How to break through the bottleneck of dementia treatment?

Recently, WHO launched a new online platform to promote the exchange of information and knowledge about dementia.

This new tool is called the "Global Dementia Observatory Knowledge Exchange Platform" and contains key resources to support the implementation of the 2017-2025 Global Dementia Public Health Response Action Plan and its seven action areas.

This provides a space for global users to share resources, such as policies, guidelines, case studies, etc.
, to promote mutual learning and promote knowledge exchange in the field of dementia.

Global Dementia Observatory Knowledge Exchange Platform, https://globaldementia.
org/en Among the many causes of dementia, Alzheimer's disease (AD) accounts for up to 70%.

AD is a neurodegenerative disease, usually seen in the elderly, rarely onset before the age of 60.

The incidence and prevalence of AD increase exponentially with age, and its prevalence will basically double every 5 years after the age of 65.

According to the "2018 World Alzheimer's Disease Report", there are approximately 50 million dementia patients worldwide, and this number is expected to increase to 152 million by 2050.

In China, there are 15.
07 million dementia patients in people aged 60 and above, of which 9.
83 million are Alzheimer's disease, the prevalence of mild cognitive impairment is 5.
54%, and the number of patients reaches 38.
77 million.

In my country, one third of the elderly population over the age of 85 suffer from AD.

In April this year, the "Survey Report on the Diagnosis and Treatment Status of Alzheimer's Disease Patients in China" was released in full, which portrayed many aspects of AD patients in my country, such as the medical status, medication status, caregiver pressure, and policy expectations.

The report shows that from the perspective of the overall age distribution structure, elderly patients account for the vast majority.

The oldest patients interviewed were 99 years old, and the average age was 73 years old.
Among them, the proportion of patients 66 years old and above was 77.
48%.

The proportion of female patients (58.
00%) interviewed is higher than that of male patients (42.
00%).

78.
70% of the interviewed patients have a high school education or below.

70.
66% of the interviewed patients spend less than 40,000 yuan each year for various therapeutic drugs and nutrients, of which 39.
94% are less than 20,000 yuan, and 30.
72% are 20,000-40,000.

The vast majority of patients seek medical treatment because of various symptoms.
Among them, "the phenomenon of memory loss, forgetting things, confusion, and not knowing familiar people" has become the primary reason for medical treatment.
It is 10.
06%.

67.
71% of the interviewed patients went to the hospital for treatment within one year of the onset of symptoms.

Among the 2038 patients interviewed, 60.
06% are still taking anti-dementia drugs, while the proportion of patients who have taken but stopped taking the drug is 20.
26%, and 19.
68% of the interviewed patients said they have never taken drugs.

Among the interviewed patients who are currently taking medication, the highest proportion of anti-dementia drugs used are conventional drugs donepezil (36.
68%) and memantine (31.
68%).

91.
36% of the interviewed patients felt the benefits brought by the treatment, 34.
74% of the interviewed patients thought that “the condition has worsened but is relatively slow”, and 30.
32% of the interviewed patients said that “the condition is basically stable”.

However, 43.
49% of patients discontinued the drug due to the poor treatment effect, high price of the drug, and obvious side effects.

In general, the Alzheimer's disease interviewed patients believe that the main pain points of existing treatment drugs in the market are high price (64.
87%), poor efficacy (63.
79%) and more side effects (34.
74%).

With the continuous increase of life expectancy in our country, Alzheimer's disease has become a serious disease threatening the health and quality of life of the elderly in an aging society.

According to the Global Health Estimates Report 2019 released by the World Health Organization in 2020, among the top ten causes of death in the world in the past 20 years, Alzheimer's disease and other forms of dementia alone have been among the top ten causes of death in the world.

The most basic and often earliest clinical manifestation of AD is selective memory impairment, but there are exceptions.

In fact, many years before the clinical signs of AD were observed, peptide plaques containing misfolding were formed in the brain, called amyloid β (Aβ) protein.

These plaques and neurofibrillary tangles together constitute the pathological hallmark of the disease.

In addition, although some treatments may temporarily improve symptoms, no treatment can stop or reverse their progression.
Patients will gradually get worse.
Although the rate of progression will vary, the typical life expectancy after diagnosis is 3-9 years.

AD is the top priority of global health, so the scientific community has never stopped exploring its causes and diagnosis and treatment methods.

On May 14, 2021, a large-scale study on plasma protein and AD published in the journal Nature Aging clarified the biological characteristics of AD, which may help us find a way to treat AD .

The study was led by researchers from the Bloomberg School of Public Health at Johns Hopkins University.
The results are based on a new analysis of blood samples from more than 10,000 middle-aged and elderly people.

Researchers linked abnormal blood levels of 38 proteins to a higher risk of AD within five years.

The results showed that of these 38 proteins, 16 seem to be able to predict the risk of AD 20 years in advance.

The preliminary analysis covered the protein levels of nearly 5,000 blood samples from 2011-2013 and more than 11,000 blood samples from 1993-1995.

