Accurate diagnosis, early intervention, multi-party cohesion to alleviate the "Alzheimer's dilemma"

Precise diagnosis and treatment, moving forward the intervention window, or will delay the progression of
AD.

Every year in September is World Alzheimer's Month, for which the medical community specially invites Professor Chen Xiaochun, Secretary of the Party Committee of Fujian Medical University and Chief Physician of the Department of Neurology of the Affiliated Union Hospital, and Professor Shi Jiong, Vice President of the First Affiliated Hospital of the University of Science and Technology of China, to talk about the establishment of the AD prevention and control system and help the realization of the
national strategic goal of healthy aging.

AD has become a serious public health problem

AD is one of the most common types of dementia in old age, accounting for approximately 60% to 80% of patients with dementia in old age ^[1].

The development of AD is divided into three major stages: preclinical AD, mild cognitive impairment (MCI) of AD origin, and AD, which in turn is divided into light, medium and severe, collectively known as the five small stages
.
Flow survey data show that the prevalence of AD in the population over 65 years old in China is as high as 5.
56%, and the prevalence of MCI in the population over 60 years old is as high as 15.
5%, about 38.
77 million people, of which about one-third is AD-derived MCI ^[2-3].

Professor Chen Xiaochun introduced, "Due to the relative lack of health education in AD, the proportion of patients who believe that they are ill does not exceed 30%; Of those who know they have cognitive impairment, only one-third of patients attend hospitals, and less than 20 percent
are treated properly.
Combined, only about 2% of patients are likely to receive effective treatment
.
To sum up, AD has the characteristics of "one high and three low", that is, high incidence, low awareness rate, low consultation rate, and low
effective control rate.

AD also places a heavy financial burden on
patients and their families.
Professor Chen Xiaochun said, "At present, the per capita cost of treatment is about 50,000 yuan
.
In addition to direct medical expenses, there are direct non-medical expenses and indirect economic losses
.
Among them, due to the continuous decline of the daily life function of AD patients, it is necessary for families to spend more and more time on full-time care, and the indirect economic loss is quite high
.
As China's population ages, every family may face the challenge
of caring for AD patients.
”

"Comprehensive estimates, China's AD and AD-derived MCI patients totaling nearly 20 million, bringing great pressure on economic and social development, is a very prominent and severe public health problem to be faced in the past ten or twenty years, affecting thousands of households
.
" Professor Chen Xiaochun added
.

early screening, early diagnosis, early intervention,

Effectively delays the course of AD

AD prevention and control is a worldwide problem, the primary reason is that it is difficult to diagnose
early.
Professor Shi Jiong pointed out, "AD onset is insidious, the course of the disease is slow, and it is easy to be mistaken by patients and their families for senile memory loss, thereby neglecting to seek medical treatment, resulting in unclear onset time of the main complaint at the time of treatment, which brings great challenges
to diagnosis.
" ”

Professor Shi Jiong believes that "when diagnosing AD, routine tests should first be performed to rule out other factors
that may cause cognitive dysfunction.
Diagnosis of AD requires a neuropsychiatric scale score and detection of biomarkers in the brain, namely amyloid and tau, according to internationally recognized ATN standards, usually with the help of cerebrospinal fluid or positron emission tomography (PET), the former is invasive and often less easily accepted by older patients, and the latter is expensive
.
Therefore, there is an urgent need for a non-invasive, relatively simple method, in which peripheral blood is a very good choice
.
”

However, there are still many difficulties
in the application of peripheral blood to the diagnosis of AD.
On the one hand, the NMPA has not yet approved instruments to detect amyloid and tau levels in peripheral blood, such as the Roche AD in vitro diagnostic test, which has been granted breakthrough medical devices by the US FDA, which can help simplify the patient's journey and improve the accessibility of AD diagnosis by detecting biomarkers in the blood^[4]; On the other hand, many biomarker indicators are based on the study of European and American populations, due to different factors such as race, living habits and other factors, the normal value of the same biomarker may be greatly biased
.

