: PET-CT, cerebrospinal fluid examination, and peripheral blood detection.
PET-CT technology threshold is high, the cost is high, and there are certain difficulties in popularization; CSF examination requires lumbar puncture, which is aggressive and difficult to accept
by most people.
When talking about the non-invasive examination method with application prospects, Professor Zhao Qianhua replied that this is a problem that needs to be solved in the clinic, and peripheral blood detection has more application prospects
than PET-CT and cerebrospinal fluid examination.
As research progresses, the boundaries of peripheral blood demarcation become clearer and more clearly defined, which will have better diagnostic value
.
In addition to peripheral blood testing, other non-invasive tests, such as: gait, eye movements, retinal imaging, electrophysiological examination, etc.
, multi-dimensional collection of human body information, is expected to form an AD comprehensive diagnostic model, with good application prospects
.
What are the conditions for an ideal biological marker? idealProfessor Zhao Qianhua pointed out: 1.
Early diagnosis:
can be identified at the beginning of AD pathological progression, that is, it should be closely related to the pathological changes of AD core or directly reflect the pathological changes
of the core of the disease.
2.
Dynamic disease surveillance: AD disease course is long, the ideal detection index should be able to be used for disease dynamic monitoring, can stratify the severity of the disease, and can reflect the treatment effect
in real time.
3.
Helps with accurate diagnosis: the sensitivity of detecting AD > 80%, and the specificity of distinguishing AD from other dementia > 80%.
4.
Predict clinical outcome: predict the disease development trend
of patients in the next 5 to 10 years.
5.
Easy to mass popularization: simple operation, low cost, suitable for large-scale community screening and routine clinical practice
.
Expert profile
Zhao Qianhua
- Associate Professor of Department of Neurology, Huashan Hospital Affiliated to Fudan University, Master Supervisor, Doctor of Medicine
- National Clinical Research Center for Geriatric Diseases (Huashan) PI
- He is a member of the Dementia and Cognitive Impairment Group of the Neurology Branch of the Chinese Medical Association
- He is a member of the Dementia and Cognitive Impairment Group of Shanghai Medical Association
- Young member of the Medical Research Ethics Branch of Shanghai Medical Association
- Member of the Cognitive Impairment Branch of the Chinese Geriatrics Society, Good Doctor Online "Good Doctor of the Year"
- He has been engaged in the clinical diagnosis and treatment of various neurodegenerative diseases such as senile dementia and the clinical trials of phase I and IV drugs at home and abroad for more than ten years
- He is familiar with neuropsychological assessment, geriatric epidemiology, and cognitive intervention research, and serves as a lecturer in the cognitive intervention course of the Municipal Old Cadre University
- He went to the Erasmus Medical Center in Rotterdam, the United States, the Mayo Clinic in the United States, and the University of California, Los Angeles for further study, under the supervision of Professor
Ronald C Petersen.
He has presided over nearly 10 national, provincial and ministerial projects, and participated in more than 10 national research, major chronic disease prevention and control, Shanghai Municipal Science and Technology Commission, and international cooperation
.
He has published more than 100 SCI treatises, edited / translated many works, won national patents, and won the Shanghai Science and Technology Progress Award
Come to the "Doctor's Station" and take a look 👇
Source of this articleMedical Neurology ChannelHope this article is reviewZhao Qianhua Responsible Editor of Huashan Hospital
Affiliated to Fudan UniversityMr.
Lu Li Xiang Yu
Copyright noticeThis
article is original, reproduced please contact the authorization-End-submitted/reprinted/business cooperation, please contact: yxjsjbx@yxj.
org.
cn*The medical community strives to be accurate and reliable when the published content is approved, but does not make any commitment and guarantee for the timeliness of the published content, as well as the accuracy and completeness of the cited information (if any), etc.
, and does not assume that the content is outdated, Any liability arising from the possible inaccuracy or incompleteness of the referenced materials
.
Relevant parties are invited to verify separately when adopting or using this as a basis for decision-making
.