In order to verify these findings in different patient groups, the researchers also reviewed the results of blood samples during the 2002-2006 Iceland study.

The study tested proteins, including 13 of the 16 proteins found in the previous analysis.

The results showed that of these 13 proteins, 6 were once again proved to be associated with AD risk during approximately 10 years of follow-up.

Two studies have shown that 6 proteins have been proved to be associated with AD risk, among which SVEP1 is strongly correlated.
In further statistical analysis, the researchers compared the identified proteins with the data from previous studies on the genetic link of AD.

The comparison results strongly indicate that one of the identified proteins, SVEP1, is not just an accidental marker of AD risk, but is involved in the trigger or drive of the disease.

SVEP1 is a protein, and its normal function is still somewhat mysterious.

A study published earlier this year showed that it is related to thickening of the arteries, or atherosclerosis, which is the basis for heart attacks and strokes.

In this new study, other proteins related to AD risk include several key immune proteins, which are consistent with decades of research that have linked AD to abnormally strong immune activity in the brain.

In short, the development of dementia in the later stages of life is related to abnormal levels of dozens of proteins in the blood for five years.

We did not know that some proteins are related to dementia, and this research provides new targets for preventive therapy.

Although most of these risk markers may only be accidental by-products of the slow disease process leading to AD, this analysis pointed out that the high level of SVEP1 results seems to indicate a causal relationship with the disease.

The senior author of the study, Professor Josef Coresh, MD, pointed out: "This is the most comprehensive analysis to date, and it reveals a variety of biological pathways related to AD.

" Scientists generally believe that the best treatment for Alzheimer's disease The timing is before the symptoms of dementia appear.

Some of the proteins discovered in the study may only be incidental indicators of the occurrence of diseases, but a subset of them may be causal, which provides the possibility for targeted treatments in the future.

Before the appearance of dementia symptoms, people mainly used the aforementioned Aβ protein and tau protein to measure the risk of AD.

Studies have shown that brain imaging of plaques, and the levels of Aβ protein or tau protein in blood or cerebrospinal fluid, have certain value in predicting Alzheimer's disease several years in advance.

But the measurement technology of blood or cerebrospinal fluid samples also needs continuous improvement.

Are there other ways to find the harbinger of AD? A recent study on retinal scanning is trying to answer this question.

A study by the Weir Institute of Neuroscience at the University of California, San Francisco, shows that retinal scans can detect critical changes in blood vessels, which may provide early signs of Alzheimer’s disease and at the same time be the most common risk of Alzheimer’s disease.
How one of the genes contributes to the disease provides important insights; the study was published on May 11 in the journal Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring.

The most common genetic risk of AD is a variant of the APOE gene, called APOE4.

This study in mice explored the effects of APOE4 on the capillaries in the brain.

In theory, tiny blood vessels may play an important role in AD because they transport nutrients and oxygen through the blood-brain barrier, take away waste products, and monitor the immune system's response.

The damage of these blood vessels can lead to a series of problems, including protein accumulation and cognitive decline in AD patients.

Since there is currently no technology that can visualize individual capillaries in a living human brain, the researchers turned their research goals to the eyes.

They used an advanced retinal imaging technique, optical coherence tomography (OCTA), to peer into the eyes of elderly people with and without APOE4 variants to assess the condition of the capillaries behind the eyes.

The results showed that the capillary density of APOE4 carriers decreased, and this effect increased with the age of the participants.

Single comparison of optical coherence tomography angiography (OCTA) scans of carriers and non-carriers.
Capillary changes associated with APOE4 can be detected on humans with a simple and comfortable eye scan.

Researchers believe that as a light-transmitting tissue that shares biology with the brain, the retina may help determine the effects that APOE4 variants may have on similar capillaries in the brain.

The research team also found that capillary density did not differ between groups with and without amyloid plaques, nor did it change with the burden of amyloid plaques.

This independence suggests that capillary abnormalities are unlikely to be driven by amyloid pathology, or that their relationship is at best indirect.

This is the first time that scientists have demonstrated that the smallest blood vessels are affected by carriers of the APOE4 gene in asymptomatic, alive people.

This suggests that the brain degeneration and the increased risk of AD in APOE4 gene carriers may be through the effects on blood vessels.

This work may help detect the onset of AD before major damage to the brain occurs and identify new blood vessel targets for early treatment.

In short, early detection and possible interventions may be of great significance in combating AD and other neurodegenerative diseases.

Although existing treatments can improve some of the symptoms of the disease, there is currently no cure or delay the course of the disease, and all patients cannot avoid disease progression.

Global research on measures to prevent or delay the onset of AD often produces inconsistent results.

Only further research, including clinical trials, can reveal whether these factors can help prevent AD.

References: 1.
Large-scale plasma proteomic analysis identifies proteins and pathways associated with dementia risk.
Nature Aging, 2021; DOI: 10.
1038/s43587-021-00064-02.
Retinal imaging demonstrates reduced capillary density in clinically unimpaired APOE ε4 gene carriers .
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 2021;DOI: 10.
1002/dad2.
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