Professor Du Yifeng: What issues should be paid attention to in AD diagnosis?

*Only for medical professionals to refer to the diagnostic criteria, diagnostic markers, timing and content of detection.
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Alzheimer's disease (AD) is the most common neurodegenerative disease with a long course of disease and a high disability rate.
The patient's family and society bring a huge spiritual and economic burden
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At present, there are still many questions that need to be considered in the diagnosis and treatment of AD.
These questions inspire us clinicians and promote our further exploration of AD diagnosis and treatment
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At the 14th Annual Meeting of Neurologists of the Chinese Medical Doctor Association, Professor Du Yifeng from the Department of Neurology of Shandong Provincial Hospital gave a wonderful report on the topic of "Problems that Need to Be Concerned in the Diagnosis of AD"
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01AD's background Figure 1: AD's historical background Professor Du Yifeng introduced: Since the discovery of AD, the exploration of AD diagnosis and treatment has not stopped
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So far, clinical diagnosis is still the mainstay of AD.
In addition to clinical manifestations, neuropsychological evaluation and neuroimaging are the important clinical diagnosis basis for most hospitals in China
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However, there are no modified treatment methods and measures to change the course of AD in the treatment of AD.
Therefore, the diagnosis level of AD needs to be improved urgently, and more clinical and basic research is needed to explore
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02Focus on the evolution of AD diagnostic criteria, 1984 edition: The first diagnostic criteria for AD was jointly developed by the American Institute of Neurolinguistic Disorders and Stroke-Alzheimer's Disease and Related Diseases Association Working Group
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1994 edition: The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, which incorporates the diagnostic criteria for dementia and AD
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2007 version: The new standard breaks the previous model of AD exclusionary diagnosis, and for the first time realizes the active identification and diagnosis of AD through the combination of neuropsychological features and biomarkers
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2018: NIA-AA research (diagnosis) framework, suggesting the important significance of markers in the diagnosis of AD
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Figure 2: Evolution and review of AD diagnostic criteria (1) Figure 3: Evolution and review of AD diagnostic criteria (2) Therefore, Professor Du Yifeng emphasized that from the perspective of the evolution and review of AD diagnostic criteria, the development of biomarkers The status is becoming more and more important, and it is also an important way for us to diagnose early and increase the positive rate of diagnosis
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03 Pay attention to AD diagnostic markers▌ AD dynamic biomarker cascade hypothesis (dynamic biomarker cascade) 1.
Amyloid pathological changes and neurodegeneration have occurred before the appearance of clinical symptoms of AD; 2.
The sequence of neurodegenerative pathological changes The sequence is: Aβ aggregation→tau protein phosphorylation→synaptic dysfunction-abnormal brain structure-decreased cognitive function; 3.
This hypothesis proposes that all clinical stages of AD (including pre-MCI stage, MCI stage and dementia stage) are present Specific markers reflecting its pathophysiological characteristics
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Figure 4: AD dynamic biomarker waterfall hypothesis Professor Du Yifeng emphasized: From the pathological changes of AD to the appearance of clinical symptoms is a continuous disease process.
The entire process of AD occurrence and development involves the participation of multiple markers, and understand the markers of each stage , Diagnosing and intervening as early as possible will achieve multiplier results with half the effort
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▌ Markers of cerebrospinal fluid Core markers of cerebrospinal fluid: Aβ40, Aβ42, t-tau, p-tau181
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New markers of cerebrospinal fluid: 1.
Axon and synaptic function damage: neurogranin, SNAP25, neuronal sensitivity protein VLP1; 2.
glial cell markers: chitinase protein 40 (YKL-40), soluble TREM2
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Professor Du Yifeng introduced that from the current research and meta-analysis, it can be seen that the most important marker is the marker of cerebrospinal fluid, so the marker of cerebrospinal fluid is an important support for the diagnosis of AD
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However, cerebrospinal fluid markers also have their shortcomings.
They are traumatic and expensive but not popular.
Therefore, while paying attention to cerebrospinal fluid markers, it is also necessary to pay attention to peripheral biomarkers
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Figure 5: Meta-analysis of cerebrospinal fluid blood markers▌ Peripheral blood markers Aβ40, Aβ42, tau, NFL in peripheral blood have a certain value in the diagnosis of AD; plasma Ab42 and Ab40/Ab42 ratios are more consistent with cerebrospinal fluid; plasma Ab42 is more effective Reflects Amyloid deposition in cerebrospinal fluid; plasma Aβ level is an early indicator of pathological changes in AD patients; in the Formingham cohort study, people with a moderately elevated peripheral blood tau protein at baseline have a significantly higher probability of developing AD than those with low levels ; Peripheral blood tau protein levels are related to auditory vocabulary tests, visual memory and visual spatial function; suggesting that peripheral blood tau protein can be used to predict the occurrence of AD
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In recent years, a number of studies have shown that the level of NFL in the peripheral blood of AD patients and MCI patients is significantly higher than that of the normal control group, and its diagnostic sensitivity and specificity are consistent with indicators such as cerebrospinal fluid Aβ and tau
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It suggests that NFL in peripheral blood can be used as an effective biomarker for diagnosis and prediction of AD
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In recent years, nature medicine studies have found that the dynamic changes of NFL can predict the transition of AD from asymptomatic stage to dementia stage
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Figure 6: Nature medicine research▌ Imaging markers Imaging markers include: anatomical imaging, pathological imaging, vascular imaging, functional imaging, and molecular imaging
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Figure 7: Common methods of imaging markers 04AD detection timing and content ▌ Detection timing: ①Pre-clinical AD stage (PCAD; Pre-MCI): This stage may be as long as 15-20 years without any symptoms and can be detected AD pathological biomarkers (such as Aβ42 and Tau protein, only pathological biomarkers); ②MCI stage: neuropsychological + pathological biomarkers can be detected at this stage; ③AD dementia stage: neuropsychological + can be detected at this stage Pathological biomarkers
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▌ Test content: ①Diagnostic markers: cerebrospinal fluid Aβ42, phosphorylated Tau protein/total Tau protein, amyloid PET and autosomal dominant pathogenic genes; ②Progress markers: brain structure MRI and FDG PET
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▌ Differential diagnostic and therapeutic testing: ①Blood test: complete blood count (CBC), metabolic function assessment, vitamin B12, etc.
; ②infection: such as syphilis antibody test, herpes virus, Lyme disease, fungus, etc.
; ③homocysteine Amino acid: This amino acid has a direct causal relationship with brain atrophy and the formation of AD; ④Diabetes: pre-diabetes, fasting insulin level; ⑤Hormone status: check thyroid function, thyroxine detection indicators; ⑥Toxin exposure: mercury and aluminum, etc.
⑦Body mass index (BMI): obesity
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Summary: A biomarker is an objectively measurable substance that can assess disease risk or prognosis, and is of great significance to the diagnosis and treatment of AD
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The diagnostic markers of AD currently mainly include two types: one is a marker of brain Aβ deposition, cerebrospinal fluid Aβ42 reduction and PETAβ imaging; the other is a biomarker of neuronal damage, including increased cerebrospinal fluid tau protein, FDG PET display Decreased glucose metabolism in the temporal parietal cortex and structural MRI showed atrophy of the basal, medial or lateral temporal lobe, and atrophy of the medial parietal cortex
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Combining AD early imaging markers with body fluids and other markers to construct a comprehensive early warning model of dementia is an important content of future AD prevention and treatment
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