Professor Shi Jiong introduced, "I cooperated with Professor Shen Yong of the University of Science and Technology of China to establish a research cohort of Chinese own, including 411 participants, based on single-molecule immune array technology to detect amyloid and tau content in cerebrospinal fluid and plasma, and found that the normal values of biomarker indicators in Chinese are very different from those in Europe and the United States, which is also the first time that the changes of AD core biomarkers have been systematically studied in the Chinese group, which is of great benefit to the formation of Chinese own data.
" ^[5]
。 ”

Early intervention is the current consensus on the prevention and treatment of AD, and since AD is a chronic disease, it is crucial
to accurately grasp the timing of intervention.
Professor Xiaochun Chen pointed out, "AD-derived MCI is an intermediate stage between cognitive normal and AD dementia, with a high probability of outgrowth to AD dementia, so MCI is an important threshold for
intervention in the prevention and control of AD.
" ”

Professor Shi Jiong also said, "In the preclinical stage, patients do not have symptoms, it is difficult to get diagnosis and intervention, the real 'golden window' is the MCI stage and AD early, when the symptoms begin to appear, if you can actively intervene, at least to a certain extent, you can delay the progression of
the disease.
" "It can be seen that intervention in the MCI phase may be the most effective strategy
for delaying the occurrence of AD.
"

At present, there are two main treatment modalities for AD, namely pharmacotherapy and non-pharmacological therapy
.
For the former, Professor Chen Xiaochun introduced, "At present, the drugs for AD treatment can be summarized into four categories, the first and most commonly used cholinesterase inhibitors, the second is NMDA receptor antagonists, the third is small molecule drugs, and the fourth is disease modifying treatment (DMT).

The last class of drugs is a very hot field of new drug research and development in the past decade, with the main targets being amyloid and tau
.
”

Professor Shi Jiong pointed out, "At present, all drugs on the market can only delay the progression of AD disease, so now many large pharmaceutical companies and clinical research have proposed the concept of 'disease modification therapy', that is, active intervention
for clear targets.
" Many companies have made some progress
in drug development of amyloid as a therapeutic target.
”

At this year's AAIC Annual Meeting, Roche's innovative drug Gantenerumab released a series of findings
.
The results of the study showed that high doses of Gantenerumab showed strong amyloid plaque clearance capabilities
.
As the leader of a related China study, Professor Shi Jiong introduced: "In the phase II clinical trial, Gantenerumab antibody was found to be effective in clearing amyloid, and the patient's cognitive function was also improved
to a certain extent.
In addition to proving the effectiveness and safety of the drug, the results of the current phase III clinical study worldwide are yet to be released, and the results will further verify whether amyloid is the underlying cause of AD and its research value
as a therapeutic target for improving cognitive function.
”

In terms of drug therapy, Professor Chen Xiaochun added: "In the brain parenchyma of AD stage patients, most of the neurons related to cognitive function may have been lost and damaged, and at this time, to correct the pathophysiological defects, cognitive function cannot be improved, so in terms of drug intervention, early treatment must be emphasized and the window
of clinical diagnosis and treatment should be further advanced.
" It is expected that more therapeutic drugs with a clear mechanism of action will be successfully marketed, so as to prepare
clinicians and patients for smooth treatment.
”

For non-pharmacological interventions, risk factors for preventing cardiovascular and cerebrovascular diseases, such as three highs (hypertension, hyperlipidemia, and high blood sugar), and smoking, are very effective
in preventing cognitive impairment to a certain extent.
Active exercise (including mental exercise and physical exercise), a reasonable diet, and an optimistic mood can also play a role in preventing AD to a certain extent
.
"For example, for high-risk groups of AD, such as carriers of the ApoEε4 allele, reasonable control of these risk factors can also delay the age of
onset.
" Professor Chen Xiaochun said
.

All parties help build an AD prevention and control ecosystem

In recent years, the state has paid more attention to the prevention and treatment of cognitive disorders, including AD, and has issued a series of policy opinions such as "Healthy China Action (2019-2030)", "14th Five-Year Plan", "Exploring the Work Plan for the Prevention and Treatment of Alzheimer's Disease", etc.
, which have injected a shot in the arm
to further strengthen the prevention and treatment of AD.
The establishment of the AD prevention and control ecosystem needs to start from the construction of a medical ecosystem and a social ecosystem
.

In terms of the medical service system, Professor Chen Xiaochun summarized the following three points:

• First of all, it is necessary to popularize the knowledge of cognitive functions to the public and actively carry out public health education
  .
  Educate more patients that they should actively seek medical attention once cognitive decline occurs;

• The second is to popularize the knowledge of cognitive function to general practitioners in primary medical institutions, launch "memory workshops" or "cognitive workshops" at the grassroots level, train grassroots doctors who can screen or identify cognitive disorders in each community or township health center, remind patients to seek medical treatment in a timely manner, and better serve patients as "gatekeepers";

• Finally, it is necessary to improve the standardized diagnosis and treatment level of AD by neurology specialists, and establish an advanced cognitive impairment center and a clinical dementia diagnosis and
  treatment center.
  

Professor Shi Jiong also said, "In terms of the community, it is hoped that cognitive function screening will be included in the routine physical examination, especially for people over 40 years old who have a family history of AD or over 50 years old who have a decline in self-perception and memory, so that problems can be found in time, and patients can be reminded to go to the hospital in time to get further diagnosis and treatment
.
" ”

Professor Chen Xiaochun further pointed out, "At the level of the state and the government, it is hoped that the prevention and treatment of AD can be like the prevention and treatment of tumors and cerebrovascular diseases, as a national strategy, and the establishment of corresponding institutions to coordinate the prevention and treatment of
cognitive dysfunction nationwide.
" Professor Shi Jiong also appealed, "I hope that the country will include AD in the chronic disease management directory as soon as possible, so that more patients can receive effective and sustained treatment and long-term attention and follow-up
.
" ”

At present, the National Health Commission's "Exploring the Special Service Work Plan for the Prevention and Treatment of Alzheimer's Disease" has been introduced, and the goal of "Double 80" has been proposed, one is that by 2022, the public's knowledge of the prevention and treatment of Alzheimer's disease will increase to 80%, and the other is that the cognitive function screening rate of the elderly over 65 years old in the community (village) will reach 80%.

Professor Chen Xiaochun believes that "with relevant policies, we should increase our efforts to promote the implementation of policies from the national and government levels, in order to achieve higher resource utilization, stronger influence and appeal, and greater and more effective
promotion.
" ”

In terms of social ecosystem, Professor Chen Xiaochun pointed out, "The construction of the health care system is worthy of attention, compared with Europe and the United States, China's current construction work in this system is relatively weak, severe AD patients need more care, in addition to the social institutions, it is expected that the civil affairs department also has corresponding measures and plans to reasonably promote the health care of this part of the population, which can greatly reduce the burden of
some families.
" ”

The next 10 years will be an important "window of opportunity" for China to deal with AD
.
"All in all, the construction of the AD prevention and control ecosystem is a systematic project, which requires the efforts of all walks of life to better promote this work
.
" Professor Chen Xiaochun concluded
.

References

Tian Jinzhou, Xie Hengge, Wang Luning, et al.
Guidelines for the diagnosis and treatment of Alzheimer's disease in China (2020 edition)[J].
Chinese Journal of Geriatrics, 2021,40(03):269-283.

Dementia and Cognitive Impairment Group of Neurology Branch of Chinese Medical Association.
Chinese Expert Consensus on the Diagnosis and Treatment of Alzheimer's Iatric Mild Cognitive Impairment 2021[J].
Chinese Journal of Neurology, 2022, 55(5):20.

[3] Jia L, Du Y, Chu L, et al.
Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study[J].
Lancet Public Health, 2020,5(12):e661-e671.

[4] Roche's Elecsys Amyloid Plasma Panel granted FDA Breakthrough Device Designation to enable a timely diagnosis of Alzheimer’s disease.
Retrieved July 19, 2022, from Gao F, Lv X, Dai L, et al.
A combination model of AD biomarkers revealed by machine learning precisely predicts Alzheimer's dementia: China Aging and Neurodegenerative Initiative (CANDI) study[J].
Alzheimers Dement, 2022.

*This article is for the sole purpose of providing scientific information to healthcare professionals and does not represent the views of the Platform